|
1
|
Cai M, Wu X, Jin H, Li Z, Li Y, Chen Z. Association of serum folate concentrations with cancer mortality among patients with arthritis: a prospective cohort study. BMC Public Health 2024; 24:3494. [PMID: 39696139 DOI: 10.1186/s12889-024-21004-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Accepted: 12/06/2024] [Indexed: 12/20/2024] Open
Abstract
BACKGROUND Patients with arthritis exhibit abnormal serum folate concentrations and have a higher incidence of cancer. The aim of this study was to investigate the association of serum folate concentrations with cancer mortality among individuals with arthritis. METHODS This cohort study included 7,514 patients with arthritis from National Health and Nutrition Examination Survey (NHANES) 1999 to 2016 and NHANES III (1988-1994). Death outcomes were ascertained by linkage to National Death Index records through 31 December 2019. Serum folate concentrations were categorized into 4 groups, group 1 (≤ 17 nmol/L); group 2 (17-≤34 nmol/L); group 3 (34-≤51 nmol/L); and group 4 (> 51 nmol/L). Cox regression models were used to calculate hazard ratios and 95% confidence intervals for the associations between folate concentrations and the risk of mortality. RESULTS During a median follow-up of 9.75 [interquartile range, IQR, 5.75-14.5] years, there were 2,602 all-cause deaths, 949 deaths due to cardiovascular disease, and 478 deaths due to cancer. A non-linear association was observed for folate concentrations with the risk of cancer mortality (P < 0.001) among arthritis patients. Compared with the reference group 2, the hazard ratios for cancer mortality were 1.75 (95% CI, 1.15-2.69) in group 1, 1.70 (95% CI, 1.17-2.46) in group 3, and 1.60 (95% CI, 1.13-2.25) in group 4. CONCLUSIONS This study shows that both low and high levels of serum folate are associated with an increased risk of cancer mortality among individuals with arthritis, indicating a potential beneficial role of maintaining moderate serum folate concentrations in decreasing the risk of cancer mortality among this population.
Collapse
Affiliation(s)
- Minglong Cai
- Department of Rheumatology and Immunology, Division of Life Sciences and Medicine, the First Affiliated Hospital of USTC, University of Science and Technology of China, 230001, Hefei, Anhui, China
| | - Xiaoting Wu
- Department of Gynecology, Division of Life Sciences and Medicine, the First Affiliated Hospital of USTC, University of Science and Technology of China, 230001, Hefei, Anhui, China
| | - Huizhi Jin
- Department of Rheumatology and Immunology, Division of Life Sciences and Medicine, the First Affiliated Hospital of USTC, University of Science and Technology of China, 230001, Hefei, Anhui, China
| | - Zhenyu Li
- Department of Rheumatology and Immunology, Division of Life Sciences and Medicine, the First Affiliated Hospital of USTC, University of Science and Technology of China, 230001, Hefei, Anhui, China
| | - Yujing Li
- Department of Rheumatology and Immunology, Division of Life Sciences and Medicine, the First Affiliated Hospital of USTC, University of Science and Technology of China, 230001, Hefei, Anhui, China
| | - Zhu Chen
- Department of Rheumatology and Immunology, Division of Life Sciences and Medicine, the First Affiliated Hospital of USTC, University of Science and Technology of China, 230001, Hefei, Anhui, China.
| |
Collapse
|
|
2
|
Chai GS, Gong J, Mao YM, Wu JJ, Bi SG, Wang F, Zhang YQ, Shen MT, Lei ZY, Nie YJ, Yu H. H3K4 Trimethylation Mediate Hyperhomocysteinemia Induced Neurodegeneration via Suppressing Histone Acetylation by ANP32A. Mol Neurobiol 2024; 61:6788-6804. [PMID: 38351418 DOI: 10.1007/s12035-024-03995-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Accepted: 01/29/2024] [Indexed: 08/22/2024]
Abstract
Homocysteine (Hcy) is an independent and serious risk factor for dementia, including Alzheimer's disease (AD), but the precise mechanisms are still poorly understood. In the current study, we observed that the permissive histone mark trimethyl histone H3 lysine 4 (H3K4me3) and its methyltransferase KMT2B were significantly elevated in hyperhomocysteinemia (HHcy) rats, with impairment of synaptic plasticity and cognitive function. Further research found that histone methylation inhibited synapse-associated protein expression, by suppressing histone acetylation. Inhibiting H3K4me3 by downregulating KMT2B could effectively restore Hcy-inhibited H3K14ace in N2a cells. Moreover, chromatin immunoprecipitation revealed that Hcy-induced H3K4me3 resulted in ANP32A mRNA and protein overexpression in the hippocampus, which was regulated by increased transcription Factor c-fos and inhibited histone acetylation and synapse-associated protein expression, and downregulating ANP32A could reverse these changes in Hcy-treated N2a cells. Additionally, the knockdown of KMT2B restored histone acetylation and synapse-associated proteins in Hcy-treated primary hippocampal neurons. These data have revealed a novel crosstalk mechanism between KMT2B-H3K4me3-ANP32A-H3K14ace, shedding light on its role in Hcy-related neurogenerative disorders.
Collapse
Affiliation(s)
- Gao-Shang Chai
- Department of Fundamental Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, 214122, People's Republic of China.
| | - Juan Gong
- Department of Fundamental Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, 214122, People's Republic of China
| | - Yu-Ming Mao
- Department of Fundamental Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, 214122, People's Republic of China
| | - Jia-Jun Wu
- Department of Electrophysiology, Wuhan Children's Hospital (Wuhan Maternal and Children's Healthcare Center), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430010, People's Republic of China
| | - Shu-Guang Bi
- Department of Fundamental Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, 214122, People's Republic of China
| | - Fangzhou Wang
- Department of Fundamental Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, 214122, People's Republic of China
| | - Yu-Qi Zhang
- Department of Fundamental Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, 214122, People's Republic of China
| | - Meng-Ting Shen
- Department of Fundamental Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, 214122, People's Republic of China
| | - Zhuo-Ya Lei
- Department of Fundamental Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, 214122, People's Republic of China
| | - Yun-Juan Nie
- Department of Fundamental Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, 214122, People's Republic of China
| | - Haitao Yu
- Department of Fundamental Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, 214122, People's Republic of China.
| |
Collapse
|
|
3
|
Ting CP, Ma MC, Chang HI, Huang CW, Chou MC, Chang CC. Diet Pattern Analysis in Alzheimer's Disease Implicates Gender Differences in Folate-B12-Homocysteine Axis on Cognitive Outcomes. Nutrients 2024; 16:733. [PMID: 38474861 DOI: 10.3390/nu16050733] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 02/24/2024] [Accepted: 02/29/2024] [Indexed: 03/14/2024] Open
Abstract
BACKGROUND & AIMS Low plasma B12 and folate levels or hyperhomocysteinemia are related to cognitive impairment. This study explores the relationships among diet pattern, blood folate-B12-homocysteine levels, and cognition measurement in Alzheimer's disease (AD) while exploring whether a gender effect may exist. METHODS This cross-sectional study enrolled 592 AD patients (246 males, 346 females) and the demographic data, blood biochemical profiles, Mini-Mental State Examination (MMSE), and a Food Frequency Questionnaire (FFQ) for quantitative assessment of dietary frequency were collected. Structural Equation Modeling (SEM) was employed to explore the associations among dietary patterns, blood profiles, and cognition. A least absolute shrinkage and selection operator regression model, stratified by gender, was constructed to analyze the weighting of possible confounders. RESULTS Higher MMSE scores were related to higher frequencies of coffee/tea and higher educational levels, body mass index, and younger age. The SEM model revealed a direct influence of dietary frequencies (skimmed milk, thin pork, coffee/tea) and blood profiles (homocysteine, B12, and folate) on cognitive outcomes. At the same time, the influence of dietary pattern on cognition was not mediated by folate-B12-homocysteine levels. In males, a direct influence on the MMSE is attributed to B12, while in females, homocysteine is considered a more critical factor. CONCLUSIONS Dietary patterns and blood profiles are both associated with cognitive domains in AD, and there are gender differences in the associations of dietary patterns and the levels of B12 and homocysteine. To enhance the quality of dietary care and nutritional status for individuals with dementia, our study results still require future validations with multi-center and longitudinal studies.
Collapse
Affiliation(s)
- Chi-Ping Ting
- Department of Nursing, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan
- School of Nursing, Meiho University, Pingtung 91202, Taiwan
| | - Mi-Chia Ma
- Department of Statistics, National Cheng Kung University, Tainan 704, Taiwan
| | - Hsin-I Chang
- Department of Neurology, Cognition and Aging Center, Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta Pei Road, Kaohsiung 83301, Taiwan
| | - Chi-Wei Huang
- Department of Neurology, Cognition and Aging Center, Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta Pei Road, Kaohsiung 83301, Taiwan
| | - Man-Chun Chou
- School of Nursing, Meiho University, Pingtung 91202, Taiwan
- School of Nursing, Fooyin University, Kaohsiung 83102, Taiwan
| | - Chiung-Chih Chang
- Department of Neurology, Cognition and Aging Center, Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta Pei Road, Kaohsiung 83301, Taiwan
- School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung 80421, Taiwan
| |
Collapse
|
|
4
|
Gillies NA, Milan AM, Cameron-Smith D, Mumme KD, Conlon CA, von Hurst PR, Haskell-Ramsay CF, Jones B, Roy NC, Coad J, Wall CR, Beck KL. Vitamin B and One-Carbon Metabolite Profiles Show Divergent Associations with Cardiometabolic Risk Markers but not Cognitive Function in Older New Zealand Adults: A Secondary Analysis of the REACH Study. J Nutr 2023; 153:3529-3542. [PMID: 37863266 DOI: 10.1016/j.tjnut.2023.10.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Revised: 10/05/2023] [Accepted: 10/16/2023] [Indexed: 10/22/2023] Open
Abstract
BACKGROUND Vitamin B inadequacies and elevated homocysteine status have been associated with impaired cognitive and cardiometabolic health with aging. There is, however, a scarcity of research investigating integrated profiles of one-carbon (1C) metabolites in this context, including metabolites of interconnected folate, methionine, choline oxidation, and transsulfuration pathways. OBJECTIVES The study aimed to examine associations between vitamins B and 1C metabolites with cardiometabolic health and cognitive function in healthy older adults, including the interactive effects of Apolipoprotein E-ε4 status. METHODS Three hundred and thirteen healthy participants (65-74 y, 65% female) were analyzed. Vitamins B were estimated according to dietary intake (4-d food records) and biochemical status (serum folate and vitamin B12). Fasting plasma 1C metabolites were quantified by liquid chromatography with tandem mass spectrometry. Measures of cardiometabolic health included biochemical (lipid panel, blood glucose) and anthropometric markers. Cognitive function was assessed by the Computerized Mental Performance Assessment System (COMPASS) and Montreal Cognitive Assessment (MoCA). Associations were analyzed using multivariate linear (COMPASS, cardiometabolic health) and Poisson (MoCA) regression modeling. RESULTS Over 90% of participants met dietary recommendations for riboflavin and vitamins B6 and B12, but only 78% of males and 67% of females achieved adequate folate intakes. Higher serum folate and plasma betaine and glycine concentrations were associated with favorable cardiometabolic markers, whereas higher plasma choline and homocysteine concentrations were associated with greater cardiometabolic risk based on body mass index and serum lipids concentration values (P< 0.05). Vitamins B and homocysteine were not associated with cognitive performance in this cohort, though higher glycine concentrations were associated with better global cognitive performance (P = 0.017), episodic memory (P = 0.016), and spatial memory (P = 0.027) scores. Apolipoprotein E-ε4 status did not modify the relationship between vitamins B or 1C metabolites with cognitive function in linear regression analyses. CONCLUSIONS Vitamin B and 1C metabolite profiles showed divergent associations with cardiometabolic risk markers and limited associations with cognitive performance in this cohort of healthy older adults.
Collapse
Affiliation(s)
- Nicola A Gillies
- The Liggins Institute, The University of Auckland, New Zealand; The Riddet Institute, New Zealand
| | - Amber M Milan
- The Liggins Institute, The University of Auckland, New Zealand; The High-Value Nutrition National Science Challenge, New Zealand; AgResearch Ltd, Grasslands Research Centre, New Zealand
| | - David Cameron-Smith
- The Liggins Institute, The University of Auckland, New Zealand; The Riddet Institute, New Zealand; School of Agriculture, Food and Ecosystem Sciences, The University of Melbourne, Australia
| | - Karen D Mumme
- School of Sport Exercise and Nutrition, Massey University, New Zealand
| | - Cathryn A Conlon
- School of Sport Exercise and Nutrition, Massey University, New Zealand
| | | | | | - Beatrix Jones
- Department of Statistics, University of Auckland, New Zealand; The High-Value Nutrition National Science Challenge, New Zealand
| | - Nicole C Roy
- The Riddet Institute, New Zealand; The High-Value Nutrition National Science Challenge, New Zealand; Department of Human Nutrition, University of Otago, New Zealand
| | - Jane Coad
- College of Sciences, Massey University, New Zealand
| | - Clare R Wall
- Discipline of Nutrition and Dietetics, University of Auckland, Auckland, New Zealand
| | - Kathryn L Beck
- School of Sport Exercise and Nutrition, Massey University, New Zealand.
| |
Collapse
|
|
5
|
Luzzi S, Cherubini V, Falsetti L, Viticchi G, Silvestrini M, Toraldo A. Homocysteine, Cognitive Functions, and Degenerative Dementias: State of the Art. Biomedicines 2022; 10:2741. [PMID: 36359260 PMCID: PMC9687733 DOI: 10.3390/biomedicines10112741] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2022] [Revised: 10/19/2022] [Accepted: 10/25/2022] [Indexed: 07/30/2023] Open
Abstract
There is strong evidence that homocysteine is a risk factor not only for cerebrovascular diseases but also for degenerative dementias. A recent consensus statement renewed the importance and the role of high levels of homocysteine in cognitive decline in several forms of degenerative dementia, such as Alzheimer's disease. Although the molecular mechanisms by which homocysteine causes cell dysfunction are known, both the impact of homocysteine on specific cognitive functions and the relationship between homocysteine level and non-Alzheimer dementias have been poorly investigated. Most of the studies addressing the impact of hyperhomocysteinemia on dementias have not examined the profile of performance across different cognitive domains, and have only relied on screening tests, which provide a very general and coarse-grained picture of the cognitive status of the patients. Yet, trying to understand whether hyperhomocysteinemia is associated with the impairment of specific cognitive functions would be crucial, as it would be, in parallel, learning whether some brain circuits are particularly susceptible to the damage caused by hyperhomocysteinemia. These steps would allow one to (i) understand the actual role of homocysteine in the pathogenesis of cognitive decline and (ii) improve the diagnostic accuracy, differential diagnosis and prognostic implications. This review is aimed at exploring and revising the state of the art of these two strictly related domains. Suggestions for future research are provided.
Collapse
Affiliation(s)
- Simona Luzzi
- Neurology Unit, Department of Experimental and Clinical Medicine, Polytechnic University of Marche, 60126 Ancona, Italy
| | - Veronica Cherubini
- Neurology Unit, Department of Experimental and Clinical Medicine, Polytechnic University of Marche, 60126 Ancona, Italy
| | - Lorenzo Falsetti
- Internal and Subintensive Medicine Department, Azienda Ospedaliero-Universitaria “Ospedali Riuniti” di Ancona, 60126 Ancona, Italy
| | - Giovanna Viticchi
- Neurology Unit, Azienda Ospedaliero-Universitaria “Ospedali Riuniti” di Ancona, 60126 Ancona, Italy
| | - Mauro Silvestrini
- Neurology Unit, Department of Experimental and Clinical Medicine, Polytechnic University of Marche, 60126 Ancona, Italy
| | - Alessio Toraldo
- Department of Brain and Behavioral Sciences, University of Pavia, 27100 Pavia, Italy
- Milan Center for Neuroscience (NeuroMI), 20126 Milan, Italy
| |
Collapse
|
|
6
|
One-Carbon Metabolism Biomarkers and Risks of Incident Neurocognitive Disorder among Cognitively Normal Older Adults. Nutrients 2022; 14:nu14173535. [PMID: 36079793 PMCID: PMC9459953 DOI: 10.3390/nu14173535] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Revised: 08/22/2022] [Accepted: 08/24/2022] [Indexed: 11/17/2022] Open
Abstract
There is a lack of evidence supporting an association between folate and vitamin B12 exposure with cognitive outcomes. We examined serum folate and vitamin B12 and plasma homocysteine in 690 cognitively-normal adults (aged ≥ 55) from the Singapore Longitudinal Aging Study (SLAS-2) followed-up over 4.5 years on incident neurocognitive disorder (NCD): mild cognitive impairment (MCI) and dementia. At follow-up, 5.7% (39) of participants developed NCD (34 MCI and 5 dementia). Comparing with those who remained cognitively-normal, participants progressed to NCD had significantly lower mean baseline vitamin B12 (420 [SD ± 221] vs. 510 [SD ± 290] pmol/L, p = 0.026), higher homocysteine (14.6 [SD ± 4.2] vs. 12.9 [SD ± 4.3], p = 0.018) and lower one-carbon index (Z-scores: −0.444 [SD ± 0.819] vs. −0.001 [SD ± 0.990], p = 0.006). Adjusted for confounders, significant associations with incident NCD were found for lower vitamin B12 (per-SD OR = 2.10, 95%CI = 1.26–3.52), higher homocysteine (per-SD OR = 1.96, 95%CI = 1.18–3.24) and lower one-carbon index (per-SD OR = 1.67, 95%CI = 1.06–2.64). Folate was not significantly associated with progression to NCD. Notably, low B12 in the presence of high folate was significantly associated with incident NCD (adjusted OR = 3.81, 95%CI = 1.04–13.9). Low B12, high homocysteine, low B12 in the presence of high folate, and a one-carbon index of hypo-methylation were independently associated with progression to NCD among cognitively normal.
Collapse
|
|
7
|
Pravst I, Lavriša Ž, Hribar M, Hristov H, Kvarantan N, Seljak BK, Gregorič M, Blaznik U, Gregorič N, Zaletel K, Oblak A, Osredkar J, Žmitek K, Kušar A. Dietary Intake of Folate and Assessment of the Folate Deficiency Prevalence in Slovenia Using Serum Biomarkers. Nutrients 2021; 13:3860. [PMID: 34836112 PMCID: PMC8620305 DOI: 10.3390/nu13113860] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Revised: 10/21/2021] [Accepted: 10/25/2021] [Indexed: 12/26/2022] Open
Abstract
Folate deficiency is associated with various health issues, including anemia, cardiovascular disease, and birth defects. Low folate intake and suboptimal folate status were found in several countries; however, this topic has not yet been investigated in Slovenia. Dietary folate intake and serum folate status were investigated through the nationally representative food consumption study SI.Menu/Nutrihealth. Folate intake was estimated using a sample of N = 1248 subjects aged 10-74 years, stratified in three age groups (adolescents, adults, elderly population), through two 24 h-dietary recalls and food propensity questionnaire. Data on serum folate and homocysteine was available for 280 participants. Very low folate intake (<300 µg/day) was observed in 59% of adolescents, 58% of adults and 68% of elderlies, and only about 12% achieved the WHO recommended level of 400 µg/day. Major dietary contributors were vegetables and fruit, and cereal products. Living environment, education, employment status and BMI were linked with low folate intake in adults; BMI, and sex in adolescents; and sex in elderlies. Considering low serum folate (<7 nmol/L) and high serum homocysteine (>15 nmol/L), folate deficiency was found in 7.6 and 10.5% in adults and elderlies, respectively. Additional public health strategies should be employed to promote the consumption of folate-rich foods. With current folate intakes, supplementation with folic acid is relevant especially in specific vulnerable populations, particularly in women planning and during pregnancy.
Collapse
Affiliation(s)
- Igor Pravst
- Nutrition Institute, Tržaška cesta 40, SI-1000 Ljubljana, Slovenia; (Ž.L.); (M.H.); (H.H.); (N.K.); (K.Ž.); (A.K.)
- Biotechnical Faculty, University of Ljubljana, Jamnikarjeva 101, SI-1000 Ljubljana, Slovenia
- VIST–Higher School of Applied Sciences, Gerbičeva cesta 51A, SI-1000 Ljubljana, Slovenia
| | - Živa Lavriša
- Nutrition Institute, Tržaška cesta 40, SI-1000 Ljubljana, Slovenia; (Ž.L.); (M.H.); (H.H.); (N.K.); (K.Ž.); (A.K.)
| | - Maša Hribar
- Nutrition Institute, Tržaška cesta 40, SI-1000 Ljubljana, Slovenia; (Ž.L.); (M.H.); (H.H.); (N.K.); (K.Ž.); (A.K.)
- Biotechnical Faculty, University of Ljubljana, Jamnikarjeva 101, SI-1000 Ljubljana, Slovenia
| | - Hristo Hristov
- Nutrition Institute, Tržaška cesta 40, SI-1000 Ljubljana, Slovenia; (Ž.L.); (M.H.); (H.H.); (N.K.); (K.Ž.); (A.K.)
| | - Naska Kvarantan
- Nutrition Institute, Tržaška cesta 40, SI-1000 Ljubljana, Slovenia; (Ž.L.); (M.H.); (H.H.); (N.K.); (K.Ž.); (A.K.)
- Division of Human Nutrition and Health, Wageningen University & Research, NL-6708 Wageningen, The Netherlands
| | | | - Matej Gregorič
- National Institute of Public Health, Trubarjeva 2, SI-1000 Ljubljana, Slovenia; (M.G.); (U.B.)
| | - Urška Blaznik
- National Institute of Public Health, Trubarjeva 2, SI-1000 Ljubljana, Slovenia; (M.G.); (U.B.)
| | - Nadan Gregorič
- University Medical Centre Ljubljana, Zaloška cesta 7, SI-1000 Ljubljana, Slovenia; (N.G.); (K.Z.); (A.O.); (J.O.)
| | - Katja Zaletel
- University Medical Centre Ljubljana, Zaloška cesta 7, SI-1000 Ljubljana, Slovenia; (N.G.); (K.Z.); (A.O.); (J.O.)
- Faculty of Medicine, University of Ljubljana, Vrazov trg 2, SI-1000 Ljubljana, Slovenia
| | - Adrijana Oblak
- University Medical Centre Ljubljana, Zaloška cesta 7, SI-1000 Ljubljana, Slovenia; (N.G.); (K.Z.); (A.O.); (J.O.)
| | - Joško Osredkar
- University Medical Centre Ljubljana, Zaloška cesta 7, SI-1000 Ljubljana, Slovenia; (N.G.); (K.Z.); (A.O.); (J.O.)
- Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, SI-1000 Ljubljana, Slovenia
| | - Katja Žmitek
- Nutrition Institute, Tržaška cesta 40, SI-1000 Ljubljana, Slovenia; (Ž.L.); (M.H.); (H.H.); (N.K.); (K.Ž.); (A.K.)
- VIST–Higher School of Applied Sciences, Gerbičeva cesta 51A, SI-1000 Ljubljana, Slovenia
| | - Anita Kušar
- Nutrition Institute, Tržaška cesta 40, SI-1000 Ljubljana, Slovenia; (Ž.L.); (M.H.); (H.H.); (N.K.); (K.Ž.); (A.K.)
| |
Collapse
|
|
8
|
Teichert J, Cais-Sokolińska D, Bielska P, Danków R, Chudy S, Kaczyński ŁK, Biegalski J. Milk fermentation affects amino acid and fatty acid profile of mare milk from Polish Coldblood mares. Int Dairy J 2021. [DOI: 10.1016/j.idairyj.2021.105137] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
|
|
9
|
Association of Methylenetetrahydrofolate Reductase C677T Gene Polymorphisms with Mild Cognitive Impairment Susceptibility: A Systematic Review and Meta-Analysis. Behav Neurol 2021; 2021:2962792. [PMID: 34580600 PMCID: PMC8464412 DOI: 10.1155/2021/2962792] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2021] [Accepted: 08/26/2021] [Indexed: 12/02/2022] Open
Abstract
Background Methylenetetrahydrofolate reductase (MTHFR) C677T (rs1801133) gene polymorphisms are related to a growing risk of Alzheimer's disease; however, whether this association applies to mild cognitive impairment (MCI) remains unclear. Objective We conducted this meta-analysis to evaluate the contribution of MTHFR C677T (rs1801133) gene variants to the risk of MCI. Methods PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases were searched from their inception to March 21, 2021, with language restricted to English or Chinese. We used fixed or random effects to examine the association between MTHFR C677T (rs1801133) gene variants and MCI susceptibility. Forest plots of pooled odds ratios (ORs) and 95% confidence intervals (CIs) were generated. Results Eight articles with 2,175 participants were included in the present meta-analysis. There was no significant association between MTHFR C677T (rs1801133) gene variants and MCI susceptibility under the allelic (OR, 1.318; 95% CI, 0.964–1.801; p = 0.084), dominant (OR, 1.296; 95% CI, 0.925–1.817; p = 0.132), recessive (OR, 1.397; 95% CI, 0.845–2.312; p = 0.193), heterozygous (OR, 1.031; 95% CI, 0.855–1.243; p = 0.749), or homozygous (OR, 1.506; 95% CI, 0.850–2.667; p = 0.160) models. Conclusion The results suggest that MTHFR C677T (rs1801133) gene polymorphisms are not associated with MCI susceptibility. However, large-scale studies covering various factors are required.
Collapse
|
|
10
|
Zhang C, Luo J, Yuan C, Ding D. Vitamin B12, B6, or Folate and Cognitive Function in Community-Dwelling Older Adults: A Systematic Review and Meta-Analysis. J Alzheimers Dis 2021; 77:781-794. [PMID: 32773392 DOI: 10.3233/jad-200534] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
BACKGROUND Previous studies have indicated that B vitamin deficiencies are an essential cause of neurological pathology. There is a need to provide evidence of the benefit of B vitamins for the prevention of cognitive decline in community-dwelling older adults. OBJECTIVE To examine the association between intake and plasma levels of vitamins B12, B6, and folate and cognitive function in older populations through a systematic review and meta-analysis. METHODS Medline (PubMed), EMBASE, and Cochrane databases were used to search the literature though August 8, 2019. We included observational population-based studies evaluating the association between concentrations or intake levels of vitamins B6, B12, or folate and cognition in older adults aged ≥45 years. The quality of all studies was assessed by the modified Newcastle-Ottawa Scale. Odds ratios (ORs) and hazard ratios (HRs) were analyzed by the random-effects model. Sensitivity analyses were conducted by excluding the studies with significant heterogeneity. RESULTS Twenty-one observational studies with sample sizes ranging from 155-7030 were included in the meta-analysis. Higher levels of vitamin B12 (OR = 0.77, 95% CI = 0.61-0.97) and folate concentration (OR = 0.68, 95% CI = 0.51-0.90) were associated with better cognition in cross-sectional studies, but not in sensitivity analyses or prospective studies. High vitamin B6 concentrations showed no significant benefit on cognition and dementia risk. Prospective studies did not provide substantial evidence for the relationship. CONCLUSION The results from our meta-analysis suggest that vitamins B12, B6, and folate may not be modifiable risk factors for slowing cognitive decline among community-dwelling older individuals.
Collapse
Affiliation(s)
- Chenbo Zhang
- Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China.,NHC Key Laboratory of Health Technology Assessment (Fudan University), Shanghai, China.,Key Laboratory of Public Health Safety of Ministry of Education (Fudan University), Shanghai, China
| | - Jianfeng Luo
- Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China.,NHC Key Laboratory of Health Technology Assessment (Fudan University), Shanghai, China.,Key Laboratory of Public Health Safety of Ministry of Education (Fudan University), Shanghai, China
| | - Changzheng Yuan
- School of Public Health, Zhejiang University, Hangzhou, China
| | - Ding Ding
- Institute of Neurology, Huashan Hospital, Fudan University, Shanghai, China.,National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China
| |
Collapse
|
|
11
|
França VF, Barbosa AR, d’Orsi E. Vitamin B12, Folate and Cognitive Function in Older Adults from Southern Brazil. AGEING INTERNATIONAL 2021. [DOI: 10.1007/s12126-020-09389-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
|
|
12
|
Frank J, Kisters K, Stirban OA, Obeid R, Lorkowski S, Wallert M, Egert S, Podszun MC, Eckert GP, Pettersen JA, Venturelli S, Classen HG, Golombek J. The role of biofactors in the prevention and treatment of age-related diseases. Biofactors 2021; 47:522-550. [PMID: 33772908 DOI: 10.1002/biof.1728] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Revised: 03/03/2021] [Accepted: 03/11/2021] [Indexed: 02/07/2023]
Abstract
The present demographic changes toward an aging society caused a rise in the number of senior citizens and the incidence and burden of age-related diseases (such as cardiovascular diseases [CVD], cancer, nonalcoholic fatty liver disease [NAFLD], diabetes mellitus, and dementia), of which nearly half is attributable to the population ≥60 years of age. Deficiencies in individual nutrients have been associated with increased risks for age-related diseases and high intakes and/or blood concentrations with risk reduction. Nutrition in general and the dietary intake of essential and nonessential biofactors is a major determinant of human health, the risk to develop age-related diseases, and ultimately of mortality in the older population. These biofactors can be a cost-effective strategy to prevent or, in some cases, even treat age-related diseases. Examples reviewed herein include omega-3 fatty acids and dietary fiber for the prevention of CVD, α-tocopherol (vitamin E) for the treatment of biopsy-proven nonalcoholic steatohepatitis, vitamin D for the prevention of neurodegenerative diseases, thiamine and α-lipoic acid for the treatment of diabetic neuropathy, and the role of folate in cancer epigenetics. This list of potentially helpful biofactors in the prevention and treatment of age-related diseases, however, is not exhaustive and many more examples exist. Furthermore, since there is currently no generally accepted definition of the term biofactors, we here propose a definition that, when adopted by scientists, will enable a harmonization and consistent use of the term in the scientific literature.
Collapse
Affiliation(s)
- Jan Frank
- University of Hohenheim, Institute of Nutritional Sciences, Stuttgart, Germany
| | - Klaus Kisters
- Medical Clinic I, St. Anna-Hospital & ESH Excellence Centre, Herne, Germany
| | | | - Rima Obeid
- Department of Clinical Chemistry and Laboratory Medicine, Saarland University Hospital, Homburg/Saar, Germany
| | - Stefan Lorkowski
- Institute of Nutritional Sciences, Friedrich Schiller University Jena, Jena, Germany
- Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD) Halle-Jena-Leipzig, Germany
| | - Maria Wallert
- Institute of Nutritional Sciences, Friedrich Schiller University Jena, Jena, Germany
- Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD) Halle-Jena-Leipzig, Germany
| | - Sarah Egert
- University of Hohenheim, Institute of Nutritional Medicine, Stuttgart, Germany
| | - Maren C Podszun
- University of Hohenheim, Institute of Nutritional Sciences, Stuttgart, Germany
| | - Gunter P Eckert
- Department of Nutritional Sciences, Laboratory for Nutrition in Prevention and Therapy, Justus-Liebig-University of Giessen, Giessen, Germany
| | - Jacqueline A Pettersen
- Northern Medical Program, University of Northern British Columbia, Prince George, Canada
- Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, Canada
| | - Sascha Venturelli
- University of Hohenheim, Institute of Nutritional Sciences, Stuttgart, Germany
| | - Hans-Georg Classen
- University of Hohenheim, Institute of Nutritional Sciences, Stuttgart, Germany
| | | |
Collapse
|
|
13
|
Agarwal V, Joshi I. Need for Nutritious Convenience Foods for the Elderly Population: A Review. CURRENT NUTRITION & FOOD SCIENCE 2021. [DOI: 10.2174/1573401316999201009144719] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Worldwide, the population of elderly persons is rising at a very fast rate. Elderly people
have difficulties in performing day to day activities as the aging process deteriorates the normal
functioning of their body. There is risk of inadequate nutrition because of difficulties in shopping
for food, cooking a meal, chewing and putting food in mouth. Vision loss makes cooking, and even
eating, more difficult. Some elderly people live alone or with their spouses. Cooking for one or two
persons/s is not very stimulating. These changes have a great role to play in changing the eating
habits of the elderly which may affect their nutrient intake. All these factors may cause nutritional
deficiencies, malnutrition and other health problems among them. There are major opportunities to
develop convenience food products in order to meet the changing needs of aging population. In order
to get maximum product acceptance, it is important to combine the elements of convenience
and affordability. While designing products for elderly, it is desirable to modify the food consistency
to assist in swallowing, make it nutrient-dense and design it in a way that it can be easily handled
and eaten. The packaging can be easy to open, information written in large fonts and contrasting
colours to help in easy reading. The availability of nutritious ‘ready-meals’ can serve as an opportunity
for elderly people who do not want to cook or have low interest in cooking. This can provide
a variety of healthier food choices to them and help to reduce malnutrition. Access to nutritious
convenience food products can facilitate a positive intervention to the aging consumers.
Collapse
Affiliation(s)
- Vyoma Agarwal
- Department of Home Science, IIS (Deemed to be University), Jaipur 302020, India
| | - Ila Joshi
- Department of Home Science, IIS (Deemed to be University), Jaipur 302020, India
| |
Collapse
|
|
14
|
Santos IDS, Suemoto CK, ValladÃo-Junior JBR, Liu S, Barreto SM, Fedeli LMG, Lotufo PA, Bensenor IM. Serum folate levels and cognitive performance in the ELSA-Brasil baseline assessment. ARQUIVOS DE NEURO-PSIQUIATRIA 2020; 78:672-680. [PMID: 33263638 DOI: 10.1590/0004-282x20200074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Accepted: 05/13/2020] [Indexed: 11/21/2022]
Abstract
BACKGROUND Most studies that analyze the association between serum folate levels and cognitive function either restrict their assessments to specific clinical scenarios or do not include middle-aged individuals, to whom strategies for preventing cognitive impairment may be more feasible. OBJECTIVE To examine the association between serum folate levels and cognitive function in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) baseline assessment. METHODS Data from 4,571 ELSA-Brasil participants who live in the state of São Paulo, aged 35-74 years, were analyzed. The word list learning, delayed recall, word recognition, verbal fluency, and Trail Making Test Part B consisted in the cognitive tests. For each test, age, sex, and education-specific standardized scores and a global cognitive score were calculated. Crude and adjusted linear regression models were used to examine the associations of serum folate levels with cognitive test scores. RESULTS In multivariable-adjusted models, serum folate was not associated with global cognitive score (β=-0.043; 95% confidence interval [95%CI] -0.135 to 0.050 for lowest vs. highest quintile group), nor with any cognitive test performance. We did not find associations between serum folate and global cognitive scores in subgroups stratified by age, sex, or use of vitamin supplements either. CONCLUSIONS We did not find significant associations between serum folate and cognitive performance in this large sample, which is characterized by a context of food fortification policies and a consequent low frequency of folate deficiency. Positive results from previous studies may not apply to the increasingly common contexts in which food fortification is implemented, or to younger individuals.
Collapse
Affiliation(s)
- Itamar de Souza Santos
- Universidade de São Paulo, Hospital Universitário, Centro de Pesquisa Clínica e Epidemiológica, São Paulo SP, Brazil.,Universidade de São Paulo. Faculdade de Medicina, Departamento de Clínica Médica, São Paulo SP, Brazil
| | - Claudia Kimie Suemoto
- Universidade de São Paulo, Hospital Universitário, Centro de Pesquisa Clínica e Epidemiológica, São Paulo SP, Brazil.,Universidade de São Paulo. Faculdade de Medicina, Departamento de Clínica Médica, São Paulo SP, Brazil
| | | | - Simin Liu
- Brown University, School of Public Health, Department of Epidemiology, Providence, RI, United States of America
| | - Sandhi Maria Barreto
- Universidade Federal de Minas Gerais, Faculdade de Medicina, Departamento de Medicina Preventiva e Social, Belo Horizonte MG, Brazil
| | - Ligia Maria Giongo Fedeli
- Universidade de São Paulo, Hospital Universitário, Centro de Pesquisa Clínica e Epidemiológica, São Paulo SP, Brazil
| | - Paulo Andrade Lotufo
- Universidade de São Paulo, Hospital Universitário, Centro de Pesquisa Clínica e Epidemiológica, São Paulo SP, Brazil.,Universidade de São Paulo. Faculdade de Medicina, Departamento de Clínica Médica, São Paulo SP, Brazil
| | - Isabela Martins Bensenor
- Universidade de São Paulo, Hospital Universitário, Centro de Pesquisa Clínica e Epidemiológica, São Paulo SP, Brazil.,Universidade de São Paulo. Faculdade de Medicina, Departamento de Clínica Médica, São Paulo SP, Brazil
| |
Collapse
|
|
15
|
Blood total antioxidant status is associated with cortical glucose uptake and factors related to accelerated aging. Brain Struct Funct 2020; 225:841-851. [PMID: 32048020 DOI: 10.1007/s00429-020-02039-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2019] [Accepted: 01/29/2020] [Indexed: 12/16/2022]
Abstract
Identifying cerebral vulnerability in late life is of paramount importance to prevent pathological trajectories of aging before the onset of symptoms. Considerable evidence suggests that impaired antioxidant mechanisms are a fingerprint of aging-related conditions, but there is a lack of human research linking total antioxidant capacity (TAC) measured in peripheral blood to in vivo brain changes and other factors featuring accelerated aging. To address this issue, we have assessed in cognitively normal elderly subjects (N = 100) correlations between serum TAC, using the oxygen radical absorbance capacity assay, surface-based cortical thickness, surface-based 18F-fluorodeoxyglucose positron emission tomography cortical uptake, and different factors associated with accelerated aging [i.e., serum homocysteine (HCY), self-reported memory problems, and self-reported patterns of physical activity]. While no relationship was observed between serum TAC and variations in cortical thickness, decreased TAC level was significantly associated with lower FDG uptake in temporal lobes bilaterally. Remarkably, decreased TAC level was linked to increased HCY concentrations, more subjective memory complaints, and lower frequency of physical activity. Overall, our results suggest that decreased serum TAC level may be helpful to detect vulnerable trajectories of aging.
Collapse
|
|
16
|
Trześniowska-Drukała B, Kalinowska S, Safranow K, Kłoda K, Misiak B, Samochowiec J. Evaluation of hyperhomocysteinemia prevalence and its influence on the selected cognitive functions in patients with schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2019; 95:109679. [PMID: 31254573 DOI: 10.1016/j.pnpbp.2019.109679] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2019] [Revised: 05/30/2019] [Accepted: 06/21/2019] [Indexed: 02/07/2023]
Abstract
There is evidence that hyperhomocysteinemia may be associated with the development of schizophrenia and cognitive impairment. Therefore, the aim of this study was to analyze the relationship between cognitive functions and normal homocysteine concentrations vs. hyperhomocysteinemia in schizophrenia patients before and after supplementation with vitamins B6, B12 and folate. An 8-week prospective, non-randomized study enrolled 122 adult patients with schizophrenia (67F/55M, mean age 43.54 ± 11.94 years). Homocysteine concentrations were measured in all individuals and afterwards hyperhomocysteinemia patients (n = 42) were divided into two subgroups: treated with oral vitamins supplementation (B6 - 25 mg/d, B12 - 20 μg/d, folate - 2,5 mg/d) (n = 22) and without supplementation (n = 20). The assessment of schizophrenia symptoms severity in study group was performed using the Positive and Negative Syndrome Scale (PANSS). Cognitive functions were evaluated using the Stroop test and the Trail Making Test (TMT). We observed a higher prevalence of hyperhomocysteinemia in schizophrenia patients (34.4%) in comparison to the general population. Individuals with schizophrenia and coexisting hyperhomocysteinemia had worse performance on the Stroop and the TMT tests as well as higher PANSS scores. In these patients, supplementation with vitamins effectively decreased the homocysteine concentrations to the normal values, however there was no statistically significant improvement in the PANSS and cognitive test scores, except a significant decrease in the number of the Stroop test errors. We conclude that significant results obtained in this study show that there is a relationship between homocysteine blood concentration and schizophrenia severity. Moreover, homocysteine concentration lowering might be beneficial in schizophrenia patients with hyperhomocysteinemia in terms of cognitive functions improvement.
Collapse
Affiliation(s)
| | - Sylwia Kalinowska
- Department of Psychiatry, Pomeranian Medical University, 26 Broniewski Street, 71-460 Szczecin, Poland
| | - Krzysztof Safranow
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, 72 Powstancow Wlkp Street, 70-111 Szczecin, Poland
| | - Karolina Kłoda
- Independent Laboratory of Family Physician Education, Pomeranian Medical University in Szczecin, 1 Rybacka Street, 70-204 Szczecin, Poland
| | - Błażej Misiak
- Department of Genetics, Wroclaw Medical University, 1 Marcinkowski Street, 50-368 Wroclaw, Poland
| | - Jerzy Samochowiec
- Department of Psychiatry, Pomeranian Medical University, 26 Broniewski Street, 71-460 Szczecin, Poland
| |
Collapse
|
|
17
|
Ji Y, Lyu P, Jin W, Li X, Li X, Dong Y. Homocysteine: A modifiable culprit of cognitive impairment for us to conquer? J Neurol Sci 2019; 404:128-136. [DOI: 10.1016/j.jns.2019.07.015] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2019] [Revised: 07/10/2019] [Accepted: 07/11/2019] [Indexed: 12/13/2022]
|
|
18
|
Cajavilca CE, Gadhia RR, Román GC. MTHFR Gene Mutations Correlate with White Matter Disease Burden and Predict Cerebrovascular Disease and Dementia. Brain Sci 2019; 9:brainsci9090211. [PMID: 31443445 PMCID: PMC6770069 DOI: 10.3390/brainsci9090211] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Revised: 08/10/2019] [Accepted: 08/19/2019] [Indexed: 02/02/2023] Open
Abstract
The incidence of dementia is on the rise and expected to continue to increase in the foreseeable future. Two of the most common subtypes of dementia are Alzheimer's subtype and vascular dementia. Hyperhomocysteinemia has been shown to serve as a risk factor for dementia due to an associated blood-brain barrier dysfunction and subsequent small-vessel disease pathology. There are varying causes for hyperhomocysteinemia, including genetic and dietary, among others. We highlight the importance of identifying hyperhomocysteinemia as a potential etiologic and therapeutic target for the most common subtypes of dementia.
Collapse
Affiliation(s)
- Christian E Cajavilca
- Vascular Neurology, Houston Methodist Hospital Neurological Institute, Houston, TX 77030, USA
| | - Rajan R Gadhia
- Vascular Neurology, Houston Methodist Hospital Neurological Institute, Houston, TX 77030, USA.
- Weill Cornell Medical College, Department of Neurology, Cornell University, New York, NY 10065, USA.
| | - Gustavo C Román
- Alzheimer Clinic, Houston Methodist Hospital Neurological Institute, Houston, TX 77030, USA
- Weill Cornell Medical College, Department of Neurology, Cornell University, New York, NY 10065, USA
| |
Collapse
|
|
19
|
Fiocco AJ, Krieger L, D'Amico D, Parrott MD, Laurin D, Gaudreau P, Greenwood C, Ferland G. A systematic review of existing peripheral biomarkers of cognitive aging: Is there enough evidence for biomarker proxies in behavioral modification interventions?: An initiative in association with the nutrition, exercise and lifestyle team of the Canadian Consortium on Neurodegeneration in Aging. Ageing Res Rev 2019; 52:72-119. [PMID: 31059801 DOI: 10.1016/j.arr.2019.04.008] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2018] [Revised: 03/09/2019] [Accepted: 04/29/2019] [Indexed: 12/15/2022]
Abstract
Peripheral biomarkers have shown significant value in predicting brain health and may serve as a useful proxy measurement in the assessment of evidence-based lifestyle behavior modification programs, including physical activity and nutrition programs, that aim to maintain cognitive function in late life. The aim of this systematic review was to elucidate which peripheral biomarkers are robustly associated with cognitive function among relatively healthy non-demented older adults. Following the standards for systematic reviews (PICO, PRIMSA), and employing MEDLINE and Scopus search engines, 222 articles were included in the review. Based on the review of biomarker proxies of cognitive health, it is recommended that a comprehensive biomarker panel, or biomarker signature, be developed as a clinical end point for behavior modification trials aimed at enhancing cognitive function in late life. The biomarker signature should take a multisystemic approach, including lipid, immune/inflammatory, and metabolic biomarkers in the biological signature index of cognitive health.
Collapse
Affiliation(s)
| | - Laura Krieger
- Department of Psychology, Ryerson University, Toronto, ON, Canada
| | - Danielle D'Amico
- Department of Psychology, Ryerson University, Toronto, ON, Canada
| | | | - Danielle Laurin
- Laval University, Centre de recherche du CHU de Québec, QC, Canada
| | | | | | | |
Collapse
|
|
20
|
Pavlov CS, Damulin IV, Shulpekova YO, Andreev EA. Neurological disorders in vitamin B12 deficiency. TERAPEVT ARKH 2019; 91:122-129. [PMID: 31094486 DOI: 10.26442/00403660.2019.04.000116] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The review discusses thesteps of vitamin B12 metabolism and its role in maintaining of neurological functions. The term "vitamin B12 (cobalamin)" refers to several substances (cobalamins) of a very similar structure. Cobalamin enters the body with animal products. On the peripherу cobalamin circulates only in binding with proteins transcobalamin I and II (complex cobalamin-transcobalamin II is designated as "holotranscobalamin"). Holotranscobalamin is absorbed by different cells, whereas transcobalamin I-binded vitamin B12 - only by liver and kidneys. Two forms of cobalamin were identified as coenzymes of cellular reactions which are methylcobalamin (in cytoplasm) and hydroxyadenosylcobalamin (in mitochondria). The main causes of cobalamin deficiency are related to inadequate intake of animal products, autoimmune gastritis, pancreatic insufficiency, terminal ileum disease, syndrome of intestinal bacterial overgrowth. Relative deficiency may be seen in excessive binding of vitamin B12 to transcobalamin I. Cobalamin deficiency most significantly affects functions of blood, nervous system and inflammatory response. Anemia occurs in 13-15% of cases; macrocytosis is an early sign. The average size of neutrophils and monocytes is the most sensitive marker of megaloblastic hematopoiesis. The demands in vitamin B12 are particularly high in nervous tissue. Hypovitaminosis is accompanied by pathological lesions both in white and gray brain matter. Several types of neurological manifestations are described: subacute combined degeneration of spinal cord (funicular myelinosis), sensomotor polyneuropathy, optic nerve neuropathy, cognitive disorders. The whole range of neuropsychiatric disorders with vitamin B12 deficiency has not been studied well enough. Due to certain diagnostic difficulties they are often regarded as "cryptogenic", "reactive", "vascular» origin. Normal or decreased total plasma cobalamin level could not a reliable marker of vitamin deficiency. In difficult cases the content of holotranscobalamin, methylmalonic acid / homocysteine, and folate in the blood serum should be investigated besides carefully analysis of clinical manifestations.
Collapse
Affiliation(s)
- Ch S Pavlov
- I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia
| | - I V Damulin
- I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia
| | - Yu O Shulpekova
- I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia
| | - E A Andreev
- I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia
| |
Collapse
|
|
21
|
Chuang SY, Lo YL, Wu SY, Wang PN, Pan WH. Dietary Patterns and Foods Associated With Cognitive Function in Taiwanese Older Adults: The Cross-sectional and Longitudinal Studies. J Am Med Dir Assoc 2019; 20:544-550.e4. [DOI: 10.1016/j.jamda.2018.10.017] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2018] [Revised: 10/11/2018] [Accepted: 10/12/2018] [Indexed: 12/31/2022]
|
|
22
|
Hooshmand B, Rusanen M, Ngandu T, Leiviskä J, Sindi S, von Arnim CAF, Falkai P, Soininen H, Tuomilehto J, Kivipelto M. Serum Insulin and Cognitive Performance in Older Adults: A Longitudinal Study. Am J Med 2019; 132:367-373. [PMID: 30502316 DOI: 10.1016/j.amjmed.2018.11.013] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2018] [Revised: 11/17/2018] [Accepted: 11/19/2018] [Indexed: 01/26/2023]
Abstract
PURPOSE The aim of this study was to examine the association of serum glucose, insulin, and insulin resistance with cognitive functioning 7 years later in a longitudinal population-based study of Finnish older adults. METHODS Serum glucose and insulin were measured at baseline in 269 dementia-free individuals aged 65-79 years, from the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study. Insulin resistance was estimated with the homeostasis model assessment (HOMA-IR). Participants were reexamined 7 years later, and global cognition, episodic memory, executive functioning, verbal expression, and psychomotor speed were assessed, both at baseline and at follow-up. Multiple linear regression was used to investigate the associations with cognitive performance at follow-up, after adjusting for several potential confounders, including common vascular risk factors. RESULTS In the multivariable-adjusted linear regression models, no associations of insulin resistance with cognitive functioning were observed. After excluding 19 incident dementia cases, higher baseline HOMA-IR values were related to worse performance in global cognition (β [standard error (SE)] -.050 [0.02]; P = .043) and psychomotor speed (β [SE] -.064 [.03]; P = [.043]) 7 years later. Raised serum insulin levels were associated with lower scores on global cognition (β [SE] -.054 [.03]; P = .045) and tended to relate to poorer performance in psychomotor speed (β [SE] -.061 [.03]; P = .070). CONCLUSIONS Serum insulin and insulin resistance may be independent predictors of cognitive performance 7 years later in elderly individuals without dementia. Randomized controlled trials are needed to determine this issue.
Collapse
Affiliation(s)
- Babak Hooshmand
- Aging Research Center, Karolinska Institute, Stockholm, Sweden; Department of Neurology, Ulm University Hospital, Germany.
| | - Minna Rusanen
- Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio; Chronic Disease Prevention Unit, Department of Public Health Solutions, National Institute for Health and Welfare, University of Helsinki, Finland
| | - Tiia Ngandu
- Chronic Disease Prevention Unit, Department of Public Health Solutions, National Institute for Health and Welfare, University of Helsinki, Finland
| | - Jaana Leiviskä
- Genomics and Biomarkers Unit, Department of Public Health Solutions, National Institute for Health and Welfare, University of Helsinki, Finland
| | - Shireen Sindi
- Aging Research Center, Karolinska Institute, Stockholm, Sweden
| | | | - Peter Falkai
- Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Germany
| | - Hilkka Soininen
- Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio; Neurocenter, Neurology, Kuopio University Hospital, Finland
| | - Jaakko Tuomilehto
- Genomics and Biomarkers Unit, Department of Public Health Solutions, National Institute for Health and Welfare, University of Helsinki, Finland; Department of Public Health, HJELT Institute, University of Helsinki, Finland; University of Helsinki, Helsinki University Central Hospital, Finland; South Ostrobothnia Central Hospital, Seinäjoki, Finland; Diabetes Research Group, King Abdulaziz University, Jeddah, Saudi Arabia; Dasman Diabetes Institute, Kuwait City, Kuwait
| | - Miia Kivipelto
- Aging Research Center, Karolinska Institute, Stockholm, Sweden; Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio; Division of Clinical Geriatrics, Center for Alzheimer Research, Karolinska Institute, Stockholm, Sweden
| |
Collapse
|
|
23
|
Román GC, Mancera-Páez O, Bernal C. Epigenetic Factors in Late-Onset Alzheimer's Disease: MTHFR and CTH Gene Polymorphisms, Metabolic Transsulfuration and Methylation Pathways, and B Vitamins. Int J Mol Sci 2019; 20:E319. [PMID: 30646578 PMCID: PMC6359124 DOI: 10.3390/ijms20020319] [Citation(s) in RCA: 59] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2018] [Revised: 01/10/2019] [Accepted: 01/11/2019] [Indexed: 12/17/2022] Open
Abstract
DNA methylation and other epigenetic factors are important in the pathogenesis of late-onset Alzheimer's disease (LOAD). Methylenetetrahydrofolate reductase (MTHFR) gene mutations occur in most elderly patients with memory loss. MTHFR is critical for production of S-adenosyl-l-methionine (SAM), the principal methyl donor. A common mutation (1364T/T) of the cystathionine-γ-lyase (CTH) gene affects the enzyme that converts cystathionine to cysteine in the transsulfuration pathway causing plasma elevation of total homocysteine (tHcy) or hyperhomocysteinemia-a strong and independent risk factor for cognitive loss and AD. Other causes of hyperhomocysteinemia include aging, nutritional factors, and deficiencies of B vitamins. We emphasize the importance of supplementing vitamin B12 (methylcobalamin), vitamin B₉ (folic acid), vitamin B₆ (pyridoxine), and SAM to patients in early stages of LOAD.
Collapse
Affiliation(s)
- Gustavo C Román
- Department of Neurology, Methodist Neurological Institute, Institute for Academic Medicine Houston Methodist Research Institute, Houston Methodist Hospital, Houston, TX 77030, USA.
- Weill Cornell Medical College, Department of Neurology, Cornell University, New York, NY 10065, USA.
| | - Oscar Mancera-Páez
- Universidad Nacional de Colombia, Hospital Universitario Nacional, Faculty of Medicine, Department of Neurology, Bogotá ZC 57, Colombia.
- David Cabello International Alzheimer Disease Scholarship Fund, Houston Methodist Hospital, Houston, TX77030, USA.
| | - Camilo Bernal
- Universidad Nacional de Colombia, Hospital Universitario Nacional, Faculty of Medicine, Department of Neurology, Bogotá ZC 57, Colombia.
| |
Collapse
|
|
24
|
Chhetri J, de Souto Barreto P, Soriano G, Gennero I, Cantet C, Vellas B. Vitamin D, homocysteine and n−3PUFA status according to physical and cognitive functions in older adults with subjective memory complaint: Results from cross-sectional study of the MAPT trial. Exp Gerontol 2018; 111:71-77. [DOI: 10.1016/j.exger.2018.07.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2018] [Revised: 06/25/2018] [Accepted: 07/07/2018] [Indexed: 01/01/2023]
|
|
25
|
Franco ÁDO, Starosta RT, Roriz-Cruz M. The specific impact of uremic toxins upon cognitive domains: a review. ACTA ACUST UNITED AC 2018; 41:103-111. [PMID: 30095142 PMCID: PMC6534037 DOI: 10.1590/2175-8239-jbn-2018-0033] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2018] [Accepted: 05/14/2018] [Indexed: 12/13/2022]
Abstract
One of the mechanisms proposed for chronic kidney disease (CKD)-related cognitive impairment is the accumulation of uremic toxins due to the deterioration of the renal clearance function. Cognition can be categorized into five major domains according to its information processing functions: memory, attention, language, visual-spatial, and executive. We performed a review using the terms 'uric acid', 'indoxyl sulfate', 'p-cresyl sulfate', 'homocysteine', 'interleukins' and 'parathyroid hormone'. These are the compounds that were found to be strongly associated with cognitive impairment in CKD in the literature. The 26 selected articles point towards an association between higher levels of uric acid, homocysteine, and interleukin 6 with lower cognitive performance in executive, attentional, and memory domains. We also reviewed the hemodialysis effects on cognition. Hemodialysis seems to contribute to an amelioration of CKD-related encephalopathic dysfunction, although this improvement occurs more in some cognitive domains than in others.
Collapse
Affiliation(s)
| | - Rodrigo Tzovenos Starosta
- Universidade Federal do Rio Grande do Sul, Faculdade de Medicina, Porto Alegre, RS, Brasil.,Universidade Federal do Rio Grande do Sul, Programa de Pós-Graduação em Genética e Biologia Molecular, Porto Alegre, RS, Brasil
| | - Matheus Roriz-Cruz
- Universidade Federal do Rio Grande do Sul, Departamento de Medicina Interna, Porto Alegre, RS, Brasil.,Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brasil
| |
Collapse
|
|
26
|
Cho HS, Huang LK, Lee YT, Chan L, Hong CT. Suboptimal Baseline Serum Vitamin B12 Is Associated With Cognitive Decline in People With Alzheimer's Disease Undergoing Cholinesterase Inhibitor Treatment. Front Neurol 2018; 9:325. [PMID: 29867734 PMCID: PMC5954104 DOI: 10.3389/fneur.2018.00325] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2017] [Accepted: 04/24/2018] [Indexed: 12/25/2022] Open
Abstract
Objectives Cholinesterase inhibitors (ChEIs) are the mainstream treatment for delaying cognitive decline in Alzheimer’s disease (AD). Low vitamin B12 is associated with cognitive dysfunction, and its supplementation has been applied as the treatment for certain types of reversible dementia. The present study hypothesized that baseline serum vitamin B12 is associated with the deterioration of cognitive function in people with AD undergoing ChEI treatment. Materials and methods Between 2009 and 2016, medical records from 165 Taiwanese with mild to moderate AD who underwent ChEI treatment for at least 2 years were reviewed. Their baseline serum vitamin B12 levels were measured before treatment initiation. Their cognitive function was assessed using the Mini–Mental State Examination (MMSE) and Cognitive Abilities Screening Instrument (CASI). Student’s t test and multivariable logistic regression were used to analyze the association between cognitive decline and vitamin B12 level. Statistical analyses were performed using SPSS 19.0. Results Overall, 122 participants were women. Their median age was 76 years (ranging from 54 to 91). For people with optimal baseline vitamin B12 (above the median level of 436 ng/L), the rates of MMSE and CASI decline were 0.78 ± 1.28 and 2.84 ± 4.21 per year, respectively, which were significantly slower than those with suboptimal vitamin B12 (1.42 ± 1.67 and 4.94 ± 5.88 per year; p = 0.007 and 0.009, respectively). After adjustment for age, sex, education level, hypertension, diabetes, history of stroke, and baseline cognitive function, the baseline serum vitamin B12 level was negatively associated with MMSE and CASI decline. Conclusion Suboptimal baseline serum vitamin B12 level is associated with cognitive decline in people with AD undergoing ChEI treatment.
Collapse
Affiliation(s)
- Hsiao Shan Cho
- Department of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
| | - Li Kai Huang
- Department of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.,Graduate Institute of Humanities in Medicine, Taipei Medical University, Taipei, Taiwan
| | - Yao Tung Lee
- Department of Psychiatry, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.,Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Lung Chan
- Department of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.,Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Chien Tai Hong
- Department of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.,Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| |
Collapse
|
|
27
|
Abstract
The biosynthesis of B12, involving up to 30 different enzyme-mediated steps, only occurs in bacteria. Thus, most eukaryotes require an external source of B12, and yet the vitamin appears to have only two functions in eukaryotes: as a cofactor for the enzymes methionine synthase and methylmalonylCoA mutase. These two functions are crucial for normal health in humans, and in particular, the formation of methionine is essential for providing methyl groups for over 100 methylation processes. Interference with the methionine synthase reaction not only depletes the body of methyl groups but also leads to the accumulation of homocysteine, a risk factor for many diseases. The syndrome pernicious anemia, characterized by lack of intrinsic factor, leads to a severe, sometimes fatal form of B12 deficiency. However, there is no sharp cutoff for B12 deficiency; rather, there is a continuous inverse relationship between serum B12 and a variety of undesirable outcomes, including neural tube defects, stroke, and dementia. The brain is particularly vulnerable; in children, inadequate B12 stunts brain and intellectual development. Suboptimal B12 status (serum B12<300pmol/L) is very common, occurring in 30%-60% of the population, in particular in pregnant women and in less-developed countries. Thus, many tens of millions of people in the world may suffer harm from having a poor B12 status. Public health steps are urgently needed to correct this inadequacy.
Collapse
Affiliation(s)
- A David Smith
- Department of Pharmacology, University of Oxford, Oxford, United Kingdom.
| | - Martin J Warren
- School of Biosciences, University of Kent, Canterbury, Kent, United Kingdom
| | - Helga Refsum
- Department of Nutrition, University of Oslo, Oslo, Norway
| |
Collapse
|
|
28
|
Qin B, Xun P, Jacobs DR, Zhu N, Daviglus ML, Reis JP, Steffen LM, Van Horn L, Sidney S, He K. Intake of niacin, folate, vitamin B-6, and vitamin B-12 through young adulthood and cognitive function in midlife: the Coronary Artery Risk Development in Young Adults (CARDIA) study. Am J Clin Nutr 2017; 106:1032-1040. [PMID: 28768650 PMCID: PMC5611785 DOI: 10.3945/ajcn.117.157834] [Citation(s) in RCA: 52] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2017] [Accepted: 07/10/2017] [Indexed: 02/03/2023] Open
Abstract
Background: Epidemiologic evidence regarding niacin, folate, vitamin B-6, and vitamin B-12 intake in relation to cognitive function is limited, especially in midlife.Objective: We hypothesize that higher intake of these B vitamins in young adulthood is associated with better cognition later in life.Design: This study comprised a community-based multicenter cohort of black and white men and women aged 18-30 y in 1985-1986 (year 0, i.e., baseline) from the Coronary Artery Risk Development in Young Adults (CARDIA) study (n = 3136). We examined participants' CARDIA diet history at years 0, 7, and 20 to assess nutrient intake, including dietary and supplemental B vitamins. We measured cognitive function at year 25 (mean ± SD age: 50 ± 4 y) through the use of the Rey Auditory Verbal Learning Test (RAVLT) for verbal memory, the Digit Symbol Substitution Test (DSST) for psychomotor speed, and a modified Stroop interference test for executive function. Higher RAVLT and DSST scores and a lower Stroop score indicated better cognitive function. We used multivariable-adjusted linear regressions to estimate mean differences in cognitive scores and 95% CIs.Results: Comparing the highest quintile with the lowest (quintile 5 compared with quintile 1), cumulative total intake of niacin was significantly associated with 3.92 more digits on the DSST (95% CI: 2.28, 5.55; P-trend < 0.01) and 1.89 points lower interference score on the Stroop test (95% CI: -3.10, -0.68; P-trend = 0.05). Total folate was associated with 2.56 more digits on the DSST (95% CI: 0.82, 4.31; P-trend = 0.01). We also found that higher intakes of vitamin B-6 (quartile 5 compared with quartile 1: 2.62; 95% CI: 0.97, 4.28; P-trend = 0.02) and vitamin B-12 (quartile 5 compared with quartile 1: 2.08; 95% CI: 0.52, 3.65; P-trend = 0.02) resulted in better psychomotor speed measured by DSST scores.Conclusion: Higher intake of B vitamins throughout young adulthood was associated with better cognitive function in midlife.
Collapse
Affiliation(s)
- Bo Qin
- Department of Population Science, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ
| | - Pengcheng Xun
- Department of Epidemiology and Biostatistics, School of Public Health, Indiana University Bloomington, Bloomington, IN
| | - David R Jacobs
- Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN
| | - Na Zhu
- Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN
| | - Martha L Daviglus
- Department of Medicine, University of Illinois at Chicago, Chicago, IL
| | - Jared P Reis
- Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, Bethesda, MD
| | - Lyn M Steffen
- Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN
| | - Linda Van Horn
- Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL; and
| | - Stephen Sidney
- Division of Research, Kaiser Permanente Northern California, Oakland, CA
| | - Ka He
- Department of Epidemiology and Biostatistics, School of Public Health, Indiana University Bloomington, Bloomington, IN;
| |
Collapse
|
|
29
|
Mendonça N, Granic A, Mathers JC, Martin-Ruiz C, Wesnes KA, Seal CJ, Jagger C, Hill TR. One-Carbon Metabolism Biomarkers and Cognitive Decline in the Very Old: The Newcastle 85+ Study. J Am Med Dir Assoc 2017; 18:806.e19-806.e27. [PMID: 28647580 PMCID: PMC5576913 DOI: 10.1016/j.jamda.2017.05.008] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2016] [Revised: 05/09/2017] [Accepted: 05/09/2017] [Indexed: 11/22/2022]
Abstract
OBJECTIVES Although the biological rationale for the association between folate, vitamin B12, and homocysteine with cognitive function seems plausible, conflicting results have been reported. This study aimed to determine the associations between 1-carbon (1-C) metabolism biomarkers (folate, vitamin B12, and homocysteine), and cognitive impairment at baseline and the rate of cognitive decline over 5 years in the very old. DESIGN The Newcastle 85+ Study was a prospective longitudinal study of people 85 years old and followed over 5 years in Northeast England. SETTING Community-dwelling and institutionalized. PARTICIPANTS The analytical sample included 765 very old participants with 1-C metabolism biomarkers and cognitive measures. MEASUREMENTS Global cognition was measured by the Standardized Mini-Mental State Examination (SMMSE) at baseline, and at 3 and 5 years of follow-up and, attention-specific cognition with the Cognitive Drug Research (CDR) System at baseline, and at 1.5 and 3.0 years of follow-up. Baseline red blood cell folate (RBC folate), plasma vitamin B12, and total homocysteine (tHcy) concentrations were determined by immunoassay. Linear mixed models were used to estimate the associations between quartiles of 1-C metabolism biomarkers and cognition over 3 (CDR) and 5 years (SMMSE). RESULTS Compared with participants in the lowest quartile of RBC folate concentrations (<612 nmol/L), those in the highest quartile of RBC folate concentrations (>1280 nmol/L) had 1 more point on the SMMSE at baseline (β = +1.02, SE = 0.43, P = .02). Those in quartile 4 of tHcy (>21.4 μmol/L) had 1 point less in the SMMSE at baseline than those in the lowest quartile (<13.5 μmol/L) (β = -1.05, SE = 0.46, P = .02). Plasma vitamin B12 was not predictive of global or attention-specific cognition at baseline and at follow-up. None of the 1-C metabolism biomarkers except tHcy was associated with the rate of decline in attention scores over 3 years. CONCLUSION RBC folate and tHcy, but not plasma vitamin B12, were associated with better global cognition in the very old at baseline but were not predictive of rate of decline over 5 years.
Collapse
Affiliation(s)
- Nuno Mendonça
- School of Agriculture, Food, and Rural Development, Newcastle University, Newcastle-upon-Tyne, UK; Newcastle University Institute for Ageing, Newcastle-upon-Tyne, UK; Human Nutrition Research Centre, Newcastle University, Newcastle-upon-Tyne, UK; Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, UK.
| | - Antoneta Granic
- Newcastle University Institute for Ageing, Newcastle-upon-Tyne, UK; Institute of Neuroscience, Newcastle University, Newcastle-upon-Tyne, UK; NIHR Newcastle Biomedical Research Centre in Ageing and Chronic Disease, Newcastle University and Newcastle-upon-Tyne NHS Foundation Trust, Newcastle-upon-Tyne, UK
| | - John C Mathers
- Newcastle University Institute for Ageing, Newcastle-upon-Tyne, UK; Human Nutrition Research Centre, Newcastle University, Newcastle-upon-Tyne, UK; Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, UK
| | | | - Keith A Wesnes
- Wesnes Cognition Ltd, Streatley-on-Thames, UK; Department of Psychology, Northumbria University, Newcastle-upon-Tyne, UK; Medical School, University of Exeter, Exeter, UK
| | - Chris J Seal
- School of Agriculture, Food, and Rural Development, Newcastle University, Newcastle-upon-Tyne, UK; Human Nutrition Research Centre, Newcastle University, Newcastle-upon-Tyne, UK; Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, UK
| | - Carol Jagger
- Newcastle University Institute for Ageing, Newcastle-upon-Tyne, UK; Institute of Health and Society, Newcastle University, Newcastle-upon-Tyne, UK
| | - Tom R Hill
- School of Agriculture, Food, and Rural Development, Newcastle University, Newcastle-upon-Tyne, UK; Newcastle University Institute for Ageing, Newcastle-upon-Tyne, UK; Human Nutrition Research Centre, Newcastle University, Newcastle-upon-Tyne, UK; Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, UK
| |
Collapse
|
|
30
|
B-Vitamin Intake and Biomarker Status in Relation to Cognitive Decline in Healthy Older Adults in a 4-Year Follow-Up Study. Nutrients 2017; 9:nu9010053. [PMID: 28075382 PMCID: PMC5295097 DOI: 10.3390/nu9010053] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2016] [Revised: 12/23/2016] [Accepted: 01/04/2017] [Indexed: 11/16/2022] Open
Abstract
Advancing age can be associated with an increase in cognitive dysfunction, a spectrum of disability that ranges in severity from mild cognitive impairment to dementia. Folate and the other B-vitamins involved in one-carbon metabolism are associated with cognition in ageing but the evidence is not entirely clear. The hypothesis addressed in this study was that lower dietary intake or biomarker status of folate and/or the metabolically related B-vitamins would be associated with a greater than expected rate of cognitive decline over a 4-year follow-up period in healthy older adults. Participants (aged 60-88 years; n = 155) who had been previously screened for cognitive function were reassessed four years after initial investigation using the Mini-Mental State Examination (MMSE). At the 4-year follow-up assessment when participants were aged 73.4 ± 7.1 years, mean cognitive MMSE scores had declined from 29.1 ± 1.3 at baseline to 27.5 ± 2.4 (p < 0.001), but some 27% of participants showed a greater than expected rate of cognitive decline (i.e., decrease in MMSE > 0.56 points per year). Lower vitamin B6 status, as measured using pyridoxal-5-phosphate (PLP; <43 nmol/L) was associated with a 3.5 times higher risk of accelerated cognitive decline, after adjustment for age and baseline MMSE score (OR, 3.48; 95% CI, 1.58 to 7.63; p < 0.05). Correspondingly, lower dietary intake (0.9-1.4 mg/day) of vitamin B6 was also associated with a greater rate of cognitive decline (OR, 4.22; 95% CI, 1.28-13.90; p < 0.05). No significant relationships of dietary intake or biomarker status with cognitive decline were observed for the other B-vitamins. In conclusion, lower dietary and biomarker status of vitamin B6 at baseline predicted a greater than expected rate of cognitive decline over a 4-year period in healthy older adults. Vitamin B6 may be an important protective factor in helping maintain cognitive health in ageing.
Collapse
|
|
31
|
|
|
32
|
Porter K, Hoey L, Hughes CF, Ward M, McNulty H. Causes, Consequences and Public Health Implications of Low B-Vitamin Status in Ageing. Nutrients 2016; 8:E725. [PMID: 27854316 PMCID: PMC5133110 DOI: 10.3390/nu8110725] [Citation(s) in RCA: 75] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2016] [Revised: 10/26/2016] [Accepted: 11/09/2016] [Indexed: 12/11/2022] Open
Abstract
The potential protective roles of folate and the metabolically related B-vitamins (vitamins B12, B6 and riboflavin) in diseases of ageing are of increasing research interest. The most common cause of folate and riboflavin deficiencies in older people is low dietary intake, whereas low B12 status is primarily associated with food-bound malabsorption, while sub-optimal vitamin B6 status is attributed to increased requirements in ageing. Observational evidence links low status of folate and the related B-vitamins (and/or elevated concentrations of homocysteine) with a higher risk of degenerative diseases including cardiovascular disease (CVD), cognitive dysfunction and osteoporosis. Deficient or low status of these B-vitamins alone or in combination with genetic polymorphisms, including the common MTHFR 677 C → T polymorphism, could contribute to greater disease risk in ageing by causing perturbations in one carbon metabolism. Moreover, interventions with the relevant B-vitamins to optimise status may have beneficial effects in preventing degenerative diseases. The precise mechanisms are unknown but many have been proposed involving the role of folate and the related B-vitamins as co-factors for one-carbon transfer reactions, which are fundamental for DNA and RNA biosynthesis and the maintenance of methylation reactions. This review will examine the evidence linking folate and related B-vitamins with health and disease in ageing, associated mechanisms and public health implications.
Collapse
Affiliation(s)
- Kirsty Porter
- Northern Ireland Centre for Food and Health, Ulster University, Cromore Road, Coleraine BT52 1SA, UK.
| | - Leane Hoey
- Northern Ireland Centre for Food and Health, Ulster University, Cromore Road, Coleraine BT52 1SA, UK.
| | - Catherine F Hughes
- Northern Ireland Centre for Food and Health, Ulster University, Cromore Road, Coleraine BT52 1SA, UK.
| | - Mary Ward
- Northern Ireland Centre for Food and Health, Ulster University, Cromore Road, Coleraine BT52 1SA, UK.
| | - Helene McNulty
- Northern Ireland Centre for Food and Health, Ulster University, Cromore Road, Coleraine BT52 1SA, UK.
| |
Collapse
|
|
33
|
Biomarcadores sanguíneos diferenciales de las dimensiones psicopatológicas de la esquizofrenia. REVISTA DE PSIQUIATRIA Y SALUD MENTAL 2016; 9:219-227. [DOI: 10.1016/j.rpsm.2016.04.003] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/12/2016] [Revised: 04/28/2016] [Accepted: 04/28/2016] [Indexed: 12/20/2022]
|
|
34
|
Wilson LB, Martindale RG. What’s in Your Pillbox? Appropriate Supplements for Healthy Adults Across the Life Cycle. Curr Nutr Rep 2016. [DOI: 10.1007/s13668-016-0174-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
|
|
35
|
Setién-Suero E, Suárez-Pinilla M, Suárez-Pinilla P, Crespo-Facorro B, Ayesa-Arriola R. Homocysteine and cognition: A systematic review of 111 studies. Neurosci Biobehav Rev 2016; 69:280-98. [PMID: 27531233 DOI: 10.1016/j.neubiorev.2016.08.014] [Citation(s) in RCA: 59] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2015] [Revised: 06/14/2016] [Accepted: 08/10/2016] [Indexed: 12/15/2022]
Abstract
BACKGROUND Elevated plasma homocysteine (Hcy) levels have been associated with cognitive dysfunction in a wide range of conditions. The aim of this review is to establish which cognitive domains and populations are the most affected. METHODS We systematically review the literature and consider all articles that showed any relationship between plasma Hcy levels and scores achieved on cognitive performance tests in both, the general population and patients suffering from central nervous system disorders and other diseases. When effect sizes were available and combinable, several meta-analyses were performed. RESULTS We found 111 pertinent articles. There were 24 cohort studies, 18 randomized trials, 21 case-control studies, and 48 cross-sectional studies. This review reveals a positive trend between cognitive decline and increased plasma Hcy concentrations in general population and in patients with cognitive impairments. Results from the meta-analyses also confirm this trend. Treatment with vitamin supplementation fails to show a reduction in cognitive decline. DISCUSSION Further investigations are warranted to clarify this relationship. Earlier detection of the elevated Hcy levels may be an effective intervention to prevent cognitive impairment and dementia.
Collapse
Affiliation(s)
- Esther Setién-Suero
- University Hospital Marqués de Valdecilla, Department of Psychiatry, School of Medicine, University of Cantabria, Santander, Spain; CIBERSAM, Biomedical Research Network on Mental Health Area, Madrid, Spain; IDIVAL, Valdecilla Biomedical Research Institute, Santander, Spain.
| | - Marta Suárez-Pinilla
- Sackler Centre for Consciousness Science, Department of Informatics, University of Sussex, United Kingdom
| | - Paula Suárez-Pinilla
- University Hospital Marqués de Valdecilla, Department of Psychiatry, School of Medicine, University of Cantabria, Santander, Spain; CIBERSAM, Biomedical Research Network on Mental Health Area, Madrid, Spain; IDIVAL, Valdecilla Biomedical Research Institute, Santander, Spain
| | - Benedicto Crespo-Facorro
- University Hospital Marqués de Valdecilla, Department of Psychiatry, School of Medicine, University of Cantabria, Santander, Spain; CIBERSAM, Biomedical Research Network on Mental Health Area, Madrid, Spain; IDIVAL, Valdecilla Biomedical Research Institute, Santander, Spain
| | - Rosa Ayesa-Arriola
- University Hospital Marqués de Valdecilla, Department of Psychiatry, School of Medicine, University of Cantabria, Santander, Spain; CIBERSAM, Biomedical Research Network on Mental Health Area, Madrid, Spain; IDIVAL, Valdecilla Biomedical Research Institute, Santander, Spain
| |
Collapse
|
|
36
|
Abstract
Cognitive impairment is very common in chronic kidney disease (CKD) and is strongly associated with increased mortality. This review article will discuss the pathophysiology of cognitive impairment in CKD, as well as the effect of dialysis and transplantation on cognitive function. In CKD, uremic toxins, hyperparathyroidism and Klotho deficiency lead to chronic inflammation, endothelial dysfunction and vascular calcifications. This results in an increased burden of cerebrovascular disease in CKD patients, who consistently have more white matter hyperintensities, microbleeds, microinfarctions and cerebral atrophy on magnetic resonance imaging scans. Hemodialysis, although beneficial in terms of uremic toxin clearance, also contributes to cognitive decline by causing rapid fluid and osmotic shifts. Decreasing the dialysate temperature and increasing total dialysis time limits these shifts and helps maintain cognitive function in hemodialysis patients. For many patients, kidney transplantation is the preferred treatment modality, because it reverses the underlying mechanisms causing cognitive impairment in CKD. These positive effects have to be balanced against the possible neurotoxicity of infections and immunosuppressive medications, especially glucocorticosteroids and calcineurin inhibitors. A limited number of studies have addressed the overall effect of transplantation on cognitive function. These have mostly found an improvement after transplantation, but have a limited applicability to daily practice because they have only included relatively young patients.
Collapse
|
|
37
|
Affiliation(s)
- A. David Smith
- OPTIMA, Department of Pharmacology, University of Oxford, Oxford OX1 3QT, United Kingdom;
| | - Helga Refsum
- OPTIMA, Department of Pharmacology, University of Oxford, Oxford OX1 3QT, United Kingdom;
- Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, 0316 Oslo, Norway;
| |
Collapse
|
|
38
|
From Heart Health to Brain Health: Legacy of the North Karelia Project
for Dementia Research. Glob Heart 2016; 11:235-42. [DOI: 10.1016/j.gheart.2016.04.013] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2016] [Accepted: 04/25/2016] [Indexed: 12/30/2022] Open
|
|
39
|
Golding PH. Holotranscobalamin (HoloTC, Active-B12) and Herbert's model for the development of vitamin B12 deficiency: a review and alternative hypothesis. SPRINGERPLUS 2016; 5:668. [PMID: 27350907 PMCID: PMC4899389 DOI: 10.1186/s40064-016-2252-z] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/07/2015] [Accepted: 04/29/2016] [Indexed: 02/07/2023]
Abstract
The concentration of total vitamin B12 in serum is not a sufficiently sensitive or specific indicator for the reliable diagnosis of vitamin B12 deficiency. Victor Herbert proposed a model for the staged development of vitamin B12 deficiency, in which holotranscobalamin (HoloTC) is the first indicator of deficiency. Based on this model, a commercial immunoassay has been controversially promoted as a replacement for the total vitamin B12 test. HoloTC is cobalamin (vitamin B12) attached to the transport protein transcobalamin, in the serum, for delivery to cells for metabolism. Although there have been many published reports supporting the claims for HoloTC, the results of some studies were inconsistent with the claim of HoloTC as the most sensitive marker of vitamin B12 deficiency. This review examines the evidence for and against the use of HoloTC, and concludes that the HoloTC immunoassay cannot be used to measure vitamin B12 status any more reliably than total vitamin B12, or to predict the onset of a metabolic deficiency, because it is based on an erroneous hypothesis and a flawed model for the staged development of vitamin B12 deficiency. The author proposes an alternative model for the development of vitamin B12 deficiency.
Collapse
|
|
40
|
Obeid R, Oexle K, Rißmann A, Pietrzik K, Koletzko B. Folate status and health: challenges and opportunities. J Perinat Med 2016; 44:261-8. [PMID: 25825915 DOI: 10.1515/jpm-2014-0346] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2014] [Accepted: 02/25/2015] [Indexed: 01/21/2023]
Abstract
Each year approximately 2400 pregnancies develop folic acid-preventable spina bifida and anencephaly in Europe. Currently, 70% of all affected pregnancies are terminated after prenatal diagnosis. The prevalence of neural tube defects (NTDs) has been significantly lowered in more than 70 countries worldwide by applying fortification with folic acid. Periconceptional supplementation of folic acid also reduces the risk of congenital heart diseases, preterm birth, low birth weight, and health problems associated with child mortality and morbidity. All European governments failed to issue folic acid fortification of centrally processed and widely eaten foods in order to prevent NTDs and other unwanted birth outcomes. The estimated average dietary intake of folate in Germany is 200 μg dietary folate equivalents (DFE)/day. More than half of German women of reproductive age do not consume sufficient dietary folate to achieve optimal serum or red blood cell folate concentrations (>18 or 1000 nmol/L, respectively) necessary to prevent spina bifida and anencephaly. To date, targeted supplementation is recommended in Europe, but this approach failed to reduce the rate of NTDs during the last 10 years. Public health centers for prenatal care and fortification with folic acid in Europe are urgently needed. Only such an action will sufficiently improve folate status, prevent at least 50% of the NTD cases, reduce child mortality and morbidity, and alleviate other health problems associated with low folate such as anemia.
Collapse
|
|
41
|
Metabolic vitamin B12 deficiency: a missed opportunity to prevent dementia and stroke. Nutr Res 2016; 36:109-16. [DOI: 10.1016/j.nutres.2015.10.003] [Citation(s) in RCA: 85] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2015] [Revised: 10/16/2015] [Accepted: 10/19/2015] [Indexed: 12/17/2022]
|
|
42
|
Horvat P, Gardiner J, Kubinova R, Pajak A, Tamosiunas A, Schöttker B, Pikhart H, Peasey A, Jansen E, Bobak M. Serum folate, vitamin B-12 and cognitive function in middle and older age: The HAPIEE study. Exp Gerontol 2016; 76:33-8. [PMID: 26808046 PMCID: PMC4839985 DOI: 10.1016/j.exger.2016.01.011] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2015] [Revised: 01/20/2016] [Accepted: 01/21/2016] [Indexed: 12/22/2022]
Abstract
Background Nutrient status of B vitamins, particularly folate and vitamin B-12, may be related to cognitive ageing but epidemiological evidence remains inconclusive. Objective The aim of this study was to estimate the association of serum folate and vitamin B-12 concentrations with cognitive function in middle-aged and older adults from three Central and Eastern European populations. Methods Men and women aged 45–69 at baseline participating in the Health, Alcohol and Psychosocial factors in Eastern Europe (HAPIEE) study were recruited in Krakow (Poland), Kaunas (Lithuania) and six urban centres in the Czech Republic. Tests of immediate and delayed recall, verbal fluency and letter search were administered at baseline and repeated in 2006–2008. Serum concentrations of biomarkers at baseline were measured in a sub-sample of participants. Associations of vitamin quartiles with baseline (n = 4166) and follow-up (n = 2739) cognitive domain-specific z-scores were estimated using multiple linear regression. Results After adjusting for confounders, folate was positively associated with letter search and vitamin B-12 with word recall in cross-sectional analyses. In prospective analyses, participants in the highest quartile of folate had higher verbal fluency (p < 0.01) and immediate recall (p < 0.05) scores compared to those in the bottom quartile. In addition, participants in the highest quartile of vitamin B-12 had significantly higher verbal fluency scores (β = 0.12; 95% CI = 0.02, 0.21). Conclusions Folate and vitamin B-12 were positively associated with performance in some but not all cognitive domains in older Central and Eastern Europeans. These findings do not lend unequivocal support to potential importance of folate and vitamin B-12 status for cognitive function in older age. Long-term longitudinal studies and randomised trials are required before drawing conclusions on the role of these vitamins in cognitive decline.
Epidemiological evidence linking B vitamins to cognitive ageing is inconclusive. Serum folate, vitamin B-12 and cognition were studied in older Eastern Europeans. Both vitamins were positively associated with 3-year verbal fluency. Folate and vitamin B-12 may be related to performance in some cognitive domains. More research is needed to clarify the causal relevance of B vitamins to cognition.
Collapse
Affiliation(s)
- Pia Horvat
- Department of Epidemiology & Public Health, UCL, 1-19 Torrington Place, London WC1E 7HB, UK.
| | - Julian Gardiner
- Department of Education, University of Oxford, 15 Norham Gardens, Oxford OX2 6PY, UK
| | - Ruzena Kubinova
- National Institute of Public Health, Srobarova 48, 10042 Prague, Czech Republic
| | - Andrzej Pajak
- Department of Epidemiology and Population Studies, Jagellonian University Collegium Medicum, Grzegorzecka 20, 31-531 Krakow, Poland
| | - Abdonas Tamosiunas
- Department of Population Studies, Institute of Cardiology, Lithuanian University of Health Sciences, Kaunas LT-50161, Lithuania
| | - Ben Schöttker
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany
| | - Hynek Pikhart
- Department of Epidemiology & Public Health, UCL, 1-19 Torrington Place, London WC1E 7HB, UK
| | - Anne Peasey
- Department of Epidemiology & Public Health, UCL, 1-19 Torrington Place, London WC1E 7HB, UK
| | - Eugene Jansen
- Center for Health Protection, National Institute for Public Health and the Environment, PO Box 1, 3720 BA, Bilthoven, The Netherlands
| | - Martin Bobak
- Department of Epidemiology & Public Health, UCL, 1-19 Torrington Place, London WC1E 7HB, UK
| |
Collapse
|
|
43
|
Tu MC, Lo CP, Chen CY, Huang CF. Correlation of Tc-99 m ethyl cysteinate dimer single-photon emission computed tomography and clinical presentations in patients with low cobalamin status. BMC Neurol 2015; 15:251. [PMID: 26630935 PMCID: PMC4668675 DOI: 10.1186/s12883-015-0500-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2015] [Accepted: 11/19/2015] [Indexed: 11/10/2022] Open
Abstract
Background Cobalamin (Cbl) deficiency has been associated with various neuropsychiatric symptoms of different severities. While some studies dedicated in structural neuroimaging credibly address negative impact of low Cbl status, functional imaging reports are limited. We herein retrospectively review the correlation of Tc-99 m ethyl cysteinate dimer single-photon emission computed tomography (Tc-99 m-ECD SPECT) and clinical presentations among patients with low serum cobalamin (Cbl) status (<250 pg/ml). Methods Twelve symptomatic patients with low serum Cbl status were enrolled. Clinical presentations, Tc-99 m-ECD SPECT, and neuropsychological tests were reviewed. Results Dysexecutive syndrome (67 %), forgetfulness (50 %), attention deficits (42 %), and sleep disorders (33 %) constituted the major clinical presentations. All patients (100 %) had temporal hypoperfusion on the Tc-99 m-ECD SPECT. Five patients (42 %) had hypoperfusion restricted within temporal regions and deep nuclei; seven patients (58 %) had additional frontal hypoperfusion. In patients with hypoperfusion restricted within temporal regions and deep nuclei, psychiatric symptoms with spared cognition were their main presentations. Among patients with additional frontal hypoperfusion, six of seven patients (86 %) showed impaired cognitive performances (two of them were diagnosed as having dementia). Among ten patients who finished neuropsychological tests, abstract thinking (70 %) was the most commonly affected, followed by verbal fluency (60 %), short-term memory (50 %), and attention (50 %). Anxiety and sleep problems were the major clinically remarkable psychiatric features (33 % both). Four Tc-99 m-ECD SPECT follow-up studies were available; the degree and extent of signal reversal correlated with cognitive changes after Cbl replacement therapy. Conclusions Our TC-99 m-ECD SPECT observations provide pivotal information of neurobiological changes within basal ganglia and fronto-temporal regions in conjunction with disease severity among patients with Cbl deficiency. Hypoperfusion within thalamus/basal ganglia and temporal regions may be seen in the earlier state of Cbl deficiency, when psychiatric symptoms predominate. Hypoperfusion beyond thalamus/basal ganglia and involving frontal regions appears when cognitive problems, mostly dysexecutive syndrome, are manifested. Symmetric hypofrontality of SPECT in the context of dysexcutive syndrome serves as a distinguishing feature of non-amnestic mild cognitive impairment attributed to Cbl deficiency. Concordant with TC-99 m-ECD SPECT findings, the psychiatric symptoms and dysexcutive syndrome undergird impaired limbic and dorsolateral prefrontal circuits originating from basal ganglia respectively.
Collapse
Affiliation(s)
- Min-Chien Tu
- Department of Neurology, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan. .,School of Medicine, Tzu Chi University, Hualien, Taiwan.
| | - Chung-Ping Lo
- Department of Radiology, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Foundation, Taichung, Taiwan.,School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Ching-Yuan Chen
- Department of Nuclear Medicine, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan.,School of Medicine, Tzu Chi University, Hualien, Taiwan.,Graduate Institute of Medical Imaging and Radiological Sciences, Central Taiwan, University of Science and Technology, Taichung, Taiwan
| | - Ching-Feng Huang
- Department of Neurology, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan.,School of Medicine, Tzu Chi University, Hualien, Taiwan
| |
Collapse
|
|
44
|
Puig-Alcaraz C, Fuentes-Albero M, Calderón J, Garrote D, Cauli O. Increased homocysteine levels correlate with the communication deficit in children with autism spectrum disorder. Psychiatry Res 2015; 229:1031-7. [PMID: 26070768 DOI: 10.1016/j.psychres.2015.05.021] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2014] [Revised: 05/05/2015] [Accepted: 05/20/2015] [Indexed: 01/28/2023]
Abstract
The clinical significance of high levels of homocysteine in autism spectrum disorder (ASD) is unknown. An experimental study was conducted in order to evaluate the concentration of homocysteine in children with ASD and typically developing children and to analyse any relationships with the severity of core symptoms of ASD and other clinical features (drugs, co-morbidities, gender, age, diet). Core symptoms of autism were evaluated by DSM-IV criteria. Homocysteine, glutathione, methionine, 3-nitrotyrosine were measured in urine. The increase in homocysteine concentration was significantly and directly correlated with the severity of the deficit in communication skills, but was unrelated to deficit in socialisation or repetitive/restricted behaviour. Urinary homocysteine concentration may be a possible biomarker for communication deficits in ASD and a potential diagnostic tool useful to evaluate new treatment options since no treatment for core symptoms of ASD are available.
Collapse
Affiliation(s)
- Carmen Puig-Alcaraz
- Area of Mental Health and Psychiatry, Hospital of Sagunto, Sagunto, Valencia, Spain
| | | | | | | | - Omar Cauli
- Department of Nursing, University of Valencia, c/Jaume Roig s/n, 46010 Valencia, Spain.
| |
Collapse
|
|
45
|
Hsu YH, Huang CF, Lo CP, Wang TL, Tu MC. Vitamin B12 deficiency: Characterization of psychometrics and MRI morphometrics. Nutr Neurosci 2015; 19:47-54. [PMID: 26339714 DOI: 10.1179/1476830515y.0000000045] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
Abstract
OBJECTIVES Vitamin B12 is essential for the integrity of the central nervous system. However, performances in different cognitive domains relevant to vitamin B12 deficiency remain to be detailed. To date, there have been limited studies that examined the relationships between cognitions and structural neuroimaging in a single cohort of low-vitamin B12 status. The present study aimed to depict psychometrics and magnetic resonance imaging (MRI) morphometrics among patients with vitamin B12 deficiency, and to examine their inter-relations. METHODS We compared 34 consecutive patients with vitamin B12 deficiency (serum level ≤ 250 pg/ml) to 34 demographically matched controls by their cognitive performances and morphometric indices of brain MRI. The correlations between psychometrics and morphometrics were analyzed. RESULTS The vitamin B12 deficiency group had lower scores than the controls on total scores of Mini-Mental Status Examination (MMSE) and Cognitive Abilities Screening Instrument (CASI) (both P < 0.05), language (P < 0.01), orientation (P < 0.01), and mental manipulation (P < 0.05). The patients also showed a greater frontal horn ratio than the controls (P < 0.05). Bicaudate ratio, fronto-occipital ratio, uncotemporal index, and normalized interuncal distance all showed a strong correlation with the total score of MMSE and CASI (all P < 0.01). Among these psychometric and morphometric indices, pronounced correlations between bicaudate ratio and long-term memory, mental manipulation, orientation, language, and verbal fluency were noted (all P < 0.01). DISCUSSION Vitamin B12 deficiency is associated with a global cognition decline with language, orientation, and mental manipulation selectively impaired. Preferential atrophy in frontal regions is the main neuroimaging feature. Although the frontal ratio highlights the relevant atrophy among patients, the bicaudate ratio might be the best index on the basis of its strong association with global cognition and related cognitive domains, implying dysfunction of fronto-subcortical circuits as the fundamental pathogenesis related to vitamin B12 deficiency.
Collapse
|
|
46
|
Shakersain B, Santoni G, Larsson SC, Faxén-Irving G, Fastbom J, Fratiglioni L, Xu W. Prudent diet may attenuate the adverse effects of Western diet on cognitive decline. Alzheimers Dement 2015; 12:100-109. [PMID: 26342761 DOI: 10.1016/j.jalz.2015.08.002] [Citation(s) in RCA: 104] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2015] [Revised: 07/17/2015] [Accepted: 08/02/2015] [Indexed: 12/24/2022]
Abstract
INTRODUCTION The influence of mixed dietary patterns on cognitive changes is unknown. METHODS A total of 2223 dementia-free participants aged ≥60 were followed up for 6 years to examine the impact of dietary patterns on cognitive decline. Mini-mental state examination (MMSE) was administered. Diet was assessed by a food frequency questionnaire. By factor analysis, Western and prudent dietary patterns emerged. Mixed-effect models for longitudinal data with repeated measurements were used. RESULTS Compared with the lowest adherence to each pattern, the highest adherence to prudent pattern was related to less MMSE decline (β = 0.106, P = .011), whereas the highest adherence to Western pattern was associated with more MMSE decline (β = -0.156, P < .001). The decline associated with Western diet was attenuated when accompanied by high adherence to prudent pattern. DISCUSSION High adherence to prudent diet may diminish the adverse effects of high adherence to Western diet on cognitive decline.
Collapse
Affiliation(s)
- Behnaz Shakersain
- Aging Research Center, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden.
| | - Giola Santoni
- Aging Research Center, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden
| | - Susanna C Larsson
- Unit of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Gerd Faxén-Irving
- Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden
| | - Johan Fastbom
- Aging Research Center, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden
| | - Laura Fratiglioni
- Aging Research Center, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden; Stockholm Gerontology Research Center, Stockholm, Sweden
| | - Weili Xu
- Aging Research Center, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden; Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China.
| |
Collapse
|
|
47
|
McCaddon A, Miller JW. Assessing the association between homocysteine and cognition: reflections on Bradford Hill, meta-analyses, and causality. Nutr Rev 2015; 73:723-35. [DOI: 10.1093/nutrit/nuv022] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
|
|
48
|
Román GC. MTHFR Gene Mutations: A Potential Marker of Late-Onset Alzheimer’s Disease? J Alzheimers Dis 2015; 47:323-7. [DOI: 10.3233/jad-150304] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
|
|
49
|
Colapinto CK, O'Connor DL, Sampson M, Williams B, Tremblay MS. Systematic review of adverse health outcomes associated with high serum or red blood cell folate concentrations. J Public Health (Oxf) 2015; 38:e84-97. [PMID: 26160024 DOI: 10.1093/pubmed/fdv087] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND To examine the relationship between reported high serum or red blood cell (RBC) folate status and adverse health outcomes. METHODS We systematically searched PubMed/Medline and EMBASE (to May 2013), with no limits by study type, country or population, to identify studies reporting high folate concentrations in association with adverse health outcomes. Two reviewers screened studies and extracted data. Study quality was assessed. RESULTS We included 51 articles, representing 46 studies and 71 847 participants. Quantiles were used by 96% of studies to identify high folate concentrations. Eighty-three percent of serum folate and 50% of RBC folate studies reported a high folate cutoff that corresponded with a clinically normal concentration. Increasing values of reported high folate concentration did not demonstrate a consistent association with risk of adverse health outcomes. Overall, reported high folate concentrations appeared to be associated with a decreased risk of adverse health outcomes, though substantial methodological heterogeneity precluded complex analyses. CONCLUSIONS Our interpretation was complicated by methodological variability. High folate cutoffs varied and often corresponded with normal or desirable blood concentrations. In general, a negative association appeared to exist between reported high folate status and adverse health outcomes. Consistent methods and definitions are needed to examine high folate status and ultimately inform public health interventions.
Collapse
Affiliation(s)
- Cynthia K Colapinto
- Healthy Active Living and Obesity Research, Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario K1H 8L1, Canada University of Ottawa, Ottawa, Ontario, Canada
| | - Deborah L O'Connor
- The Hospital for Sick Children, Toronto, Ontario, Canada University of Toronto, Toronto, Ontario, Canada
| | - Margaret Sampson
- Healthy Active Living and Obesity Research, Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario K1H 8L1, Canada
| | - Brock Williams
- The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Mark S Tremblay
- Healthy Active Living and Obesity Research, Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario K1H 8L1, Canada University of Ottawa, Ottawa, Ontario, Canada
| |
Collapse
|
|
50
|
Han Y, Xi Q, Dai W, Yang S, Gao L, Su Y, Zhang X. Abnormal transsulfuration metabolism and reduced antioxidant capacity in Chinese children with autism spectrum disorders. Int J Dev Neurosci 2015; 46:27-32. [DOI: 10.1016/j.ijdevneu.2015.06.006] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2015] [Revised: 06/20/2015] [Accepted: 06/29/2015] [Indexed: 11/29/2022] Open
Affiliation(s)
- Yu Han
- School of Public HealthTianjin Medical UniversityTianjinChina
| | - Qian‐qian Xi
- School of Public HealthTianjin Medical UniversityTianjinChina
| | - Wei Dai
- School of Public HealthTianjin Medical UniversityTianjinChina
| | - Shu‐han Yang
- School of Public HealthTianjin Medical UniversityTianjinChina
| | - Lei Gao
- School of Public HealthTianjin Medical UniversityTianjinChina
| | - Yuan‐yuan Su
- School of Public HealthTianjin Medical UniversityTianjinChina
| | - Xin Zhang
- School of Public HealthTianjin Medical UniversityTianjinChina
| |
Collapse
|