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Abstract
Brain health and the health of the aging brain are topics of increased interest in recent years given the expected aging of the world's population. Many conditions associated with memory loss and other disorders of cognition have age as a risk factor. This article describes the healthy aging brain and theories about how to maintain brain health through later life. The role of gender in brain health and whether women are at increased risk of neurodegenerative disorders leading to dementia are discussed. Important factors that contribute to brain health, including nutrition, exercise, chronic disease management, and others, also are discussed.
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Affiliation(s)
- Tania Alchalabi
- Division of Geriatrics and Palliative Medicine, The George Washington University School of Medicine and Health Sciences, 2300 M Street Northwest, Suite 3-335, Washington, DC 20037, USA
| | - Christina Prather
- Division of Geriatrics and Palliative Medicine, The George Washington University School of Medicine and Health Sciences, 2300 M Street Northwest, Suite 3-335, Washington, DC 20037, USA.
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2
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Conde DM, Verdade RC, Valadares ALR, Mella LFB, Pedro AO, Costa-Paiva L. Menopause and cognitive impairment: A narrative review of current knowledge. World J Psychiatry 2021; 11:412-428. [PMID: 34513605 PMCID: PMC8394691 DOI: 10.5498/wjp.v11.i8.412] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Revised: 07/05/2021] [Accepted: 07/28/2021] [Indexed: 02/06/2023] Open
Abstract
A severe impairment of cognitive function characterizes dementia. Mild cognitive impairment represents a transition between normal cognition and dementia. The frequency of cognitive changes is higher in women than in men. Based on this fact, hormonal factors likely contribute to cognitive decline. In this sense, cognitive complaints are more common near menopause, a phase marked by a decrease in hormone levels, especially estrogen. Additionally, a tendency toward worsened cognitive performance has been reported in women during menopause. Vasomotor symptoms (hot flashes, sweating, and dizziness), vaginal dryness, irritability and forgetfulness are common and associated with a progressive decrease in ovarian function and a subsequent reduction in the serum estrogen concentration. Hormone therapy (HT), based on estrogen with or without progestogen, is the treatment of choice to relieve menopausal symptoms. The studies conducted to date have reported conflicting results regarding the effects of HT on cognition. This article reviews the main aspects of menopause and cognition, including the neuroprotective role of estrogen and the relationship between menopausal symptoms and cognitive function. We present and discuss the findings of the central observational and interventional studies on HT and cognition.
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Affiliation(s)
- Délio Marques Conde
- Department of Gynecology and Obstetrics, Federal University of Goiás, Goiânia 74605-050, Goiás, Brazil
| | - Roberto Carmignani Verdade
- Department of Obstetrics and Gynecology, School of Medical Sciences, State University of Campinas, Campinas 13083-881, São Paulo, Brazil
| | - Ana L R Valadares
- Department of Obstetrics and Gynecology, School of Medical Sciences, State University of Campinas, Campinas 13083-881, São Paulo, Brazil
| | - Lucas F B Mella
- Department of Medical Psychology and Psychiatry-Geriatric Psychiatry and Neuropsychiatric Division, State University of Campinas, Campinas 13083-887, São Paulo, Brazil
| | - Adriana Orcesi Pedro
- Department of Obstetrics and Gynecology, School of Medical Sciences, State University of Campinas, Campinas 13083-881, São Paulo, Brazil
| | - Lucia Costa-Paiva
- Department of Obstetrics and Gynecology, School of Medical Sciences, State University of Campinas, Campinas 13083-881, São Paulo, Brazil
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3
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Abstract
Objective: Recent evidence suggests that early or induced menopause increases the risk for cognitive impairment and dementia. Given the potential for different cognitive outcomes due to menopause types, it is important that present research on menopause and cognition distinguishes between types. The aim of this project was to determine to what extent research looking at cognition in postmenopausal women published in one year, 2016, accounted for menopausal type. Methods: We searched MEDLINE, EMBASE, and PsychINFO using keywords and MeSH terms for menopause and cognition. We included any research paper reporting a cognitive outcome measure in a menopausal human population. Differentiation between the types of menopause was defined by four categories: undifferentiated, demographic differentiation (menopause type reported but not analyzed), partial differentiation (some but not all types analyzed), and full differentiation (menopause types factored into analysis, or recruitment of only one type). Results: Fifty research articles were found and analyzed. Differentiation was distributed as follows: undifferentiated, 38% (19 articles); demographic differentiation, 16% (8); partial differentiation, 28% (14); and full differentiation, 18% (9). Conclusions: This review revealed that although some clinical studies differentiated between the many menopauses, most did not. This may limit their relevance to clinical practice. We found that when menopause types are distinguished, the differing cognitive outcomes of each type are clarified, yielding the strongest evidence, which in turn will be able to inform best clinical practice for treating all women.
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Abstract
There are 3 common physiological estrogens, of which estradiol (E2) is seen to decline rapidly over the menopausal transition. This decline in E2 has been associated with a number of changes in the brain, including cognitive changes, effects on sleep, and effects on mood. These effects have been demonstrated in both rodent and non-human preclinical models. Furthermore, E2 interactions have been indicated in a number of neuropsychiatric disorders, including Alzheimer's disease, schizophrenia, and depression. In normal brain aging, there are a number of systems that undergo changes and a number of these show interactions with E2, particularly the cholinergic system, the dopaminergic system, and mitochondrial function. E2 treatment has been shown to ameliorate some of the behavioral and morphological changes seen in preclinical models of menopause; however, in clinical populations, the effects of E2 treatment on cognitive changes after menopause are mixed. The future use of sex hormone treatment will likely focus on personalized or precision medicine for the prevention or treatment of cognitive disturbances during aging, with a better understanding of who may benefit from such treatment.
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Affiliation(s)
- Jason K Russell
- Department of Pharmacology, Vanderbilt University, Nashville, TN, 37232, USA
- Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN, 37232, USA
| | - Carrie K Jones
- Department of Pharmacology, Vanderbilt University, Nashville, TN, 37232, USA
- Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN, 37232, USA
| | - Paul A Newhouse
- Center for Cognitive Medicine, Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, 37212, USA.
- Geriatric Research, Education, and Clinical Center (GRECC), Tennessee VA Health Systems, Nashville, TN, 37212, USA.
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Seitz J, Kubicki M, Jacobs EG, Cherkerzian S, Weiss BK, Papadimitriou G, Mouradian P, Buka S, Goldstein JM, Makris N. Impact of sex and reproductive status on memory circuitry structure and function in early midlife using structural covariance analysis. Hum Brain Mapp 2018; 40:1221-1233. [PMID: 30548738 DOI: 10.1002/hbm.24441] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2018] [Revised: 10/11/2018] [Accepted: 10/13/2018] [Indexed: 01/13/2023] Open
Abstract
Research on age-related memory alterations traditionally targets individuals aged ≥65 years. However, recent studies emphasize the importance of early aging processes. We therefore aimed to characterize variation in brain gray matter structure in early midlife as a function of sex and menopausal status. Subjects included 94 women (33 premenopausal, 29 perimenopausal, and 32 postmenopausal) and 99 demographically comparable men from the New England Family Study. Subjects were scanned with a high-resolution T1 sequence on a 3 T whole body scanner. Sex and reproductive-dependent structural differences were evaluated using Box's M test and analysis of covariances (ANCOVAs) for gray matter volumes. Brain regions of interest included dorsolateral prefrontal cortex (DLPFC), inferior parietal lobule (iPAR), anterior cingulate cortex (ACC), hippocampus (HIPP), and parahippocampus. While we observed expected significant sex differences in volume of hippocampus with women of all groups having higher volumes than men relative to cerebrum size, we also found significant differences in the covariance matrices of perimenopausal women compared with postmenopausal women. Associations between ACC and HIPP/iPAR/DLPFC were higher in postmenopausal women and correlated with better memory performance. Findings in this study underscore the importance of sex and reproductive status in early midlife for understanding memory function with aging.
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Affiliation(s)
- Johanna Seitz
- Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Marek Kubicki
- Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.,Departments of Psychiatry, Neurology and Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Center for Morphometric Analysis, Center for Neural Systems Investigations, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts.,Department of Psychiatry, Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts
| | - Emily G Jacobs
- Department of Medicine, Harvard Medical School, Boston, Massachusetts.,Division of Women's Health, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Sara Cherkerzian
- Department of Psychiatry, Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts.,Department of Medicine, Harvard Medical School, Boston, Massachusetts.,Division of Women's Health, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Blair K Weiss
- Department of Medicine, Harvard Medical School, Boston, Massachusetts.,Division of Women's Health, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - George Papadimitriou
- Departments of Psychiatry, Neurology and Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Center for Morphometric Analysis, Center for Neural Systems Investigations, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts
| | - Palig Mouradian
- Departments of Psychiatry, Neurology and Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Center for Morphometric Analysis, Center for Neural Systems Investigations, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts
| | - Stephen Buka
- Department of Community Health, Brown University, Providence, Rhode Island
| | - Jill M Goldstein
- Departments of Psychiatry, Neurology and Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Center for Morphometric Analysis, Center for Neural Systems Investigations, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts.,Department of Psychiatry, Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts.,Department of Medicine, Harvard Medical School, Boston, Massachusetts.,Division of Women's Health, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Nikos Makris
- Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.,Departments of Psychiatry, Neurology and Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Center for Morphometric Analysis, Center for Neural Systems Investigations, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts
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6
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van Ruitenbeek P, Hernaus D, Mehta MA. A proof-of-principle study of the effect of combined haloperidol and levodopa administration on working memory-related brain activation in humans. Hum Psychopharmacol 2018; 33:e2675. [PMID: 30306671 DOI: 10.1002/hup.2675] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2018] [Revised: 08/27/2018] [Accepted: 08/29/2018] [Indexed: 11/05/2022]
Abstract
OBJECTIVE Cognitive deficits including impaired working memory are a hallmark feature of schizophrenia. Dopamine D1 receptor modulated changes in prefrontal cortex function play a potentially important role in the pathology underlying such deficits. However, pharmacological interventions that selectively engage the D1 receptor are severely restricted for research in humans. The present study is a proof-of-principle for enhancing cognitive performance and associated brain activation via indirect D1 stimulation, operationalised by combining the nonselective dopamine agonist L-dopa with the D2-antagonist haloperidol. METHODS Fourteen healthy volunteers received placebo or combined carbidopa (25 mg)/L-dopa (100 mg) plus haloperidol (2 mg) orally on two separate occasions according to a within-subjects crossover design. Drug-induced differences in brain activity were assessed during an N-back working memory task in a 3T magnetic resonance imaging environment. RESULTS Drug treatment was associated with greater functional connectivity between the dorsolateral prefrontal cortex and areas within the salience network during all N-back trials. Drug treatment was also associated with reduced activation, most prominently in the occipital/temporal brain areas during 2-back performance. CONCLUSIONS This preliminary study provides initial evidence for combined L-dopa/haloperidol modulation in cognition-related brain areas and networks, which is relevant for the treatment of cognitive impairments in mental illness.
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Affiliation(s)
- Peter van Ruitenbeek
- Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.,Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, The Netherlands
| | - Dennis Hernaus
- Department of Psychiatry; Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland
| | - Mitul Ashok Mehta
- Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
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