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Balietti M, Casoli T, Giacconi R, Giuli C. Platelet total PLA2 activity, serum oxidative level and plasma Cu/Zn ratio: a vicious cycle with a potential role to monitor MCI and Alzheimer's disease progression. Rejuvenation Res 2021; 25:16-24. [PMID: 34913745 DOI: 10.1089/rej.2021.0020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Alzheimer's disease (AD) has no cure, mainly because of late diagnosis. Early diagnostic biomarkers are crucial. Phospholipases A2 (PLA2) are hydrolases with several functions in the brain, nevertheless their deregulation contributes to neurodegeneration. We evaluated platelet total PLA2 activity (ptotPLA2) in healthy elderly subjects (HE, n = 102), patients suffering from Mild Cognitive Impairment (MCI, n = 90) and AD (n = 91). Platelets are considered "circulating neurons" and ptotPLA2 seems to mirror the cerebral activity. ptotPLA2 of the three cohorts was similar, but in MCI the higher ptotPLA2 the worse the global cognitive status (Mini Mental State Examination score, MMSE) and in AD the lower ptotPLA2 the more severe the pathology stage (Clinical Dementia Rating, CDR). Accordingly, MCI with MMSE ≥ 26 overlapped HE, in MCI with MMSE < 26 and in AD with CDR 1 ptotPLA2 increased, in AD with CDR 2 ptotPLA2 decreased. In MCI ptotPLA2 positively correlated with blood oxidation and inflammation, in AD it was the opposite. Finally, Discrimination Index (DI) - calculated multiplying ptotPLA2, oxidative level and Cu/Zn ratio (an inflammation parameter) - differentiated MCI patients who progressed to dementia in the following 24 months and AD patients with the worse pathology development. Summarizing, ptotPLA2 changes during MCI and AD progression, is linked, in opposite way, to oxidative/inflammatory status in MCI and AD and might help, when included in DI, to identify MCI converters to dementia and AD patients with the more severe prognosis. ptotPLA2 may have a diagnostic/prognostic value and be a potential therapeutic target.
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Affiliation(s)
- Marta Balietti
- INRCA, Neurobiology of Aging, Via Birrelli 8, Ancona, Italy, 60121;
| | | | | | - Cinzia Giuli
- INRCA IRCCS Hospital, Unit of Geriatrics, contrada Mossa 2, Fermo, Italy, 63900;
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Gates NJ, Rutjes AWS, Di Nisio M, Karim S, Chong L, March E, Martínez G, Vernooij RWM, Cochrane Dementia and Cognitive Improvement Group. Computerised cognitive training for 12 or more weeks for maintaining cognitive function in cognitively healthy people in late life. Cochrane Database Syst Rev 2020; 2:CD012277. [PMID: 32104914 PMCID: PMC7045394 DOI: 10.1002/14651858.cd012277.pub3] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Increasing age is associated with a natural decline in cognitive function and is the greatest risk factor for dementia. Cognitive decline and dementia are significant threats to independence and quality of life in older adults. Therefore, identifying interventions that help to maintain cognitive function in older adults or that reduce the risk of dementia is a research priority. Cognitive training uses repeated practice on standardised exercises targeting one or more cognitive domains and may be intended to improve or maintain optimal cognitive function. This review examines the effects of computerised cognitive training interventions lasting at least 12 weeks on the cognitive function of healthy adults aged 65 or older and has formed part of a wider project about modifying lifestyle to maintain cognitive function. We chose a minimum 12 weeks duration as a trade-off between adequate exposure to a sustainable intervention and feasibility in a trial setting. OBJECTIVES To evaluate the effects of computerised cognitive training interventions lasting at least 12 weeks on cognitive function in cognitively healthy people in late life. SEARCH METHODS We searched to 31 March 2018 in ALOIS (www.medicine.ox.ac.uk/alois), and we performed additional searches of MEDLINE, Embase, PsycINFO, CINAHL, ClinicalTrials.gov, and the WHO Portal/ICTRP (www.apps.who.int/trialsearch), to ensure that the search was as comprehensive and as up-to-date as possible to identify published, unpublished, and ongoing trials. SELECTION CRITERIA We included randomised controlled trials (RCTs) and quasi-RCTs, published or unpublished, reported in any language. Participants were cognitively healthy people, and at least 80% of the study population had to be aged 65 or older. Experimental interventions adhered to the following criteria: intervention was any form of interactive computerised cognitive intervention - including computer exercises, computer games, mobile devices, gaming console, and virtual reality - that involved repeated practice on standardised exercises of specified cognitive domain(s) for the purpose of enhancing cognitive function; the duration of the intervention was at least 12 weeks; cognitive outcomes were measured; and cognitive training interventions were compared with active or inactive control interventions. DATA COLLECTION AND ANALYSIS We performed preliminary screening of search results using a 'crowdsourcing' method to identify RCTs. At least two review authors working independently screened the remaining citations against inclusion criteria. At least two review authors also independently extracted data and assessed the risk of bias of included RCTs. Where appropriate, we synthesised data in random-effects meta-analyses, comparing computerised cognitive training (CCT) separately with active and inactive controls. We expressed treatment effects as standardised mean differences (SMDs) with 95% confidence intervals (CIs). We used GRADE methods to describe the overall quality of the evidence for each outcome. MAIN RESULTS We identified eight RCTs with a total of 1183 participants. The duration of the interventions ranged from 12 to 26 weeks; in five trials, the duration of intervention was 12 or 13 weeks. The included studies had moderate risk of bias, and the overall quality of evidence was low or very low for all outcomes. We compared CCT first against active control interventions, such as watching educational videos. Negative SMDs favour CCT over control. Trial results suggest slight improvement in global cognitive function at the end of the intervention period (12 weeks) (standardised mean difference (SMD) -0.31, 95% confidence interval (CI) -0.57 to -0.05; 232 participants; 2 studies; low-quality evidence). One of these trials also assessed global cognitive function 12 months after the end of the intervention; this trial provided no clear evidence of a persistent effect (SMD -0.21, 95% CI -0.66 to 0.24; 77 participants; 1 study; low-quality evidence). CCT may result in little or no difference at the end of the intervention period in episodic memory (12 to 17 weeks) (SMD 0.06, 95% CI -0.14 to 0.26; 439 participants; 4 studies; low-quality evidence) or working memory (12 to 16 weeks) (SMD -0.17, 95% CI -0.36 to 0.02; 392 participants; 3 studies; low-quality evidence). Because of the very low quality of the evidence, we are very uncertain about the effects of CCT on speed of processing and executive function. We also compared CCT to inactive control (no interventions). We found no data on our primary outcome of global cognitive function. At the end of the intervention, CCT may lead to slight improvement in episodic memory (6 months) (mean difference (MD) in Rivermead Behavioural Memory Test (RBMT) -0.90 points, 95% confidence interval (CI) -1.73 to -0.07; 150 participants; 1 study; low-quality evidence) but can have little or no effect on executive function (12 weeks to 6 months) (SMD -0.08, 95% CI -0.31 to 0.15; 292 participants; 2 studies; low-quality evidence), working memory (16 weeks) (MD -0.08, 95% CI -0.43 to 0.27; 60 participants; 1 study; low-quality evidence), or verbal fluency (6 months) (MD -0.11, 95% CI -1.58 to 1.36; 150 participants; 1 study; low-quality evidence). We could not determine any effects on speed of processing because the evidence was of very low quality. We found no evidence on quality of life, activities of daily living, or adverse effects in either comparison. AUTHORS' CONCLUSIONS We found low-quality evidence suggesting that immediately after completion of the intervention, small benefits of CCT may be seen for global cognitive function when compared with active controls, and for episodic memory when compared with an inactive control. These benefits are of uncertain clinical importance. We found no evidence that the effect on global cognitive function persisted 12 months later. Our confidence in the results was low, reflecting the overall quality of the evidence. In five of the eight trials, the duration of the intervention was just three months. The possibility that more extensive training could yield larger benefit remains to be more fully explored. We found substantial literature on cognitive training, and collating all available scientific information posed problems. Duration of treatment may not be the best way to categorise interventions for inclusion. As the primary interest of older people and of guideline writers and policymakers involves sustained cognitive benefit, an alternative would be to categorise by length of follow-up after selecting studies that assess longer-term effects.
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Affiliation(s)
- Nicola J Gates
- University of New South WalesCentre for Healthy Brain Ageing (CHeBA)Suite 407 185 Elizabeth StreetSydneyNSWAustralia2000
| | - Anne WS Rutjes
- University of BernInstitute of Social and Preventive Medicine (ISPM)Mittelstrasse 43BernBernSwitzerland3012
- University of BernInstitute of Primary Health Care (BIHAM)Mittelstrasse 43BernBernSwitzerland3012
| | - Marcello Di Nisio
- University "G. D'Annunzio" of Chieti‐PescaraDepartment of Medicine and Ageing SciencesVia dei Vestini 31Chieti ScaloItaly66013
| | - Salman Karim
- Lancashire Care NHS Foundation TrustPsychiatrySceptre Point, Sceptre WayPrestonUKPR5 6AW
| | | | - Evrim March
- St Vincent's Hospital (Melbourne)St Vincent's Adult Mental Health46 Nicholson StreetFitzroyVICAustralia3065
| | - Gabriel Martínez
- Universidad de AntofagastaFaculty of Medicine and DentistryAvenida Argentina 2000AntofagastaChile127001
| | - Robin WM Vernooij
- University Medical Center UtrechtDepartment of Nephrology and Hypertension and Julius Center for Health Sciences and Primary CareHeidelberglaan 100UtrechtNetherlands3584 CX
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Gates NJ, Rutjes AWS, Di Nisio M, Karim S, Chong L, March E, Martínez G, Vernooij RWM, Cochrane Dementia and Cognitive Improvement Group. Computerised cognitive training for maintaining cognitive function in cognitively healthy people in late life. Cochrane Database Syst Rev 2019; 3:CD012277. [PMID: 30864187 PMCID: PMC6414816 DOI: 10.1002/14651858.cd012277.pub2] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Increasing age is associated with a natural decline in cognitive function and is also the greatest risk factor for dementia. Cognitive decline and dementia are significant threats to independence and quality of life in older adults. Therefore, identifying interventions that help to maintain cognitive function in older adults or to reduce the risk of dementia is a research priority. Cognitive training uses repeated practice on standardised exercises targeting one or more cognitive domains and is intended to maintain optimum cognitive function. This review examines the effect of computerised cognitive training interventions lasting at least 12 weeks on the cognitive function of healthy adults aged 65 or older. OBJECTIVES To evaluate the effects of computerised cognitive training interventions lasting at least 12 weeks for the maintenance or improvement of cognitive function in cognitively healthy people in late life. SEARCH METHODS We searched to 31 March 2018 in ALOIS (www.medicine.ox.ac.uk/alois) and performed additional searches of MEDLINE, Embase, PsycINFO, CINAHL, ClinicalTrials.gov, and the WHO Portal/ICTRP (www.apps.who.int/trialsearch) to ensure that the search was as comprehensive and as up-to-date as possible, to identify published, unpublished, and ongoing trials. SELECTION CRITERIA We included randomised controlled trials (RCTs) and quasi-RCTs, published or unpublished, reported in any language. Participants were cognitively healthy people, and at least 80% of the study population had to be aged 65 or older. Experimental interventions adhered to the following criteria: intervention was any form of interactive computerised cognitive intervention - including computer exercises, computer games, mobile devices, gaming console, and virtual reality - that involved repeated practice on standardised exercises of specified cognitive domain(s) for the purpose of enhancing cognitive function; duration of the intervention was at least 12 weeks; cognitive outcomes were measured; and cognitive training interventions were compared with active or inactive control interventions. DATA COLLECTION AND ANALYSIS We performed preliminary screening of search results using a 'crowdsourcing' method to identify RCTs. At least two review authors working independently screened the remaining citations against inclusion criteria. At least two review authors also independently extracted data and assessed the risk of bias of included RCTs. Where appropriate, we synthesised data in random-effect meta-analyses, comparing computerised cognitive training (CCT) separately with active and inactive controls. We expressed treatment effects as standardised mean differences (SMDs) with 95% confidence intervals (CIs). We used GRADE methods to describe the overall quality of the evidence for each outcome. MAIN RESULTS We identified eight RCTs with a total of 1183 participants. Researchers provided interventions over 12 to 26 weeks; in five trials, the duration of intervention was 12 or 13 weeks. The included studies had a moderate risk of bias. Review authors noted a lot of inconsistency between trial results. The overall quality of evidence was low or very low for all outcomes.We compared CCT first against active control interventions, such as watching educational videos. Because of the very low quality of the evidence, we were unable to determine any effect of CCT on our primary outcome of global cognitive function or on secondary outcomes of episodic memory, speed of processing, executive function, and working memory.We also compared CCT versus inactive control (no interventions). Negative SMDs favour CCT over control. We found no studies on our primary outcome of global cognitive function. In terms of our secondary outcomes, trial results suggest slight improvement in episodic memory (mean difference (MD) -0.90, 95% confidence interval (CI) -1.73 to -0.07; 150 participants; 1 study; low-quality evidence) and no effect on executive function (SMD -0.08, 95% CI -0.31 to 0.15; 292 participants; 2 studies; low-quality evidence), working memory (MD -0.08, 95% CI -0.43 to 0.27; 60 participants; 1 study; low-quality evidence), or verbal fluency (MD -0.11, 95% CI -1.58 to 1.36; 150 participants; 1 study; low-quality evidence). We could not determine any effects on speed of processing at trial endpoints because the evidence was of very low quality.We found no evidence on quality of life, activities of daily living, or adverse effects in either comparison. AUTHORS' CONCLUSIONS We found little evidence from the included studies to suggest that 12 or more weeks of CCT improves cognition in healthy older adults. However, our limited confidence in the results reflects the overall quality of the evidence. Inconsistency between trials was a major limitation. In five of the eight trials, the duration of intervention was just three months. The possibility that longer periods of training could be beneficial remains to be more fully explored.
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Affiliation(s)
- Nicola J Gates
- University of New South WalesCentre for Healthy Brain Ageing (CHeBA)Suite 407 185 Elizabeth StreetSydneyNSWAustralia2000
| | - Anne WS Rutjes
- University of BernInstitute of Social and Preventive Medicine (ISPM)Mittelstrasse 43BernBernSwitzerland3012
- University of BernInstitute of Primary Health Care (BIHAM)Mittelstrasse 43BernBernSwitzerland3012
| | - Marcello Di Nisio
- University "G. D'Annunzio" of Chieti‐PescaraDepartment of Medicine and Ageing SciencesVia dei Vestini 31Chieti ScaloItaly66013
| | - Salman Karim
- Lancashire Care NHS Foundation TrustPsychiatrySceptre Point, Sceptre WayPrestonUKPR5 6AW
| | | | - Evrim March
- St Vincent's Hospital (Melbourne)St Vincent's Adult Mental Health46 Nicholson StreetFitzroyVICAustralia3065
| | - Gabriel Martínez
- Universidad de AntofagastaFaculty of Medicine and DentistryAvenida Argentina 2000AntofagastaChile127001
| | - Robin WM Vernooij
- Iberoamerican Cochrane CentreC/ Sant Antoni Maria Claret 167BarcelonaBarcelonaSpain08025
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Gates NJ, Rutjes AWS, Di Nisio M, Karim S, Chong L, March E, Martínez G, Vernooij RWM. Computerised cognitive training for maintaining cognitive function in cognitively healthy people in midlife. Cochrane Database Syst Rev 2019; 3:CD012278. [PMID: 30864746 PMCID: PMC6415131 DOI: 10.1002/14651858.cd012278.pub2] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Normal aging is associated with changes in cognitive function that are non-pathological and are not necessarily indicative of future neurocognitive disease. Low cognitive and brain reserve and limited cognitive stimulation are associated with increased risk of dementia. Emerging evidence now suggests that subtle cognitive changes, detectable years before criteria for mild cognitive impairment are met, may be predictive of future dementia. Important for intervention and reduction in disease risk, research also suggests that engaging in stimulating mental activity throughout adulthood builds cognitive and brain reserve and reduces dementia risk. Therefore, midlife (defined here as 40 to 65 years) may be a suitable time to introduce cognitive interventions for maintaining cognitive function and, in the longer term, possibly preventing or delaying the onset of clinical dementia. OBJECTIVES To evaluate the effects of computerised cognitive training interventions lasting at least 12 weeks for maintaining or improving cognitive function in cognitively healthy people in midlife. SEARCH METHODS We searched up to 31 March 2018 in ALOIS (www.medicine.ox.ac.uk/alois), the specialised register of the Cochrane Dementia and Cognitive Improvement Group (CDCIG). We ran additional searches in MEDLINE, Embase, PsycINFO, CINAHL, ClinicalTrials.gov, and the WHO Portal/ICTRP at www.apps.who.int/trialsearch, to ensure that the search was as comprehensive and as up-to-date as possible, to identify published, unpublished, and ongoing trials. SELECTION CRITERIA We included randomised controlled trials (RCTs) or quasi-RCTs, published or unpublished, reported in any language. Participants were cognitively healthy people between 40 and 65 years of age (80% of study population within this age range). Experimental interventions adhered to the following criteria: intervention was any form of interactive computerised cognitive intervention - including computer exercises, computer games, mobile devices, gaming console, and virtual reality - that involved repeated practice on standardised exercises of specified cognitive domain(s) for the purpose of enhancing cognitive function; duration of the intervention was at least 12 weeks; cognitive outcomes were measured; and cognitive training interventions were compared with active or inactive control interventions. DATA COLLECTION AND ANALYSIS For preliminary screening of search results, we used a 'crowd' method to identify RCTs. At least two review authors working independently screened remaining citations against inclusion criteria; independently extracted data; and assessed the quality of the included trial, using the Cochrane risk of bias assessment tool. We used GRADE to describe the overall quality of the evidence. MAIN RESULTS We identified one eligible study that examined the effect of computerised cognitive training (CCT) in 6742 participants over 50 years of age, with training and follow-up duration of six months. We considered the study to be at high risk of attrition bias and the overall quality of the evidence to be low.Researchers provided no data on our primary outcome. Results indicate that there may be a small advantage for the CCT group for executive function (mean difference (MD) -1.57, 95% confidence interval (CI) -1.85 to -1.29; participants = 3994; low-quality evidence) and a very small advantage for the control group for working memory (MD 0.09, 95% CI 0.03 to 0.15; participants = 5831; low-quality evidence). The intervention may have had little or no effect on episodic memory (MD -0.03, 95% CI -0.10 to 0.04; participants = 3090; low-quality evidence). AUTHORS' CONCLUSIONS We found low-quality evidence from only one study. We are unable to determine whether computerised cognitive training is effective in maintaining global cognitive function among healthy adults in midlife. We strongly recommend that high-quality studies be undertaken to investigate the effectiveness and acceptability of cognitive training in midlife, using interventions that last long enough that they may have enduring effects on cognitive and brain reserve, and with investigators following up long enough to assess effects on clinically important outcomes in later life.
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Affiliation(s)
- Nicola J Gates
- University of New South WalesCentre for Healthy Brain Ageing (CHeBA)Suite 407 185 Elizabeth StreetSydneyAustralia2000
| | | | - Marcello Di Nisio
- University "G. D'Annunzio" of Chieti‐PescaraDepartment of Medicine and Ageing SciencesVia dei Vestini 31Chieti ScaloItaly66013
| | - Salman Karim
- Lancashire Care NHS Foundation TrustPsychiatrySceptre Point, Sceptre WayPrestonUKPR5 6AW
| | | | - Evrim March
- St Vincent's Hospital (Melbourne)St Vincent's Adult Mental Health46 Nicholson StreetFitzroyAustralia3065
| | - Gabriel Martínez
- Universidad de AntofagastaFaculty of Medicine and DentistryAvenida Argentina 2000AntofagastaChile127001
| | - Robin WM Vernooij
- Iberoamerican Cochrane CentreC/ Sant Antoni Maria Claret 167BarcelonaSpain08025
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Gates NJ, Vernooij RWM, Di Nisio M, Karim S, March E, Martínez G, Rutjes AWS. Computerised cognitive training for preventing dementia in people with mild cognitive impairment. Cochrane Database Syst Rev 2019; 3:CD012279. [PMID: 30864747 PMCID: PMC6415132 DOI: 10.1002/14651858.cd012279.pub2] [Citation(s) in RCA: 54] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND The number of people living with dementia is increasing rapidly. Clinical dementia does not develop suddenly, but rather is preceded by a period of cognitive decline beyond normal age-related change. People at this intermediate stage between normal cognitive function and clinical dementia are often described as having mild cognitive impairment (MCI). Considerable research and clinical efforts have been directed toward finding disease-modifying interventions that may prevent or delay progression from MCI to clinical dementia. OBJECTIVES To evaluate the effects of at least 12 weeks of computerised cognitive training (CCT) on maintaining or improving cognitive function and preventing dementia in people with mild cognitive impairment. SEARCH METHODS We searched to 31 May 2018 in ALOIS (www.medicine.ox.ac.uk/alois) and ran additional searches in MEDLINE, Embase, PsycINFO, CINAHL, ClinicalTrials.gov, and the WHO portal/ICTRP (www.apps.who.int/trialsearch) to identify published, unpublished, and ongoing trials. SELECTION CRITERIA We included randomised controlled trials (RCTs) and quasi-RCTs in which cognitive training via interactive computerised technology was compared with an active or inactive control intervention. Experimental computerised cognitive training (CCT) interventions had to adhere to the following criteria: minimum intervention duration of 12 weeks; any form of interactive computerised cognitive training, including computer exercises, computer games, mobile devices, gaming console, and virtual reality. Participants were adults with a diagnosis of mild cognitive impairment (MCI) or mild neurocognitive disorder (MND), or otherwise at high risk of cognitive decline. DATA COLLECTION AND ANALYSIS Two review authors independently extracted data and assessed risk of bias of the included RCTs. We expressed treatment effects as mean differences (MDs) or standardised mean differences (SMDs) for continuous outcomes and as risk ratios (RRs) for dichotomous outcomes. We used the GRADE approach to describe the overall quality of evidence for each outcome. MAIN RESULTS Eight RCTs with a total of 660 participants met review inclusion criteria. Duration of the included trials varied from 12 weeks to 18 months. Only one trial used an inactive control. Most studies were at unclear or high risk of bias in several domains. Overall, our ability to draw conclusions was hampered by very low-quality evidence. Almost all results were very imprecise; there were also problems related to risk of bias, inconsistency between trials, and indirectness of the evidence.No trial provided data on incident dementia. For comparisons of CCT with both active and inactive controls, the quality of evidence on our other primary outcome of global cognitive function immediately after the intervention period was very low. Therefore, we were unable to draw any conclusions about this outcome.Due to very low quality of evidence, we were also unable to determine whether there was any effect of CCT compared to active control on our secondary outcomes of episodic memory, working memory, executive function, depression, functional performance, and mortality. We found low-quality evidence suggesting that there is probably no effect on speed of processing (SMD 0.20, 95% confidence interval (CI) -0.16 to 0.56; 2 studies; 119 participants), verbal fluency (SMD -0.16, 95% CI -0.76 to 0.44; 3 studies; 150 participants), or quality of life (mean difference (MD) 0.40, 95% CI -1.85 to 2.65; 1 study; 19 participants).When CCT was compared with inactive control, we obtained data on five secondary outcomes, including episodic memory, executive function, verbal fluency, depression, and functional performance. We found very low-quality evidence; therefore, we were unable to draw any conclusions about these outcomes. AUTHORS' CONCLUSIONS Currently available evidence does not allow us to determine whether or not computerised cognitive training will prevent clinical dementia or improve or maintain cognitive function in those who already have evidence of cognitive impairment. Small numbers of trials, small samples, risk of bias, inconsistency between trials, and highly imprecise results mean that it is not possible to derive any implications for clinical practice, despite some observed large effect sizes from individual studies. Direct adverse events are unlikely to occur, although the time and sometimes the money involved in computerised cognitive training programmes may represent significant burdens. Further research is necessary and should concentrate on improving methodological rigour, selecting suitable outcomes measures, and assessing generalisability and persistence of any effects. Trials with long-term follow-up are needed to determine the potential of this intervention to reduce the risk of dementia.
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Affiliation(s)
- Nicola J Gates
- University of New South WalesCentre for Healthy Brain Ageing (CHeBA)Suite 407 185 Elizabeth StreetSydneyAustralia2000
| | - Robin WM Vernooij
- Iberoamerican Cochrane CentreC/ Sant Antoni Maria Claret 167BarcelonaSpain08025
| | - Marcello Di Nisio
- University "G. D'Annunzio" of Chieti‐PescaraDepartment of Medicine and Ageing SciencesVia dei Vestini 31Chieti ScaloItaly66013
| | - Salman Karim
- Lancashire Care NHS Foundation TrustPsychiatrySceptre Point, Sceptre WayPrestonUKPR5 6AW
| | - Evrim March
- St Vincent's Hospital (Melbourne)St Vincent's Adult Mental Health46 Nicholson StreetFitzroyAustralia3065
| | - Gabriel Martínez
- Universidad de AntofagastaFaculty of Medicine and DentistryAvenida Argentina 2000AntofagastaChile127001
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Abstract
OBJECTIVES Subjective memory complaints (SMC) in older adults are associated with a decline in everyday functioning and an increased risk for future cognitive decline. This study examines the effect of a memory strategy training compared to a control memory training on memory functioning in daily life. METHODS This was a randomized controlled trial with baseline, post-treatment, and 6-month follow-up assessments conducted in 60 older adults (50-87 years) with SMC. Participants were randomly assigned to either seven sessions of memory strategy training or seven sessions of control memory training. Both interventions were given in small groups and included psycho-education. Primary outcome measure was memory functioning in daily life. Objective measures of memory performance and self-reported measures of strategy use were included as secondary outcome measures. RESULTS Participants in each intervention group reported an improvement in personal memory goals (p<.0005), up to 6 months after training. An interaction effect showed that participants following memory strategy training reported a larger improvement in personal memory goals (p=.002). Both intervention groups improved on two memory tests (p<.001 and p<.01). In the memory strategy training group, an increase in strategy use in daily life was the strongest predictor (p<.05) of improvement in subjective memory functioning. CONCLUSIONS Older adults with subjective memory complaints benefit from memory strategy training, especially in their memory functioning in daily life. (JINS, 2018, 24, 1110-1120).
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Giuli C, Fattoretti P, Gagliardi C, Mocchegiani E, Venarucci D, Balietti M, Casoli T, Costarelli L, Giacconi R, Malavolta M, Papa R, Lattanzio F, Postacchini D. My Mind Project: the effects of cognitive training for elderly-the study protocol of a prospective randomized intervention study. Aging Clin Exp Res 2017; 29:353-360. [PMID: 27106901 PMCID: PMC5445186 DOI: 10.1007/s40520-016-0570-1] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2016] [Accepted: 04/06/2016] [Indexed: 01/09/2023]
Abstract
BACKGROUND Cognitive decline and dementia represent a key problem for public health as they heavily impair social functioning and independent living. The development of new strategies to support recommendations for patients and their caregivers may represent an outstanding step forward. AIMS To describe the study protocol and methods of "My Mind Project: the effect of cognitive training for elderly" (Grant No. 154/GR-2009-1584108), which investigates, by the use of a multidisciplinary approach, the effects of a comprehensive cognitive training programme on performances in aged subjects with mild-moderate Alzheimer's disease, mild cognitive impairment and normal cognitive functioning. METHODS The study is a prospective randomized intervention for the assessment of cognitive training effects in three groups of elderly subjects with different cognitive status. A total of 321 elderly people were enrolled in Marche Region, Italy. Each subject was randomly assigned to an experimental group or to a control group. Cognitive performances and biochemical blood markers have also been analysed before cognitive training (baseline), immediately after termination (follow-up 1), after 6 months (follow-up 2) and after 2 years (follow-up 3). DISCUSSION The results will be useful to identify some efficient programmes for the enhancement of cognitive performance in elderly with and without cognitive decline. CONCLUSION The application of a non-pharmacological approach in the treatment of elderly with cognitive disorders could have a profound impact on National Health Service.
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Affiliation(s)
- C Giuli
- Geriatrics Operative Unit, Italian National Research Centre on Aging (INRCA) IRCCS, Contrada Mossa, 63900, Fermo, Italy.
| | - P Fattoretti
- Center for Neurobiology of Aging, Italian National Research Centre on Aging (INRCA), via Birarelli, Ancona, Italy
| | - C Gagliardi
- Centre of Socio-Economic Gerontological Research, Italian National Research Centre on Aging (INRCA), via S. Margherita, Ancona, Italy
| | - E Mocchegiani
- Nutrition and Aging Centre, Italian National Research Centre on Aging (INRCA), via Birarelli, Ancona, Italy
| | - D Venarucci
- Biochemical Operative Unit, Italian National Research Centre on Aging (INRCA), Contrada Mossa, Fermo, Italy
| | - M Balietti
- Center for Neurobiology of Aging, Italian National Research Centre on Aging (INRCA), via Birarelli, Ancona, Italy
| | - T Casoli
- Center for Neurobiology of Aging, Italian National Research Centre on Aging (INRCA), via Birarelli, Ancona, Italy
| | - L Costarelli
- Nutrition and Aging Centre, Italian National Research Centre on Aging (INRCA), via Birarelli, Ancona, Italy
| | - R Giacconi
- Nutrition and Aging Centre, Italian National Research Centre on Aging (INRCA), via Birarelli, Ancona, Italy
| | - M Malavolta
- Nutrition and Aging Centre, Italian National Research Centre on Aging (INRCA), via Birarelli, Ancona, Italy
| | - R Papa
- Centre of Socio-Economic Gerontological Research, Italian National Research Centre on Aging (INRCA), via S. Margherita, Ancona, Italy
| | - F Lattanzio
- Scientific Direction, Italian National Research Centre on Aging (INRCA), via S. Margherita, Ancona, Italy
| | - D Postacchini
- Geriatrics Operative Unit, Italian National Research Centre on Aging (INRCA) IRCCS, Contrada Mossa, 63900, Fermo, Italy
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Mury FB, da Silva WC, Barbosa NR, Mendes CT, Bonini JS, Sarkis JES, Cammarota M, Izquierdo I, Gattaz WF, Dias-Neto E. Lithium activates brain phospholipase A2 and improves memory in rats: implications for Alzheimer's disease. Eur Arch Psychiatry Clin Neurosci 2016; 266:607-18. [PMID: 26661385 DOI: 10.1007/s00406-015-0665-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2015] [Accepted: 11/30/2015] [Indexed: 02/07/2023]
Abstract
Phospholipase A2 (Pla2) is required for memory retrieval, and its inhibition in the hippocampus has been reported to impair memory acquisition in rats. Moreover, cognitive decline and memory deficits showed to be reduced in animal models after lithium treatment, prompting us to evaluate possible links between Pla2, lithium and memory. Here, we evaluated the possible modulation of Pla2 activity by a long-term treatment of rats with low doses of lithium and its impact in memory. Wistar rats were trained for the inhibitory avoidance task, treated with lithium for 100 days and tested for perdurability of long-term memory. Hippocampal samples were used for quantifying the expression of 19 brain-expressed Pla2 genes and for evaluating the enzymatic activity of Pla2 using group-specific radio-enzymatic assays. Our data pointed to a significant perdurability of long-term memory, which correlated with increased transcriptional and enzymatic activities of certain members of the Pla2 family (iPla2 and sPla2) after the chronic lithium treatment. Our data suggest new possible targets of lithium, add more information on its pharmacological activity and reinforce the possible use of low doses of lithium for the treatment of neurodegenerative conditions such as the Alzheimer's disease.
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Affiliation(s)
- Fábio B Mury
- Laboratório de Neurociências (LIM27), Instituto de Psiquiatria, Faculdade de Medicina da Universidade de São Paulo, Rua Ovídio Pires de Campos, 785, 05403-010, São Paulo, SP, Brazil
- Pós-Graduação Interunidades em Biotecnologia, Universidade de São Paulo, São Paulo, SP, Brazil
| | - Weber C da Silva
- Centro de Memória, Instituto de Pesquisas Biomédicas, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil
- Departamento de Farmácia, Universidade Estadual do Centro-Oeste, Guarapuava, PR, Brazil
| | - Nádia R Barbosa
- Laboratório de Neurociências (LIM27), Instituto de Psiquiatria, Faculdade de Medicina da Universidade de São Paulo, Rua Ovídio Pires de Campos, 785, 05403-010, São Paulo, SP, Brazil
| | - Camila T Mendes
- Laboratório de Neurociências (LIM27), Instituto de Psiquiatria, Faculdade de Medicina da Universidade de São Paulo, Rua Ovídio Pires de Campos, 785, 05403-010, São Paulo, SP, Brazil
- Pós-Graduação Interunidades em Biotecnologia, Universidade de São Paulo, São Paulo, SP, Brazil
| | - Juliana S Bonini
- Centro de Memória, Instituto de Pesquisas Biomédicas, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil
- Departamento de Farmácia, Universidade Estadual do Centro-Oeste, Guarapuava, PR, Brazil
| | - Jorge Eduardo Souza Sarkis
- Instituto de Pesquisas Energéticas e Nucleares-IPEN-CNEN/SP, Grupo de Caracterização Química e Isotópica, Universidade de São Paulo, São Paulo, SP, Brazil
| | - Martin Cammarota
- Laboratório de Pesquisa de Memória, Instituto do Cérebro, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil
| | - Ivan Izquierdo
- Centro de Memória, Instituto de Pesquisas Biomédicas, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Wagner F Gattaz
- Laboratório de Neurociências (LIM27), Instituto de Psiquiatria, Faculdade de Medicina da Universidade de São Paulo, Rua Ovídio Pires de Campos, 785, 05403-010, São Paulo, SP, Brazil.
| | - Emmanuel Dias-Neto
- Laboratório de Neurociências (LIM27), Instituto de Psiquiatria, Faculdade de Medicina da Universidade de São Paulo, Rua Ovídio Pires de Campos, 785, 05403-010, São Paulo, SP, Brazil.
- Laboratório de Genômica Médica, Centro Internacional de Pesquisas, AC Camargo Cancer Center, São Paulo, SP, Brazil.
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Balietti M, Giuli C, Fattoretti P, Fabbietti P, Postacchini D, Conti F. Cognitive Stimulation Modulates Platelet Total Phospholipases A2 Activity in Subjects with Mild Cognitive Impairment. J Alzheimers Dis 2016; 50:957-62. [PMID: 26836161 PMCID: PMC4927922 DOI: 10.3233/jad-150714] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/11/2015] [Indexed: 12/13/2022]
Abstract
We evaluated the effect of cognitive stimulation (CS) on platelet total phospholipases A2 activity (tPLA2A) in patients with mild cognitive impairment (MCI_P). At baseline, tPLA2A negatively correlated with Mini-Mental State Examination score (MMSE_s): patients with MMSE_s <26 (Subgroup 1) had significantly higher activity than those with MMSE_s ≥26 (Subgroup 2), who had values similar to the healthy elderly. Regarding CS effect, Subgroup 1 had a significant tPLA2A reduction, whereas Subgroup 2 did not significantly changes after training. Our results showed for the first time that tPLA2A correlates with the cognitive conditions of MCI_P, and that CS acts selectively on subjects with a dysregulated tPLA2A.
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Affiliation(s)
| | | | | | | | | | - Fiorenzo Conti
- Center for Neurobiology of Aging, INRCA, Ancona, Italy
- Department of Experimental and Clinical Medicine, Section of Neuroscience and Cell Biology, Università Politecnica delle Marche, Ancona, Italy
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Talib LL, Hototian SR, Joaquim HPG, Forlenza OV, Gattaz WF. Increased iPLA2 activity and levels of phosphorylated GSK3B in platelets are associated with donepezil treatment in Alzheimer's disease patients. Eur Arch Psychiatry Clin Neurosci 2015; 265:701-6. [PMID: 25920742 DOI: 10.1007/s00406-015-0600-6] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2014] [Accepted: 04/15/2015] [Indexed: 11/30/2022]
Abstract
Reduced phospholipase A2 (PLA2) activity and increased phosphorylation of glycogen synthase kinase 3B (GSK3B) participate in the production of beta-amyloid plaques and of neurofibrillary tangles, which are two neuropathological hallmarks of Alzheimer's disease (AD). Experimental evidences suggest a neuroprotective effect of the cholinesterase inhibitor donepezil in the treatment the disease. The aims of the present study were to evaluate in AD patients the effects of treatment with donepezil on PLA2 activity and GSK3B level. Thirty patients with AD were treated during 6 months with 10 mg daily of donepezil. Radio-enzymatic assays were used to measure PLA2 activity and Elisa assays for GSK3B level, both in platelets. Before treatment and after 3 and 6 months on donepezil, AD patients underwent a cognitive assessment and platelet samples were collected. Values were compared to a healthy control group of 42 sex- and age-matched elderly individuals. Before treatment, iPLA2 activity was lower in patients with AD as compared to controls (p < 0.001). At baseline, no differences were found in GSK3B level between both groups. After 3 and 6 months of treatment, we found a significant increase in iPLA2 activity (p = 0.015 and p < 0.001, respectively). iPLA2 increment was related to the cognitive improvement during treatment (p = 0.037). After 6 months, we found an increase in phosphorylated GSK3B (p = 0.02). The present findings suggest two possible mechanisms by which donepezil delays the progression of AD. The increment of iPLA2 activity may reduce the production of beta-amyloid plaques, whereas the phosphorylation of GSK3B inactivates the enzyme, reducing thus the phosphorylation of tau protein.
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Affiliation(s)
- L L Talib
- Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
| | - S R Hototian
- Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil
| | - H P G Joaquim
- Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil
| | - O V Forlenza
- Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil
| | - W F Gattaz
- Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil. .,Instituto de Psiquiatria, Hospital das Clínicas da Faculdade de Medicina da USP, Rua Dr. Ovídio Pires de Campos 785, São Paulo, SP, 05403-010, Brazil.
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Kim EY, Kim KW. A theoretical framework for cognitive and non-cognitive interventions for older adults: stimulation versus compensation. Aging Ment Health 2014; 18:304-15. [PMID: 24354740 DOI: 10.1080/13607863.2013.868404] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
BACKGROUND Recently, interest in cognitive training for older adults has grown significantly, reflecting a need for preserving the quality of life into late adulthood. In spite of increasing interest in cognitive rehabilitation, recent meta-analyses have questioned reported training gains and determined that cognitive gain from cognitive training might be no larger than the gain observed from active controls such as unspecific, non-cognitive activities. AIMS This paper presents a theoretical framework for clarifying specificity of cognitive training by exploring mechanisms of current cognitive and non-cognitive interventions for older adults. By differentiating compensatory aspects from the components of specific and non-specific stimulation in current training, two related strategies of interventions for age-related cognitive decline, i.e., stimulation versus compensation, are proposed. OVERVIEW Current interventions for age-related cognitive decline are reviewed in terms of stimulation- and compensation-focused interventions. Stimulation-focused, cognitive and non-cognitive training, with or without specific targets, tend to result in general improvement in attention and sensory or other cognitive functions. Meanwhile, compensation-focused training is likely to be the most effective when the intervention specifically supports the frontally mediating activity in accordance with the direction of indigenous adjustments in the aging brain. CONCLUSIONS It can be inferred that stimulation-focused training is to ameliorate the adverse effects of neurological aging, whereas compensation-focused cognitive training is primarily to facilitate compensatory adaptation in the brain.
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Affiliation(s)
- Eun Young Kim
- a Department of Counseling Psychology , Hanyang Cyber University , Seoul , Republic of Korea
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Veitinger M, Varga B, Guterres SB, Zellner M. Platelets, a reliable source for peripheral Alzheimer's disease biomarkers? Acta Neuropathol Commun 2014; 2:65. [PMID: 24934666 PMCID: PMC4229876 DOI: 10.1186/2051-5960-2-65] [Citation(s) in RCA: 65] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2014] [Accepted: 06/01/2014] [Indexed: 12/20/2022] Open
Abstract
Peripheral biomarkers play an indispensable role in quick and reliable diagnoses of any kind of disease. With the population ageing, the number of people suffering from age-related diseases is expected to rise dramatically over the coming decades. In particular, all types of cognitive deficits, such as Alzheimer's disease, will increase. Alzheimer's disease is characterised mainly by coexistence of amyloid plaques and neurofibrillary tangles in brain. Reliable identification of such molecular characteristics antemortem, however, is problematic due to restricted availability of appropriate sample material and definitive diagnosis is only possible postmortem. Currently, the best molecular biomarkers available for antemortem diagnosis originate from cerebrospinal fluid. Though, this is not convenient for routine diagnosis because of the required invasive lumbar puncture. As a consequence, there is a growing demand for additional peripheral biomarkers in a more readily accessible sample material. Blood platelets, due to shared biochemical properties with neurons, can constitute an attractive alternative as discussed here. This review summarises potential platelet Alzheimer's disease biomarkers, their role, implication, and alteration in the disease. For easy comparison of their performance, the Hedge effect size was calculated whenever data were available.
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Affiliation(s)
- Michael Veitinger
- />Institute of Physiology, Centre for Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstrasse 17, 1090 Vienna, EU, Austria
| | - Balazs Varga
- />Institute of Physiology, Centre for Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstrasse 17, 1090 Vienna, EU, Austria
| | - Sheila B Guterres
- />Institute of Physiology, Centre for Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstrasse 17, 1090 Vienna, EU, Austria
- />Institute of Chemistry at São Carlos, University of São Paulo, São Paulo, Brazil
| | - Maria Zellner
- />Institute of Physiology, Centre for Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstrasse 17, 1090 Vienna, EU, Austria
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Gattaz WF, Talib LL, Schaeffer EL, Diniz BS, Forlenza OV. Low platelet iPLA2 activity predicts conversion from mild cognitive impairment to Alzheimer’s disease: a 4-year follow-up study. J Neural Transm (Vienna) 2013; 121:193-200. [DOI: 10.1007/s00702-013-1088-8] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2013] [Accepted: 08/27/2013] [Indexed: 12/12/2022]
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Cognitive interventions in healthy older adults and people with mild cognitive impairment: a systematic review. Ageing Res Rev 2013; 12:263-75. [PMID: 22841936 DOI: 10.1016/j.arr.2012.07.003] [Citation(s) in RCA: 264] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2012] [Revised: 07/13/2012] [Accepted: 07/17/2012] [Indexed: 12/16/2022]
Abstract
Given that the research area of cognitive intervention studies in the aging population is growing rapidly, it is important to review and gauge more recent intervention studies, in order to determine the evidence for the effectiveness of cognitive interventions. The purpose of the present review was to update the recent systematic reviews of Papp et al. (2009) and Martin et al. (2011), to evaluate the effectiveness of cognitive interventions in healthy older adults and people with MCI, by taking into account the methodological quality of the interventions studies. A systematic review of randomized controlled trials (RCT) and clinical studies published between August 2007 and February 2012 in Pubmed and PsychINFO was performed. The quality of the included RCTs was assessed according to the CONSORT criteria for RCTs. A total of thirty-five studies were included; twenty-seven RTCs and eight clinical studies. The content of the intervention studies differed widely, as did the methodological quality of the included RCTs, but was considerably low with an average of 44% of the Consort items included. The results show evidence that cognitive training can be effective in improving various aspects of objective cognitive functioning; memory performance, executive functioning, processing speed, attention, fluid intelligence, and subjective cognitive performance. However, the issue whether the effects of cognitive interventions generalize to improvement in everyday life activities is still unresolved and needs to be addressed more explicitly in future research.
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Talib LL, Joaquim HP, Forlenza OV. Platelet biomarkers in Alzheimer’s disease. World J Psychiatry 2012; 2:95-101. [PMID: 24175175 PMCID: PMC3782189 DOI: 10.5498/wjp.v2.i6.95] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2011] [Revised: 10/23/2012] [Accepted: 11/17/2012] [Indexed: 02/05/2023] Open
Abstract
The search for diagnostic and prognostic markers in Alzheimer’s disease (AD) has been an area of active research in the last decades. Biochemical markers are correlates of intracerebral changes that can be identified in biological fluids, namely: peripheral blood (total blood, red and white blood cells, platelets, plasma and serum), saliva, urine and cerebrospinal fluid. An important feature of a biomarker is that it can be measured objectively and evaluated as (1) an indicator of disease mechanisms (markers of core pathogenic processes or the expression of downstream effects of these processes), or (2) biochemical responses to pharmacological or therapeutic intervention, which can be indicative of disease modification. Platelets have been used in neuropharmacological models since the mid-fifties, as they share several homeostatic functions with neurons, such as accumulation and release of neurotransmitters, responsiveness to variations in calcium concentration, and expression of membrane-bound compounds. Recent studies have shown that platelets also express several components related to the pathogenesis of AD, in particular to the amyloid cascade and the regulation of oxidative stress: thus they can be used in the search for biomarkers of the disease process. For instance, platelets are the most important source of circulating forms of the amyloid precursor protein and other important proteins such as Tau and glycogen synthase kinase-3B. Moreover, platelets express enzymes involved in membrane homeostasis (e.g., phospholipase A2), and markers of the inflammatory process and oxidative stress. In this review we summarize the available literature and discuss evidence concerning the potential use of platelet markers in AD.
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Affiliation(s)
- Leda L Talib
- Leda L Talib, Helena PG Joaquim, Orestes V Forlenza, Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, 05403-010 São Paulo, SP, Brazil
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Abstract
PURPOSE OF REVIEW To identify and discuss recent research studies that propose innovative psychosocial interventions in old age psychiatry. RECENT FINDINGS Studies have shown that cognitive training research for healthy elderly has advanced in several ways, particularly in the refinement of study design and methodology. Studies have included larger samples and longer training protocols. Interestingly, new research has shown changes in biological markers associated with learning and memory after cognitive training. Among mild cognitive impairment patients, results have demonstrated that they benefit from interventions displaying cognitive plasticity.Rehabilitation studies involving dementia patients have suggested the efficacy of combined treatment approaches, and light and music therapies have shown promising effects. For psychiatric disorders, innovations have included improvements in well known techniques such as cognitive behavior therapy, studies in subpopulations with comorbidities, as well as the use of new computer-aided resources. SUMMARY Research evidence on innovative interventions in old age psychiatry suggests that this exciting field is moving forward by means of methodological refinements and testing of creative new ideas.
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Schaeffer EL, Forlenza OV, Gattaz WF. Phospholipase A2 activation as a therapeutic approach for cognitive enhancement in early-stage Alzheimer disease. Psychopharmacology (Berl) 2009; 202:37-51. [PMID: 18853146 DOI: 10.1007/s00213-008-1351-0] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2008] [Accepted: 09/10/2008] [Indexed: 11/29/2022]
Abstract
RATIONALE Alzheimer disease (AD) is the leading cause of dementia in the elderly and has no known cure. Evidence suggests that reduced activity of specific subtypes of intracellular phospholipases A2 (cPLA2 and iPLA2) is an early event in AD and may contribute to memory impairment and neuropathology in the disease. OBJECTIVE The objective of this study was to review the literature focusing on the therapeutic role of PLA2 stimulation by cognitive training and positive modulators, or of supplementation with arachidonic acid (PLA2 product) in facilitating memory function and synaptic transmission and plasticity in either research animals or human subjects. METHODS MEDLINE database was searched (no date restrictions) for published articles using the keywords Alzheimer disease (mild, moderate, severe), mild cognitive impairment, healthy elderly, rats, mice, phospholipase A(2), phospholipid metabolism, phosphatidylcholine, arachidonic acid, cognitive training, learning, memory, long-term potentiation, protein kinases, dietary lipid compounds, cell proliferation, neurogenesis, and neuritogenesis. Reference lists of the identified articles were checked to select additional studies of interest. RESULTS Overall, the data suggest that PLA2 activation is induced in the healthy brain during learning and memory. Furthermore, learning seems to regulate endogenous neurogenesis, which has been observed in AD brains. Finally, PLA2 appears to be implicated in homeostatic processes related to neurite outgrowth and differentiation in both neurodevelopmental processes and response to neuronal injury. CONCLUSION The use of positive modulators of PLA2 (especially of cPLA2 and iPLA2) or supplementation with dietary lipid compounds (e.g., arachidonic acid) in combination with cognitive training could be a valuable therapeutic strategy for cognitive enhancement in early-stage AD.
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Affiliation(s)
- Evelin L Schaeffer
- Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, Rua Dr. Ovídio Pires de Campos 785, 05403-010 São Paulo, SP, Brazil.
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Schaeffer EL, Zorrón Pu L, Gagliotti DAM, Gattaz WF. Conditioning training and retrieval increase phospholipase A(2) activity in the cerebral cortex of rats. J Neural Transm (Vienna) 2008; 116:41-50. [PMID: 18982240 DOI: 10.1007/s00702-008-0133-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2008] [Accepted: 10/04/2008] [Indexed: 12/25/2022]
Abstract
In rats, phospholipase A(2) (PLA(2)) activity was found to be increased in the hippocampus immediately after training and retrieval of a contextual fear conditioning paradigm (step-down inhibitory avoidance [IA] task). In the present study we investigated whether PLA(2) is also activated in the cerebral cortex of rats in association with contextual fear learning and retrieval. We observed that IA training induces a rapid (immediately after training) and long-lasting (3 h after training) activation of PLA(2) in both frontal and parietal cortices. However, immediately after retrieval (measured 24 h after training), PLA(2) activity was increased just in the parietal cortex. These findings suggest that PLA(2) activity is differentially required in the frontal and parietal cortices for the mechanisms of contextual learning and retrieval. Because reduced brain PLA(2) activity has been reported in Alzheimer disease, our results suggest that stimulation of PLA(2) activity may offer new treatment strategies for this disease.
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Affiliation(s)
- E L Schaeffer
- Department and Institute of Psychiatry, University of São Paulo, Rua Doutor Ovídio Pires de Campos, São Paulo, SP, Brazil.
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