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      Education and Dementia in the Context of the Cognitive Reserve Hypothesis: A Systematic Review with Meta-Analyses and Qualitative Analyses

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          Abstract

          Background

          Cognitive reserve (CR) or brain reserve capacity explains why individuals with higher IQ, education, or occupational attainment have lower risks of developing dementia, Alzheimer’s disease (AD) or vascular dementia (VaD). The CR hypothesis postulates that CR reduces the prevalence and incidence of AD or VaD. It also hypothesizes that among those who have greater initial cognitive reserve (in contrast to those with less reserve) greater brain pathology occurs before the clinical symptoms of disease becomes manifest. Thus clinical disease onset triggers a faster decline in cognition and function, and increased mortality among those with initial greater cognitive reserve. Disease progression follows distinctly separate pathological and clinical paths. With education as a proxy we use meta-analyses and qualitative analyses to review the evidence for the CR hypothesis.

          Methodology/Principal Findings

          We searched PubMed, PsycoINFO, EMBASE, HealthStar, and Scopus databases from January 1980 to June 2011 for observational studies with clear criteria for dementia, AD or VaD and education. One hundred and thirty-three articles with a variety of study designs met the inclusion criteria. Prevalence and incidence studies with odds ratios (ORs), relative risks or original data were included in the meta-analyses. Other studies were reviewed qualitatively. The studies covered 437,477 subjects. Prevalence and incidence studies with pooled ORs of 2.61 (95%CI 2.21–3.07) and 1.88 (95%CI 1.51–2.34) respectively, showed low education increased the risk of dementia. Heterogeneity and sensitivity tests confirmed the evidence. Generally, study characteristics had no effect on conclusions. Qualitative analyses also showed the protective effects of higher education on developing dementia and with clinical disease onset hastening a decline in cognition and function, and greater brain pathology.

          Conclusion/Significance

          This systematic review and meta-analyses covering a wide range of observational studies and diverse settings provides robust support for the CR hypothesis. The CR hypothesis suggests several avenues for dementia prevention.

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          Most cited references35

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          Memantine in moderate-to-severe Alzheimer's disease.

          Overstimulation of the N-methyl-D-aspartate (NMDA) receptor by glutamate is implicated in neurodegenerative disorders. Accordingly, we investigated memantine, an NMDA antagonist, for the treatment of Alzheimer's disease. Patients with moderate-to-severe Alzheimer's disease were randomly assigned to receive placebo or 20 mg of memantine daily for 28 weeks. The primary efficacy variables were the Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus) and the Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory modified for severe dementia (ADCS-ADLsev). The secondary efficacy end points included the Severe Impairment Battery and other measures of cognition, function, and behavior. Treatment differences between base line and the end point were assessed. Missing observations were imputed by using the most recent previous observation (the last observation carried forward). The results were also analyzed with only the observed values included, without replacing the missing values (observed-cases analysis). Two hundred fifty-two patients (67 percent women; mean age, 76 years) from 32 U.S. centers were enrolled. Of these, 181 (72 percent) completed the study and were evaluated at week 28. Seventy-one patients discontinued treatment prematurely (42 taking placebo and 29 taking memantine). Patients receiving memantine had a better outcome than those receiving placebo, according to the results of the CIBIC-Plus (P=0.06 with the last observation carried forward, P=0.03 for observed cases), the ADCS-ADLsev (P=0.02 with the last observation carried forward, P=0.003 for observed cases), and the Severe Impairment Battery (P<0.001 with the last observation carried forward, P=0.002 for observed cases). Memantine was not associated with a significant frequency of adverse events. Antiglutamatergic treatment reduced clinical deterioration in moderate-to-severe Alzheimer's disease, a phase associated with distress for patients and burden on caregivers, for which other treatments are not available. Copyright 2003 Massachusetts Medical Society
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            Risk factors for Alzheimer's disease: a prospective analysis from the Canadian Study of Health and Aging.

            J. Lindsay (2002)
            A prospective analysis of risk factors for Alzheimer's disease was a major objective of the Canadian Study of Health and Aging, a nationwide, population-based study. Of 6,434 eligible subjects aged 65 years or older in 1991, 4,615 were alive in 1996 and participated in the follow-up study. All participants were cognitively normal in 1991 when they completed a risk factor questionnaire. Their cognitive status was reassessed 5 years later by using a similar two-phase procedure, including a screening interview, followed by a clinical examination when indicated. The analysis included 194 Alzheimer's disease cases and 3,894 cognitively normal controls. Increasing age, fewer years of education, and the apolipoprotein E epsilon4 allele were significantly associated with increased risk of Alzheimer's disease. Use of nonsteroidal anti-inflammatory drugs, wine consumption, coffee consumption, and regular physical activity were associated with a reduced risk of Alzheimer's disease. No statistically significant association was found for family history of dementia, sex, history of depression, estrogen replacement therapy, head trauma, antiperspirant or antacid use, smoking, high blood pressure, heart disease, or stroke. The protective associations warrant further study. In particular, regular physical activity could be an important component of a preventive strategy against Alzheimer's disease and many other conditions.
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              Mental, Physical and Social Components in Leisure Activities Equally Contribute to Decrease Dementia Risk

              Background: There is accumulating evidence in the literature that leisure engagement has a beneficial effect on dementia. Most studies have grouped activities according to whether they were predominantly mental, physical or social. Since many activities contain more than one component, we aimed to verify the effect of all three major components on the dementia risk, as well as their combined effect. Methods: A mental, social and physical component score was estimated for each activity by the researchers and a sample of elderly persons. The correlation between the ratings of the authors and the means of the elderly subjects’ ratings was 0.86. The study population consisted of 776 nondemented subjects, aged 75 years and above, living in Stockholm, Sweden, who were still nondemented after 3 years and were followed for 3 more years to detect incident dementia cases. Results: Multi-adjusted relative risks (RRs) of dementia for subjects with higher mental, physical and social component score sums were 0.71 (95% CI: 0.49–1.03), 0.61 (95% CI: 0.42–0.87) and 0.68 (95% CI: 0.47–0.99), respectively. The most beneficial effect was present for subjects with high scores in all or in two of the components (RR of dementia = 0.53; 95% CI: 0.36–0.78). Conclusions: These findings suggest that a broad spectrum of activities containing more than one of the components seems to be more beneficial than to be engaged in only one type of activity.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2012
                4 June 2012
                : 7
                : 6
                : e38268
                Affiliations
                [1 ]Department of Psychiatry, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
                [2 ]Canadian Center for Health and Safety in Agriculture, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
                [3 ]School of Public Health, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
                Federal University of Rio de Janeiro, Brazil
                Author notes

                Conceived and designed the experiments: XM CD. Performed the experiments: XM CD. Analyzed the data: XM CD. Contributed reagents/materials/analysis tools: XM CD. Wrote the paper: XM CD.

                Article
                PONE-D-12-04086
                10.1371/journal.pone.0038268
                3366926
                22675535
                028d5eaa-06dc-4728-97c2-e0f17528f6b2
                Meng, D’Arcy. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 6 February 2012
                : 6 May 2012
                Page count
                Pages: 16
                Categories
                Research Article
                Medicine
                Clinical Research Design
                Meta-Analyses
                Systematic Reviews
                Epidemiology
                Epidemiology of Aging
                Social Epidemiology
                Mental Health
                Psychiatry
                Dementia
                Neurology
                Dementia
                Alzheimer Disease
                Vascular Dementia
                Public Health
                Behavioral and Social Aspects of Health

                Uncategorized
                Uncategorized

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