Dataset Information

Late-life Cognitive Activity and Dementia: A Systematic Review and Bias Analysis.

ABSTRACT: Engaging in late-life cognitive activity is often proposed as a strategy to delay or prevent Alzheimer's disease (AD) and other dementias. However, it is unclear to what extent the available evidence supports a causal effect of cognitive activity in dementia prevention.We systematically searched PubMed and EMBASE through June 2014 to identify peer-reviewed epidemiologic studies of cognitive activity and incidence of AD or all-cause dementia. Eligible articles analyzed data from cohort or nested case-control studies, explicitly defined cognitive activity, evaluated participants for AD or all-cause dementia using clearly defined criteria, and provided effect estimates adjusted for at least age and sex. We describe methodologic issues and biases relevant to interpretation of these studies, and quantify the degree of bias due to confounding and reverse causation required to nullify typically observed associations.We reviewed 12 studies involving 13,939 participants and 1,663 dementia cases, of which 565 were specifically evaluated as AD. Most studies found associations between late-life cognitive activity and lower AD and/or all-cause dementia incidence. Differences in cognitive activity operationalization across studies precluded meta-analysis of effect estimates. Our bias analysis indicated that the observed inverse associations are probably robust to unmeasured confounding, and likely only partially explained by reverse causation.Our systematic review and bias analyses provide support for the hypothesis that late-life cognitive activity offers some reduction in AD and all-cause dementia risk. However, more data are needed to confirm this relationship and on the optimal type, duration, intensity, and timing of that activity.

SUBMITTER: Sajeev G

PROVIDER: S-EPMC5460628 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Late-life Cognitive Activity and Dementia: A Systematic Review and Bias Analysis.

Sajeev Gautam G Weuve Jennifer J Jackson John W JW VanderWeele Tyler J TJ Bennett David A DA Grodstein Francine F Blacker Deborah D

Epidemiology (Cambridge, Mass.) 20160901 5

<h4>Background</h4>Engaging in late-life cognitive activity is often proposed as a strategy to delay or prevent Alzheimer's disease (AD) and other dementias. However, it is unclear to what extent the available evidence supports a causal effect of cognitive activity in dementia prevention.<h4>Methods</h4>We systematically searched PubMed and EMBASE through June 2014 to identify peer-reviewed epidemiologic studies of cognitive activity and incidence of AD or all-cause dementia. Eligible articles a ...[more]

PMID: 27227783

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Project description:BackgroundFrailty is a multidimensional syndrome that increases an individual's vulnerability for developing adverse health outcomes, which include dementia. It might serve as a promising target for dementia prevention. However, there are currently no studies summarizing the association between multi-concept frailty and the risk of cognitive disorders. This study aims to summarize the evidence of associations between multi-concept frailty and cognitive disorders based on longitudinal studies.MethodsScopus, The Cochrane Library, PsycINFO, CINAHL, PubMed, and EMBASE databases were searched from inception to January 2, 2022. Longitudinal studies, which explored the association of frailty with incident risk of cognitive decline or dementia, were included. The multivariable-adjusted effect estimates were pooled by random-effects models. The evidence credibility was depicted according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method.ResultsA total of 30 longitudinal studies were included. Four types of frailty concepts were involved, including physical, cognitive, social, and biopsychosocial frailty. The meta-analysis comprised 20 studies of 252,571 older adults (mean age: 64.1-80.4 years), among whom 7,388 participants developed cognitive decline or dementia. Physical frailty was associated with higher risk of developing cognitive disorders [pooled relative risk (pRR) = 1.52, 95% confidence interval (CI): 1.28-1.80, I 2 = 21.2%, pRR = 1.62 for cognitive decline, 95% CI: 1.07-2.45, I 2 = 40.2%, pRR = 1.37 for all-cause dementia (ACD), 95% CI: 1.13-1.66, I 2 = 0.0%]. Cognitive frailty (pRR = 2.90, 95% CI: 1.28-6.55, I 2 = 78.1%) and pre-frailty (pRR = 4.24, 95% CI: 2.74-6.56, I 2 = 30.2%) were linked to higher risk of ACD. Biopsychosocial frailty could predict a 41% (pRR = 1.41, 95% CI: 1.17-1.71) elevated risk of cognitive decline or dementia [pRR = 1.53 (95% CI: 1.19-1.96) for ACD and 1.11 (95% CI: 1.05-1.17) for Alzheimer's disease (AD)]. In the systematic review, social frailty was associated with a 53% higher risk of AD. Preventing frailty could avoid a maximum of 9.9% cognitive disorders globally. The overall evidence strength is rated as low-to-moderate. Inconsistency and imprecision are major sources of bias.ConclusionFrailty in late life is a promising risk factor for cognitive disorders. Frail elderly should be monitored for their cognitive dynamics and initiate early prevention of dementia.Systematic review registrationwww.ClinicalTrials.gov, identifier CRD4202127 3434.

Project description:Involvement of life stress in Late-Onset Alzheimer's Disease (LOAD) has been evinced in longitudinal cohort epidemiological studies, and endocrinologic evidence suggests involvements of catecholamine and corticosteroid systems in LOAD. Early Life Stress (ELS) rodent models have successfully demonstrated sequelae of maternal separation resulting in LOAD-analogous pathology, thereby supporting a role of insulin receptor signalling pertaining to GSK-3beta facilitated tau hyper-phosphorylation and amyloidogenic processing. Discussed are relevant ELS studies, and findings from three mitogen-activated protein kinase pathways (JNK/SAPK pathway, ERK pathway, p38/MAPK pathway) relevant for mediating environmental stresses. Further considered were the roles of autophagy impairment, neuroinflammation, and brain insulin resistance. For the meta-analytic evaluation, 224 candidate gene loci were extracted from reviews of animal studies of LOAD pathophysiological mechanisms, of which 60 had no positive results in human LOAD association studies. These loci were combined with 89 gene loci confirmed as LOAD risk genes in previous GWAS and WES. Of the 313 risk gene loci evaluated, there were 35 human reports on epigenomic modifications in terms of methylation or histone acetylation. 64 microRNA gene regulation mechanisms were published for the compiled loci. Genomic association studies support close relations of both noradrenergic and glucocorticoid systems with LOAD. For HPA involvement, a CRHR1 haplotype with MAPT was described, but further association of only HSD11B1 with LOAD found; however, association of FKBP1 and NC3R1 polymorphisms was documented in support of stress influence to LOAD. In the brain insulin system, IGF2R, INSR, INSRR, and plasticity regulator ARC, were associated with LOAD. Pertaining to compromised myelin stability in LOAD, relevant associations were found for BIN1, RELN, SORL1, SORCS1, CNP, MAG, and MOG. Regarding epigenetic modifications, both methylation variability and de-acetylation were reported for LOAD. The majority of up-to-date epigenomic findings include reported modifications in the well-known LOAD core pathology loci MAPT, BACE1, APP (with FOS, EGR1), PSEN1, PSEN2, and highlight a central role of BDNF. Pertaining to ELS, relevant loci are FKBP5, EGR1, GSK3B; critical roles of inflammation are indicated by CRP, TNFA, NFKB1 modifications; for cholesterol biosynthesis, DHCR24; for myelin stability BIN1, SORL1, CNP; pertaining to (epi)genetic mechanisms, hTERT, MBD2, DNMT1, MTHFR2. Findings on gene regulation were accumulated for BACE1, MAPK signalling, TLR4, BDNF, insulin signalling, with most reports for miR-132 and miR-27. Unclear in epigenomic studies remains the role of noradrenergic signalling, previously demonstrated by neuropathological findings of childhood nucleus caeruleus degeneration for LOAD tauopathy.

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Dataset Information

Late-life Cognitive Activity and Dementia: A Systematic Review and Bias Analysis.

Publications

Late-life Cognitive Activity and Dementia: A Systematic Review and Bias Analysis.

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