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Cross-sectional associations of amyloid burden with semantic cognition in older adults without dementia: A systematic review and meta-analysis.

ABSTRACT: Previous research suggests the presence of subtle semantic decline in early stages of Alzheimer's disease. This study investigated associations between amyloid burden, a biomarker for Alzheimer's disease, and tasks of semantic impairment in older individuals without dementia. A systematic search in MEDLINE, PsycINFO, and Embase yielded 3691 peer-reviewed articles excluding duplicates. After screening, 41 studies with overall 7495 participants were included in the meta-analysis and quality assessment. The overall weighted effect size of the association between larger amyloid burden and larger semantic impairment was 0.10 (95% CI [-0.03; 0.22], p = 0.128) for picture naming, 0.19 (95% CI [0.11; 0.27], p < 0.001) for semantic fluency, 0.15 (95% CI [-0.15; 0.45], p = 0.326) for vocabulary, and 0.10 (95% CI [-0.14; 0.35], p = 0.405; 2 studies) for WAIS Information. Risk of bias was highest regarding comparability, as effect sizes were often not calculated on covariate-adjusted statistics. The relevance of the indicated amyloid-related decline in semantic fluency for research and clinical applications is likely negligible due to the effect's small magnitude. Future research should develop more sensitive metrics of semantic fluency to optimize its use for early detection of Alzheimer's disease-related cognitive impairment.

SUBMITTER: Vonk JMJ

PROVIDER: S-EPMC7952036 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Cross-sectional associations of amyloid burden with semantic cognition in older adults without dementia: A systematic review and meta-analysis.

Vonk Jet M J JMJ Twait Emma L EL Scholten Rob J P M RJPM Geerlings Mirjam I MI

Mechanisms of ageing and development 20201019

Previous research suggests the presence of subtle semantic decline in early stages of Alzheimer's disease. This study investigated associations between amyloid burden, a biomarker for Alzheimer's disease, and tasks of semantic impairment in older individuals without dementia. A systematic search in MEDLINE, PsycINFO, and Embase yielded 3691 peer-reviewed articles excluding duplicates. After screening, 41 studies with overall 7495 participants were included in the meta-analysis and quality assess ...[more]

PMID: 33091462

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Project description:Fatigue is a common symptom in the elderly and has also been associated with impaired cognition in older adults. Hence, we sought to explore the cross-sectional relationship between fatigue and cerebral ?-amyloid (A?) in 269 elderly individuals reporting subjective memory complaints from the Multidomain Alzheimer Preventive Trial. Standard uptake value ratios (SUVRs) were generated by [18F] florbetapir positron emission tomography (PET) using the cerebellum as a reference. Cortical-to-cerebellar SUVRs (cortical-SUVRs) were obtained using the mean signal from the frontal cortex, temporal cortex, parietal cortex, precuneus, anterior cingulate, and posterior cingulate. Other brain regions independently assessed were the anterior cingulate, anterior putamen, caudate, hippocampus, medial orbitofrontal cortex, occipital cortex, parietal cortex, pons, posterior cingulate, posterior putamen, precuneus, semioval center, and temporal cortex. Fatigue was defined according to two questions retrieved from the Center for Epidemiological Studies-Depression scale. Chronic fatigue was defined as meeting fatigue criteria at two consecutive clinical visits 6 months apart between study baseline and 1 year (visits were performed at baseline, 6 months and 1 year then annually). Cross-sectional associations between fatigue variables and cerebral A? were explored using fully adjusted multiple linear regression models. We found no statistically significant cross-sectional associations between fatigue assessed at the clinical visit closest to PET and A? in any brain region. Similarly, chronic fatigue was not significantly associated with A? load. Sensitivity analysis in subjects with a Clinical Dementia Rating of 0.5 showed that fatigue reported at the clinical visit closest to PET was, however, weakly associated with increased A? in the hippocampus (B-coefficient: 0.07, 95% CI: 0.01, 0.12, p?=?0.016). These preliminary results suggest that fatigue might be associated with A? in brain regions associated with Alzheimer's disease in subjects in the early stages of disease.

Project description:ImportanceIn the absence of disease-modifying therapies for Alzheimer disease, there is a critical need to identify modifiable risk factors that may delay the progression of Alzheimer disease.ObjectiveTo examine whether physical activity moderates the association of β-amyloid (Aβ) burden with longitudinal cognitive decline and neurodegeneration in clinically normal individuals and to examine whether these associations are independent of vascular risk.Design, setting, and participantsThis longitudinal observational study included clinically normal participants from the Harvard Aging Brain Study. Participants were required to have baseline Aβ positron emission tomography data, baseline medical data to quantify vascular risk, and longitudinal neuropsychological and structural magnetic resonance imaging data. Data were collected from April 2010 to June 2018. Data were analyzed from August to December 2018.Main outcomes and measuresBaseline physical activity was quantified with a pedometer (mean steps per day). Baseline Aβ burden was measured with carbon 11-labeled Pittsburgh Compound B positron emission tomography. Cognition was measured annually with the Preclinical Alzheimer Cognitive Composite (PACC; median [interquartile range] follow-up, 6.0 [4.3-6.3] years). Neurodegeneration was assessed with longitudinal structural magnetic resonance imaging (2 to 5 scans per participant; median [interquartile range] follow-up, 4.5 [3.0-5.0] years), with a focus on total gray matter volume and regional cortical thickness. Physical activity and Aβ burden were examined as interactive predictors of PACC decline and volume loss in separate linear mixed models, adjusting for age, sex, education, apolipoprotein E ε4 status, and, where appropriate, intracranial volume. Secondary models adjusted for vascular risk and its interaction with Aβ burden.ResultsOf the 182 included participants, 103 (56.6%) were female, and the mean (SD) age was 73.4 (6.2) years. In models examining PACC decline and volume loss, there was a significant interaction of physical activity with Aβ burden, such that greater physical activity was associated with slower Aβ-related cognitive decline (β, 0.03; 95% CI, 0.02-0.05; P < .001) and volume loss (β, 482.07; 95% CI, 189.40-774.74; P = .002). Adjusting for vascular risk did not alter these associations. In these models, lower vascular risk was independently associated with slower Aβ-related PACC decline (β, -0.04; 95% CI, -0.06 to -0.02; P < .001) and volume loss (β, -483.41; 95% CI, -855.63 to -111.20; P = .01).Conclusions and relevanceGreater physical activity and lower vascular risk independently attenuated the negative association of Aβ burden with cognitive decline and neurodegeneration in asymptomatic individuals. These findings suggest that engaging in physical activity and lowering vascular risk may have additive protective effects on delaying the progression of Alzheimer disease.

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Dataset Information

Cross-sectional associations of amyloid burden with semantic cognition in older adults without dementia: A systematic review and meta-analysis.

Publications

Cross-sectional associations of amyloid burden with semantic cognition in older adults without dementia: A systematic review and meta-analysis.

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