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Review
. 2016 Oct 18:6:108-121.
doi: 10.1016/j.dadm.2016.09.002. eCollection 2017.

Cognitive impairment and decline in cognitively normal older adults with high amyloid-β: A meta-analysis

Jenalle E Baker  1 , Yen Ying Lim  2 , Robert H Pietrzak  3 , Jason Hassenstab  4 , Peter J Snyder  5 , Colin L Masters  6 , Paul Maruff  7
Affiliations
Review

Cognitive impairment and decline in cognitively normal older adults with high amyloid-β: A meta-analysis

Jenalle E Baker et al. Alzheimers Dement (Amst). .

Abstract

Introduction: This meta-analysis aimed to characterize the nature and magnitude of amyloid (Aβ)-related cognitive impairment and decline in cognitively normal (CN) older individuals.

Method: MEDLINE Ovid was searched from 2012 to June 2016 for studies reporting relationships between cerebrospinal fluid or positron emission tomography (PET) Aβ levels and cognitive impairment (cross-sectional) and decline (longitudinal) in CN older adults. Neuropsychological data were classified into domains of episodic memory, executive function, working memory, processing speed, visuospatial function, semantic memory, and global cognition. Type of Aβ measure, how Aβ burden was analyzed, inclusion of control variables, and clinical criteria used to exclude participants, were considered as moderators. Random-effects models were used for analyses with effect sizes expressed as Cohen's d.

Results: A total of 38 studies met inclusion criteria contributing 30 cross-sectional (N = 5005) and 14 longitudinal (N = 2584) samples. Aβ-related cognitive impairment was observed for global cognition (d = 0.32), visuospatial function (d = 0.25), processing speed (d = 0.18), episodic memory, and executive function (both d's = 0.15), with decline observed for global cognition (d = 0.30), semantic memory (d = 0.28), visuospatial function (d = 0.25), and episodic memory (d = 0.24). Aβ-related impairment was moderated by age, amyloid measure, type of analysis, and inclusion of control variables and decline moderated by amyloid measure, type of analysis, inclusion of control variables, and exclusion criteria used.

Discussion: CN older adults with high Aβ show a small general cognitive impairment and small to moderate decline in episodic memory, visuospatial function, semantic memory, and global cognition.

Keywords: Amyloid-beta; Cognition; Decline; Impairment; Meta-analysis; Preclinical Alzheimer's disease.

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Figures

Fig. 1
Fig. 1
Forest plots from the meta-analysis of studies with cross-sectional designs. Effect sizes are presented as Cohen's d with 95% confidence intervals. The dotted lines represent no effect of amyloid on cognition. Negative values represent greater impairment in performance in the presence of high Aβ. The size of the dots represents study weighting due to sample size.
Fig. 2
Fig. 2
Forest plots from the meta-analysis of studies with longitudinal designs. Effect sizes are presented as Cohen's d with 95% confidence intervals. The dotted lines represent no effect of amyloid on cognition. Negative values represent greater decline in performance in the presence of high Aβ. The domain of working memory is not included as only one study contributed data for this domain. The size of the dots represents study weighting due to sample size.
See this image and copyright information in PMC

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