Meta-analysis of amyloid-cognition relations in cognitively normal older adults

Objective: We conducted a meta-analysis of relationships between amyloid burden and cognition in cognitively normal, older adult humans.

Methods: Methods of assessing amyloid burden included were CSF or plasma assays, histopathology, and PET ligands. Cognitive domains examined were episodic memory, executive function, working memory, processing speed, visuospatial function, semantic memory, and global cognition. Sixty-four studies representing 7,140 subjects met selection criteria, with 3,495 subjects from 34 studies representing independent cohorts. Weighted effect sizes were obtained for each study. Primary analyses were conducted limiting to independent cohort studies using only the most common assessment method (Pittsburgh compound B). Exploratory analyses included all assessment methods.

Results: Episodic memory (r = 0.12) had a significant relationship to amyloid burden. Executive function and global cognition did not have significant relationships to amyloid in the primary analysis of Pittsburgh compound B (r = 0.05 and r = 0.08, respectively), but did when including all assessment methods (r = 0.08 and r = 0.09, respectively). The domains of working memory, processing speed, visuospatial function, and semantic memory did not have significant relationships to amyloid. Differences in the method of amyloid assessment, study design (longitudinal vs cross-sectional), or inclusion of control variables (age, etc.) had little influence.

Conclusions: Based on this meta-analytic survey of the literature, increased amyloid burden has small but nontrivial associations with specific domains of cognitive performance in individuals who are currently cognitively normal. These associations may be useful for identifying preclinical Alzheimer disease or developing clinical outcome measures.