Meta-analysis of amyloid-cognition relations in cognitively normal older adults
Abstract
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.
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© 2013 American Academy of Neurology.
Publication History
Received: October 1, 2012
Accepted: December 6, 2012
Published online: April 1, 2013
Published in issue: April 2, 2013
Disclosure
T. Hedden received funding from NIH grants K01 AG040197, P01 AG036694, and R01 AG034556. H. Oh received funding from the Alzheimer's Association and NIH grant R01 AG034570. A.P. Younger has received funding from NIH grants P01 AG036694 and R01 AG034556. T.A. Patel reports no disclosures. Go to Neurology.org for full disclosures.
Study Funding
This work was supported in part by the National Institute on Aging (grant numbers P01 AG036694, R01 AG034556, R01 AG034570, and K01 AG040197); and by the Alzheimer's Association. This research was performed in part at the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital, using resources provided by the Center for Functional Neuroimaging Technologies (grant number P41 RR14075), a P41 Regional Resource supported by the Biomedical Technology Program of the National Center for Research Resources, NIH.
Authors
Author Contributions
Trey Hedden, PhD: drafted the manuscript, conceptualized and designed the study, analyzed and interpreted the data, acquired data, performed statistical analysis, and coordinated the analysis. Hwamee Oh, PhD: revised the manuscript, conceptualized and designed the study, analyzed and interpreted data, and acquired data. Alayna P. Younger, BA: revised the manuscript, acquired data, and analyzed data. Tanu A. Patel: acquired data and analyzed data.
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