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April 1, 2013

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

April 2, 2013 issue
80 (14) 1341-1348

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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Information & Authors

Information

Published In

Neurology®
Volume 80Number 14April 2, 2013
Pages: 1341-1348
PubMed: 23547267

Publication History

Received: October 1, 2012
Accepted: December 6, 2012
Published online: April 1, 2013
Published in print: April 2, 2013

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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

Affiliations & Disclosures

Trey Hedden, PhD
From the Athinoula A. Martinos Center for Biomedical Imaging (T.H., A.P.Y.), Department of Radiology, Massachusetts General Hospital, Charlestown; Departments of Radiology (T.H.) and Psychiatry (A.P.Y.), Massachusetts General Hospital, Harvard Medical School, Boston, MA; and Helen Wills Neuroscience Institute (H.O., T.A.P.), University of California, Berkeley, CA.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
(1) NIH/NIA, K01 AG040197, PI, 2012, (2) NIH/NIA, P01 AG036694, co-Investigator, 2010-2012, (3) NIH/NIA, R01 AG034556, co-Investigator, 2010-2012
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
(3) Alzheimer's Association, ZEN-10-174210, co-Investigator, 2012
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Hwamee Oh, PhD
From the Athinoula A. Martinos Center for Biomedical Imaging (T.H., A.P.Y.), Department of Radiology, Massachusetts General Hospital, Charlestown; Departments of Radiology (T.H.) and Psychiatry (A.P.Y.), Massachusetts General Hospital, Harvard Medical School, Boston, MA; and Helen Wills Neuroscience Institute (H.O., T.A.P.), University of California, Berkeley, CA.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
(1) NIA, R01-AG034570, postdoc researcher, 2012
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
(1) Alzheimer's Association
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Alayna P. Younger, BA
From the Athinoula A. Martinos Center for Biomedical Imaging (T.H., A.P.Y.), Department of Radiology, Massachusetts General Hospital, Charlestown; Departments of Radiology (T.H.) and Psychiatry (A.P.Y.), Massachusetts General Hospital, Harvard Medical School, Boston, MA; and Helen Wills Neuroscience Institute (H.O., T.A.P.), University of California, Berkeley, CA.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
Funded by NIH grants P01 AG036694 (research assistant, 2011-present)and R01 AG034556 (research assistant, 2011-present).
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Tanu A. Patel
From the Athinoula A. Martinos Center for Biomedical Imaging (T.H., A.P.Y.), Department of Radiology, Massachusetts General Hospital, Charlestown; Departments of Radiology (T.H.) and Psychiatry (A.P.Y.), Massachusetts General Hospital, Harvard Medical School, Boston, MA; and Helen Wills Neuroscience Institute (H.O., T.A.P.), University of California, Berkeley, CA.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE

Notes

Correspondence to Dr. Hedden: [email protected]
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

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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