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Articles
June 24, 2015

Cognitive impairment 18 years before clinical diagnosis of Alzheimer disease dementia

September 8, 2015 issue
85 (10) 898-904

Abstract

Objective:

To examine the relation of performance on brief cognitive tests to development of clinically diagnosed Alzheimer disease (AD) dementia over the following 18 years in a sample of African Americans and European Americans.

Methods:

A composite cognitive test score based on tests of episodic memory, executive function, and global cognition was constructed in a prospective population-based sample of 2,125 participants (55% African American and 61% female) aged 65 years and older residing in 4 Chicago neighborhoods. Time before AD dementia diagnosis was categorized into 6 groups corresponding to data collection periods: 0.1–0.9, 1.0–3.9, 4.0–6.9, 7.0–9.9, 10.0–12.9, and 13.0–17.9 years.

Results:

Of 2,125 participants without clinical AD dementia, 442 (21%) developed clinical AD dementia over 18 years of follow-up. Lower composite cognitive test scores were associated with the development of AD dementia over the duration of the study. The magnitude of association between composite cognitive test score and development of AD dementia increased from an odds ratio of 3.39 (95% confidence interval 1.72, 6.67; p < 0.001) at 13.0–17.9 years to 9.84 (95% confidence interval 7.41, 13.06; p < 0.001) at 0.1–0.9 years, per SD increment. These associations were consistently larger among European Americans than among African Americans. Performance on individual cognitive tests of episodic memory, executive function, and global cognition also significantly predicted the development of AD dementia, with associations exhibiting a similar trend over 18 years.

Conclusions:

Our findings suggest that cognitive impairment may manifest in the preclinical phase of AD dementia substantially earlier than previously established.

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Supplementary Material

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Information & Authors

Information

Published In

Neurology®
Volume 85Number 10September 8, 2015
Pages: 898-904
PubMed: 26109713

Publication History

Received: February 24, 2015
Accepted: May 8, 2015
Published online: June 24, 2015
Published in print: September 8, 2015

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Disclosure

K. Rajan receives support from the Alzheimer's Association (NIRG-14-302587 [principal investigator]), and the NIH (R44DK088525 [coinvestigator], R01AT007143 [biostatistician], R01MD006173 [biostatistician], R01AG030146 [biostatistician], R34AT008347 [coinvestigator], R01NR014846 [biostatistician], and R01DA039522 [biostatistician]). R. Wilson serves as a consulting editor for Aging, Neuropsychology, and Cognition, Psychology and Aging, and Neuropsychology; has served as a consultant for Pain Therapeutics, Inc.; and receives research support from the NIH (P30AG010161 [coinvestigator], RF1AG015819 [coinvestigator], R01AG017917 [coinvestigator], R01AG034374 [coinvestigator], R01AG039478 [coinvestigator], R01AG036042 [coinvestigator], R01AG036836 [coinvestigator], R01AG041797 [coinvestigator], R01AG042210 [coinvestigator], and R01NR013151 [coinvestigator]), the Alzheimer's Association (NIRGD-11-205469), and Zinfandel Pharmaceuticals. J. Weuve is a consultant for the Alzheimer's Association and the AlzRisk Project (www.alzrisk.org). She is also funded by NIH (R21ES020404 [principal investigator]). L. Barnes receives research support from the NIH (R01AG022018 [principal investigator], P20MD006886 [principal investigator], and P30AG010161 [co-core leader]) and Zinfandel Pharmaceuticals. D. Evans is recipient of grants from the NIH (R01-AG09966 [present, principal investigator] and R01-AG11101 [past, principal investigator]). Go to Neurology.org for full disclosures.

Study Funding

Supported by National Institute on Aging grants R01-AG11101 and R01-AG09966 and in part by Alzheimer's Association New Investigator Research grant NIRG-14-302587.

Authors

Affiliations & Disclosures

Kumar B. Rajan, PhD
From the Department of Internal Medicine, Rush Institute for Healthy Aging (K.B.R., J.W., D.A.E.), Rush Alzheimer Disease Center (R.S.W., L.L.B.), and Departments of Neurological Sciences (R.S.W., L.L.B.) and Behavioral Sciences (R.S.W., L.L.B.), Rush University Medical Center, Chicago, IL.
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.
Associate Professor, Rush University Medical Center
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
Robert S. Wilson, PhD
From the Department of Internal Medicine, Rush Institute for Healthy Aging (K.B.R., J.W., D.A.E.), Rush Alzheimer Disease Center (R.S.W., L.L.B.), and Departments of Neurological Sciences (R.S.W., L.L.B.) and Behavioral Sciences (R.S.W., L.L.B.), Rush University Medical Center, Chicago, IL.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
(1) Aging, Neuropsychology, and Cognition, Consulting Editor, 2004-present; (2) Psychology and Aging, Consulting Editor, 2007-present; (3) Neuropsychology, Consulting Editor, 2014-present.
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
(1) Pain Therapeutics, Inc.
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 R01AG17917, Co-I, 2001-2014; (2) NIH/NIA P30AG10161, Co-I, 1991-2014; (3) NIH/NIA R01AG34374, Co-I, 2008-2014; (4) NIH/NIA R01AG15819, Co-I, 1998-2014.
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
Jennifer Weuve, MPH, ScD
From the Department of Internal Medicine, Rush Institute for Healthy Aging (K.B.R., J.W., D.A.E.), Rush Alzheimer Disease Center (R.S.W., L.L.B.), and Departments of Neurological Sciences (R.S.W., L.L.B.) and Behavioral Sciences (R.S.W., L.L.B.), Rush University Medical Center, Chicago, IL.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
(1) Health Effects Institute, a non-profit entity [speaker honorarium]
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
(1) Fidelity Biosciences (2) Alzheimer's Drug Discovery Foundation (2) Alzheimer's Association
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-NIEHS/R21ES019712, co-investigator, 2010-2013 (2) NIH-NIEHS/R21ES020404, PI, 2012-2015
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
(1) Alzheimer's Association NIRG-12-242395, PI, 2012-2014
Stock/stock Options/board of Directors Compensation:
1.
(1) Exxon Mobile (stocks)
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
Lisa L. Barnes, PhD
From the Department of Internal Medicine, Rush Institute for Healthy Aging (K.B.R., J.W., D.A.E.), Rush Alzheimer Disease Center (R.S.W., L.L.B.), and Departments of Neurological Sciences (R.S.W., L.L.B.) and Behavioral Sciences (R.S.W., L.L.B.), Rush University Medical Center, Chicago, IL.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
Journal of Aging And Health, member of editorial board, 2006 - present. No compensation received.
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, P30-10161, PI of Clinical Core, 9/30/91 ? 6/30/16 (2)NIA, R01-22018, PI, 8/01/2010-7/31/2015 (3)NIMHD,P20-6886, PI 6/15/2012 - 2/1/2017
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
Denis A. Evans, MD
From the Department of Internal Medicine, Rush Institute for Healthy Aging (K.B.R., J.W., D.A.E.), Rush Alzheimer Disease Center (R.S.W., L.L.B.), and Departments of Neurological Sciences (R.S.W., L.L.B.) and Behavioral Sciences (R.S.W., L.L.B.), Rush University Medical Center, Chicago, IL.
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.
Principal Investigator or Co-Investigator) of NIH grants AG11101, AG036650, AG030146, AG10161, AG021972, ES10902, NR009543, HL084209, and AG12505l
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. Rajan: [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

Dr. Rajan designed and conceptualized the study, conducted data analysis, interpreted the findings, and drafted and revised the manuscript. Dr. Wilson designed and conceptualized the study, reviewed and revised the manuscript. Dr. Weuve reviewed and revised the manuscript. Dr. Barnes reviewed and revised the revision of this manuscript. Dr. Evans designed and conceptualized the study, reviewed and revised the manuscript, and supervised the study.

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