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September 08, 2015; 85 (10) Article

Cognitive impairment 18 years before clinical diagnosis of Alzheimer disease dementia

Kumar B. Rajan, Robert S. Wilson, Jennifer Weuve, Lisa L. Barnes, Denis A. Evans
First published June 24, 2015, DOI: https://doi.org/10.1212/WNL.0000000000001774
Kumar B. Rajan
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.
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Robert S. Wilson
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.
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Jennifer Weuve
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.
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Lisa L. Barnes
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.
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Denis A. Evans
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.
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Citation
Cognitive impairment 18 years before clinical diagnosis of Alzheimer disease dementia
Kumar B. Rajan, Robert S. Wilson, Jennifer Weuve, Lisa L. Barnes, Denis A. Evans
Neurology Sep 2015, 85 (10) 898-904; DOI: 10.1212/WNL.0000000000001774

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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.

GLOSSARY

AD=
Alzheimer disease;
CI=
confidence interval;
OR=
odds ratio

Footnotes

  • 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.

  • Supplemental data at Neurology.org

  • Received February 24, 2015.
  • Accepted in final form May 8, 2015.
  • © 2015 American Academy of Neurology
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