The neuropsychology of normal aging and preclinical Alzheimer's disease

Richard J. Caselli; Dona E.C. Locke; Amylou C. Dueck; David S. Knopman; Bryan K. Woodruff; Charlene Hoffman-Snyder; Rosa Rademakers; Adam S. Fleisher; Eric M. Reiman

doi:10.1016/j.jalz.2013.01.004

The neuropsychology of normal aging and preclinical Alzheimer's disease

Richard J. Caselli, Dona E.C. Locke, Amylou C. Dueck, David S. Knopman, Bryan K. Woodruff, Charlene Hoffman-Snyder, Rosa Rademakers, Adam S. Fleisher, Eric M. Reiman

Research output: Contribution to journal › Article › peer-review

43 Scopus citations

Abstract

Objective: A National Institute on Aging-sponsored work group on preclinical Alzheimer's disease (AD) articulated the need to characterize cognitive differences between normal aging and preclinical AD. Methods: Seventy-one apolipoprotein E (APOE) ε4 homozygotes, 194 ε3/ε4 heterozygotes, and 356 ε4 noncarriers age 21 to 87 years who were cognitively healthy underwent neuropsychological testing every 2 years. Longitudinal trajectories of test scores were compared between APOE subgroups. Results: There was a significant effect of age on all cognitive domains in both APOE ε4 carriers and noncarriers. A significant effect of APOE ε4 gene dose was confined to the memory domain and the Dementia Rating Scale. Cross-sectional comparisons did not discriminate the groups. Conclusions: Although cognitive aging patterns are similar in APOE ε4 carriers and noncarriers, preclinical AD is characterized by a significant ε4 gene dose effect that impacts memory and is detectable longitudinally. Preclinical neuropsychological testing strategies should emphasize memory-sensitive measures and longitudinal design.

Original language	English (US)
Pages (from-to)	84-92
Number of pages	9
Journal	Alzheimer's and Dementia
Volume	10
Issue number	1
DOIs	https://doi.org/10.1016/j.jalz.2013.01.004
State	Published - Jan 2014

Keywords

Age-related memory loss
Apolipoprotein E
Cognitive aging
Longitudinal testing
Mild cognitive impairment
Preclinical Alzheimer's disease

ASJC Scopus subject areas

Clinical Neurology
Geriatrics and Gerontology
Psychiatry and Mental health
Cellular and Molecular Neuroscience
Health Policy
Developmental Neuroscience
Epidemiology

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10.1016/j.jalz.2013.01.004

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title = "The neuropsychology of normal aging and preclinical Alzheimer's disease",

abstract = "Objective: A National Institute on Aging-sponsored work group on preclinical Alzheimer's disease (AD) articulated the need to characterize cognitive differences between normal aging and preclinical AD. Methods: Seventy-one apolipoprotein E (APOE) ε4 homozygotes, 194 ε3/ε4 heterozygotes, and 356 ε4 noncarriers age 21 to 87 years who were cognitively healthy underwent neuropsychological testing every 2 years. Longitudinal trajectories of test scores were compared between APOE subgroups. Results: There was a significant effect of age on all cognitive domains in both APOE ε4 carriers and noncarriers. A significant effect of APOE ε4 gene dose was confined to the memory domain and the Dementia Rating Scale. Cross-sectional comparisons did not discriminate the groups. Conclusions: Although cognitive aging patterns are similar in APOE ε4 carriers and noncarriers, preclinical AD is characterized by a significant ε4 gene dose effect that impacts memory and is detectable longitudinally. Preclinical neuropsychological testing strategies should emphasize memory-sensitive measures and longitudinal design.",

keywords = "Age-related memory loss, Apolipoprotein E, Cognitive aging, Longitudinal testing, Mild cognitive impairment, Preclinical Alzheimer's disease",

author = "Caselli, {Richard J.} and Locke, {Dona E.C.} and Dueck, {Amylou C.} and Knopman, {David S.} and Woodruff, {Bryan K.} and Charlene Hoffman-Snyder and Rosa Rademakers and Fleisher, {Adam S.} and Reiman, {Eric M.}",

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doi = "10.1016/j.jalz.2013.01.004",

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AU - Locke, Dona E.C.

AU - Dueck, Amylou C.

AU - Knopman, David S.

AU - Woodruff, Bryan K.

AU - Hoffman-Snyder, Charlene

AU - Rademakers, Rosa

AU - Fleisher, Adam S.

AU - Reiman, Eric M.

N1 - Funding Information: Bryan K. Woodruff receives research funding support from Genetech .

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N2 - Objective: A National Institute on Aging-sponsored work group on preclinical Alzheimer's disease (AD) articulated the need to characterize cognitive differences between normal aging and preclinical AD. Methods: Seventy-one apolipoprotein E (APOE) ε4 homozygotes, 194 ε3/ε4 heterozygotes, and 356 ε4 noncarriers age 21 to 87 years who were cognitively healthy underwent neuropsychological testing every 2 years. Longitudinal trajectories of test scores were compared between APOE subgroups. Results: There was a significant effect of age on all cognitive domains in both APOE ε4 carriers and noncarriers. A significant effect of APOE ε4 gene dose was confined to the memory domain and the Dementia Rating Scale. Cross-sectional comparisons did not discriminate the groups. Conclusions: Although cognitive aging patterns are similar in APOE ε4 carriers and noncarriers, preclinical AD is characterized by a significant ε4 gene dose effect that impacts memory and is detectable longitudinally. Preclinical neuropsychological testing strategies should emphasize memory-sensitive measures and longitudinal design.

AB - Objective: A National Institute on Aging-sponsored work group on preclinical Alzheimer's disease (AD) articulated the need to characterize cognitive differences between normal aging and preclinical AD. Methods: Seventy-one apolipoprotein E (APOE) ε4 homozygotes, 194 ε3/ε4 heterozygotes, and 356 ε4 noncarriers age 21 to 87 years who were cognitively healthy underwent neuropsychological testing every 2 years. Longitudinal trajectories of test scores were compared between APOE subgroups. Results: There was a significant effect of age on all cognitive domains in both APOE ε4 carriers and noncarriers. A significant effect of APOE ε4 gene dose was confined to the memory domain and the Dementia Rating Scale. Cross-sectional comparisons did not discriminate the groups. Conclusions: Although cognitive aging patterns are similar in APOE ε4 carriers and noncarriers, preclinical AD is characterized by a significant ε4 gene dose effect that impacts memory and is detectable longitudinally. Preclinical neuropsychological testing strategies should emphasize memory-sensitive measures and longitudinal design.

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KW - Longitudinal testing

KW - Mild cognitive impairment

KW - Preclinical Alzheimer's disease

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The neuropsychology of normal aging and preclinical Alzheimer's disease

Abstract

Keywords

ASJC Scopus subject areas

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