The neuropsychology of normal aging and preclinical Alzheimer's disease - PubMed (original) (raw)

The neuropsychology of normal aging and preclinical Alzheimer's disease

Richard J Caselli et al. Alzheimers Dement. 2014 Jan.

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.

Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

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Figures

Figure one. Selective Reminding Test, Free Recall (Total)

There is accelerating decline with increasing age that exhibits a significant APOE e4 gene dose effect.

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References

1. 1. Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, et al. Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alz Dem. 2011;7:280–292. - PMC - PubMed
2. 1. Saunders AM, Strittmatter WJ, Schmechel D, George-Hyslop PH, Pericak-Vance MA, Joo SH, et al. Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer's disease. Neurology. 1993;43:1467–1472. - PubMed
3. 1. Caselli RJ, Dueck AC, Osborne D, Sabbagh MN, Connor DJ, Ahern GL, et al. Longitudinal modeling of age-related memory decline and the APOE epsilon4 effect. N Engl J Med. 2009;361:255–263. - PMC - PubMed
4. 1. Howieson DB, Carlson NE, Moore MM, Wasserman D, Abendroth CD, Payne-Murphy J, Kaye JA. Trajectory of mild cognitive impairment onset. J Int Neuropsychol Soc. 2008;14:192–198. - PubMed
5. 1. Bouras C, Hof PR, Giannakopoulos P, Michel JP, Morrison JH. Regional distribution of neurofibrillary tangles and senile plaques in the cerebral cortex of elderly patients: a quantitative evaluation of a one-year autopsy population from a geriatric hospital. Cereb Cortex. 1994;4:138–150. - PubMed

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