Cognitive domain decline in healthy apolipoprotein E ε4 homozygotes before the diagnosis of mild cognitive impairment

Richard J. Caselli, Eric M. Reiman, Dona E C Locke, Michael L. Hutton, Joseph G. Hentz, Charlene Hoffman-Snyder, Bryan K. Woodruff, Gene E Alexander, David Osborne

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

Background: Memory declines more rapidly with age in apolipoprotein E (APOE) ε4 carriers than in APOE ε4 noncarriers, and APOE ε4 homozygotes' cognitive performances correlate with stressors. These changes could represent presymptomatic disease in some, despite their youth. Objective: To show that presymptomatic APOE ε4 homozygotes experience greater psychometric decline at a younger age than APOE ε4 heterozygotes and noncarriers before the diagnosis of mild cognitive impairment (MCI) and Alzheimer disease (AD). Design: Prospective observational study Setting: Academic medical center. Participants: A total of 43 APOE ε4 homozygotes, 59 APOE ε4 heterozygotes, and 112 APOE ε4 noncarriers aged 50 to 69 years were cognitively healthy and matched at entry according to age, educational level, and sex. Intervention: Neuropsychological battery given every 2 years. Main Outcome Measures: Predefined test and cognitive domain decline criteria applied to consecutive epochs. Results: Of 214 participants, 48 showed no decline on any test, 126 showed decline on only 1 test in 1 or more domains, and 40 showed decline on 2 or more tests in 1 or more domains. Cognitive domain decline occurred in 4 of 10 APOE ε4 homozygotes 60 years and older at entry (40.0%) compared with 5 of 66 APOE ε4 heterozygotes and noncarriers (7.6%) (P=.02) and was more predictive of subsequent decline than nondomain decline (17 of 24 [70.8%] vs 29 of 70 [41.4%]; P=.01). Decline on any memory test was predictive of further decline (P<.001), as was memory domain decline (P=.006) in all genetic subgroups. Seven participants developed MCI (in 6) or AD (in 1), of whom 5 were APOE ε4 homozygotes (P=.008). Retrospective comparison showed that those who experienced multidomain, memory, and language domain decline had lower spatial and memory scores at entry than those who experienced no decline. Conclusions: APOE ε4 homozygotes in their 60s have higher rates of cognitive domain decline than APOE ε4 heterozygotes or noncarriers before the diagnosis of MCI and AD, thus confirming and characterizing the existence of a pre-MCI state in this genetic subset.

Original languageEnglish (US)
Pages (from-to)1306-1311
Number of pages6
JournalArchives of Neurology
Volume64
Issue number9
DOIs
StatePublished - Sep 2007

Fingerprint

Apolipoprotein E4
Homozygote
Heterozygote
Cognitive Dysfunction
Mild Cognitive Impairment
Alzheimer Disease
Asymptomatic Diseases
Psychometrics
Observational Studies

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Caselli, R. J., Reiman, E. M., Locke, D. E. C., Hutton, M. L., Hentz, J. G., Hoffman-Snyder, C., ... Osborne, D. (2007). Cognitive domain decline in healthy apolipoprotein E ε4 homozygotes before the diagnosis of mild cognitive impairment. Archives of Neurology, 64(9), 1306-1311. https://doi.org/10.1001/archneur.64.9.1306

Cognitive domain decline in healthy apolipoprotein E ε4 homozygotes before the diagnosis of mild cognitive impairment. / Caselli, Richard J.; Reiman, Eric M.; Locke, Dona E C; Hutton, Michael L.; Hentz, Joseph G.; Hoffman-Snyder, Charlene; Woodruff, Bryan K.; Alexander, Gene E; Osborne, David.

In: Archives of Neurology, Vol. 64, No. 9, 09.2007, p. 1306-1311.

Research output: Contribution to journalArticle

Caselli, RJ, Reiman, EM, Locke, DEC, Hutton, ML, Hentz, JG, Hoffman-Snyder, C, Woodruff, BK, Alexander, GE & Osborne, D 2007, 'Cognitive domain decline in healthy apolipoprotein E ε4 homozygotes before the diagnosis of mild cognitive impairment', Archives of Neurology, vol. 64, no. 9, pp. 1306-1311. https://doi.org/10.1001/archneur.64.9.1306
Caselli, Richard J. ; Reiman, Eric M. ; Locke, Dona E C ; Hutton, Michael L. ; Hentz, Joseph G. ; Hoffman-Snyder, Charlene ; Woodruff, Bryan K. ; Alexander, Gene E ; Osborne, David. / Cognitive domain decline in healthy apolipoprotein E ε4 homozygotes before the diagnosis of mild cognitive impairment. In: Archives of Neurology. 2007 ; Vol. 64, No. 9. pp. 1306-1311.
@article{4c884d7c97694f1a83f7b9a3a17ef936,
title = "Cognitive domain decline in healthy apolipoprotein E ε4 homozygotes before the diagnosis of mild cognitive impairment",
abstract = "Background: Memory declines more rapidly with age in apolipoprotein E (APOE) ε4 carriers than in APOE ε4 noncarriers, and APOE ε4 homozygotes' cognitive performances correlate with stressors. These changes could represent presymptomatic disease in some, despite their youth. Objective: To show that presymptomatic APOE ε4 homozygotes experience greater psychometric decline at a younger age than APOE ε4 heterozygotes and noncarriers before the diagnosis of mild cognitive impairment (MCI) and Alzheimer disease (AD). Design: Prospective observational study Setting: Academic medical center. Participants: A total of 43 APOE ε4 homozygotes, 59 APOE ε4 heterozygotes, and 112 APOE ε4 noncarriers aged 50 to 69 years were cognitively healthy and matched at entry according to age, educational level, and sex. Intervention: Neuropsychological battery given every 2 years. Main Outcome Measures: Predefined test and cognitive domain decline criteria applied to consecutive epochs. Results: Of 214 participants, 48 showed no decline on any test, 126 showed decline on only 1 test in 1 or more domains, and 40 showed decline on 2 or more tests in 1 or more domains. Cognitive domain decline occurred in 4 of 10 APOE ε4 homozygotes 60 years and older at entry (40.0{\%}) compared with 5 of 66 APOE ε4 heterozygotes and noncarriers (7.6{\%}) (P=.02) and was more predictive of subsequent decline than nondomain decline (17 of 24 [70.8{\%}] vs 29 of 70 [41.4{\%}]; P=.01). Decline on any memory test was predictive of further decline (P<.001), as was memory domain decline (P=.006) in all genetic subgroups. Seven participants developed MCI (in 6) or AD (in 1), of whom 5 were APOE ε4 homozygotes (P=.008). Retrospective comparison showed that those who experienced multidomain, memory, and language domain decline had lower spatial and memory scores at entry than those who experienced no decline. Conclusions: APOE ε4 homozygotes in their 60s have higher rates of cognitive domain decline than APOE ε4 heterozygotes or noncarriers before the diagnosis of MCI and AD, thus confirming and characterizing the existence of a pre-MCI state in this genetic subset.",
author = "Caselli, {Richard J.} and Reiman, {Eric M.} and Locke, {Dona E C} and Hutton, {Michael L.} and Hentz, {Joseph G.} and Charlene Hoffman-Snyder and Woodruff, {Bryan K.} and Alexander, {Gene E} and David Osborne",
year = "2007",
month = "9",
doi = "10.1001/archneur.64.9.1306",
language = "English (US)",
volume = "64",
pages = "1306--1311",
journal = "Archives of Neurology",
issn = "0003-9942",
publisher = "American Medical Association",
number = "9",

}

TY - JOUR

T1 - Cognitive domain decline in healthy apolipoprotein E ε4 homozygotes before the diagnosis of mild cognitive impairment

AU - Caselli, Richard J.

AU - Reiman, Eric M.

AU - Locke, Dona E C

AU - Hutton, Michael L.

AU - Hentz, Joseph G.

AU - Hoffman-Snyder, Charlene

AU - Woodruff, Bryan K.

AU - Alexander, Gene E

AU - Osborne, David

PY - 2007/9

Y1 - 2007/9

N2 - Background: Memory declines more rapidly with age in apolipoprotein E (APOE) ε4 carriers than in APOE ε4 noncarriers, and APOE ε4 homozygotes' cognitive performances correlate with stressors. These changes could represent presymptomatic disease in some, despite their youth. Objective: To show that presymptomatic APOE ε4 homozygotes experience greater psychometric decline at a younger age than APOE ε4 heterozygotes and noncarriers before the diagnosis of mild cognitive impairment (MCI) and Alzheimer disease (AD). Design: Prospective observational study Setting: Academic medical center. Participants: A total of 43 APOE ε4 homozygotes, 59 APOE ε4 heterozygotes, and 112 APOE ε4 noncarriers aged 50 to 69 years were cognitively healthy and matched at entry according to age, educational level, and sex. Intervention: Neuropsychological battery given every 2 years. Main Outcome Measures: Predefined test and cognitive domain decline criteria applied to consecutive epochs. Results: Of 214 participants, 48 showed no decline on any test, 126 showed decline on only 1 test in 1 or more domains, and 40 showed decline on 2 or more tests in 1 or more domains. Cognitive domain decline occurred in 4 of 10 APOE ε4 homozygotes 60 years and older at entry (40.0%) compared with 5 of 66 APOE ε4 heterozygotes and noncarriers (7.6%) (P=.02) and was more predictive of subsequent decline than nondomain decline (17 of 24 [70.8%] vs 29 of 70 [41.4%]; P=.01). Decline on any memory test was predictive of further decline (P<.001), as was memory domain decline (P=.006) in all genetic subgroups. Seven participants developed MCI (in 6) or AD (in 1), of whom 5 were APOE ε4 homozygotes (P=.008). Retrospective comparison showed that those who experienced multidomain, memory, and language domain decline had lower spatial and memory scores at entry than those who experienced no decline. Conclusions: APOE ε4 homozygotes in their 60s have higher rates of cognitive domain decline than APOE ε4 heterozygotes or noncarriers before the diagnosis of MCI and AD, thus confirming and characterizing the existence of a pre-MCI state in this genetic subset.

AB - Background: Memory declines more rapidly with age in apolipoprotein E (APOE) ε4 carriers than in APOE ε4 noncarriers, and APOE ε4 homozygotes' cognitive performances correlate with stressors. These changes could represent presymptomatic disease in some, despite their youth. Objective: To show that presymptomatic APOE ε4 homozygotes experience greater psychometric decline at a younger age than APOE ε4 heterozygotes and noncarriers before the diagnosis of mild cognitive impairment (MCI) and Alzheimer disease (AD). Design: Prospective observational study Setting: Academic medical center. Participants: A total of 43 APOE ε4 homozygotes, 59 APOE ε4 heterozygotes, and 112 APOE ε4 noncarriers aged 50 to 69 years were cognitively healthy and matched at entry according to age, educational level, and sex. Intervention: Neuropsychological battery given every 2 years. Main Outcome Measures: Predefined test and cognitive domain decline criteria applied to consecutive epochs. Results: Of 214 participants, 48 showed no decline on any test, 126 showed decline on only 1 test in 1 or more domains, and 40 showed decline on 2 or more tests in 1 or more domains. Cognitive domain decline occurred in 4 of 10 APOE ε4 homozygotes 60 years and older at entry (40.0%) compared with 5 of 66 APOE ε4 heterozygotes and noncarriers (7.6%) (P=.02) and was more predictive of subsequent decline than nondomain decline (17 of 24 [70.8%] vs 29 of 70 [41.4%]; P=.01). Decline on any memory test was predictive of further decline (P<.001), as was memory domain decline (P=.006) in all genetic subgroups. Seven participants developed MCI (in 6) or AD (in 1), of whom 5 were APOE ε4 homozygotes (P=.008). Retrospective comparison showed that those who experienced multidomain, memory, and language domain decline had lower spatial and memory scores at entry than those who experienced no decline. Conclusions: APOE ε4 homozygotes in their 60s have higher rates of cognitive domain decline than APOE ε4 heterozygotes or noncarriers before the diagnosis of MCI and AD, thus confirming and characterizing the existence of a pre-MCI state in this genetic subset.

UR - http://www.scopus.com/inward/record.url?scp=34548635537&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34548635537&partnerID=8YFLogxK

U2 - 10.1001/archneur.64.9.1306

DO - 10.1001/archneur.64.9.1306

M3 - Article

C2 - 17846270

AN - SCOPUS:34548635537

VL - 64

SP - 1306

EP - 1311

JO - Archives of Neurology

JF - Archives of Neurology

SN - 0003-9942

IS - 9

ER -