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Cognitive domain decline in healthy apolipoprotein E epsilon4 homozygotes before the diagnosis of mild cognitive impairment.
Arch Neurol 2007; 64(9):1306-11AN

Abstract

BACKGROUND

Memory declines more rapidly with age in apolipoprotein E (APOE) epsilon4 carriers than in APOE epsilon4 noncarriers, and APOE epsilon4 homozygotes' cognitive performances correlate with stressors. These changes could represent presymptomatic disease in some, despite their youth.

OBJECTIVE

To show that presymptomatic APOE epsilon4 homozygotes experience greater psychometric decline at a younger age than APOE epsilon4 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 epsilon4 homozygotes, 59 APOE epsilon4 heterozygotes, and 112 APOE epsilon4 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 epsilon4 homozygotes 60 years and older at entry (40.0%) compared with 5 of 66 APOE epsilon4 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 epsilon4 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 epsilon4 homozygotes in their 60s have higher rates of cognitive domain decline than APOE epsilon4 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.

Authors+Show Affiliations

Department of Neurology, Mayo Clinic, 13400 E Shea Blvd, Scottsdale, AZ 85259, USA. caselli.richard@mayo.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17846270

Citation

Caselli, Richard J., et al. "Cognitive Domain Decline in Healthy Apolipoprotein E Epsilon4 Homozygotes Before the Diagnosis of Mild Cognitive Impairment." Archives of Neurology, vol. 64, no. 9, 2007, pp. 1306-11.
Caselli RJ, Reiman EM, Locke DE, et al. Cognitive domain decline in healthy apolipoprotein E epsilon4 homozygotes before the diagnosis of mild cognitive impairment. Arch Neurol. 2007;64(9):1306-11.
Caselli, R. J., Reiman, E. M., Locke, D. E., Hutton, M. L., Hentz, J. G., Hoffman-Snyder, C., ... Osborne, D. (2007). Cognitive domain decline in healthy apolipoprotein E epsilon4 homozygotes before the diagnosis of mild cognitive impairment. Archives of Neurology, 64(9), pp. 1306-11.
Caselli RJ, et al. Cognitive Domain Decline in Healthy Apolipoprotein E Epsilon4 Homozygotes Before the Diagnosis of Mild Cognitive Impairment. Arch Neurol. 2007;64(9):1306-11. PubMed PMID: 17846270.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cognitive domain decline in healthy apolipoprotein E epsilon4 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 - 2007/9/12/pubmed PY - 2007/10/18/medline PY - 2007/9/12/entrez SP - 1306 EP - 11 JF - Archives of neurology JO - Arch. Neurol. VL - 64 IS - 9 N2 - BACKGROUND: Memory declines more rapidly with age in apolipoprotein E (APOE) epsilon4 carriers than in APOE epsilon4 noncarriers, and APOE epsilon4 homozygotes' cognitive performances correlate with stressors. These changes could represent presymptomatic disease in some, despite their youth. OBJECTIVE: To show that presymptomatic APOE epsilon4 homozygotes experience greater psychometric decline at a younger age than APOE epsilon4 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 epsilon4 homozygotes, 59 APOE epsilon4 heterozygotes, and 112 APOE epsilon4 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 epsilon4 homozygotes 60 years and older at entry (40.0%) compared with 5 of 66 APOE epsilon4 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 epsilon4 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 epsilon4 homozygotes in their 60s have higher rates of cognitive domain decline than APOE epsilon4 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. SN - 0003-9942 UR - https://www.unboundmedicine.com/medline/citation/17846270/Cognitive_domain_decline_in_healthy_apolipoprotein_E_epsilon4_homozygotes_before_the_diagnosis_of_mild_cognitive_impairment_ L2 - https://jamanetwork.com/journals/jamaneurology/fullarticle/10.1001/archneur.64.9.1306 DB - PRIME DP - Unbound Medicine ER -