Amyloid and APOE epsilon 4 interact to influence short-term decline in preclinical Alzheimer disease

Elizabeth C. Mormino*, Rebecca A. Betensky, Trey Hedden, Aaron P. Schultz, Andrew Ward, Willem Huijbers, Dorene M. Rentz, Keith A. Johnson, Reisa A. Sperling, Alzheimer's Dis Neuroimaging Initi, Australian Imaging Biomarkers Life, Harvard Aging Brain Study

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Objective:To examine whether -amyloid (A) and APOE epsilon 4 status independently contribute or interact to influence longitudinal cognitive decline in clinically normal older individuals (CN).Methods:Data from 490 CNs were aggregated across 3 observational cohort studies (Harvard Aging Brain Study, Alzheimer's Disease Neuroimaging Initiative, and Australian Imaging Biomarkers and Lifestyle Study of Ageing; median age = 75.0 years, 255 female), and the contributions of APOE epsilon 4 and A on longitudinal change over a median of 1.49 years were examined. Cognitive decline was assessed with the Mini-Mental State Examination (MMSE) and Logical Memory (immediate and delayed recall scores).Results:High A participants were more likely to be APOE epsilon 4+ than low A participants. CNs who were both high A and APOE epsilon 4+ showed greater decline in Logical Memory immediate recall (p <0.087), Logical Memory delayed recall (p <0.024), and MMSE (p <0.034) compared to all other groups (low A/APOE epsilon 4-, low A/APOE epsilon 4+, and high A/APOE epsilon 4-). No other pairwise contrast was significant for any cognitive measure.Conclusions:Clinically normal individuals who are APOE epsilon 4+ and have high A showed the highest cognitive decline. These results suggest that A and APOE epsilon 4 are not redundant contributors of decline in aging but rather interact to promote decline during the short follow-up period examined in this study. Longer follow-up periods will be essential to fully elucidate the influence of Alzheimer disease risk factors on cognitive decline in aging.

Original languageEnglish
Pages (from-to)1760-1767
Number of pages8
JournalNeurology
Volume82
Issue number20
DOIs
Publication statusPublished - 20 May 2014
Externally publishedYes

Keywords

  • NORMAL OLDER-ADULTS
  • HUMAN CEREBRAL-CORTEX
  • APOLIPOPROTEIN-E
  • A-BETA
  • COGNITIVE IMPAIRMENT
  • GENETIC RISK
  • DEPOSITION
  • GENOTYPE
  • ONSET
  • ASSOCIATION

Cite this

Mormino, E. C., Betensky, R. A., Hedden, T., Schultz, A. P., Ward, A., Huijbers, W., ... Harvard Aging Brain Study (2014). Amyloid and APOE epsilon 4 interact to influence short-term decline in preclinical Alzheimer disease. Neurology, 82(20), 1760-1767. https://doi.org/10.1212/WNL.0000000000000431