Amyloid-associated depression and ApoE4 allele: longitudinal follow-up for the development of Alzheimer's disease

Int J Geriatr Psychiatry. 2016 Mar;31(3):316-22. doi: 10.1002/gps.4339. Epub 2015 Aug 6.

Abstract

Background: Amyloid-associated depression is associated with cognitive impairment cross sectionally. This follow-up study was to determine the relationship between amyloid-associated depression and the development of Alzheimer's disease (AD).

Methods: Two hundred and twenty three subjects who did not have dementia at baseline were given a repeat cognitive evaluation for incident AD. Depression was defined by having a Center for Epidemiological Studies Depression (CES-D) score ≥ 16, and non-amyloid vs. amyloid-associated depression by having a low vs. high plasma amyloid-β peptide 40 (Aβ40)/Aβ42 ratio. Apolipoprotein E (ApoE) genotype was determined, and antidepressant usage was documented.

Results: Fifteen subjects developed AD (7%) after an average follow-up time of 6.2 years. While none of those with non-amyloid depression developed AD, 9% of those with amyloid-associated depression developed AD. Further, among those with amyloid-associated depression, ApoE4 carriers tended to have a higher risk of AD than ApoE4 non-carriers (40% vs. 4%, p = 0.06). In contrast, 8% of those who did not have depression at baseline developed AD, but ApoE4 carriers and non-carriers did not show a difference in the AD risk. After adjusting for age, the interaction between ApoE4 and amyloid-associated depression (β = +0.113, SE = 0.047, P = 0.02) and the interaction between ApoE4 and antidepressant use (β = +0.174, SE = 0.064, P = 0.007) were associated with the AD risk.

Conclusions: Amyloid-associated depression may be prodromal depression of AD especially in the presence of ApoE4. Future studies with a larger cohort and a longer follow-up are warranted to further confirm this conclusion.

Keywords: Alzheimer's disease; amyloid-associated depression; apolipoprotein E4 allele (ApoE4).

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alleles
  • Alzheimer Disease / psychology*
  • Amyloid beta-Peptides / blood*
  • Analysis of Variance
  • Apolipoprotein E4 / genetics*
  • Cognition Disorders / blood
  • Cognition Disorders / psychology
  • Depressive Disorder / blood*
  • Depressive Disorder / complications
  • Depressive Disorder / genetics
  • Female
  • Follow-Up Studies
  • Genotype
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged

Substances

  • Amyloid beta-Peptides
  • Apolipoprotein E4