The moderating effect of the APOE [small element of] 4 allele on the relationship between hippocampal volume and cognitive decline in older depressed patients

Am J Geriatr Psychiatry. 2011 Jan;19(1):23-32. doi: 10.1097/jgp.0b013e3181f61ae8.

Abstract

Objective: the apolipoprotein E epsilon-4 (APOE [small element of] 4) allele and depression are independently associated with increased risk for cognitive decline (CD). The authors have reported that depressed elders with an APOE [small element of]4 allele had greater CD compared with depressed elders without the allele. Depression affects the hippocampus, and reduced hippocampal volume has been associated with CD. This study sought to examine in depressed patients the relationships between hippocampal volume, the APOE [small element of] 4 allele, and their interaction on CD. Analyses were performed to examine the influence of baseline hippocampal volume, the APOE [small element of] 4 allele, and their interactions on change in cognitive functioning overtime.

Design: secondary data analysis using linear regression analyses.

Setting: clinical Research Center for the Study of Depression in Later Life conducted at Duke University.

Participants: depressed older patients (N = 61) followed up for 4 years.

Measures: At baseline, cognitive functioning (assessed by the Mini-Mental State Examination), left and right hippocampal volume (assessed by magnetic resonance imaging), and APOE genotype were obtained. At 4-year follow-up, cognitive functioning was reassessed.

Results: the APOE [small element of] 4 allele and left hippocampal volume, but not right hippocampal volume, were independently associated with CD. Importantly, the authors found the APOE [small element of]4 allele to moderate the effects of left hippocampal volume on CD. The APOE [small element of]4 allele seemed to have little effect among those with larger left hippocampal volumes, whereas the allele influenced CD among those with smaller hippocampal volumes.

Conclusion: future studies of cognitive impairment and decline should examine both individual and conjoint effects of putative risk factors.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alleles
  • Apolipoprotein E4 / genetics*
  • Atrophy / pathology
  • Cognition Disorders / complications
  • Cognition Disorders / genetics*
  • Cognition Disorders / pathology*
  • Depression / complications
  • Depression / genetics*
  • Depression / pathology*
  • Female
  • Functional Laterality
  • Genetic Predisposition to Disease
  • Genotype
  • Hippocampus / pathology*
  • Humans
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged

Substances

  • Apolipoprotein E4