Lifetime History of Depression Predicts Increased Amyloid-β Accumulation in Patients with Mild Cognitive Impairment

J Alzheimers Dis. 2015;45(3):907-19. doi: 10.3233/JAD-142931.


Mounting evidence associates a lifetime history of major depression (LMD) with an increased risk for Alzheimer's disease (AD). Studies have shown that major depression (MD) is strongly linked to pathophysiological markers of AD, such as cortical amyloid-β (Aβ) burden. However, no imaging studies have shown in vivo whether an LMD is linked to increased Aβ accumulation in patients with mild cognitive impairment (MCI) in four cortical regions that have been highly associated with increased Aβ deposition in previous literature: frontal, cingulate, parietal, and temporal. Drawing from the ADNI database, we found that patients with amnestic MCI (aMCI) and an LMD (n = 39) had significantly higher 18F-Florbetapir standardized uptake value ratios, a surrogate measure of Aβ deposition, mainly in the bilateral frontal cortex, compared to patients with aMCI without an LMD (n = 39) (p = 0.02). This difference was not explained by current depressive symptoms, vascular risk factors, or the use of different PET scanners. The results were reliable employing two independent methods for analysis: region-of-interest and voxel-based analyses. Increased Aβ in the bilateral frontal lobes may be a biomarker of depressive symptomology in aMCI patients. Further studies should test whether higher Aβ predicts future conversion into AD in this population.

Keywords: Alzheimer's disease; amyloid-β; major depression; mild cognitive impairment; positron emission tomography.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Amyloid beta-Peptides / metabolism*
  • Analysis of Variance
  • Apolipoprotein E4 / genetics
  • Brain Mapping
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / pathology*
  • Cognitive Dysfunction / complications*
  • Cognitive Dysfunction / diagnosis*
  • Cognitive Dysfunction / psychology
  • Databases, Factual
  • Depression / etiology*
  • Depression / metabolism*
  • Female
  • Fluorodeoxyglucose F18 / metabolism
  • Humans
  • Male
  • Middle Aged
  • Positron-Emission Tomography


  • Amyloid beta-Peptides
  • Apolipoprotein E4
  • Fluorodeoxyglucose F18