Preliminary Evidence That Cortical Amyloid Burden Predicts Poor Response to Antidepressant Medication Treatment in Cognitively Intact Individuals With Late-Life Depression

Am J Geriatr Psychiatry. 2021 May;29(5):448-457. doi: 10.1016/j.jagp.2020.09.019. Epub 2020 Sep 28.


Objective: Amyloid accumulation, the pathological hallmark of Alzheimer's disease, may predispose some older adults to depression and cognitive decline. Deposition of amyloid also occurs prior to the development of cognitive decline. It is unclear whether amyloid influences antidepressant outcomes in cognitively intact depressed elders.

Design: A pharmacoimaging trial utilizing florbetapir (18F) PET scanning followed by 2 sequential 8-week antidepressant medication trials.

Participants: Twenty-seven depressed elders who were cognitively intact on screening.

Measurements and interventions: After screening, diagnostic testing, assessment of depression severity and neuropsychological assessment, participants completed florbetapir (18F) PET scanning. They were then randomized to receive escitalopram or placebo for 8 weeks in a double-blinded two-to-one allocation rate. Individuals who did not respond to initial treatment transitioned to a second open-label trial of bupropion for another 8 weeks.

Results: Compared with 22 amyloid-negative participants, 5 amyloid-positive participants exhibited significantly less change in depression severity and a lower likelihood of remission. In the initial blinded trial, 4 of 5 amyloid-positive participants were nonremitters (80%), while only 18% (4 of 22) of amyloid-negative participants did not remit (p = 0.017; Fisher's Exact test). In separate models adjusting for key covariates, both positive amyloid status (t = 3.07, 21 df, p = 0.003) and higher cortical amyloid binding by standard uptake value ratio (t = 2.62, 21 df, p = 0.010) were associated with less improvement in depression severity. Similar findings were observed when examining change in depression status across both antidepressant trials.

Conclusions: In this preliminary study, amyloid status predicted poor antidepressant response to sequential antidepressant treatment. Alternative treatment approaches may be needed for amyloid-positive depressed elders.

Keywords: Aging; Alzheimer's disease; amyloid; antidepressant; clinical trial; dementia; depressive disorder; neuropathology; remission; response.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Alzheimer Disease* / diagnostic imaging
  • Alzheimer Disease* / drug therapy
  • Amyloid
  • Antidepressive Agents / therapeutic use
  • Cognitive Dysfunction* / drug therapy
  • Depression / drug therapy
  • Double-Blind Method
  • Humans
  • Positron-Emission Tomography


  • Amyloid
  • Antidepressive Agents