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

Abstract

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.

Figure 1.

Study CONSORT Diagram

Figure 2.. Amyloid effects on depression severity change with treatment

Figure 2a displays change in MADRS score across by Aβ-status in Trial 1 (escitalopram vs placebo, weeks 0–8). Error bars display the standard error at each timepoint. Figure 2b displays the relationship between cortical Aβ SUVr and percent change in depressive symptoms from baseline across both trials to study completion, showing the regression line and 95% confidence interval.