Affective Symptoms and Amyloid Plaques: Antidepressant Response and Clinical Outcome Associated With Brain Amyloid Load in a 2-Year Cohort of Nondemented Older Adults With Depression-The ASAP Study

Abstract

Objectives: The ASAP study investigated whether amyloid load in the brain would be associated with poor antidepressant response in the short term (8 weeks) and worse clinical outcomes (remission status) in the long term (2 years).

Methods: Nondemented older adults with non-treatment-resistant depression were enrolled in an 8-week observational study to assess the relationship between amyloid load and antidepressant response and subsequently followed for 2 years. Amyloid load was measured using ¹⁸F-Florbetapir Positron Emission Tomography scans, and treatment response was evaluated using the Montgomery-Åsberg Depression Rating Scale. The primary analysis compared amyloid load in responders versus nonresponders at week 8 and in remitters versus non-remitters at year 1 and year 2, employing logistic regressions controlled for potential confounders.

Results: A total of 73 (among which 56% were responders and 30% were remitters), 63 (48% remitters) and 56 (54% remitters) participants were included in the analysis at week 8, year 1 and year 2, respectively. We found no significant association between amyloid load and treatment response at week 8. However, remission status at year 2 was positively associated with higher total amyloid load at baseline, independent of confounders (OR = 1.28, 95% CI [1.02-1.60]).

Conclusions: In this observational cohort of nondemented depressed older adults, amyloid load does not appear to modify response status in the short term. Conversely, greater amyloid load was associated with better clinical outcomes in the long term. Amyloid may influence the long-term course of depressive symptoms by altering the serotoninergic system and/or modifying the clinical presentation of depression.

Keywords: Brain amyloid; antidepressant response; late-life depression.