Abstract
Depressive symptoms are prevalent among older adults and may be early manifestations of Alzheimer disease (AD) before onset of mild cognitive impairment. However, it remains unclear whether worsening depressive symptoms in the presence of AD pathology are associated with cognitive decline in older adults. To determine the longitudinal association between depressive symptoms, cognition, and cortical amyloid in community-dwelling older adults. Participants from the Harvard Aging Brain Study, a cohort study, underwent annual assessments of depression and cognition and baseline cortical amyloid measurement (mean, 4.42 years; range, 2-7 years). Data collection was from September 2010 to August 2017 in a convenience sample of community-dwelling adults (276 participants, all cognitively unimpaired) with at most mild depression at entry. Depression (Geriatric Depression Scale [GDS]), cognition (Preclinical Alzheimer Cognitive Composite [PACC]), and a continuous measure of cortical amyloid (Pittsburgh Compound-B positron emission tomography imaging). Change in GDS and baseline amyloid were examined as interactive predictors of PACC decline in a linear mixed model with backward elimination, adjusting for age, sex, and education. Participants were 164 women and 112 men (mean [SD] age, 73.5 [6.0] years). At baseline, the mean (SD) GDS score was 3.0 (2.8) (range, 0-12), the mean (SD) PACC score was -0.004 (0.67) (range, -2.32 to 1.88), and the mean (SD) amyloid positron emission tomography distribution volume ratio was 1.16 (0.20) (range, 0.92-1.94). At last follow-up, the mean (SD) GDS score was 3.9 (2.9) (range, 0-12), and the mean (SD) PACC score was -0.09 (1.27) (range, -5.66 to 1.67). The interaction between cortical amyloid and increasing GDS was associated with declining cognition (β = -0.19; 95% CI, -0.27 to -0.12; P < .001). In this study, cortical amyloid moderated the association between worsening depressive symptoms and declining cognition in older adults. While future work is needed to better understand causal associations, these findings may enhance early detection and prevention of AD clinical symptoms.
Highlights
Depressive symptoms, including those in the subthreshold and mild range, are prevalent and distressing among older adults
The interaction between cortical amyloid and increasing Geriatric Depression Scale (GDS) was associated with declining cognition (β = −0.19; 95% CI, −0.27 to −0.12; P < .001)
In this study, cortical amyloid moderated the association between worsening depressive symptoms and declining cognition in older adults
Summary
Depressive symptoms, including those in the subthreshold and mild range, are prevalent and distressing among older adults. Such symptoms might serve as clinical indicators or modifiers of cognitive performance and Alzheimer disease (AD). AD observational and intervention research has focused on the preclinical stage of AD, in which there is evidence of elevated amyloid and pathological change well before the development of mild cognitive impairment (MCI).[1,2,3] Interventions at this preclinical stage may have the potential to prevent subsequent decline.[4] Secondary prevention trials in preclinical AD rely on sensitive measures of cognition weighted toward episodic memory to detect subtle changes in cognitive performance before there is clearly defined cognitive impairment.[5] Such trials focus on cognitive outcomes and do not incorporate depression as an outcome measure
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