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Original Research

Amyloid Burden and Depressive Symptom Trajectories in Older Adults at Risk of Developing Cognitive Decline

Ismael Conejero, MD, PhDa,*; Jonathan Dubois, PhDb; Laure-Anne Gutierrez, PhDb; Julien Delrieu, MD, PhDc; Christophe Arbus, MD, PhDd; Magalie Garcia, MDc; Jorge Lopez-Castroman, MD, PhDa; Philippe Courtet, MD, PhDb; and Audrey Gabelle, MD, PhD,e for the MAPT/DSA Study Groupf

Published: August 3, 2021


Objective: Little is known about the amyloid load impact on depressive symptoms or disorders, although it can modulate the cognitive trajectory in older adults. Here, we analyzed, in individuals at risk of Alzheimer’s dementia, the relationship between amyloid load and depressive symptoms changes over time.

Methods: This study included ≥ 70-year-old participants from the French Multidomain Alzheimer Preventive Trial (MAPT) (May 2008 to February 2011) who underwent brain amyloid load measurement by β-amyloid-[18F] florbetapir-PET at baseline and had spontaneous memory complaints and/or limitation in 1 instrumental activity of daily living or slow walking gait (N = 264). Symptoms of depression were measured with the Geriatric Depression Scale–15 items (GDS) at baseline and 6, 12, 24, and 36 months of follow-up. Four GDS factors were determined by principal component analysis (PCA): life satisfaction, level of apathy, self-esteem, and anxiety. Amyloid positive status was defined based on the amyloid load in 6 Alzheimer’s dementia–related regions. Regional amyloid load was based on 3 dimensions defined by PCA. The longitudinal links between depressive symptomatology and amyloid load (ie, cortical AV45 and amyloid load dimensions) were analyzed using linear mixed-multivariate models.

Results: At baseline, 11% of participants had depressive symptoms (GDS > 5) and 34% were amyloid-positive. The global amyloid load was not associated with worsening of the total GDS score but only with the impairment of self-esteem factor during the follow-up after adjustment for age, sex, education level, and drug intake, dementia, and Mini-Mental State Examination score (β = −0.029, 95% CI [−0.052 to −0.007], P = .003). Regional amyloid load in hippocampus and bilateral caudate nucleus protected significantly from self-esteem decrease during the 3-year follow-up.

Conclusions: Although amyloid load shows no impact on GDS score in subjects at risk of Alzheimer’s dementia, amyloid load may influence the progression of depressive dimension (self-esteem) with different effects according to the regional burden.

Trial Registration: identifier: NCT00672685

Volume: 82

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