Depressive symptoms and amyloid pathology

Why do depressive symptoms frequently accompany cognitive decline in later life? And to what extent is this relationship explained by Alzheimer’s disease pathology?

In this short lecture, I will discuss recent large-scale evidence examining the relationship between depressive symptoms and amyloid pathology in older adults without dementia. Drawing on data from the Amyloid Biomarker Study, a major international data-pooling initiative combining harmonized clinical and biomarker data from 49 studies and 95 centers, we examined almost 13,000 individuals with either normal cognition or mild cognitive impairment.

I will present the key findings and discuss what they tell us about the biological mechanisms linking depression and cognitive decline. Interestingly, depressive symptoms were not associated with amyloid pathology in cognitively normal individuals, while in people with mild cognitive impairment, depressive symptoms were associated with a lower likelihood of amyloid pathology.

We will also consider the role of APOE ε4, as well as age, sex, and education, and discuss why these findings challenge a simple amyloid-based explanation for late-life depressive symptoms.

The lecture will conclude by considering what mechanisms beyond amyloid accumulation may contribute to the intersection between depression and cognitive decline, and what these findings may mean for future research and clinical practice.