Subcortical grey matter structures in relation to symptoms of depression and anxiety on the spectrum from cognitively healthy to dementia.

Background: Anxiety and depression are common in prodromal dementia, possibly due to changes in subcortical grey matter structures involved in emotion regulation. We aimed to determine the association between subcortical grey matter volumes and depression and anxiety symptoms.

Methods: We included dementia-free participants from the population-based Rotterdam Study, who underwent brain MRI between 2009 and 2015. Depression and anxiety symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) scale and the Hospital Anxiety and Depression scale- Anxiety subscale (HADS-A). We determined cross-sectional associations of standardized volumes with log-transformed CES-D and HADS scores using multivariable linear regression models. We repeated analyses among outpatients who attended the Alzheimer Center Erasmus Medical Center between 2016 and 2021.

Results: Among 3451 community-dwelling participants (mean age 69.3 years, 55.2 % women), median CES-D score was 3 (IQR:1-7) and HADS-A score 2 (IQR:0-4). Clinically relevant depressive symptoms (CES-D ≥ 16) were present in 284 (8.2 %) participants, and anxiety (HADS≥8) in 270 (8.2 %). Lower volumes of the caudate and pallidum were associated with fewer depressive symptoms (mean difference [95 %CI] for the caudate: -0.06[-0.10;-0.02], pallidum: -0.04[-0.08;0.00]), and less anxiety (caudate: -0.04[-0.07;-0.01], pallidum: -0.05[-0.09;-0.02]). Lower hippocampal volume was associated with higher odds of clinical depressive symptoms (OR: 1.27[1.05-1.52]), albeit not significant after multiple testing correction. We observed no associations for other structures. Among 315 memory clinic patients, (mean age 68.9 years, 43.5 % women), no associations were observed after multiple testing correction.

Conclusion: Volumes of the caudate and pallidum are inversely associated with depression and anxiety symptoms in community-dwelling older adults, but not in a memory clinic population.