Associations of neuroimaging markers with depressive symptoms over time in middle-aged and elderly persons

Abstract

Background Cerebrovascular disease is regarded as a potential cause of late-life depression. Yet, evidence for associations of neuroimaging markers of vascular brain disease with depressive symptoms is inconclusive. We examined the associations of neuroimaging markers and depressive symptoms in a large population-based study of middle-aged and elderly persons over time. Methods A total of 4943 participants (mean age = 64.6 ± 11.1 years, 55.7% women) from the Rotterdam Study were included. At baseline, total brain volume, gray matter volume, white matter volume, white matter hyperintensities volume, cortical infarcts, lacunar infarcts, microbleeds, white matter fractional anisotropy, and mean diffusivity (MD) were measured with a brain MRI (1.5T). Depressive symptoms were assessed twice with the Center for Epidemiologic Studies Depression scale (median follow-up time: 5.5 years, IQR = 0.9). To assess temporal associations of neuroimaging markers and depressive symptoms, linear mixed models were used. Results A smaller total brain volume (β = −0.107, 95% CI −0.192 to −0.022), larger white matter hyperintensities volume (β = 0.047, 95% CI 0.010–0.084), presence of cortical infarcts (β = 0.194, 95% CI 0.047–0.341), and higher MD levels (β = 0.060, 95% CI 0.022–0.098) were cross-sectionally associated with more depressive symptoms. Longitudinal analyses showed that small total brain volume (β = −0.091, 95% CI −0.167 to −0.015) and presence of cortical infarcts (β = 0.168, 95% CI 0.022–0.314) were associated with increasing depressive symptoms over time. After stratification on age, effect sizes were more pronounced at older ages. Conclusions Neuroimaging markers of white matter microstructural damage were associated with depressive symptoms longitudinally in this study of middle-aged and elderly persons. These associations were more pronounced at older ages, providing evidence for the role of white matter structure in late-life depressive symptomatology.

Chronic Cough-Related Differences in Brain Morphometry in Adults

“…In model 2, we additionally adjusted for age 3 (as cubic function, meaning polynomial function of degree 3), age and sex interaction, smoking, asthma, COPD, clinically relevant depressive symptoms (CESD score, > 16), and chronic pain, given that they are prevalent in chronic cough, 17 , 20 , 22 and have been associated with volumetric brain changes in adults. 23 , 24 , 25 , 26 , 27 , 28 Furthermore, we estimated the annualized percentage volume decline rate, examined hemispheric lateralization, and performed stratified analyses for sex, focusing on brain regions that demonstrated statistical significance. We also explored the relationship between chronic cough phenotype (explained and unexplained) and regional brain volumes using multivariable linear regression models that were adjusted for potential confounding factors (models 1 and 2).…”

The heterogeneity of late-life depression and its pathobiology: a brain network dysfunction disorder

“…A population-based study showed that reduced total brain volume, larger WMH volume, presence of cortical microinfarcts, and higher levels of mean diffusivity (indicating WM microstructural integrity) were cross-sectionally associated with higher depressive symptoms. These associations were more pronounced in older age, indicating that damage of WM structure might be crucial for the pathogenesis of LLD (Özel et al 2022 ). On the other hand, LLD accentuates cognitive weaknesses in older adults with small vessel disease (Oberlin et al 2022 ).…”

Challenges in Identifying Individualized Brain Biomarkers of Late Life Depression

“…Firstly, the evaluation of depression is inconsistent. Some studies evaluate depressive symptoms [ 68 ], some use a self-report questionnaire to identify depressed individuals [ 69 ], and some undergo a structured clinical interview [ 1 , 22 ]. Importantly, these approaches may capture different ranges of depression severity.…”