The association of depression with structural brain markers and cognitive impairment: The Maastricht study

Abstract Background The risk of dementia is doubled in depression. However, the underlying etiology remains unclear. Clinical studies suggest that depression is related to brain atrophy and cerebral small vessel disease (cSVD), which are themselves related to cognition. We studied the associations between depression, structural brain markers and cognition in a general population aged between the 40 and 75 years. Method We used cross‐sectional data from the Maastricht Study (n=7,066; mean age 59.6±8.7 years, 50.1% women), which, by design, oversampled participants with type 2 diabetes (T2D). Major depressive disorder (MDD, n=236) was assessed by the Mini‐International Neuropsychiatric Interview. From a comprehensive neuropsychological battery, we derived standardized sum scores on tests for memory, information processing speed, and executive functioning and attention. Presence of significant overall cognitive impairment was defined as a score <‐.1.5 SD below norms scores for age, gender and education. Volumes of cerebral spinal fluid (CSF), white matter (WM), grey matter (GM) and white matter hyperintensities (WMH), and presence of lacunar infarcts, cerebral microbleeds and total cSVD burden were assessed by 3 Tesla MRI. Multiple linear and logistic regression analyses tested the associations between MDD, brain markers and cognitive functioning, adjusted for a range of demographic, cardiovascular, and lifestyle risk factors. Result In fully adjusted models, MDD was associated with lower scores in memory (B=‐0.11(‐0.22;0.00)), information processing speed (B=‐0.24(‐0.32;‐0.15)), executive functioning and attention (B=‐0.23(‐0.32;‐0.14)), and with presence of significant cognitive impairment (OR=2.37(1.77;3.17)). In those with available MRI data (n=4,734), MDD was associated with a lower GM volume only in older participants (p‐interaction=0.023), and with total WMH (B=0.17(0.01;0.34)), periventricular WMH (B=0.18(0.01;0.35)), and total cSVD burden (OR=1.70(1.09;2.65)) in participants without T2D (OR=1.70(1.09;2.65)). Conclusion This study shows that MDD is associated with cognitive impairment, including worse memory, information processing speed, and executive functioning and attention, independent of major demographical, cardiovascular and lifestyle risk factors. In older participants, MDD is related to a lower GM volume, while in the wider general population without T2D, MDD is related to markers of cSVD burden. Longitudinal studies are needed to examine the role of structural brain damage in the development of cognitive impairment and dementia in depression.