The relation of depression with structural brain abnormalities and cognitive functioning: the Maastricht study

Abstract

Background Individuals with depression often experience widespread and persistent cognitive deficits, which might be due to brain atrophy and cerebral small vessel disease (CSVD). We therefore studied the associations between depression, markers of brain atrophy and CSVD, and cognitive functioning. Methods We used cross-sectional data from the population-based Maastricht study (n = 4734; mean age 59.1 ± 8.6 years, 50.2% women), which focuses on type 2 diabetes. A current episode of major depressive disorder (MDD, n = 151) was assessed by the Mini-International Neuropsychiatric Interview. Volumes of cerebral spinal fluid, white matter, gray matter and white matter hyperintensities, presence of lacunar infarcts and cerebral microbleeds, and total CSVD burden were assessed by 3 T magnetic resonance imaging. Multiple linear and logistic regression analyses tested the associations between MDD, brain markers and cognitive functioning in memory, information processing speed, and executive functioning & attention, and presence of cognitive impairment. Structural equation modeling was used to test mediation. Results In fully adjusted models, MDD was associated with lower scores in information processing speed [mean difference = −0.18(−0.28;−0.08)], executive functioning & attention [mean difference = −0.13(−0.25;−0.02)], and with higher odds of cognitive impairment [odds ratio (OR) = 1.60(1.06;2.40)]. MDD was associated with CSVD in participants without type 2 diabetes [OR = 1.65(1.06;2.56)], but CSVD or other markers of brain atrophy or CSVD did not mediate the association with cognitive functioning. Conclusions MDD is associated with more impaired information processing speed and executive functioning & attention, and overall cognitive impairment. Furthermore, MDD was associated with CSVD in participants without type 2 diabetes, but this association did not explain an impaired cognitive profile.

Pathomechanisms of Vascular Depression in Older Adults

“…Moreover, no significant association of these CSVD markers and depression was found for individuals below the age of 60 years, while others also underscored the association of LLD with increased WMH burden, which is in line with the VDH [ 71 ]. Another recent study combined the presence of lacunar infarcts, cerebral microbleeds, and WMHs in a combined CSVD score, but did not find an association between this and incident depression [ 20 ]. Moreover, CSVD was associated with apathy in the general population, supporting the hypothesis of vascular apathy [ 84 ].…”

“…While some could not demonstrate a long-term association between WMH progression and depression [ 176 ], large confluent WMHs were associated with a higher incidence of depression in individuals over age 60 years [ 83 ], with persistent depressive symptoms, poorer executive function, and cognitive impairment [ 20 , 177 , 178 ]. WMHs especially within cortico–subcortical neuronal circuits can be interpreted as sequelae of microstructural dysfunctions affecting major brain connections, indicating an association between CVD and depression [ 179 , 180 ], whereas, according to others, structural alterations in the cerebellum may underlie the mechanisms of depressive symptoms in patients with LLD [ 181 ].…”

“…Depression and cerebrovascular risk factors are common in late life and LLD is often present in elderly individuals with cardio- and/or cerebrovascular disease [ 20 , 21 ]; it is difficult to determine what is the essential causal factor and to those apart normal functioning from an abnormality in the older population. There are several possible interrelations between CVD and depressive symptoms: (1) depression is the consequence of (cerebro)vascular disease, (2) development of depression is independent of vascular disease, which, however, may stimulate the onset and course of depression, (3) CVD and depression may appear without obvious connection as two manifestations of the same genetic predisposition and pathogenetic mechanisms, (4) depression may cause/induce/promote cardiovascular and/or cerebrovascular disease, and there may be a bidirectional relationship between both disorders [ 206 ], but further studies are needed to clarify the mechanisms involved in these complex correlations.…”

“…It is important to distinguish between LLD with early- and late-onset [ 20 , 21 ]. Early-onset depression may predispose to LLD by accumulating depressive episodes over a lifetime and is associated with a positive family history of mood disorders, lower cardiovascular risk factors, and lower risk for cognitive decline, while late-onset depression (LOD) shows a higher risk of cardiovascular risk burden, a higher risk for cognitive decline, and greater treatment resistance [ 22 ].…”

Depressive symptoms and cognitive impairment: A 10-year follow-up study from the Survey of Health, Ageing and Retirement in Europe

“…A growing body of evidence support that depression is one of the modifiable risk factors for dementia [9], which is characterized by progressive decline in cognitive function [10,11]. Depressive symptom and cognitive impairment often co-occur in advanced age, leading to a variety of emotional and physical problems that affect the ability of individuals in work and life and further reduce the quality of life [12,13].…”