Pathomechanisms of Vascular Depression in Older Adults

Abstract

Depression in older individuals is a common complex mood disorder with high comorbidity of both psychiatric and physical diseases, associated with high disability, cognitive decline, and increased mortality The factors predicting the risk of late-life depression (LLD) are incompletely understood. The reciprocal relationship of depressive disorder and age- and disease-related processes has generated pathogenic hypotheses and provided various treatment options. The heterogeneity of depression complicates research into the underlying pathogenic cascade, and factors involved in LLD considerably differ from those involved in early life depression. Evidence suggests that a variety of vascular mechanisms, in particular cerebral small vessel disease, generalized microvascular, and endothelial dysfunction, as well as metabolic risk factors, including diabetes, and inflammation that may induce subcortical white and gray matter lesions by compromising fronto–limbic and other important neuronal networks, may contribute to the development of LLD. The “vascular depression” hypothesis postulates that cerebrovascular disease or vascular risk factors can predispose, precipitate, and perpetuate geriatric depression syndromes, based on their comorbidity with cerebrovascular lesions and the frequent development of depression after stroke. Vascular burden is associated with cognitive deficits and a specific form of LLD, vascular depression, which is marked by decreased white matter integrity, executive dysfunction, functional disability, and poorer response to antidepressive therapy than major depressive disorder without vascular risk factors. Other pathogenic factors of LLD, such as neurodegeneration or neuroimmune regulatory dysmechanisms, are briefly discussed. Treatment planning should consider a modest response of LLD to antidepressants, while vascular and metabolic factors may provide promising targets for its successful prevention and treatment. However, their effectiveness needs further investigation, and intervention studies are needed to assess which interventions are appropriate and effective in clinical practice.

Association of Cardiovascular Health With Risk of Clinically Relevant Depressive Symptoms

“…A focus on prevention is, therefore, key to reduce the burden of late-life depression. Vascular risk factors are increasingly recognized as potential contributors to the development of late-life depression and, thus, as potential targets for early preventive therapies …”

Synergistic associations of depressive symptoms and aging on cognitive decline in early Parkinson’s disease

“…In contrast, depression that begins around or after the age of 60 year (i.e., late-onset depression) is hypothesized to be a contributor to, or result of, accelerated brain and cognitive aging and both major and minor depression in older adults increases the risk of cognitive decline and conversion to dementia [ 34 ]. This may be due to both depression and aging having combined adverse effects on similar neural networks [ [35] , [36] , [37] ], neurotransmitter functions [ 38 ], and other biological processes (e.g., vascular changes, neuroinflammation) [ [39] , [40] ].…”

The pathobiological basis of depression in Parkinson disease: challenges and outlooks

“…Whereas vascular risk factors failed to verify the vascular depression hypothesis in PD (Ou et al 2018 ), others suggested that co-morbid cerebral small-vessel disease (CSVD), marked by WM hypointensity, number of lacunes and microbleeds, may affect multiple functional domains in PD, including motor, cognitive and emotional impairments (Chen et al 2021 ). Many studies have provided evidence that large WM hypointensity volumes, subcortical lacunes and other markers for CSVD are associated with increased risk for depressive symptoms (Geraets et al 2021 ; Jellinger 2021 , 2022b ; Nunes et al 2022 ; Wang et al 2020 ), since they are disturbing cortico-subcortical neuronal circuits causing microstructural dysfunctions of major brain connections involved in emotion and other important behaviors, thus suggesting an association between CSVD and depression (Empana et al 2021 ; Kim and Han 2021 ; Nunes et al 2022 ).…”