Late-life depression accentuates cognitive weaknesses in older adults with small vessel disease

Lauren E Oberlin,Matteo Respino,George S Alexopoulos,Lindsay Victoria,Lila Abreu,Faith M Gunning,Matthew J Hoptman

doi:10.1038/s41386-021-00973-z

Abstract

Neuroimaging features of small vessel disease (SVD) are highly prevalent in older adulthood and associated with significant variability in clinical symptoms, yet the factors predicting these symptom disparities are poorly understood. We employed a novel metric of SVD, peak width of skeletonized mean diffusivity (PSMD), to elucidate the relationship of late-life depression (LLD) to the cognitive presentation of vascular pathology. A total of 109 older adults without a diagnosis of a neurocognitive disorder were enrolled in the study; 44 with major depressive disorder and 65 age-matched controls. Subjects completed neuropsychological testing and magnetic resonance imaging including FLAIR and diffusion tensor imaging sequences, from which white matter hyperintensity volume and diffusion metrics (fractional anisotropy, mean diffusivity, PSMD) were quantified. In hierarchical models, the relationship between vascular burden and cognitive performance varied as a function of diagnostic status, such that the negative association between PSMD and processing speed was significantly stronger in participants with LLD compared to controls. Greater PSMD also predicted poorer performance on delayed memory and executive function tasks specifically among those with LLD, while there were no associations between PSMD and task performance among controls. PSMD outperformed conventional SVD and diffusion markers in predicting cognitive performance and dysexecutive behaviors in participants with LLD. These data suggest that LLD may confer a vulnerability to the cognitive manifestations of white matter abnormalities in older adulthood. PSMD, a novel biomarker of diffuse microstructural changes in SVD, may be a more sensitive marker of subtle cognitive deficits stemming from vascular pathology in LLD.

Highlights

Cerebral small vessel disease (SVD) refers to a set of pathological processes impacting the small perforating arterioles, capillaries, and venules
Neuroradiologic evidence of SVD is present to some extent in most individuals aged 60 years and over [1,2,3] and is a significant contributor to cognitive deficits, gait disturbances, stroke, and progression to dementia [2, 4, 5]
peak width of skeletonized mean diffusivity (PSMD) surpassed conventional SVD and diffusion markers in detecting relationships with executive performance and dysexecutive behaviors. These observations provide insight into the relationship of depression to the cognitive sequalae of white matter abnormalities in older adulthood and demonstrate the usefulness of PSMD as a sensitive and robust marker of subtle cognitive weaknesses associated with vascular pathology in late-life depression (LLD)

Summary

Introduction

Cerebral small vessel disease (SVD) refers to a set of pathological processes impacting the small perforating arterioles, capillaries, and venules. Neuroradiologic evidence of SVD is present to some extent in most individuals aged 60 years and over [1,2,3] and is a significant contributor to cognitive deficits, gait disturbances, stroke, and progression to dementia [2, 4, 5]. Cognitive deficits frequently associated with SVD include reduced processing speed and executive dysfunction [1, 6,7,8]. Individual differences in the cognitive manifestation and course of SVD suggest that other factors may compromise the capacity to preserve cognitive abilities in the setting of white matter abnormalities [2, 3, 9]. A better understanding of the factors that contribute to these symptom disparities would inform pathophysiologic mechanisms underlying specific cognitive phenotypes in SVD

Objectives

Methods

Findings

Discussion

Conclusion