Association of homocysteine-related subcortical brain atrophy with white matter lesion volume and cognition in healthy aging

• Published in: Neurobiology of aging Vol. 121; pp. 129 - 138
• Main Authors: Song, Hyun, Bharadwaj, Pradyumna K., Raichlen, David A., Habeck, Christian G., Huentelman, Matthew, J., Hishaw, Georg A., Trouard, Theodore P., Alexander, Gene E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2023
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - pathology; Atrophy - pathology; Brain - pathology; Cognition; Cognitive aging; Cognitive Dysfunction - complications; Cognitive Dysfunction - etiology; Gray matter atrophy; Healthy Aging; Homocysteine; Humans; Magnetic Resonance Imaging; Male; Neuropsychological Tests; Scaled Subprofile Model; Vascular risk; White Matter - diagnostic imaging; White Matter - pathology; White matter hyperintensity; White matter hyperintensity; Cognitive aging; Vascular risk; Gray matter atrophy; Scaled Subprofile Model
• ISSN: 0197-4580; 1558-1497; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2022.10.011

Homocysteine (Hcy) is a vascular risk factor associated with cognitive impairment and cerebrovascular disease but has also been implicated in Alzheimer's disease (AD). Using multivariate Scaled Subprofile Model (SSM) analysis, we sought to identify a network pattern in structural neuroimaging reflecting the regionally distributed association of plasma Hcy with subcortical gray matter (SGM) volumes and its relation to other health risk factors and cognition in 160 healthy older adults, ages 50–89. We identified an SSM Hcy-SGM pattern that was characterized by bilateral hippocampal and nucleus accumbens volume reductions with relative volume increases in bilateral caudate, pallidum, and putamen. Greater Hcy-SGM pattern expression was associated with greater white matter hyperintensity (WMH) volume, older age, and male sex, but not with other vascular and AD-related risk factors. Mediation analyses revealed that age predicted WMH volume, which predicted Hcy-SGM pattern expression, which, in turn, predicted cognitive processing speed performance. These findings suggest that the multivariate SSM Hcy-SGM pattern may be indicative of cognitive aging, reflecting a potential link between vascular health and cognitive dysfunction in healthy older adults.