Are neuropsychiatric symptoms a marker of small vessel disease progression in older adults? Evidence from the Lothian Birth Cohort 1936

Background Neuropsychiatric symptoms could form part of an early cerebral small vessel disease prodrome that is detectable before stroke or dementia onset. We aimed to identify whether apathy, depression, anxiety, and subjective memory complaints associate with longitudinal white matter hyperintensity (WMH) progression. Methods Community‐dwelling older adults from the observational Lothian Birth Cohort 1936 attended three visits at mean ages 73, 76, and 79 years, repeating MRI, Mini‐Mental State Examination, neuropsychiatric (Dimensional Apathy Scale, Hospital Anxiety and Depression Scale), and subjective memory symptoms. We ran regression and mixed‐effects models for symptoms and normalised WMH volumes (cube root of WMH:ICV × 10). Results At age 73, 76, and 79, m = 672, n = 476, and n = 382 participants attended MRI respectively. Worse apathy at age 79 was associated with WMH volume increase (β = 0.27, p = 0.04) in the preceding 6 years. A 1SD increase in apathy score at age 79 associated with a 0.17 increase in WMH (β = 0.17 normalised WMH percent ICV, p = 0.009). In apathy subscales, executive (β = 0.13, p = 0.05) and emotional (β = 0.13, p = 0.04) scores associated with increasing WMH more than initiation scores (β = 0.11, p = 0.08). Increasing WMH also associated with age (β = 0.40, p = 0.002) but not higher depression (β = ‐0.01, p = 0.78), anxiety (β = 0.05, p = 0.13) scores, or subjective memory complaints (β = 1.12, p = 0.75). Conclusions Apathy independently associates with preceding longitudinal WMH progression, while depression, anxiety, and subjective memory complaints do not. Patients with apathy should be considered for enrolment to small vessel disease trials. Key points Worse apathy at age 79 associates with greater progression of white matter hyperintensities (WMH) in the preceding 6 years. In this population of community‐dwelling older adults, WMH progression is not associated with anxiety, depression, or subjective memory complaints. Apathy has potential as a key clinical marker of SVD progression.