Abstract
OBJECTIVE: We aimed to investigate the relation between apathy symptoms and structural brain changes on MRI, including white matter lesions (WMLs) and atrophy, in a large cohort of older persons. METHODS: Cross-sectional analyses are based on 4,354 persons without dementia (aged 76 ± 5 years) participating in the population-based Age, Gene/Environment Susceptibility-Reykjavik Study. Apathy symptoms were assessed with 3 items from the 15-item Geriatric Depression Scale. Brain volumes and total WML volume were estimated on 1.5-tesla MRI using an automated segmentation program; regional WML load was calculated using a semiquantitative scale. Regression analyses were adjusted for age, sex, education, intracranial volume, vascular risk factors, physical activity, brain infarcts, depressive symptoms, antidepressants, and cognitive status. RESULTS: Compared to those with <2 apathy symptoms, participants with ≥ 2 apathy symptoms (49% of the cohort) had significantly smaller gray matter volumes (mean adjusted difference -3.6 mL, 95% confidence interval [CI] -6.2 to -1.0), particularly in the frontal and temporal lobes; smaller white matter volumes (mean adjusted difference -1.9 mL, 95% CI -3.6 to -0.3), mainly in the parietal lobe; and smaller thalamus volumes. They were also more likely to have WMLs in the frontal lobe (adjusted odds ratio = 1.08, 95% CI 0.9-1.3). Excluding participants with a depression diagnosis did not change the associations. CONCLUSIONS: In this older population without dementia, apathy symptoms are associated with a more diffuse loss of both gray and white matter volumes, independent of depression.