Structural MRI correlates of apathy symptoms in older persons without dementia: AGES-Reykjavik Study

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.

Figure 1. Relations between the presence of one or more apathy symptoms and brain volumes

Shown are the z scores of total brain volume, total gray matter volume, total white matter volume, and natural log-transformed total white matter lesion (WML) volume (mL) for participants with no apathy symptoms (reference) and 1 to 3 apathy symptoms, adjusted for age, sex, education, and intracranial volume. Statistically significant trends (p < 0.001) are indicated with an asterisk.

Figure 2. Relations between the presence of 2 or more apathy symptoms and regional white matter lesion load

Odds ratios of high white matter lesion (WML) load (highest quintile of WML volume) in different brain regions for participants with 2 or 3 apathy symptoms compared with those with 0 or 1 symptom (reference), adjusted for age, sex, education, and intracranial volume. Error bars indicate 95% confidence intervals. Statistically significant associations (p < 0.050) are indicated with an asterisk.