Regional cortical network atrophy predicts progression to dementia in the Lewy body diseases

Abstract

INTRODUCTION: The timeline from symptom onset to the loss of independent functioning varies across patients with Lewy body disease (LBD). Here, we investigate whether the magnitude of cortical atrophy within functional networks that subserve cognitive and affective functions has utility in predicting progression to dementia in LBD. METHODS: Forty-six LBD patients with intact instrumental and basic activities of daily living at baseline underwent brain magnetic resonance imaging scans and longitudinal clinical assessments. Cortical atrophy was estimated in LBD patients relative to an amyloid-negative control group. RESULTS: Multivariate Cox regression analysis demonstrated that atrophy in the affective salience and limbic networks, but not in cognitive, motor, or visual networks, predicted progression to dementia after controlling for disease duration, diagnosis, amyloid beta status, and baseline cognitive severity. DISCUSSION: Baseline atrophy in the salience and limbic networks is an important predictor of progression to dementia and may have value in identifying early-stage LBD patients at risk for faster progression. Highlights: In this longitudinal study of the Massachusetts Alzheimer's Disease Research Center's Memory and Aging Cohort, although the magnitude of cortical atrophy in the early stages of Lewy body disease (LBD) was highly variable at the individual level, atrophy in the salience–limbic network predicted progression to dementia in LBD. In the early stages of LBD, each one standard deviation increase in salience–limbic atrophy doubled the risk of dementia. These findings were robust to adjustment for disease duration, diagnosis, amyloid beta status, and baseline cognitive severity.