Microstructural changes in the inferior tuberal hypothalamus correlate with daytime sleepiness in Lewy body disease.

Background: Excessive daytime sleepiness (EDS) is a disabling symptom of Lewy body disorders (LBD). The hypothalamus is a key sleep-wake regulator, but its contribution to EDS in LBD remains unclear. Objectives: Use diffusion MRI to evaluate the relationship of hypothalamic microstructure to EDS symptoms in LBD. Methods: We studied 102 patients with clinically-defined LBD (Parkinson's disease, n=93; Parkinson's disease dementia, n=4; and dementia with Lewy bodies, n=5) and Epworth Sleepiness Scale (ESS) within 2 years of MRI. Mean diffusivity (MD) was compared between EDS+ (ESS≥10, n=37) and EDS- (ESS<10, n=65) groups in the whole hypothalamus and three subregions, covarying for age and sex. Secondary analyses tested correlations between subregion MD and continuous ESS, global cognition, and motor scores; and between subregion volume and continuous ESS. Results: MD was increased in EDS+ compared to EDS- only in the inferior tuberal subregion (Cohen's d=0.43, p=0.043, β=0.117±0.057), with trend level differences in the whole hypothalamus (Cohen's d=0.39, p=0.064, β=0.070±0.037) and superior tuberal subregion (Cohen's d=0.38, p=0.073, β=0.063±0.035). No difference was seen in the posterior subregion (Cohen's d=0.1, p=0.628, β=0.019±0.038). Significant correlations with continuous ESS were seen in MD of whole hypothalamus (r Conclusions: Daytime sleepiness associates with increased MD in the inferior tuberal hypothalamus in an LBD cohort. This suggests degeneration within this region could contribute to EDS symptoms.