The Locus Coeruleus-Basal Forebrain tract in Lewy body disease: autonomic dysfunction and cognition

Background Cardiovascular autonomic dysfunction and cognition associate with each other throughout the disease course in Lewy body disease, and this relationship is poorly understood. Methods We performed a cross-sectional imaging analysis to investigate the locus coeruleus basal forebrain tract. Deterministic tractography based on quantitative anisotropy was performed. Using Bayesian semiparametric proportional-odds modeling, we evaluated the association between neurogenic orthostatic hypotension and tract characteristics with adjustment for age at imaging, sex, and education. Results In the demographic adjusted model, neurogenic orthostatic hypotension was associated with lower bilateral fourth-quarter volume (OR = 0.19; Pr[OR < 1] = 0.987), left fourth-quarter volume (OR = 0.13; Pr[OR < 1] = 0.997), left total surface area (OR = 0.19; Pr[OR < 1] = 0.990), and left total volume (OR = 0.22; Pr[OR < 1] = 0.982). These associations were directionally consistent and of similar magnitude after additional adjustment for cognitive severity, high blood pressure, disease duration, and combined high blood pressure and disease duration. Participants with impaired cognition showed lower bilateral fourth quartervolume (OR = 0.33; Pr[OR < 1] = 0.964) Conclusion Neurogenic orthostatic hypotension is associated with lower locus coeruleus basal forebrain tract volume. The inverse correlation between volume and cognitive impairment suggest a mechanistic relationship.