Autonomic Dysfunction in Patients With Dementia With Lewy Bodies and Its Relationship With Nigrostriatal Denervation

Background and Objectives Diagnosing dementia with Lewy bodies (DLBs) is challenging because of symptom overlap with other neurodegenerative diseases. Although dysautonomia is a recognized supportive diagnostic criterion, its prevalence and extent remain underexplored. We aimed to evaluate autonomic dysfunction in patients with DLB using a comprehensive battery of autonomic function tests (AFTs) and to investigate whether this dysfunction differs between patients with and without nigrostriatal denervation.Methods This prospective cohort study was performed at a Memory Clinic in Rome, Italy. Patients meeting diagnostic criteria for possible DLB were enrolled and underwent AFTs including head-up tilt test (HUTT), Valsalva maneuver, deep breathing, cold face, hand grip (HG), and electrochemical skin conductance. Dopamine transporter SPECT (DaT-SPECT) was performed to assess nigrostriatal transmission. We compared results from AFTs in (1) patients with DLB vs healthy controls (HCs) and (2) patients with DLB with pathologic vs normal DaT-SPECT.RESULTS Twenty-two patients with DLB (median age: 72.00 [10.00] years, þmale: 21.75) and 20 HCs (median age: 69.00 [5.25] years, þmale: 40) were enrolled. Only 1 patient (4.5%) showed neurogenic orthostatic hypotension (nOH) at HUTT. However, patients with DLB showed cardiovascular adrenergic dysfunction, represented by lower Valsalva overshoot (r = -0.553, 95% CI -0.773 to -0.214, p = 0.008) and HG Δdiastolic blood pressure (r = -0.703, 95% CI -0.844 to -0.470, p < 0.0001); parasympathetic cardiovagal dysfunction, reflected in the lower Valsalva ratio (r = -0.812, 95% CI -0.912 to -0.622, p < 0.0001) and sinus arrhythmia at deep breathing (r = -0.682, 95% CI -0.837 to -0.426, p < 0.001); and reduced sudomotor function in hands (r = -0.648, 95% CI -0.809 to -0.395, p < 0.001) and feet (r = -0.600, 95% CI -0.781 to -0.327, p < 0.001). Multivariable analyses found that age and sex were not associated with AFTs, but a higher Mini-Mental State Examination score was associated with better Valsalva ratio (B = 0.038, 95% CI 0.010-0.066, p = 0.010). Patients with normal DaT-SPECT had worse HG responses than those with pathologic DaT-SPECT (r = -0.686, 95% CI -0.895 to -0.231, p = 0.029).DiscussionDespite the absence of overt nOH, patients with DLB show covert dysautonomia encompassing adrenergic, parasympathetic, and sudomotor dysfunction, highlighting the importance of standardized autonomic evaluation. Patients with normal DaT-SPECT exhibited greater peripheral autonomic impairment, reflected by lower HG responses, suggesting diverse α-synuclein pathology trajectories within DLB. Further research is needed to explore autonomic nervous system dysfunctions across different DLB subtypes and stages.