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, %female: 21.75) and 20 HCs (median age: 69.00 [5.25] years, %female: 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).

Discussion: Despite 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.