Baroreflex-sympathoneural Dysfunction Characterizes At-risk Individuals with Preclinical Central Lewy Body Diseases

Purpose: In central Lewy body diseases (LBDs) such as Parkinson's disease (PD) and dementia with Lewy bodies (DLB), by the time parkinsonism or cognitive dysfunction becomes manifest, substantial central neurodegeneration has already occurred. Cardiovascular autonomic biomarkers might detect preclinical central LBDs in at-risk individuals, enabling possibly effective disease-modifying treatment.

Methods: In the prospective, longitudinal PDRisk study, 59 participants provided information about family history of PD, olfactory dysfunction, dream enactment behavior, and orthostatic intolerance or hypotension at a protocol-specific website and were screened as outpatients. Thirty-four had three or more confirmed risk factors and were followed until PD was diagnosed or up to 7.5 years. Dependent measures included assessments of baroreflex-sympathoneural function, via the blood pressure recovery time (PRT) after release of the Valsalva maneuver and baroreflex areas; and baroreflex-cardiovagal function, via heart rate variability in the time and frequency domains and Valsalva baroslopes. Data were compared from groups with or without a subsequent diagnosis of a central LBD (LBD+, N = 9; LBD-, N = 25) and PDRisk participants with fewer than three confirmed risk factors (PDRisk-, N = 25).

Results: The LBD+ group had larger orthostatic falls in systolic blood pressure than did the LBD- and PDRisk- groups (p < 0.0001 each). The LBD+ group had increased PRTs (p = 0.0114 versus LBD-, p = 0.0094 versus PDRisk-) and baroreflex areas after the Valsalva maneuver (p = 0.0225 versus LBD-, p = 0.0028 versus PDRisk-), whereas the groups did not differ in indices of baroreflex-cardiovagal function.

Conclusion: Orthostatic hypotension and baroreflex-sympathoneural dysfunction characterize at-risk individuals who go on to be diagnosed with a central LBD during longitudinal follow-up.