Pure autonomic failure may precede brain disorders driven by alpha-synuclein. Across nine longitudinal studies and 900 patients followed for a mean 6.4 years, 270 patients (30%) phenoconverted: 12% to MSA, 11% to DLB and 7% to Parkinson disease. The pooled rate was 5.09 per 100 person-years. Hyposmia favored PD/DLB over MSA, while REM sleep behavior disorder and subtle motor signs were consistent predictors of phenoconversion overall.
Key findings
- Thirty percent of 900 patients phenoconverted: 12% to MSA, 11% to DLB and 7% to PD. The pooled rate was 5.09 per 100 person-years (95% CI 3.79-6.85). MSA conversion clustered earlier, whereas Lewy body disorders were more constant. Hyposmia partly distinguished PD/DLB from MSA (RR 1.88; 95% CI 1.26-2.97).
Why this matters globally
Disease-specific rates can inform surveillance clinics, risk counseling and recruitment into prevention trials before overt motor disease. Combined with validated biomarkers, PAF could become an important window for early intervention.
Thai researcher contribution
Sasivimol Virameteekul of King Chulalongkorn Memorial Hospital is a coauthor, placing a Thai institution within an international evidence-synthesis effort on neurodegeneration. Individual author roles are not reported in the abstract.
Limitations to consider
Only nine studies were available, and heterogeneity was partly related to follow-up duration. Diagnostic criteria and referral patterns may influence pooled rates. Many predictors are group-level associations rather than sufficiently calibrated individual predictions, and meta-analysis cannot remove confounding embedded in the source studies.