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This systematic review and meta-analysis investigated the likelihood of patients with pure autonomic failure (PAF) developing central α-synucleinopathies, including Parkinson disease, dementia with Lewy bodies and multiple system atrophy. The analysis included nine longitudinal studies comprising 900 individuals with PAF, with a mean follow-up of 6.4 years. During follow-up, 270 patients (30%) developed a central α-synucleinopathy, including 12% who developed multiple system atrophy, 11% dementia with Lewy bodies and 7% Parkinson disease. The pooled phenoconversion incidence rate was 5.09 per 100 person-years (95% CI, 3.79–6.85), suggesting that approximately 5% of patients with PAF may develop a central α-synucleinopathy each year. Multiple system atrophy showed a higher conversion rate during the initial years of follow-up, whereas conversion to Parkinson disease and dementia with Lewy bodies occurred at relatively more consistent rates. Hyposmia was associated with a greater likelihood of conversion to Parkinson disease or dementia with Lewy bodies compared with multiple system atrophy (risk ratio, 1.88; 95% CI, 1.26–2.97). REM sleep behaviour disorder and subtle motor abnormalities were also identified as consistent clinical predictors. The findings highlight the importance of longitudinal neurological monitoring and the potential value of identifying early clinical markers in patients presenting with autonomic dysfunction.
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This systematic review and meta-analysis investigated the likelihood of patients with pure autonomic failure (PAF) developing central α-synucleinopathies, including Parkinson disease, dementia with Lewy bodies and multiple system atrophy. The analysis included nine longitudinal studies comprising 900 individuals with PAF, with a mean follow-up of 6.4 years. During follow-up, 270 patients (30%) developed a central α-synucleinopathy, including 12% who developed multiple system atrophy, 11% dementia with Lewy bodies and 7% Parkinson disease. The pooled phenoconversion incidence rate was 5.09 per 100 person-years (95% CI, 3.79–6.85), suggesting that approximately 5% of patients with PAF may develop a central α-synucleinopathy each year. Multiple system atrophy showed a higher conversion rate during the initial years of follow-up, whereas conversion to Parkinson disease and dementia with Lewy bodies occurred at relatively more consistent rates. Hyposmia was associated with a greater likelihood of conversion to Parkinson disease or dementia with Lewy bodies compared with multiple system atrophy (risk ratio, 1.88; 95% CI, 1.26–2.97). REM sleep behaviour disorder and subtle motor abnormalities were also identified as consistent clinical predictors. The findings highlight the importance of longitudinal neurological monitoring and the potential value of identifying early clinical markers in patients presenting with autonomic dysfunction.
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