Savica, Rodolfo

ObjectiveThe aim was to analyze the timeline, prevalence, and survival of rapid eye movement (REM) sleep behavior disorder (RBD) in patients who developed alpha‐synucleinopathies (Parkinson disease, dementia with Lewy bodies, and Parkinson disease dementia) compared with age‐ and sex‐matched controls in a population‐based incident‐cohort study.MethodsWe used a population‐based, 1991 to 2010 incident‐cohort study of alpha‐synucleinopathies. A movement‐disorder specialist reviewed medical records to confirm diagnoses. RBD was diagnosed by reported dream‐enactment symptoms or polysomnography. Probable RBD and polysomnographically confirmed RBD were analyzed separately and combined.ResultsAmong the 444 incident cases of alpha‐synucleinopathy, 86 were clinically diagnosed with RBD (19.8%), including 30 (35%) by polysomnography and 56 (65%) as probable. The prevalence of idiopathic RBD at alpha‐synucleinopathy diagnosis was 3.4%, increasing to 23.8% after 15 years. Cumulative lifetime incidence was 53 times greater in alpha‐synucleinopathy patients than in controls (odds ratio [OR] = 53.1, 95% confidence interval [CI]: 13.0–217.2, p < 0.0001), higher in dementia with Lewy bodies than in Parkinson disease (OR = 2.57, 95% CI: 1.50–4.40, p = 0.0004), and higher in men than in women with Parkinson disease, dementia with Lewy bodies, or Parkinson disease dementia (OR = 3.70, 95% CI: 2.07–6.62, p < 0.0001), but did not increase mortality risk.InterpretationOur cohort had RBD incidence of 3.4%. Overall RBD increased to 23.8% after 15 years, with an overall incidence of 2.5 cases per 100 person‐years. With 53 times greater lifetime incidence in alpha‐synucleinopathy patients than in controls, RBD was more likely to develop in dementia with Lewy bodies than in Parkinson disease or Parkinson disease dementia, and in men than in women, but did not increase mortality risk within our cohort. ANN NEUROL 2021;89:293–303

AbstractBackgroundSeveral studies have proposed a role for infections to induce an inflammatory response triggering Parkinson's disease. This remains controversial and the influence of severe infections on other α‐synucleinopathies (Dementia with Lewy Bodies, Parkinson's disease dementia, and Multiple System Atrophy) has not been adequately investigated.ObjectivesTo assess the association between hospitalization‐required infections or sepsis and risk of clinically diagnosed α‐synucleinopathies.MethodsUsing the medical records‐linkage system (Rochester Epidemiology Project), we identified all α‐synucleinopathy cases of in Olmsted County (1991–2010). Cases were matched by symptom‐onset age and sex to controls. We reviewed complete medical records to detect hospital‐required infections or sepsis preceding clinical‐motor onset of α‐synucleinopathies. We used conditional logistic regression to calculate the odds ratio of all α‐synucleinopathies, adjusting for medications, coffee, and smoking.ResultsThere was no association between infection‐related hospitalization (odds ratio: 1.05; 95% confidence interval: 0.78–1.40; P = 0.76) or sepsis (odds ratio: 0.86; 95% confidence interval: 0.40–1.85; P = 0.70) and all α‐synucleinopathies in multivariable analyses. We did not identify any associations after stratifying for type of α‐synucleinopathy, sex, and age at clinical‐motor onset. We analyzed sepsis separately with similar results.ConclusionWe did not observe any associations between infections leading to hospitalization or sepsis and development of any α‐synucleinopathies. © 2020 International Parkinson and Movement Disorder Society

Abstract Background Multiple system atrophy (MSA) is a neurodegenerative disorder from α‐synuclein aggregation. in vitro studies suggest vitamin B12 may interrupt α‐synuclein‐mediated neurodegeneration. The objective of this study was to determine whether serum vitamin B12 level at MSA diagnosis is associated with survival. Methods One hundred eighty‐two MSA patients evaluated at Mayo Clinic with vitamin B12 testing were studied. We determined the risk of death in relationship to serum vitamin B12 levels at MSA diagnosis, adjusting for predictors of poor survival. Results Predictors of shorter survival included vitamin B12 < 367 ng/L (HR, 1.8; 95% CI, 1.3–2.7), falls within 3 years of MSA diagnosis (HR, 1.6; 95% CI, 1.1–2.3), bladder symptoms (HR, 1.6; 95% CI, 1.0–2.6), urinary catheter requirement (HR, 1.7; 95% CI, 1.0–2.8), male sex (HR, 1.4; 95% CI, 1.0–2.0), and MSA‐P subtype (HR, 1.5; 95% CI, 1.0–2.0). Conclusions Low vitamin B12 levels are associated with shorter survival in MSA. Additional studies to explore this observation and assess the potential role of vitamin B12 as a modifiable survival factor are needed. © 2020 International Parkinson and Movement Disorder Society