Risk factors for neurodegeneration in idiopathic rapid eye movement sleep behavior disorder: A multicenter study

Ann Neurol. 2015 Mar 13. doi: 10.1002/ana.24385. [Epub ahead of print]

Postuma RB, Iranzo A, Hogl B, Arnulf I, Ferini-Strambi L, Manni R, Miyamoto T, Oertel W, Dauvilliers Y, Ju YE, Puligheddu M, Sonka K, Pelletier A, Santamaria J, Frauscher B, Leu-Semenescu S, Zucconi M, Terzaghi M, Miyamoto M, Unger MM, Carlander B, Fantini ML, Montplaisir JY

OBJECTIVE:

To assess whether risk factors for Parkinson disease and dementia with Lewy bodies increase rate of defined neurodegenerative disease in idiopathic rapid eye movement (REM) sleep behavior disorder (RBD).

METHODS:

Twelve centers administered a detailed questionnaire assessing risk factors for neurodegenerative synucleinopathy to patients with idiopathic RBD. Variables included demographics, lifestyle factors, pesticide exposures, occupation, comorbid conditions, medication use, family history, and autonomic/motor symptoms. After 4 years of follow-up, patients were assessed for dementia or parkinsonism. Disease risk was assessed with Kaplan-Meier analysis, and epidemiologic variables were compared between convertors and those still idiopathic using logistic regression.

RESULTS:

Of 305 patients, follow-up information was available for 279, of whom 93 (33.3%) developed defined neurodegenerative disease. Disease risk was 25% at 3 years and 41% after 5 years. Patients who converted were older (difference = 4.5 years, p < 0.001), with similar sex distribution. Neither caffeine, smoking, nor alcohol exposure predicted conversion. Although occupation was similar between groups, those who converted had a lower likelihood of pesticide exposure (occupational insecticide = 2.3% vs 9.0%). Convertors were more likely to report family history of dementia (odds ratio [OR] = 2.09), without significant differences in Parkinson disease or sleep disorders. Medication exposures and medical history were similar between groups. Autonomic and motor symptoms were more common among those who converted. Risk factors for primary dementia and parkinsonism were generally similar, except for a notably higher clonazepam use in dementia convertors (OR = 2.6).

INTERPRETATION:

Patients with idiopathic RBD are at very high risk of neurodegenerative synucleinopathy. Risk factor profiles between convertors and nonconvertors have both important commonalities and differences.