Objective:: For development of neuroprotective therapy, neurodegenerative disease must be identified as early as possible. However, current means of identifying “preclinical” neurodegeneration are limited. Patients with idiopathic rapid eye movement (REM) sleep behavior disorder (RBD) are at >50% risk of synuclein‐mediated neurodegenerative disease—this provides a unique opportunity to directly observe preclinical synucleinopathy and to test potential markers of preclinical disease. Methods:: Patients with RBD without neurodegenerative disease were enrolled in a prospective cohort starting in 2004. Olfaction and color vision were tested at baseline, then annually for 5 years. Test results were compared between patients who developed neurodegenerative disease and those who remained disease‐free. Results:: Out of 64 patients, 62 (97%) participated in annual follow‐up. During follow‐up, 21 developed disease, and 41 remained disease‐free. Out of 21, 16 developed a combination of parkinsonism and dementia, 4 developed isolated parkinsonism (all with tremor), and 1 developed isolated dementia. Compared to those remaining disease‐free, patients destined to develop disease had worse baseline olfaction (University of Pennsylvania Smell Identification Test [UPSIT] = 58.3 ± 27.0% age/sex‐adjusted normal vs 80.2 ± 26.3%; p = 0.003) and color vision (Farnsworth‐Munsell 100‐Hue color test [FM‐100] errors 153.0 ± 82.2% normal vs 120.2 ± 26.5%; p = 0.022). Kaplan‐Meier 5‐year‐disease‐free survival in those with normal olfaction was 86.0%, vs 35.4% with impaired olfaction (p = 0.029). Disease‐free survival with normal color vision was 70.3%, vs 26.0% with impaired vision (p = 0.009). Both olfaction and color vision were reduced as much as 5 years before disease diagnosis, with only slight decline in preclinical stages. Interpretation:: Olfaction and color vision identify early‐stage synuclein‐mediated neurodegenerative diseases. In most cases, abnormalities are measurable at least 5 years before disease onset, and progress slowly in the preclinical stages. Ann Neurol 2011;

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   |texte=   Olfaction and color vision identify impending neurodegeneration in rapid eye movement sleep behavior disorder
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