Lewy bodies and olfactory dysfunction in old age.

As part of a clinical-pathologic project, older people completed a standard odor identification test at study entry. During a mean of 3.5 years of observation, 201 people died and underwent brain autopsy and neuropathologic examination (6 with a history of Parkinson's disease were excluded). Lewy bodies were identified with antibodies to alpha-synuclein and classified as nigral, limbic, or neocortical based on their distribution in 6 brain regions. Plaques and tangles in 5 regions were summarized with a previously established composite measure, and neuron loss in the substantia nigra was rated on 6-point scale. Odor identification scores ranged from 0 to 12 correct (mean = 8.0, standard deviation = 2.6). On neuropathologic examination, 26 persons had Lewy bodies (13 neocortical, 9 limbic, and 4 nigral). In an analysis adjusted for age, sex, education, and time from olfactory testing to death, limbic (estimate = -2.47, standard error [SE] = 0.73, P < 0.001) and neocortical (estimate = -4.36, SE = 0.63, P < 0.001) Lewy body subgroups were associated with impaired olfaction. Results were comparable in analyses that controlled for dementia or parkinsonism during the study or postmortem measures of plaques and tangles or nigral cell loss. A final set of analyses suggested that impaired olfactory performance may aid detection of underlying Lewy body disease. The findings indicate that Lewy body disease impairs late life olfactory function even in otherwise asymptomatic individuals.