Neocortical Lewy bodies are associated with impaired odor identification in community-dwelling elders without clinical PD

Background The association of Lewy bodies (LBs) with olfactory dysfunction was investigated in community-dwelling elders without clinical Parkinson’s disease (PD) using the 12-item Brief Smell Identification Test (BSIT), a standard measure of odor identification. Methods 280 participants in the Rush Memory and Aging Project completed the BSIT annually. Lewy bodies were detected in 13 brain regions by immunohistochemistry and were assigned to the Braak PD stages 1–6. Results Of the 280 participants, 101 (36.1%) had LBs which were maximal in the olfactory bulb and tract (85.1%) and least in Heschl’s cortex (21.8%). Due to the small number of cases in Braak PD stages 2, 3 and 5, the distribution of LBs in the 6 Braak PD stages was contracted into 3 main LB stages: (1) LBs in olfactory bulbs and dorsal motor nucleus of vagus, (2) further extension of LBs to limbic and other brainstem regions and (3) additional extension of LBs to neocortical areas. MMSE, global cognition and odor test scores were lower and frequency of dementia was higher at the time of the last valid BSIT, in cases with LBs as compared to those without LBs. Linear regression analyses showed that LBs were associated with impaired olfaction. However, on stratification of LBs into 3 stages, only the stage 3 cases were independently associated with impaired olfaction. Conclusion Although LB pathology was detected in olfactory bulbs in the early stage of LB progression (stage 1), the strongest association of LBs with olfactory dysfunction was observed in the late pathological stage (stage 3) when LBs extended to neocortical areas.