P4-160: Cortical Lewy body disease is related to dementia and lower memory scores in older persons with and without Alzheimer’s disease pathology

Abstract

Dementia with Lewy bodies is a common cause of dementia in older persons. Pathologically there is often coexisting Alzheimer's disease (AD). The relative contribution of Lewy body disease in persons with varying levels of AD pathology is not well understood. Investigate the contribution of cortical Lewy body disease to dementia and cognitive function in older persons with and without dementia. We studied 282 autopsied persons from the Religious Order Study, a longitudinal study of older Catholic clergy. The mean age at death was 85.6 years. Cognitive function was assessed about 7 months before death with 19 neuropsychologic tests which were used to create a global z–score and z–scores for episodic, semantic and working memory, perceptual speed and visual–spatial skills. The diagnosis of dementia was rendered by an experienced neurologist after review of all clinical data. We examined paraffin–embedded 6μm sections of frontal, temporal, parietal, cingulate, and entorhinal cortices, and substantia nigra, using alpha–synuclein immunostain (Zymed 1:100). Bielschowsky silver stain was used to count plaques and tangles in four cortical regions, and counts were summarized to create a global AD pathology measure. Macroscopic chronic cerebral infarctions were recorded. Analyses included Spearman Rank correlations and multiple logistic and linear regression controlling for age, sex, and education. 52 persons exhibited Lewy body disease (41 cortical type and 11 nigra predominant). Lewy bodies were not related to age (rho = 0.02, p=0.69) or AD pathology (rho = 0.03, p=0.63). After controlling for age, sex, education, AD pathology and infarctions, cortical Lewy body disease increased the odds of dementia by over 3 fold (OR=3.4, 95% CI=1.4–8.2), whereas nigra predominant disease was not associated with increased odds of dementia (OR=0.59, 95% CI=0.11–3.2). Cortical Lewy body disease was associated with lower episodic (parameter estimate = 0.81, p<0.001), semantic (parameter estimate = 0.73, p<0.01), and working memory (parameter estimate = 0.38, p=0.02) and lower perceptual speed (parameter estimate = 0.54, p<0.01). Cortical Lewy body disease increases the odds of dementia and is associated with lower memory function and processing speed in older persons, and this effect does not depend on the level of AD pathology.