• Eun Joo Chung, Ganesh M Babulal, Sarah E Monsell, Nigel J Cairns, Catherine M Roe, and John C Morris.
• Department of Neurology, Busan Paik Hospital, Inje University College of Medicine, Busan, Korea.
• JAMA Neurol. 2015 Jul 1;72(7):789-96.

ImportanceLewy bodies are a frequent coexisting pathology in late-onset Alzheimer disease (AD). Previous studies have examined the contribution of Lewy bodies to the clinical phenotype of late-onset AD with variable findings.ObjectiveTo determine whether the presence of Lewy body pathology influences the clinical phenotype and progression of symptoms in longitudinally assessed participants with AD.Design, Setting, And ParticipantsRetrospective clinical and pathological cohort study of 531 deceased participants who met the neuropathologic criteria for intermediate or high likelihood of AD according to the National Institute on Aging-Ronald Reagan Institute guidelines for the neuropathologic diagnosis of AD. All participants had a clinical assessment within 2 years of death. The data were obtained from 34 AD centers maintained by the National Alzheimer Coordinating Center and spanned from September 12, 2005, to April 30, 2013.ExposuresStandardized neuropathologic assessment and then brain autopsy after death.Main Outcomes And MeasuresClinical and neuropsychiatric test scores.ResultsThe mean (SD) age at death was statistically significantly younger for participants who had AD with Lewy bodies (77.9 [9.5] years) than for participants who had AD without Lewy bodies (80.2 [11.1] years) (P = .01). The mean (SD) age at onset of dementia symptoms was also younger for participants who had AD with Lewy bodies (70.0 [9.9] years) than for participants who had AD without Lewy bodies (72.2 [12.3] years) (P = .03). More men than women had AD with Lewy bodies (P = .01). The frequency of having at least 1 APOE ε4 allele was higher for participants who had AD with Lewy bodies than for participants who had AD without Lewy bodies (P = .03). After adjusting for age, sex, education, frequency of plaques (neuritic and diffuse), and tangle stage, we found that participants who had AD with Lewy bodies had a statistically significantly higher mean (SD) Neuropsychiatric Inventory Questionnaire score (6.59 [1.44] [95% CI, 3.75-9.42] vs 5.49 [1.39] [95% CI, 2.76-8.23]; P = .04) and a statistically significantly higher mean (SD) Unified Parkinson Disease Rating Scale motor score (0.81 [0.18] [95% CI, 0.45-1.17] vs 0.54 [0.18] [95% CI, 0.19-0.88]; P < .001) than did participants who had AD without Lewy bodies.Conclusions And RelevanceParticipants with both AD and Lewy body pathology have a clinical phenotype that may be distinguished from AD alone. The frequency of Lewy bodies in AD and the association of Lewy bodies with the APOE ε4 allele suggest potential common mechanisms for AD and Lewy body pathologies.

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