Background and Objectives:Evaluating and understanding the heterogeneity in dementia course has important implications for clinical practice, healthcare decision-making, and research. However, inconsistent findings have been reported with regard to the disease courses of the two most common dementias, Alzheimer’s disease (AD) and Dementia with Lewy bodies (DLB). Using autopsy-confirmed diagnoses, we aimed to examine the disease trajectories in the years before death among dementia patients with pure AD, pure DLB, or mixed (AD and DLB) pathologies.Methods:The current retrospective longitudinal study included 62 participants with autopsy-confirmed diagnoses of pure AD (n=34), mixed AD and DLB (AD+DLB, n = 17), or pure DLB (n=11) from the Predictors 2 Cohort Study, a prospective, clinic-based, cohort of dementia patients. Generalized estimating equation models, with time zero at death, were used to examine the trajectory of cognition (Folstein Mini-Mental State Examination, MMSE), function (Activities of Daily Living, ADL), and dependence scale among patients with different autopsy-confirmed diagnosis (pure AD, AD+DLB, and pure DLB). The models were adjusted for age, sex, education, and baseline features including extrapyramidal signs, MMSE, ADL, and dependence scale.Results:The participants on average received 9.4±4.6 assessments at 6-month intervals during a mean 5.4±2.9 years of follow-up time. The three groups were similar in both cognition and function status at baseline. Cognition and function were highly correlated among AD+DLB patients but not in pure AD or pure DLB patients at baseline. Patients of the three groups all declined in both cognition and function but had different trajectories of decline. More specifically, the pure DLB patients experienced approximately double the rate of both cognitive decline and functional decline than the pure AD patients, and the mixed pathology group showed double the rate of functional decline as compared to pure AD patients.Discussion:In this longitudinal study, we found that among patients with dementia, those with Lewy body pathology experienced faster cognitive and functional decline than those with pure AD pathology.