Lewy body pathology in Alzheimer's disease: A clinicopathological prospective study

Objective: Identify clinical features predictive of Lewy body pathology in Alzheimer's disease (AD) patients in an ongoing longitudinal clinicopathologic study. Material and Methods: We queried the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND) database for dementia cases with AD pathology (1997-2015). Subjects received longitudinal comprehensive clinical evaluations including motor/neuropsychological assessment and Apo-E4 genotyping. All cases were autopsied and had standard neuropathological assessments for AD and Lewy-type synucleinopathy (LTS). Subjects were categorized based on standardized pathological criteria with AD cases that had LTS but did not meet DLB pathologic criteria being categorized as ADLB. We performed pairwise comparison between the different diagnoses and multivariable modelling to identify clinical symptoms that predict the pathological diagnosis. Results: We identified 32 DLB/AD, 54 ADLB, 70 AD only and 41 PDD/AD cases. AD subjects with LTS pathology had higher UPDRS II and III total scores as well as generally higher individual scores compared to AD alone. While depression scales and Trail-making Test A correlated significantly with LTS, other neuropsychological variables were not significantly different. Apo E4 occurrence was similar in all groups (40%-49%). Conclusions: Our study suggests that the presence (or absence) of LTS influences motor and non-motor clinical findings in AD patients. These findings may lead to biomarkers that allow for more targeted treatment of AD.