BACKGROUND: Dementia with Lewy bodies (DLB) is the second most common cause of neurodegenerative dementia and is characterized by progressive cognitive decline accompanied by core clinical features, including cognitive fluctuations (CF), visual hallucinations (VH), and spontaneous parkinsonism. While these features define the clinical diagnosis of DLB, their relationships with dementia severity and longitudinal progression are not well known.

Methods: The United States (U.S.) Dementia with Lewy Bodies Consortium (DLBC) is a prospective cohort study conducted across nine sites. Participants (n = 262) underwent standardized cognitive, neuropsychological, and motor assessments at baseline and up to three annual follow-up visits. Dementia severity was measured using the Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) and the Montreal Cognitive Assessment (MoCA). 

DISCUSSION: In this deeply phenotyped Lewy Body dementia cohort, the neuropathologic results are remarkable for a wide range of co-pathologies. However, the results suggest CSF SAA performed well with 100% specificity based on neuropathologic confirmation of limbic or neocortical Lewy body neuropathologic change (LBNC). False negatives were seen in cases with restricted distribution of LBNC, that is amygdala predominant or brainstem only. Alzheimer’s disease (AD) biomarkers also performed well and were notable for early variable changes in Ab pathology and subsequent tau abnormalities, the latter when a higher stage AD neuropathologic change was present. Frequent TDP-43 pathology and less frequent associated hippocampal sclerosis were also observed and emphasize the need for LATE biomarkers.