Tau Co-Pathology in DLB Clinical Heterogeneity

SUMMARY

# Tau Co-Pathology in DLB Clinical Heterogeneity ## Background and Rationale Dementia with Lewy bodies (DLB) represents the second most common neurodegenerative dementia, characterized by alpha-synuclein pathology. However, 30-50% of DLB cases exhibit concomitant tau pathology, creating significant clinical heterogeneity that complicates diagnosis, prognosis, and treatment selection. This tau co-pathology may explain the variable presentation of core DLB features including cognitive fluctuations

METHODOLOGY NOTES

Phase 1 (Months 1-6): Recruit 200 DLB patients meeting consensus criteria and 50 cognitively normal controls. Obtain informed consent, medical history, and baseline demographics. Phase 2 (Months 4-12): Conduct comprehensive baseline assessments including Unified Parkinson's Disease Rating Scale (UPDRS), Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI), and Montreal Cognitive Assessment (MoCA). Perform tau PET imaging using [18F]MK-6240 tracer (370 MBq injection, 90-110 minute post-injection scanning), amyloid PET with [18F]florbetapir, and 3T MRI with structural, diffusion tensor, and resting-state sequences. Phase 3 (Months 6-24): Implement 6-month follow-up visits with repeated clinical assessments, medication tracking, and adverse event monitoring. Perform annual repeat tau PET imaging in subset of 100 patients. Collect cerebrospinal fluid at baseline and 12 months for tau, phospho-tau, and alpha-synuclein quantification using ELISA and Simoa platforms. Phase 4