Cross-sectional and prognostic associations of baseline [18F]GTP1 tau PET signal and white matter lesion volumes for cognitive and functional decline in prodromal-to-mild Alzheimer's disease.

Background: In Alzheimer's disease (AD), tau and white matter lesion pathology are associated with clinical severity and subsequent decline, but their relative relationships with clinical assessments remain uncertain.

Objective: To examine cross-sectional and prognostic associations between baseline [¹⁸F]GTP1 tau positron emission tomography (PET) standardized uptake value ratio (SUVRs) and T1 white matter hypointensity (WMHypo) volumes with clinical indices.

Methods: We analyzed participants with biomarker-confirmed prodromal (n = 127) or mild (n = 233) AD with baseline [¹⁸F]GTP1 tau PET and MRI and longitudinal Clinical Dementia Rating-Sum of Boxes (CDR-SB), 13-item version of the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog13), Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Mini-Mental Status Examination (MMSE), and Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) data.

Results: Higher baseline [¹⁸F]GTP1 SUVRs were independently associated with poorer baseline performance and faster rates of subsequent decline on all five clinical outcome measures. Higher baseline WMHypo volumes were independently associated with poorer baseline performance on the CDR-SB, ADAS-Cog13, RBANS, and MMSE and faster rates of subsequent decline on the CDR-SB and ADCS-ADL.

Conclusions: The independent associations of tau and white matter lesion pathology with clinical decline in AD suggest future prognostic models should include both imaging modalities.