Amyloid-Tau-Neurodegeneration Profiles and Longitudinal Cognition in Sporadic Young-Onset Dementia

We examined amyloid-tau-neurodegeneration biomarker effects on cognition in a Southeast-Asian cohort of 84 sporadic young-onset dementia (YOD; age-at-onset <65 years) patients. They were stratified into A+N+, A– N+, and A– N– profiles via cerebrospinal fluid amyloid-β(1–42) (A), phosphorylated-tau (T), MRI medial temporal atrophy (neurodegeneration– N), and confluent white matter hyperintensities cerebrovascular disease (CVD). A, T, and CVD effects on longitudinal Mini-Mental State Examination (MMSE) were evaluated. A+N+ patients demonstrated steeper MMSE decline than A– N+ (β = 1.53; p = 0.036; CI 0.15:2.92) and A– N– (β = 4.68; p = 0.001; CI 1.98:7.38) over a mean follow-up of 1.24 years. Within A– N+, T– CVD+ patients showed greater MMSE decline compared to T+CVD– patients (β = – 2.37; p = 0.030; CI – 4.41:– 0.39). A+ results in significant cognitive decline, while CVD influences longitudinal cognition in the A– sub-group.