INTRODUCTION: Thalamic nuclei support multiple cognitive processes, yet their integrity in biologically-defined Alzheimer's disease (AD) remains unknown. METHOD: Amyloid status was determined using PET Centiloids >24 in 1,327 participants from ADNI. Combined with clinical diagnosis, this yielded six groups: amyloid-negative or positive CN-MCI-dementia/AD. Thalamic nuclei volumes were extracted from T1-weighted MRI using the HIPS-THOMAS algorithm. RESULTS: Large volume reductions in the anteroventral, mediodorsal, and pulvinar nuclei were observed in amyloid-positive MCI and AD. Reduced volumes were also evident in amyloid-positive CN, supporting preclinical AD. Adding the anteroventral nucleus improved cognitive status classification in Random Forest analyses. A phenotypic model integrating thalamic nuclei clearly distinguished amyloid-positive groups from amyloid-negative CN and reclassified non-AD patients with 68% of amyloid-negative MCI subjects as CN-like, and 27% of amyloid-positive CN as MCI-like. DISCUSSION: Thalamic volumetry from conventional T1-weighted MRI enhances clinical insight into AD and provides a practical biomarker for disease intervention.
Vidal, J. P., Myall, D., Pariente, J., Pitcher, T., Roberts, R. P., Cawston, E., Leheron, C., Anderson, T., Morgan, C., Melzer, T., Kirk, I., Tippett, L., Peran, P., Dalrymple-alford, J.
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