Asymmetrical atrophy of thalamic subnuclei in Alzheimer's disease and amyloid-positive mild cognitive impairment is associated with key clinical features

INTRODUCTION: Although widespread cortical asymmetries have been identified in Alzheimer's disease (AD), thalamic asymmetries and their relevance to clinical severity in AD remain unclear. METHODS: Lateralization indices were computed for individual thalamic subnuclei of 65 participants (33 healthy controls, 14 amyloid-positive patients with mild cognitive impairment, and 18 patients with AD dementia). We compared lateralization indices across diagnostic groups and correlated them with clinical measures. RESULTS: Although overall asymmetry of the thalamus did not differ between groups, greater leftward lateralization of atrophy in the ventral nuclei was demonstrated in AD, compared with controls and amyloid-positive mild cognitive impairment. Increased posterior ventrolateral and ventromedial nuclei asymmetry were associated with worse cognitive dysfunction, informant-reported neuropsychiatric symptoms, and functional ability. DISCUSSION: Leftward ventral thalamic atrophy was associated with disease severity in AD. Our findings suggest the clinically relevant involvement of thalamic nuclei in the pathophysiology of AD.