Differential putaminal morphology in Huntington’s disease, frontotemporal dementia and Alzheimer’s disease

Author:

Looi Jeffrey CL1,Rajagopalan Priya2,Walterfang Mark3,Madsen Sarah K2,Thompson Paul M2,Macfarlane Matthew D1,Ching Chris2,Chua Phyllis4,Velakoulis Dennis3

Affiliation:

1. Research Centre for the Neurosciences of Ageing, Academic Unit of Psychological and Addiction Medicine, Australian National University Medical School, Canberra, Australia

2. Laboratory of Neuro Imaging, Department of Neurology, UCLA School of Medicine, Los Angeles, USA

3. Melbourne Neuropsychiatry Centre, Royal Melbourne Hospital, and University of Melbourne, Melbourne, Australia

4. School of Psychology and Psychiatry, Monash University, Melbourne, Australia

Abstract

Objective: Direct neuronal loss or deafferentation of the putamen, a critical hub in corticostriatal circuits, may result in diverse and distinct cognitive and motoric dysfunction in neurodegenerative disease. Differential putaminal morphology, as a quantitative measure of corticostriatal integrity, may thus be evident in Huntington’s disease (HD), Alzheimer’s disease (AD) and frontotemporal dementia (FTD), diseases with differential clinical dysfunction. Methods: HD ( n = 17), FTD ( n = 33) and AD ( n = 13) patients were diagnosed according to international consensus criteria and, with healthy controls ( n = 17), were scanned on the same MRI scanner. Patients underwent brief cognitive testing using the Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG). Ten MRI scans from this dataset were manually segmented as a training set for the Adaboost algorithm, which automatically segmented all remaining scans for the putamen, yielding the following subset of the data: 9 left and 12 right putamen segmentations for AD; 25 left and 26 right putamina for FTD; 16 left and 15 right putamina for HD; 12 left and 12 right putamina for controls. Shape analysis was performed at each point on the surface of each structure using a multiple regression controlling for age and sex to compare radial distance across diagnostic groups. Results: Age, but not sex and intracranial volume (ICV), were significantly different in the segmentation subgroups by diagnosis. The AD group showed significantly poorer performance on cognitive testing than FTD. Mean putaminal volumes were HD < FTD < AD ≤ controls, controlling for age and ICV. The greatest putaminal shape deflation was evident in HD, followed by FTD, in regions corresponding to the interconnections to motoric cortex. Conclusions: Differential patterns of putaminal atrophy in HD, FTD and AD, with relevance to corticostriatal circuits, suggest the putamen may be a suitable clinical biomarker in neurodegenerative disease.

Publisher

SAGE Publications

Subject

Psychiatry and Mental health,General Medicine

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