Abstract

Frontostriatal (including the putamen) circuit-mediated cognitive dysfunction has been implicated in frontotemporal lobar degeneration (FTLD), but not in Alzheimer disease (AD) or healthy aging. We sought to assess putaminal volume as a measure of the structural basis of relative frontostriatal dysfunction in these groups. We measured putaminal volume in FTLD subtypes: frontotemporal dementia (FTD, n = 12), semantic dementia (SD, n = 13), and progressive nonfluent aphasia (PNFA, n = 9) in comparison with healthy controls (n = 25) and patients with AD (n = 18). Diagnoses were based on accepted clinical criteria. We conducted manual volume measurement of the putamen blinded to the diagnosis on T1 brain MR imaging by using a standardized protocol. Paired t tests (P < .05) showed that the left putaminal volume was significantly larger than the right in all groups combined. Multivariate analysis of covariance with a Bonferroni correction was used to assess statistical significance among the subject groups (AD, FTD, SD, PNFA, and controls) as independent variables and right/left putaminal volumes as dependent variables (covariates, age and intracranial volume; P < .05). The right putamen in FTD was significantly smaller than in AD and controls; whereas in SD, it was smaller compared with controls with a trend toward being smaller than in AD. There was also a trend toward the putamen in the PNFA being smaller than that in controls and in patients with AD. Across the groups, there was a positive partial correlation between putaminal volume and Mini-Mental State Examination (MMSE). Right putaminal volume was significantly smaller in FTD, the FTLD subtype with the greatest expected frontostriatal dysfunction; whereas in SD and PNFA, it showed a trend towards being smaller, consistent with expectation, compared to controls and AD; and in SD, compared with AD and controls. Putaminal volume weakly correlated with MMSE.

Highlights

  • AND PURPOSE: Frontostriatal circuitϪmediated cognitive dysfunction has been implicated in frontotemporal lobar degeneration (FTLD), but not in Alzheimer disease (AD) or healthy aging

  • Right putaminal volume was significantly smaller in frontotemporal dementia (FTD), the FTLD subtype with the greatest expected frontostriatal dysfunction; whereas in semantic dementia (SD) and progressive nonfluent aphasia (PNFA), it showed a trend towards being smaller, consistent with expectation, compared to controls and AD; and in SD, compared with AD and controls

  • In relation to hypothesis 1, we have shown that there is an overall group hemispheric asymmetry of the putamen, but this may be due to selective atrophy on the right in the disease groups

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Summary

Methods

We measured putaminal volume in FTLD subtypes: frontotemporal dementia (FTD, n ϭ 12), semantic dementia (SD, n ϭ 13), and progressive nonfluent aphasia (PNFA, n ϭ 9) in comparison with healthy controls (n ϭ 25) and patients with AD (n ϭ 18). We conducted manual volume measurement of the putamen blinded to the diagnosis on T1 brain MR imaging by using a standardized protocol. AD diagnoses were based on clinical criteria including the Diagnostic and Statistical Manual of Mental Disorders, 4th text revision (DSM-IV-TR) and the International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10).[15,16] Patients with FTLD were diagnosed according to consensus diagnostic criteria for FTLD syndromes presented by Neary et al.[17] Diagnoses on all subjects included in this study were reviewed by an experienced neurologist

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