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Atrophy patterns in histologic vs clinical groupings of frontotemporal lobar degeneration

From the Department of Clinical Neurosciences, University of Cambridge School of Clinical Medicine (J.M.S.P., G.B.W., J.A.-C., G.P., M.G.S., P.J.N.), and University of Cambridge, Department of Pathology, Molecular Histopathology (J.H.X.), Addenbrooke's Hospital, Cambridge, UK; and Prince of Wales Medical Research Institute (J.R.H.), Randwick, Australia.

Address correspondence and reprint requests to Dr. Peter J. Nestor, University of Cambridge, Addenbrooke's Hospital, Box 83, Cambridge CB2 2QQ UK pjn23{at}hermes.cam.ac.uk.

Objective: Predictable patterns of atrophy are associated with the clinical subtypes of frontotemporal dementia (FTD): behavioral variant (bvFTD), semantic dementia (SEMD), and progressive nonfluent aphasia (PNFA). Some studies of pathologic subtypes have also suggested specific atrophy patterns; however, results are inconsistent. Our aim was to test the hypothesis that clinical, but not pathologic, classification (FTD with ubiquitin inclusions [FTD-U] and FTD with tau inclusions [FTD-T]) is associated with predictable patterns of regional atrophy.

Methods: Magnetic resonance scans of nine FTD-U and six FTD-T patients (histologically confirmed) were compared with 25 controls using voxel-based morphometry (VBM). Analyses were conducted with the patient group classified according to histologic or clinical variant. Additionally, three Alzheimer pathology patients who had the syndrome of SEMD in life (FTD-A) were analyzed.

Results: The VBM studies in clinical variants confirmed established patterns of atrophy (SEMD, rostral temporal; bvFTD, mesial frontal; PNFA, left insula). FTD-U and FTD-T VBM results were very similar, showing severe atrophy in the temporal poles, mesial frontal lobe, and insulae. A conjunction analysis confirmed this similarity. Subgroup analysis found that SEMD associated with either FTD-T or FTD-U was associated with similar rostral temporal atrophy; however, FTD-A had a qualitatively different pattern of left hippocampal atrophy.

Conclusions: While there is predictable atrophy for clinical variants of frontotemporal dementia (FTD), histologic FTD variants show no noticeable differences. Reports of specific atrophy profiles are likely the result of idiosyncrasies in small groups. Semantic dementia associated with Alzheimer pathology, however, presented a distinct atrophy pattern.

Abbreviations: AD = Alzheimer disease; bvFTD = behavioral variant frontotemporal dementia; FTD = frontotemporal dementia; FTD-A = Alzheimer pathology with semantic dementia; FTD-T = frontotemporal dementia with tau inclusions; FTD-U = frontotemporal dementia with ubiquitin inclusions; FTLD = frontotemporal lobar degeneration; MMSE = Mini-Mental State Examination; PNFA = progressive nonfluent aphasia; SEMD = semantic dementia; VBM = voxel-based morphometry.

Supplemental data at www.neurology.org.

Funded by Medical Research Council (UK) grants to P.J.N. and to M.G.S. G.P. is supported by Alzheimer Research Trust (UK). J.R.H. is supported by an Australian Research Council Federation Fellowship (FF0776229). J.M.S.P. is funded by Fundação para a Ciência e a Tecnologia, Portugal.

Disclosure: The authors report no disclosures.

Medical Devices: GE MRI scanner (GE Medical Systems, Milwaukee, WI).

Received November 28, 2008. Accepted in final form February 9, 2009.

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