Magnetic resonance imaging signatures of tissue pathology in frontotemporal dementia.

BACKGROUND The pathologic substrates of frontotemporal dementia (FTD) are difficult to predict in vivo. OBJECTIVE To determine whether different pathologic substrates of FTD have distinct patterns of regional atrophy on magnetic resonance imaging (MRI). DESIGN Retrospective case study. SETTING The Institute of Neurology, University College London, and the Institute of Psychiatry, King's College London. Patients Twenty-one cases of FTD selected on pathologic grounds (9 with ubiquitin-positive [tau- and alpha-synuclein-negative] inclusions [FTD-U], 7 with Pick disease [PiD], and 5 with familial FTD with tau exon 10+16 mutations [tau exon 10+16]) and 20 healthy controls were studied. MAIN OUTCOME MEASURES Patterns of gray matter atrophy in each group as assessed by voxel-based morphometry (VBM) and a blinded visual assessment of each MRI study. RESULTS All pathologic substrates were associated with atrophy that involved the inferior and medial temporal and inferior frontal lobes. Additionally, specific VBM signatures were identified for each subgroup: FTD-U was associated with asymmetric (left > right) temporal lobe atrophy, PiD was associated with severe dorsolateral bifrontal atrophy, and tau exon 10+16 was associated with asymmetric (right > left) medial temporal lobe atrophy. The VBM findings were supported by blinded visual assessment. CONCLUSION These findings suggest that MRI patterns of regional gray matter atrophy constitute signatures of tissue pathology in FTD.

[1]  J. Hodges,et al.  Clinicopathological correlates in frontotemporal dementia , 2004, Annals of neurology.

[2]  M. Weiner,et al.  Cognition and anatomy in three variants of primary progressive aphasia , 2004, Annals of neurology.

[3]  J Mazziotta,et al.  A probabilistic atlas and reference system for the human brain: International Consortium for Brain Mapping (ICBM). , 2001, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[4]  D. Dickson.  Neuropathology of Pick’s disease , 2001, Neurology.

[5]  M N Rossor,et al.  Patterns of temporal lobe atrophy in semantic dementia and Alzheimer's disease , 2001, Annals of neurology.

[6]  M N Rossor,et al.  Frontotemporal lobar degeneration and ubiquitin immunohistochemistry , 2004, Neuropathology and applied neurobiology.

[7]  D. Geschwind,et al.  Inheritance of frontotemporal dementia. , 1999, Archives of neurology.

[8]  B L Miller,et al.  Patterns of brain atrophy in frontotemporal dementia and semantic dementia , 2002, Neurology.

[9]  C. P. Hughes,et al.  A New Clinical Scale for the Staging of Dementia , 1982, British Journal of Psychiatry.

[10]  Karl J. Friston,et al.  A Voxel-Based Morphometric Study of Ageing in 465 Normal Adult Human Brains , 2001, NeuroImage.

[11]  J. Kril,et al.  Clinicopathological Staging of Frontotemporal Dementia Severity: Correlation with Regional Atrophy , 2004, Dementia and Geriatric Cognitive Disorders.

[12]  P. Lantos,et al.  Neuropathologic variation in frontotemporal dementia due to the intronic tau 10+16 mutation , 2002, Neurology.

[13]  Clinical and neuropathological criteria for frontotemporal dementia. The Lund and Manchester Groups. , 1994, Journal of neurology, neurosurgery, and psychiatry.

[14]  T D Bird,et al.  Familial frontotemporal dementia with ubiquitin-positive, tau-negative inclusions , 2000, Neurology.

[15]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[16]  Karl J. Friston,et al.  Automatic Differentiation of Anatomical Patterns in the Human Brain: Validation with Studies of Degenerative Dementias , 2002, NeuroImage.

[17]  J R Hodges,et al.  The prevalence of frontotemporal dementia , 2002, Neurology.

[18]  Nick C Fox,et al.  Interactive algorithms for the segmentation and quantitation of 3-D MRI brain scans. , 1997, Computer methods and programs in biomedicine.

[19]  B Miller,et al.  Clinical and pathological diagnosis of frontotemporal dementia: report of the Work Group on Frontotemporal Dementia and Pick's Disease. , 2001, Archives of neurology.

[20]  G. Schellenberg,et al.  A clinical pathological comparison of three families with frontotemporal dementia and identical mutations in the tau gene (P301L) , 1999, Brain : a journal of neurology.

[21]  E. Bigio,et al.  Contribution of asymmetric synapse loss to lateralizing clinical deficits in frontotemporal dementias. , 2001, Archives of neurology.