Neurocognitive contributions to verbal fluency deficits in frontotemporal lobar degeneration

Objective: To test the hypothesis that different neurocognitive networks underlie verbal fluency deficits in frontotemporal lobar degeneration (FTLD). Methods: Letter (“FAS”) and semantic (“animal”) fluency tests were administered to patients with a behavioral/dysexecutive disorder (bvFTLD; n = 71), semantic dementia (SemD; n = 21), and progressive nonfluent aphasia (PNFA; n = 26). Tests measuring working memory, naming/lexical retrieval, and semantic knowledge were also obtained. MRI voxel-based morphometry (VBM) studies were obtained on a subset of these patients (bvFTLD, n = 51; PNFA, n = 11; SemD, n = 10). Results: Patients with SemD were disproportionately impaired on the semantic fluency measure. Reduced output on this test was correlated with impaired performance on naming/lexical retrieval tests. VBM analyses related reduced letter and semantic fluency to anterior and inferior left temporal lobe atrophy. Patients with bvFTLD were equally impaired on both fluency tests. Poor performance on both fluency tests was correlated with low scores on working memory and naming/lexical retrieval measures. In this group, MRI-VBM analyses related letter fluency to bilateral frontal atrophy and semantic fluency to left frontal/temporal atrophy. Patients with PNFA were also equally impaired on fluency tests. Reduced semantic fluency output was correlated with reduced performance on naming/lexical retrieval tests. MRI-VBM analyses related semantic fluency to the right frontal lobe and letter fluency to left temporal atrophy. Conclusions: Distinct neurocognitive networks underlie impaired performance on letter and semantic fluency tests in frontotemporal lobar degeneration subgroups.

[1]  J. Morris,et al.  The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part I. Clinical and neuropsychological assesment of Alzheimer's disease , 1989, Neurology.

[2]  Howard J. Rosen,et al.  Distinctive Neuropsychological Patterns in Frontotemporal Dementia, Semantic Dementia, And Alzheimer Disease , 2003, Cognitive and behavioral neurology : official journal of the Society for Behavioral and Cognitive Neurology.

[3]  Adrian Ivanoiu,et al.  Semantic memory in Alzheimer's disease and the frontotemporal dementias: a longitudinal study of 236 patients. , 2006, Neuropsychology.

[4]  J. Gee,et al.  What's in a name: voxel-based morphometric analyses of MRI and naming difficulty in Alzheimer's disease, frontotemporal dementia and corticobasal degeneration. , 2003, Brain : a journal of neurology.

[5]  J D Van Horn,et al.  A comparison of rCBF patterns during letter and semantic fluency. , 2000, Neuropsychology.

[6]  Ali R. Khan,et al.  Symmetric Data Attachment Terms for Large Deformation Image Registration , 2007, IEEE Transactions on Medical Imaging.

[7]  L. Thal,et al.  Disparate letter and semantic category fluency deficits in autopsy-confirmed frontotemporal dementia and Alzheimer's disease. , 2007, Neuropsychology.

[8]  J. Trojanowski,et al.  Cognitive and motor assessment in autopsy-proven corticobasal degeneration , 2007, Neurology.

[9]  D. Neary,et al.  Distinct behavioural profiles in frontotemporal dementia and semantic dementia , 2001, Journal of neurology, neurosurgery, and psychiatry.

[10]  G. Cosgrove,et al.  Reversible Kernohan notch , 2007, Neurology.

[11]  D. Stuss,et al.  The effects of focal anterior and posterior brain lesions on verbal fluency , 1998, Journal of the International Neuropsychological Society.

[12]  Jennifer Farmer,et al.  Distinct antemortem profiles in patients with pathologically defined frontotemporal dementia. , 2007, Archives of neurology.

[13]  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.

[14]  M. D’Esposito,et al.  Language comprehension profiles in Alzheimer's disease, multi-infarct dementia, and frontotemporal degeneration , 1996, Neurology.

[15]  M. Freedman,et al.  Frontotemporal lobar degeneration , 1998, Neurology.

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

[17]  A. Hillis,et al.  Neural regions essential for distinct cognitive processes underlying picture naming. , 2007, Brain : a journal of neurology.

[18]  Murray Grossman,et al.  Neural Basis of Semantic Memory: Process and content in semantic memory , 2007 .

[19]  Jennifer Farmer,et al.  Frontotemporal dementia: Clinicopathological correlations , 2006, Annals of neurology.

[20]  Katy A. Cross,et al.  Patterns of neuropsychological impairment in frontotemporal dementia , 2007, Neurology.

[21]  Can Ceritoglu,et al.  Increasing the power of functional maps of the medial temporal lobe by using large deformation diffeomorphic metric mapping. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[22]  P Garrard,et al.  The differentiation of semantic dementia and frontal lobe dementia (temporal and frontal variants of frontotemporal dementia) from early Alzheimer's disease: a comparative neuropsychological study. , 1999, Neuropsychology.

[23]  T. Carew,et al.  Impairment in category fluency in ischemic vascular dementia. , 1997, Neuropsychology.

[24]  J. Hodges,et al.  Generating ‘tiger’ as an animal name or a word beginning with T: differences in brain activation , 1996, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[25]  B L Miller,et al.  Behavioral disorders in the frontal and temporal variants of frontotemporal dementia , 2004, Neurology.

[26]  O. Selnes.  A Compendium of Neuropsychological Tests , 1991, Neurology.

[27]  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.

[28]  Murray Grossman,et al.  Screening for Frontotemporal Dementias and Alzheimer’s Disease with the Philadelphia Brief Assessment of Cognition: A Preliminary Analysis , 2007, Dementia and Geriatric Cognitive Disorders.

[29]  M. Grossman,et al.  Primary Progressive Aphasia: A Review , 2004, Neurocase.

[30]  A. Alavi,et al.  Constraints on the cerebral basis for semantic processing from neuroimaging studies of Alzheimer’s disease , 1997, Journal of neurology, neurosurgery, and psychiatry.

[31]  J. Gee,et al.  Geodesic estimation for large deformation anatomical shape averaging and interpolation , 2004, NeuroImage.

[32]  Stephen M Smith,et al.  Fast robust automated brain extraction , 2002, Human brain mapping.

[33]  Murray Grossman,et al.  Sentence comprehension and voxel-based morphometry in progressive nonfluent aphasia, semantic dementia, and nonaphasic frontotemporal dementia , 2008, Journal of Neurolinguistics.

[34]  Stephen M. Smith,et al.  Hidden Markov random field model and segmentation of brain MR images , 2001 .

[35]  R. D. Norman.  A revised deterioration formula for the Wechsler Adult Intelligence Scale. , 1966, Journal of clinical psychology.

[36]  J. Hodges,et al.  Semantic dementia: a unique clinicopathological syndrome , 2007, The Lancet Neurology.

[37]  M. Grossman,et al.  Verbal and nonverbal fluency in patients with probable Alzheimer's disease. , 1994 .

[38]  J. Hodges,et al.  Differentiating frontal and temporal variant frontotemporal dementia from Alzheimer’s disease , 2000, Neurology.

[39]  R. Faber,et al.  Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. , 1999, Neurology.

[40]  Jonathan D. Cohen,et al.  Improved Assessment of Significant Activation in Functional Magnetic Resonance Imaging (fMRI): Use of a Cluster‐Size Threshold , 1995, Magnetic resonance in medicine.

[41]  Dana L. Penney,et al.  Alterations in working memory as a function of leukoaraiosis in dementia , 2007, Neuropsychologia.