Loss of frontal fMRI activation in early frontotemporal dementia compared to early AD

Objective: To compare frontal cortex activation in patients with early frontotemporal dementia (FTD) with that in patients with early AD. Methods: Seven patients with FTD and seven patients with AD were studied (Clinical Dementia Rating: four patients with FTD 0.5, three patients with FTD 1, all patients with AD 1; mean Mini-Mental State Examination score: FTD 28.0 ± 2.1, AD 23.1 ± 2.7). Cerebral atrophy on MRI was mild, with no differences between FTD and AD. A parametric working memory task was applied to assess frontal activation as a function of working memory load. Results: The activated working memory network in FTD and AD included frontal and parietal lobe and thalamus. In frontal and parietal cortex, brain activation was significantly decreased in FTD. Frontal regions in patients with FTD showed less linear activation increase with working memory load than in AD. Possibly as a compensation mechanism, the cerebellum showed a stronger increasing response in FTD. Conclusions: These data on regional functional loss in the frontal cortex in early FTD suggest that fMRI can identify FTD when results on structural MRI are normal.

[1]  A. Wunderlich,et al.  Subjective memory complaints: Objective neural markers in patients with Alzheimer's disease and major depressive disorder , 2002, Annals of neurology.

[2]  P. Strick,et al.  Cerebellar Projections to the Prefrontal Cortex of the Primate , 2001, The Journal of Neuroscience.

[3]  Douglas Greve,et al.  Functional MRI detection of pharmacologically induced memory impairment , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[4]  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.

[5]  D. Knopman,et al.  Dissociation of regional activation in mild AD during visual encoding , 2001, Neurology.

[6]  Julie S. Snowden,et al.  Fronto-Temporal Lobar Degeneration: Fronto-Temporal Dementia, Progressive Aphasia, Semantic Dementia , 1996 .

[7]  M. D’Esposito,et al.  Human Prefrontal Cortex Is Not Specific for Working Memory: A Functional MRI Study , 1998, NeuroImage.

[8]  J. Morris.  The Clinical Dementia Rating (CDR) , 1993, Neurology.

[9]  M. Hallett,et al.  Cognitive planning deficit in patients with cerebellar atrophy , 1992, Neurology.

[10]  M. Witter,et al.  Functional MR imaging in Alzheimer's disease during memory encoding. , 2000, AJNR. American journal of neuroradiology.

[11]  Thomas E. Nichols,et al.  Thresholding of Statistical Maps in Functional Neuroimaging Using the False Discovery Rate , 2002, NeuroImage.

[12]  Edward E. Smith,et al.  Verbal Working Memory Load Affects Regional Brain Activation as Measured by PET , 1997, Journal of Cognitive Neuroscience.

[13]  Michael E. Phelps,et al.  Clinical Value of Neuroimaging in the Diagnosis of Dementia. Sensitivity and Specificity of Regional Cerebral Metabolic and Other Parameters for Early Identification of Alzheimer's Disease. , 1999, Clinical positron imaging : official journal of the Institute for Clinical P.E.T.

[14]  P Pietrini,et al.  Increasing required neural response to expose abnormal brain function in mild versus moderate or severe Alzheimer's disease: PET study using parametric visual stimulation. , 1998, The American journal of psychiatry.

[15]  M. Torrens.  Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268 , 1990 .

[16]  R. Coppola,et al.  Physiological characteristics of capacity constraints in working memory as revealed by functional MRI. , 1999, Cerebral cortex.

[17]  Edward E. Smith,et al.  A Parametric Study of Prefrontal Cortex Involvement in Human Working Memory , 1996, NeuroImage.

[18]  J L Lancaster,et al.  Automated Talairach Atlas labels for functional brain mapping , 2000, Human brain mapping.

[19]  H J Testa,et al.  A clinical role for 99mTc-HMPAO SPECT in the investigation of dementia? , 1998, Journal of neurology, neurosurgery, and psychiatry.

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

[21]  F Barkhof,et al.  Alterations in brain activation during cholinergic enhancement with rivastigmine in Alzheimer’s disease , 2002, Journal of neurology, neurosurgery, and psychiatry.

[22]  R. Mayeux,et al.  Differential regional dysfunction of the hippocampal formation among elderly with memory decline and Alzheimer's disease , 1999, Annals of neurology.

[23]  J. Baron,et al.  In Vivo Mapping of Gray Matter Loss with Voxel-Based Morphometry in Mild Alzheimer's Disease , 2001, NeuroImage.

[24]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease , 1984, Neurology.

[25]  H. Braak,et al.  Neuropathology of Alzheimer’s disease: what is new since A. Alzheimer? , 1999, European Archives of Psychiatry and Clinical Neuroscience.

[26]  Frederik Barkhof,et al.  Unbiased whole-brain analysis of gray matter loss in Alzheimer's disease , 2000, Neuroscience Letters.

[27]  Mark S. Cohen,et al.  Patterns of brain activation in people at risk for Alzheimer's disease. , 2000, The New England journal of medicine.

[28]  M. D’Esposito,et al.  Functional MRI studies of spatial and nonspatial working memory. , 1998, Brain research. Cognitive brain research.

[29]  R. Coppola,et al.  Specific versus Nonspecific Brain Activity in a Parametric N-Back Task , 2000, NeuroImage.

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

[31]  Karl J. Friston,et al.  Statistical parametric maps in functional imaging: A general linear approach , 1994 .

[32]  K. Ishii,et al.  Cerebral glucose metabolism in patients with frontotemporal dementia. , 1998, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[33]  E E Smith,et al.  Components of verbal working memory: evidence from neuroimaging. , 1998, Proceedings of the National Academy of Sciences of the United States of America.