Distinct MRI Atrophy Patterns in Autopsy-Proven Alzheimer's Disease and Frontotemporal Lobar Degeneration

To better define the anatomic distinctions between Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD), we retrospectively applied voxel-based morphometry to the earliest magnetic resonance imaging scans of autopsy-proven AD (N = 11), FTLD (N = 18), and controls (N = 40). Compared with controls, AD patients showed gray matter reductions in posterior temporoparietal and occipital cortex; FTLD patients showed atrophy in medial prefrontal and medial temporal cortex, insula, hippocampus, and amygdala; and patients with both disorders showed atrophy in dorsolateral and orbital prefrontal cortex and lateral temporal cortex (P FWE-corr < .05). Compared with FTLD, AD patients had decreased gray matter in posterior parietal and occipital cortex, whereas FTLD patients had selective atrophy in anterior cingulate, frontal insula, subcallosal gyrus, and striatum (P < .001, uncorrected). These findings suggest that AD and FTLD are anatomically distinct, with degeneration of a posterior parietal network in AD and degeneration of a paralimbic fronto-insular-striatal network in FTLD.

[1]  C. Jack,et al.  Voxel-based morphometry in autopsy proven PSP and CBD , 2008, Neurobiology of Aging.

[2]  S. Thibodeau,et al.  Preclinical evidence of Alzheimer's disease in persons homozygous for the epsilon 4 allele for apolipoprotein E. , 1996, The New England journal of medicine.

[3]  John Q. Trojanowski,et al.  Consensus Recommendations for the Postmortem Diagnosis of Alzheimer’s Disease , 1997, Neurobiology of Aging.

[4]  Panteleimon Giannakopoulos,et al.  Neural substrates of cognitive and behavioral deficits in atypical Alzheimer's disease , 2006, Brain Research Reviews.

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

[6]  Nick C Fox,et al.  Visual assessment of atrophy on magnetic resonance imaging in the diagnosis of pathologically confirmed young-onset dementias. , 2005, Archives of neurology.

[7]  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.

[8]  M. Greicius,et al.  Default-mode network activity distinguishes Alzheimer's disease from healthy aging: Evidence from functional MRI , 2004, Proc. Natl. Acad. Sci. USA.

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

[10]  Clifford R Jack,et al.  Comparisons Between Alzheimer Disease, Frontotemporal Lobar Degeneration, and Normal Aging With Brain Mapping , 2005, Topics in magnetic resonance imaging : TMRI.

[11]  Nick C Fox,et al.  A Volumetric Magnetic Resonance Imaging Study of the Amygdala in Frontotemporal Lobar Degeneration and Alzheimer’s Disease , 2005, Dementia and Geriatric Cognitive Disorders.

[12]  A. Brun,et al.  Limbic lobe involvement in presenile dementia , 1978, Archiv für Psychiatrie und Nervenkrankheiten.

[13]  J. Allman,et al.  Early frontotemporal dementia targets neurons unique to apes and humans , 2006, Annals of neurology.

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

[15]  Griselda J. Garrido,et al.  A voxel-based morphometry study of temporal lobe gray matter reductions in Alzheimer’s disease , 2003, Neurobiology of Aging.

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

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

[18]  Karalyn Patterson,et al.  Clinical and pathological characterization of progressive aphasia , 2006, Annals of neurology.

[19]  G. Frisoni,et al.  Brain atrophy in frontotemporal dementia. , 1996, Journal of neurology, neurosurgery, and psychiatry.

[20]  N. Foster,et al.  Metabolic reduction in the posterior cingulate cortex in very early Alzheimer's disease , 1997, Annals of neurology.

[21]  G. V. Van Hoesen,et al.  The topographical and neuroanatomical distribution of neurofibrillary tangles and neuritic plaques in the cerebral cortex of patients with Alzheimer's disease. , 1991, Cerebral cortex.

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

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

[24]  H. Critchley.  Neural mechanisms of autonomic, affective, and cognitive integration , 2005, The Journal of comparative neurology.

[25]  C. Jack,et al.  Imaging correlates of posterior cortical atrophy , 2007, Neurobiology of Aging.

[26]  Benjamin J. Shannon,et al.  Molecular, Structural, and Functional Characterization of Alzheimer's Disease: Evidence for a Relationship between Default Activity, Amyloid, and Memory , 2005, The Journal of Neuroscience.

[27]  A. Brun,et al.  Neuropsychological tests as discriminators between dementia of alzheimer type and frontotemporal dementia , 1994 .

[28]  Marina Boccardi,et al.  The MRI pattern of frontal and temporal brain atrophy in fronto-temporal dementia , 2003, Neurobiology of Aging.

[29]  Richard S. J. Frackowiak,et al.  A voxel‐based morphometry study of semantic dementia: Relationship between temporal lobe atrophy and semantic memory , 2000, Annals of neurology.

[30]  N. Schuff,et al.  Different regional patterns of cortical thinning in Alzheimer's disease and frontotemporal dementia. , 2006, Brain : a journal of neurology.

[31]  Karl J. Friston,et al.  Voxel-Based Morphometry—The Methods , 2000, NeuroImage.

[32]  M. Weiner,et al.  Patterns of MRI atrophy in tau positive and ubiquitin positive frontotemporal lobar degeneration , 2007, Journal of Neurology, Neurosurgery, and Psychiatry.

[33]  R. Kraftsik,et al.  Primary motor cortex involvement in Alzheimer disease. , 1999, Journal of neuropathology and experimental neurology.

[34]  Maria Luisa Gorno-Tempini,et al.  Patterns of brain atrophy that differentiate corticobasal degeneration syndrome from progressive supranuclear palsy. , 2006, Archives of neurology.

[35]  B. Vogt,et al.  Contributions of anterior cingulate cortex to behaviour. , 1995, Brain : a journal of neurology.

[36]  S Minoshima,et al.  Diagnosis and management of dementia with Lewy bodies , 2005, Neurology.

[37]  Emma J. Burton,et al.  A comprehensive study of gray matter loss in patients with Alzheimer’s disease using optimized voxel-based morphometry , 2003, NeuroImage.

[38]  E. Rolls.  The functions of the orbitofrontal cortex , 1999, Brain and Cognition.

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

[40]  Norbert Schuff,et al.  Cinguloparietal atrophy distinguishes Alzheimer disease from semantic dementia. , 2003, Archives of neurology.

[41]  G. Frisoni,et al.  Detection of grey matter loss in mild Alzheimer's disease with voxel based morphometry , 2002, Journal of neurology, neurosurgery, and psychiatry.

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

[43]  Catherine Lomen-Hoerth,et al.  The overlap of amyotrophic lateral sclerosis and frontotemporal dementia , 2002, Neurology.

[44]  J. Allman,et al.  A neuronal morphologic type unique to humans and great apes. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[45]  J. R. Augustine.  Circuitry and functional aspects of the insular lobe in primates including humans , 1996, Brain Research Reviews.

[46]  Jesper Andersson,et al.  Valid conjunction inference with the minimum statistic , 2005, NeuroImage.

[47]  Kiralee M. Hayashi,et al.  The topography of grey matter involvement in early and late onset Alzheimer's disease. , 2007, Brain : a journal of neurology.

[48]  D. Neary,et al.  Behaviour in frontotemporal dementia, Alzheimer's disease and vascular dementia , 2001, Acta neurologica Scandinavica.

[49]  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.

[50]  K. Ishii,et al.  Voxel-based morphometric comparison between early- and late-onset mild Alzheimer's disease and assessment of diagnostic performance of z score images. , 2005, AJNR. American journal of neuroradiology.

[51]  Dick F Swaab,et al.  Pain processing in dementia and its relation to neuropathology , 2003, The Lancet Neurology.

[52]  E. Rolls,et al.  Emotion-related learning in patients with social and emotional changes associated with frontal lobe damage. , 1994, Journal of neurology, neurosurgery, and psychiatry.

[53]  Sandra E. Black,et al.  Topographical Patterns of Lobar Atrophy in Frontotemporal Dementia and Alzheimer’s Disease , 2006, Dementia and Geriatric Cognitive Disorders.

[54]  Fred L. Bookstein,et al.  “Voxel-Based Morphometry” Should Not Be Used with Imperfectly Registered Images , 2001, NeuroImage.

[55]  Nick C. Fox,et al.  Atrophy rates of the cingulate gyrus and hippocampus in AD and FTLD , 2007, Neurobiology of Aging.

[56]  D. Bowen,et al.  Regional weight loss of the cerebral cortex and some subcortical nuclei in senile dementia of the Alzheimer type , 2004, Acta Neuropathologica.

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

[58]  Sasha Bozeat,et al.  Which neuropsychiatric and behavioural features distinguish frontal and temporal variants of frontotemporal dementia from Alzheimer's disease? , 2000, Journal of neurology, neurosurgery, and psychiatry.

[59]  C. Jack,et al.  Patterns of atrophy in pathologically confirmed FTLD with and without motor neuron degeneration , 2006, Neurology.

[60]  J. Caviness.  Myoclonus and neurodegenerative disease--what's in a name? , 2003, Parkinsonism & related disorders.

[61]  J. Price,et al.  The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans. , 2000, Cerebral cortex.

[62]  B L Miller,et al.  Behavioral features in semantic dementia vs other forms of progressive aphasias , 2006, Neurology.

[63]  A. Damasio,et al.  The return of Phineas Gage: clues about the brain from the skull of a famous patient. , 1994, Science.

[64]  L A Hansen,et al.  Cognitive profiles differ in autopsy-confirmed frontotemporal dementia and AD , 2002, Neurology.

[65]  Alan C. Evans,et al.  Spatial patterns of cortical thinning in mild cognitive impairment and Alzheimer's disease. , 2006, Brain : a journal of neurology.

[66]  Bruce L. Miller,et al.  Ubiquitinated TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis , 2006, Science.

[67]  J. Hodges,et al.  Staging disease severity in pathologically confirmed cases of frontotemporal dementia , 2003, Neurology.

[68]  Andrew Kertesz,et al.  The evolution and pathology of frontotemporal dementia. , 2005, Brain : a journal of neurology.

[69]  Clifford R. Jack,et al.  Comparison of different methodological implementations of voxel-based morphometry in neurodegenerative disease , 2005, NeuroImage.

[70]  Martin Rossor,et al.  Measurements of the amygdala and hippocampus in pathologically confirmed Alzheimer disease and frontotemporal lobar degeneration. , 2006, Archives of neurology.

[71]  B. Sahakian,et al.  Differing patterns of temporal atrophy in Alzheimer’s disease and semantic dementia , 2001, Neurology.

[72]  T. Robbins,et al.  Comparative Cognitive Neuropsychological Studies of Frontal Lobe Function: Implications for Therapeutic Strategies in Frontal Variant Frontotemporal Dementia , 1999, Dementia and Geriatric Cognitive Disorders.

[73]  D. Amaral,et al.  Macaque monkey retrosplenial cortex: II. Cortical afferents , 2003, The Journal of comparative neurology.

[74]  M. Laakso,et al.  Amygdaloid atrophy in frontotemporal dementia and Alzheimer's disease , 2002, Neuroscience Letters.

[75]  Guido F. Schauer,et al.  Neuroanatomical correlates of behavioural disorders in dementia. , 2005, Brain : a journal of neurology.

[76]  H. Matsuda,et al.  Comparison of the diagnostic performance of FDG-PET and VBM-MRI in very mild Alzheimer’s disease , 2006, European Journal of Nuclear Medicine and Molecular Imaging.

[77]  M. Mesulam,et al.  From sensation to cognition. , 1998, Brain : a journal of neurology.

[78]  C. Economo,et al.  Eine neue art spezialzellen des lobus cinguli und lobus insulae , 1926 .

[79]  A. Kertesz,et al.  Volumetric study of lobar atrophy in Pick complex and Alzheimer’s disease , 2000, Journal of the Neurological Sciences.

[80]  G. Glover,et al.  Dissociable Intrinsic Connectivity Networks for Salience Processing and Executive Control , 2007, The Journal of Neuroscience.

[81]  Alberto Beltramello,et al.  A comparison between the accuracy of voxel‐based morphometry and hippocampal volumetry in Alzheimer's disease , 2004, Journal of magnetic resonance imaging : JMRI.

[82]  Clifford R Jack,et al.  Voxel-based morphometry in frontotemporal lobar degeneration with ubiquitin-positive inclusions with and without progranulin mutations. , 2007, Archives of neurology.

[83]  S. Baron-Cohen,et al.  Theory of mind in patients with frontal variant frontotemporal dementia and Alzheimer's disease: theoretical and practical implications. , 2002, Brain : a journal of neurology.

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

[85]  Nick C Fox,et al.  Amyloid, hypometabolism, and cognition in Alzheimer disease , 2007, Neurology.

[86]  K. Kosaka,et al.  Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB) , 1996, Neurology.

[87]  Karl J. Friston,et al.  Cerebral Asymmetry and the Effects of Sex and Handedness on Brain Structure: A Voxel-Based Morphometric Analysis of 465 Normal Adult Human Brains , 2001, NeuroImage.

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

[89]  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.

[90]  Nick C Fox,et al.  Mapping the evolution of regional atrophy in Alzheimer's disease: Unbiased analysis of fluid-registered serial MRI , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[91]  B. Sahakian,et al.  Temporal lobe rating scale: application to Alzheimer's disease and frontotemporal dementia , 2001, Journal of neurology, neurosurgery, and psychiatry.

[92]  K. Heilman,et al.  Relative Frequencies of Alzheimer Disease, Lewy Body, Vascular and Frontotemporal Dementia, and Hippocampal Sclerosis in the State of Florida Brain Bank , 2002, Alzheimer disease and associated disorders.

[93]  Nick C Fox,et al.  Magnetic resonance imaging signatures of tissue pathology in frontotemporal dementia. , 2005, Archives of neurology.

[94]  Marina Boccardi,et al.  Frontotemporal dementia as a neural system disease , 2005, Neurobiology of Aging.

[95]  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.

[96]  Benjamin J. Shannon,et al.  Functional-Anatomic Correlates of Memory Retrieval That Suggest Nontraditional Processing Roles for Multiple Distinct Regions within Posterior Parietal Cortex , 2004, The Journal of Neuroscience.