Frontal Paralimbic Network Atrophy in Very Mild Behavioral Variant Frontotemporal Dementia | Dementia and Cognitive Impairment | JAMA Neurology | JAMA Network
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Neary  DSnowden  JSGustafson  L  et al.  Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria.  Neurology 1998;51 (6) 1546- 1554PubMedGoogle Scholar
Rosen  HJGorno-Tempini  MLGoldman  WP  et al.  Patterns of brain atrophy in frontotemporal dementia and semantic dementia.  Neurology 2002;58 (2) 198- 208PubMedGoogle Scholar
Rascovsky  KSalmon  DPLipton  AM  et al.  Rate of progression differs in frontotemporal dementia and Alzheimer disease.  Neurology 2005;65 (3) 397- 403PubMedGoogle Scholar
Roberson  EDHesse  JHRose  KD  et al.  Frontotemporal dementia progresses to death faster than Alzheimer disease.  Neurology 2005;65 (5) 719- 725PubMedGoogle Scholar
Hodges  JRDavies  RXuereb  JKril  JHalliday  G Survival in frontotemporal dementia.  Neurology 2003;61 (3) 349- 354PubMedGoogle Scholar
Boccardi  MSabattoli  FLaakso  MP  et al.  Frontotemporal dementia as a neural system disease.  Neurobiol Aging 2005;26 (1) 37- 44PubMedGoogle Scholar
Whitwell  JLJack  CR  JrSenjem  MLJosephs  KA Patterns of atrophy in pathologically confirmed FTLD with and without motor neuron degeneration.  Neurology 2006;66 (1) 102- 104PubMedGoogle Scholar
Ibach  BPoljansky  SMarienhagen  JSommer  MManner  PHajak  G Contrasting metabolic impairment in frontotemporal degeneration and early onset Alzheimer's disease.  Neuroimage 2004;23 (2) 739- 743PubMedGoogle Scholar
Varrone  APappata  SCaraco  C  et al.  Voxel-based comparison of rCBF SPET images in frontotemporal dementia and Alzheimer's disease highlights the involvement of different cortical networks.  Eur J Nucl Med Mol Imaging 2002;29 (11) 1447- 1454PubMedGoogle Scholar
Hyman  BTDamasio  AR Hierarchical vulnerability of the entorhinal cortex and the hippocampal formation to Alzheimer neuropathological changes: a semiquantitative study.  Neurology 1990;40403Google Scholar
Perry  RJGraham  AWilliams  G  et al.  Patterns of frontal lobe atrophy in frontotemporal dementia: a volumetric MRI study.  Dement Geriatr Cogn Disord 2006;22 (4) 278- 287PubMedGoogle Scholar
Davies  RRKipps  CMMitchell  JKril  JJHalliday  GMHodges  JR Progression in frontotemporal dementia: identifying a benign behavioral variant by magnetic resonance imaging.  Arch Neurol 2006;63 (11) 1627- 1631PubMedGoogle Scholar
Ishii  KSakamoto  SSasaki  M  et al.  Cerebral glucose metabolism in patients with frontotemporal dementia.  J Nucl Med 1998;39 (11) 1875- 1878PubMedGoogle Scholar
Franceschi  MAnchisi  DPelati  O  et al.  Glucose metabolism and serotonin receptors in the frontotemporal lobe degeneration.  Ann Neurol 2005;57 (2) 216- 225PubMedGoogle Scholar
Schroeter  MLRaczka  KNeumann  Jvon Cramon  DY Neural networks in frontotemporal dementia: a meta-analysis [published online ahead of print, November 29, 2006].  Neurobiol Aging doi:10.1016/j.neurobiolaging.2006.10.023.17140704PubMedGoogle Scholar
Broe  MHodges  JRSchofield  EShepherd  CEKril  JJHalliday  GM Staging disease severity in pathologically confirmed cases of frontotemporal dementia.  Neurology 2003;60 (6) 1005- 1011PubMedGoogle Scholar
Alberici  AGobbo  CPanzacchi  A  et al.  Frontotemporal dementia: impact of P301L tau mutation on a healthy carrier.  J Neurol Neurosurg Psychiatry 2004;75 (11) 1607- 1610PubMedGoogle Scholar
Seeley  WWCarlin  DAAllman  JM  et al.  Early frontotemporal dementia targets neurons unique to apes and humans.  Ann Neurol 2006;60 (6) 660- 667PubMedGoogle Scholar
Morris  JC The Clinical Dementia Rating (CDR): current version and scoring rules.  Neurology 1993;43 (11) 2412- 2414PubMedGoogle Scholar
Good  CDJohnsrude  ISAshburner  JHenson  RNFriston  KJFrackowiak  RS A voxel-based morphometric study of ageing in 465 normal adult human brains.  Neuroimage 2001;14 (1, pt 1) 21- 36PubMedGoogle Scholar
Brun  AGustafson  L Limbic lobe involvement in presenile dementia.  Arch Psychiatr Nervenkr 1978;226 (2) 79- 93PubMedGoogle Scholar
Kril  JJMacdonald  VPatel  SPng  FHalliday  GM Distribution of brain atrophy in behavioral variant frontotemporal dementia.  J Neurol Sci 2005;232 (1-2) 83- 90PubMedGoogle Scholar
Nimchinsky  EAGilissen  EAllman  JMPerl  DPErwin  JMHof  PR A neuronal morphologic type unique to humans and great apes.  Proc Natl Acad Sci U S A 1999;96 (9) 5268- 5273PubMedGoogle Scholar
Hof  PRVan Der Gucht  E Structure of the cerebral cortex of the humpback whale, Megaptera novaeangliae (Cetacea, Mysticeti, Balaenopteridae) [published online ahead of print, November 27, 2006].  Anat Rec A Discov Mol Cell Evol Biol PubMedGoogle Scholar
Allman  JMWatson  KKTetreault  NAHakeem  AY Intuition and autism: a possible role for von Economo neurons.  Trends Cogn Sci 2005;9 (8) 367- 373PubMedGoogle Scholar
von Economo  C Eine neue Art Spezialzellen des Lobus cinguli und Lobus insulae.  Z Ges Neurol Psychiatr 1926;100706- 712Google Scholar
Beckmann  CFDeLuca  MDevlin  JTSmith  SM Investigations into resting-state connectivity using independent component analysis.  Philos Trans R Soc Lond B Biol Sci 2005;360 (1457) 1001- 1013PubMedGoogle Scholar
Seeley  WWMenon  VSchatzberg  AF  et al.  Dissociable intrinsic connectivity networks for salience processing and executive control.  J Neurosci 2007;27 (9) 2349- 2356PubMedGoogle Scholar
Diehl-Schmid  JGrimmer  TDrzezga  A  et al.  Decline of cerebral glucose metabolism in frontotemporal dementia: a longitudinal 18F-FDG-PET-study.  Neurobiol Aging 2007;28 (1) 48- 50PubMedGoogle Scholar
Chan  DFox  NCJenkins  RScahill  RICrum  WRRossor  MN Rates of global and regional cerebral atrophy in AD and frontotemporal dementia.  Neurology 2001;57 (10) 1756- 1763PubMedGoogle Scholar
Kitagaki  HMori  EHirono  N  et al.  Alteration of white matter MR signal intensity in frontotemporal dementia.  AJNR Am J Neuroradiol 1997;18 (2) 367- 378PubMedGoogle Scholar
Yoshiura  TMihara  FKoga  H  et al.  Cerebral white matter degeneration in frontotemporal dementia detected by diffusion-weighted magnetic resonance imaging.  Acad Radiol 2006;13 (11) 1373- 1378PubMedGoogle Scholar
Borroni  BBrambati  SMAgosti  C  et al.  Evidence of white matter changes on diffusion tensor imaging in frontotemporal dementia.  Arch Neurol 2007;64 (2) 246- 251PubMedGoogle Scholar
Whitwell  JLAnderson  VMScahill  RIRossor  MNFox  NC Longitudinal patterns of regional change on volumetric MRI in frontotemporal lobar degeneration.  Dement Geriatr Cogn Disord 2004;17 (4) 307- 310PubMedGoogle Scholar
Avants  BGrossman  MGee  JC The correlation of cognitive decline with frontotemporal dementia induced annualized gray matter loss using diffeomorphic morphometry.  Alzheimer Dis Assoc Disord 2005;19 ((suppl 1)) S25- S28PubMedGoogle Scholar
Brambati  SMRenda  NCRankin  KP  et al.  A tensor based morphometry study of longitudinal gray matter contraction in FTD.  Neuroimage 2007;35 (3) 998- 1003PubMedGoogle Scholar
Bocti  CRockel  CRoy  PGao  FBlack  SE Topographical patterns of lobar atrophy in frontotemporal dementia and Alzheimer's disease.  Dement Geriatr Cogn Disord 2006;21 (5-6) 364- 372PubMedGoogle Scholar
Galton  CJGomez-Anson  BAntoun  N  et al.  Temporal lobe rating scale: application to Alzheimer's disease and frontotemporal dementia.  J Neurol Neurosurg Psychiatry 2001;70 (2) 165- 173PubMedGoogle Scholar
Seeley  WWBauer  AMMiller  BL  et al.  The natural history of temporal variant frontotemporal dementia.  Neurology 2005;64 (8) 1384- 1390PubMedGoogle Scholar
Thompson  SAPatterson  KHodges  JR Left/right asymmetry of atrophy in semantic dementia: behavioral-cognitive implications.  Neurology 2003;61 (9) 1196- 1203PubMedGoogle Scholar
Mesulam  MMMufson  EJ Insula of the old world monkey, III: Efferent cortical output and comments on function.  J Comp Neurol 1982;212 (1) 38- 52PubMedGoogle Scholar
Critchley  HD Neural mechanisms of autonomic, affective, and cognitive integration.  J Comp Neurol 2005;493 (1) 154- 166PubMedGoogle Scholar
MacDonald  AW  IIICohen  JDStenger  VACarter  CS Dissociating the role of the dorsolateral prefrontal and anterior cingulate cortex in cognitive control.  Science 2000;288 (5472) 1835- 1838PubMedGoogle Scholar
Original Contribution
February 2008

Frontal Paralimbic Network Atrophy in Very Mild Behavioral Variant Frontotemporal Dementia

Author Affiliations

Author Affiliations: Department of Neurology and Memory and Aging Center (Drs Seeley, Rascovsky, Kramer, Miller, and Gorno-Tempini and Mr Crawford) and Department of Radiology and San Francisco Veterans Affairs Hospital Magnetic Resonance Imaging Unit (Dr Weiner), University of California at San Francisco.

Arch Neurol. 2008;65(2):249-255. doi:10.1001/archneurol.2007.38

Background  Behavioral variant frontotemporal dementia (bvFTD) strikes hardest at the frontal lobes, but the sites of earliest injury remain unclear.

Objective  To determine atrophy patterns in distinct clinical stages of bvFTD, testing the hypothesis that the mildest stage is restricted to frontal paralimbic cortex.

Design  A bvFTD cohort study.

Setting  University hospital dementia clinic.

Participants  Patients with bvFTD with Clinical Dementia Rating (CDR) scale scores of 0.5 (n = 15), 1 (n = 15), or 2 to 3 (n = 15) age and sex matched to each other and to 45 healthy controls.

Main Outcome Measures  Magnetic resonance voxel-based morphometry estimated gray matter and white matter atrophy at each disease stage compared with controls.

Results  Patients with a CDR score of 0.5 had gray matter loss in frontal paralimbic cortices, but atrophy also involved a network of anterior cortical and subcortical regions. A CDR score of 1 showed more extensive frontal gray matter atrophy and white matter losses in corpus callosum and brainstem. A CDR score of 2 to 3 showed additional posterior insula, hippocampus, and parietal involvement, with white matter atrophy in presumed frontal projection fibers.

Conclusions  Very mild bvFTD targets a specific subset of frontal and insular regions. More advanced disease affects white matter and posterior gray matter structures densely interconnected with the sites of earliest injury.