title: Cognition and neuropsychiatry in behavioral variant frontotemporal dementia by disease stage.
abstract: OBJECTIVE
  To characterize the cognitive and neuropsychiatric symptoms of patients with behavioral variant frontotemporal dementia (bvFTD) over the natural course of the disease.
  
  
  METHODS
  We examined the initial and subsequent neuropsychological test performance and neuropsychiatric symptoms in a large cohort of patients with bvFTD (n = 204) across progressive stages of disease as measured by the Clinical Dementia Rating (CDR). We also compared cognitive and neuropsychiatric impairments of patients with bvFTD to those of an age-matched cohort with Alzheimer disease (AD) dementia (n = 674).
  
  
  RESULTS
  At the earliest stage (CDR = 0.5), patients with bvFTD had profound neuropsychiatric disturbances, insensitivity to errors, slower response times, and poor naming, with intact attention span, memory, and facial affect naming. Tests continuing to show progressive, statistically significant stepwise declines after the CDR = 1 stage included free recall, visuoconstruction, set-shifting, error insensitivity, semantic fluency, design fluency, emotion naming, calculations, confrontation naming, syntax comprehension, and verbal agility. At CDR = 0.5, patients with bvFTD significantly outperformed patients with AD in episodic memory and were faster in set-shifting, while scoring quantitatively worse in lexical fluency, emotion naming, and error sensitivity. The overall rate of disease progression in bvFTD was more rapid than in AD.
  
  
  CONCLUSIONS
  There are distinct patterns of cognitive deficits differentiating the earlier and later disease stages in bvFTD, with the pattern of cognitive decline revealing in greater detail the natural history of the disease. These cognitive symptoms are readily apparent clinical markers of dysfunction in the principal brain networks known to undergo molecular and anatomical changes in bvFTD, thus are important indicators of the evolving pathology in individual patients.
authors.affiliation: From the Memory and Aging Center (K.G.R., K.P.R., I.V.L., J.H.K., V.E.S., B.M.B., K.P., S.C.Y., A.K.L., T.S.-U., M.L.S., D.C.P., S.E.L., Z.A.M., M.L.G.-T., H.J.R., A.B., W.W.S., G.D.R., K.A.V., B.L.M.), Department of Neurology, University of California, San Francisco; Departments of Neurosurgery and Neurology (B.M.B.), University of Colorado Anschutz School of Medicine, Aurora; and Gladstone Institute of Neurological Disease (K.A.V.), CA.
authors.forename: Kamalini G
authors.initials: KG
authors.lastname: Ranasinghe
authors.affiliation: From the Memory and Aging Center (K.G.R., K.P.R., I.V.L., J.H.K., V.E.S., B.M.B., K.P., S.C.Y., A.K.L., T.S.-U., M.L.S., D.C.P., S.E.L., Z.A.M., M.L.G.-T., H.J.R., A.B., W.W.S., G.D.R., K.A.V., B.L.M.), Department of Neurology, University of California, San Francisco; Departments of Neurosurgery and Neurology (B.M.B.), University of Colorado Anschutz School of Medicine, Aurora; and Gladstone Institute of Neurological Disease (K.A.V.), CA. krankin@memory.ucsf.edu.
authors.forename: Katherine P
authors.initials: KP
authors.lastname: Rankin
authors.affiliation: From the Memory and Aging Center (K.G.R., K.P.R., I.V.L., J.H.K., V.E.S., B.M.B., K.P., S.C.Y., A.K.L., T.S.-U., M.L.S., D.C.P., S.E.L., Z.A.M., M.L.G.-T., H.J.R., A.B., W.W.S., G.D.R., K.A.V., B.L.M.), Department of Neurology, University of California, San Francisco; Departments of Neurosurgery and Neurology (B.M.B.), University of Colorado Anschutz School of Medicine, Aurora; and Gladstone Institute of Neurological Disease (K.A.V.), CA.
authors.forename: Iryna V
authors.initials: IV
authors.lastname: Lobach
authors.affiliation: From the Memory and Aging Center (K.G.R., K.P.R., I.V.L., J.H.K., V.E.S., B.M.B., K.P., S.C.Y., A.K.L., T.S.-U., M.L.S., D.C.P., S.E.L., Z.A.M., M.L.G.-T., H.J.R., A.B., W.W.S., G.D.R., K.A.V., B.L.M.), Department of Neurology, University of California, San Francisco; Departments of Neurosurgery and Neurology (B.M.B.), University of Colorado Anschutz School of Medicine, Aurora; and Gladstone Institute of Neurological Disease (K.A.V.), CA.
authors.forename: Joel H
authors.initials: JH
authors.lastname: Kramer
authors.affiliation: From the Memory and Aging Center (K.G.R., K.P.R., I.V.L., J.H.K., V.E.S., B.M.B., K.P., S.C.Y., A.K.L., T.S.-U., M.L.S., D.C.P., S.E.L., Z.A.M., M.L.G.-T., H.J.R., A.B., W.W.S., G.D.R., K.A.V., B.L.M.), Department of Neurology, University of California, San Francisco; Departments of Neurosurgery and Neurology (B.M.B.), University of Colorado Anschutz School of Medicine, Aurora; and Gladstone Institute of Neurological Disease (K.A.V.), CA.
authors.forename: Virginia E
authors.initials: VE
authors.lastname: Sturm
authors.affiliation: From the Memory and Aging Center (K.G.R., K.P.R., I.V.L., J.H.K., V.E.S., B.M.B., K.P., S.C.Y., A.K.L., T.S.-U., M.L.S., D.C.P., S.E.L., Z.A.M., M.L.G.-T., H.J.R., A.B., W.W.S., G.D.R., K.A.V., B.L.M.), Department of Neurology, University of California, San Francisco; Departments of Neurosurgery and Neurology (B.M.B.), University of Colorado Anschutz School of Medicine, Aurora; and Gladstone Institute of Neurological Disease (K.A.V.), CA.
authors.forename: Brianne M
authors.initials: BM
authors.lastname: Bettcher
authors.affiliation: From the Memory and Aging Center (K.G.R., K.P.R., I.V.L., J.H.K., V.E.S., B.M.B., K.P., S.C.Y., A.K.L., T.S.-U., M.L.S., D.C.P., S.E.L., Z.A.M., M.L.G.-T., H.J.R., A.B., W.W.S., G.D.R., K.A.V., B.L.M.), Department of Neurology, University of California, San Francisco; Departments of Neurosurgery and Neurology (B.M.B.), University of Colorado Anschutz School of Medicine, Aurora; and Gladstone Institute of Neurological Disease (K.A.V.), CA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Possin
authors.affiliation: From the Memory and Aging Center (K.G.R., K.P.R., I.V.L., J.H.K., V.E.S., B.M.B., K.P., S.C.Y., A.K.L., T.S.-U., M.L.S., D.C.P., S.E.L., Z.A.M., M.L.G.-T., H.J.R., A.B., W.W.S., G.D.R., K.A.V., B.L.M.), Department of Neurology, University of California, San Francisco; Departments of Neurosurgery and Neurology (B.M.B.), University of Colorado Anschutz School of Medicine, Aurora; and Gladstone Institute of Neurological Disease (K.A.V.), CA.
authors.forename: S
authors.initials: S
authors.lastname: Christine You
authors.affiliation: From the Memory and Aging Center (K.G.R., K.P.R., I.V.L., J.H.K., V.E.S., B.M.B., K.P., S.C.Y., A.K.L., T.S.-U., M.L.S., D.C.P., S.E.L., Z.A.M., M.L.G.-T., H.J.R., A.B., W.W.S., G.D.R., K.A.V., B.L.M.), Department of Neurology, University of California, San Francisco; Departments of Neurosurgery and Neurology (B.M.B.), University of Colorado Anschutz School of Medicine, Aurora; and Gladstone Institute of Neurological Disease (K.A.V.), CA.
authors.forename: Amanda K
authors.initials: AK
authors.lastname: Lamarre
authors.affiliation: From the Memory and Aging Center (K.G.R., K.P.R., I.V.L., J.H.K., V.E.S., B.M.B., K.P., S.C.Y., A.K.L., T.S.-U., M.L.S., D.C.P., S.E.L., Z.A.M., M.L.G.-T., H.J.R., A.B., W.W.S., G.D.R., K.A.V., B.L.M.), Department of Neurology, University of California, San Francisco; Departments of Neurosurgery and Neurology (B.M.B.), University of Colorado Anschutz School of Medicine, Aurora; and Gladstone Institute of Neurological Disease (K.A.V.), CA.
authors.forename: Tal
authors.initials: T
authors.lastname: Shany-Ur
authors.affiliation: From the Memory and Aging Center (K.G.R., K.P.R., I.V.L., J.H.K., V.E.S., B.M.B., K.P., S.C.Y., A.K.L., T.S.-U., M.L.S., D.C.P., S.E.L., Z.A.M., M.L.G.-T., H.J.R., A.B., W.W.S., G.D.R., K.A.V., B.L.M.), Department of Neurology, University of California, San Francisco; Departments of Neurosurgery and Neurology (B.M.B.), University of Colorado Anschutz School of Medicine, Aurora; and Gladstone Institute of Neurological Disease (K.A.V.), CA.
authors.forename: Melanie L
authors.initials: ML
authors.lastname: Stephens
authors.affiliation: From the Memory and Aging Center (K.G.R., K.P.R., I.V.L., J.H.K., V.E.S., B.M.B., K.P., S.C.Y., A.K.L., T.S.-U., M.L.S., D.C.P., S.E.L., Z.A.M., M.L.G.-T., H.J.R., A.B., W.W.S., G.D.R., K.A.V., B.L.M.), Department of Neurology, University of California, San Francisco; Departments of Neurosurgery and Neurology (B.M.B.), University of Colorado Anschutz School of Medicine, Aurora; and Gladstone Institute of Neurological Disease (K.A.V.), CA.
authors.forename: David C
authors.initials: DC
authors.lastname: Perry
authors.affiliation: From the Memory and Aging Center (K.G.R., K.P.R., I.V.L., J.H.K., V.E.S., B.M.B., K.P., S.C.Y., A.K.L., T.S.-U., M.L.S., D.C.P., S.E.L., Z.A.M., M.L.G.-T., H.J.R., A.B., W.W.S., G.D.R., K.A.V., B.L.M.), Department of Neurology, University of California, San Francisco; Departments of Neurosurgery and Neurology (B.M.B.), University of Colorado Anschutz School of Medicine, Aurora; and Gladstone Institute of Neurological Disease (K.A.V.), CA.
authors.forename: Suzee E
authors.initials: SE
authors.lastname: Lee
authors.affiliation: From the Memory and Aging Center (K.G.R., K.P.R., I.V.L., J.H.K., V.E.S., B.M.B., K.P., S.C.Y., A.K.L., T.S.-U., M.L.S., D.C.P., S.E.L., Z.A.M., M.L.G.-T., H.J.R., A.B., W.W.S., G.D.R., K.A.V., B.L.M.), Department of Neurology, University of California, San Francisco; Departments of Neurosurgery and Neurology (B.M.B.), University of Colorado Anschutz School of Medicine, Aurora; and Gladstone Institute of Neurological Disease (K.A.V.), CA.
authors.forename: Zachary A
authors.initials: ZA
authors.lastname: Miller
authors.affiliation: From the Memory and Aging Center (K.G.R., K.P.R., I.V.L., J.H.K., V.E.S., B.M.B., K.P., S.C.Y., A.K.L., T.S.-U., M.L.S., D.C.P., S.E.L., Z.A.M., M.L.G.-T., H.J.R., A.B., W.W.S., G.D.R., K.A.V., B.L.M.), Department of Neurology, University of California, San Francisco; Departments of Neurosurgery and Neurology (B.M.B.), University of Colorado Anschutz School of Medicine, Aurora; and Gladstone Institute of Neurological Disease (K.A.V.), CA.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Gorno-Tempini
authors.affiliation: From the Memory and Aging Center (K.G.R., K.P.R., I.V.L., J.H.K., V.E.S., B.M.B., K.P., S.C.Y., A.K.L., T.S.-U., M.L.S., D.C.P., S.E.L., Z.A.M., M.L.G.-T., H.J.R., A.B., W.W.S., G.D.R., K.A.V., B.L.M.), Department of Neurology, University of California, San Francisco; Departments of Neurosurgery and Neurology (B.M.B.), University of Colorado Anschutz School of Medicine, Aurora; and Gladstone Institute of Neurological Disease (K.A.V.), CA.
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Rosen
authors.affiliation: From the Memory and Aging Center (K.G.R., K.P.R., I.V.L., J.H.K., V.E.S., B.M.B., K.P., S.C.Y., A.K.L., T.S.-U., M.L.S., D.C.P., S.E.L., Z.A.M., M.L.G.-T., H.J.R., A.B., W.W.S., G.D.R., K.A.V., B.L.M.), Department of Neurology, University of California, San Francisco; Departments of Neurosurgery and Neurology (B.M.B.), University of Colorado Anschutz School of Medicine, Aurora; and Gladstone Institute of Neurological Disease (K.A.V.), CA.
authors.forename: Adam
authors.initials: A
authors.lastname: Boxer
authors.affiliation: From the Memory and Aging Center (K.G.R., K.P.R., I.V.L., J.H.K., V.E.S., B.M.B., K.P., S.C.Y., A.K.L., T.S.-U., M.L.S., D.C.P., S.E.L., Z.A.M., M.L.G.-T., H.J.R., A.B., W.W.S., G.D.R., K.A.V., B.L.M.), Department of Neurology, University of California, San Francisco; Departments of Neurosurgery and Neurology (B.M.B.), University of Colorado Anschutz School of Medicine, Aurora; and Gladstone Institute of Neurological Disease (K.A.V.), CA.
authors.forename: William W
authors.initials: WW
authors.lastname: Seeley
authors.affiliation: From the Memory and Aging Center (K.G.R., K.P.R., I.V.L., J.H.K., V.E.S., B.M.B., K.P., S.C.Y., A.K.L., T.S.-U., M.L.S., D.C.P., S.E.L., Z.A.M., M.L.G.-T., H.J.R., A.B., W.W.S., G.D.R., K.A.V., B.L.M.), Department of Neurology, University of California, San Francisco; Departments of Neurosurgery and Neurology (B.M.B.), University of Colorado Anschutz School of Medicine, Aurora; and Gladstone Institute of Neurological Disease (K.A.V.), CA.
authors.forename: Gil D
authors.initials: GD
authors.lastname: Rabinovici
authors.affiliation: From the Memory and Aging Center (K.G.R., K.P.R., I.V.L., J.H.K., V.E.S., B.M.B., K.P., S.C.Y., A.K.L., T.S.-U., M.L.S., D.C.P., S.E.L., Z.A.M., M.L.G.-T., H.J.R., A.B., W.W.S., G.D.R., K.A.V., B.L.M.), Department of Neurology, University of California, San Francisco; Departments of Neurosurgery and Neurology (B.M.B.), University of Colorado Anschutz School of Medicine, Aurora; and Gladstone Institute of Neurological Disease (K.A.V.), CA.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Vossel
authors.affiliation: From the Memory and Aging Center (K.G.R., K.P.R., I.V.L., J.H.K., V.E.S., B.M.B., K.P., S.C.Y., A.K.L., T.S.-U., M.L.S., D.C.P., S.E.L., Z.A.M., M.L.G.-T., H.J.R., A.B., W.W.S., G.D.R., K.A.V., B.L.M.), Department of Neurology, University of California, San Francisco; Departments of Neurosurgery and Neurology (B.M.B.), University of Colorado Anschutz School of Medicine, Aurora; and Gladstone Institute of Neurological Disease (K.A.V.), CA.
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Miller
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000523:psychology; D003071:Cognition; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D057180:Frontotemporal Dementia / Q000175:diagnosis / Q000503:physiopathology / Q000523:psychology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D012720:Severity of Illness Index; D012727:Sex Characteristics; D055815:Young Adult