title: Cognitive impairment in the preclinical stage of dementia in FTD-3 CHMP2B mutation carriers: a longitudinal prospective study.
abstract: OBJECTIVE
  A longitudinal study spanning over 8 years and including 17 asymptomatic individuals with CHMP2B mutations was conducted to assess the earliest neuropsychological changes in autosomal dominant neurodegenerative disease frontotemporal dementia (FTD) linked to chromosome 3 (FTD-3). Subjects were assessed with neuropsychological tests in 2002, 2005 and 2010.
  
  
  RESULTS
  Cross-sectional analyses showed that the mutation carriers scored lower on tests of psychomotor speed, working memory, executive functions and verbal memory than a control group consisting of not-at-risk family members and spouses. Longitudinal analyses showed a gradual decline in psychomotor speed, working memory capacity and global executive measures in the group of non-demented mutation carriers that was not found in the control group. In contrast, there were no significant group differences in domain scores on memory or visuospatial functions. On an individual level the cognitive changes over time varied considerably.
  
  
  CONCLUSIONS
  Subjects with CHMP2B mutation show cognitive changes dominated by executive dysfunctions, years before they fulfil diagnostic criteria of FTD. However, there is great heterogeneity in the individual cognitive trajectories.
authors.affiliation: Memory Disorders Research Group, Department of Neurology, Rigshospitalet, Copenhagen University Hospital, N6702, 9 Blegdamsvej, Copenhagen 2100, Denmark. jette.stokholm@rh.regionh.dk
authors.forename: Jette
authors.initials: J
authors.lastname: Stokholm
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Teasdale
authors.forename: Peter
authors.initials: P
authors.lastname: Johannsen
authors.forename: Jorgen E
authors.initials: JE
authors.lastname: Nielsen
authors.forename: Troels Tolstrup
authors.initials: TT
authors.lastname: Nielsen
authors.forename: Adrian
authors.initials: A
authors.lastname: Isaacs
authors.forename: Jerry M
authors.initials: JM
authors.lastname: Brown
authors.forename: Anders
authors.initials: A
authors.lastname: Gade
mesh_terms: D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D003072:Cognition Disorders / Q000150:complications / Q000235:genetics*; D003430:Cross-Sectional Studies; D042241:Early Diagnosis; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics*; D056344:Executive Function; D005260:Female; D057180:Frontotemporal Dementia / Q000235:genetics / Q000523:psychology*; D006579:Heterozygote; D006801:Humans; D008137:Longitudinal Studies / Q000706:statistics & numerical data; D008297:Male; D008570:Memory, Short-Term; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D011446:Prospective Studies; D011597:Psychomotor Performance; D014706:Verbal Learning
chemical_list: C503812:CHMP2B protein, human; D056827:Endosomal Sorting Complexes Required for Transport