title: Trajectories of brain and hippocampal atrophy in FTD with mutations in MAPT or GRN.
abstract: OBJECTIVE
  To use multiple serial MRI to assess rates and trajectories of brain and hippocampal atrophy in subjects with frontotemporal dementia (FTD) with progranulin (GRN) or microtubule-associated protein tau (MAPT) gene mutations.
  
  
  METHODS
  In this case-control study, we identified 8 subjects with mutations in GRN and 12 subjects with mutations in MAPT who had at least 2 serial MRIs. Serial MRIs were registered to baseline MRI for each subject using 9 df registration and rate of whole brain atrophy was calculated using the boundary-shift integral. Hippocampal volume was measured using Freesurfer. Mixed effects linear regression models were used to model volume change over time in both groups after adjusting for head size, age at baseline, and disease duration at baseline.
  
  
  RESULTS
  The annual rate of whole brain atrophy in the MAPT subjects was 2.4% per year (95% confidence interval [CI] 1.9-2.8). The GRN subjects showed a higher rate of whole brain atrophy at 3.5% per year (95% CI 2.8-4.2; p = 0.01). Rates of hippocampal atrophy were not different across the groups (MAPT = 7.8% [95% CI 3.9-12], GRN = 6.5% [95% CI 1.7-11], p = 0.66). Rates of whole brain atrophy in GRN, and hippocampal atrophy in MAPT, were associated with age, with older subjects showing slower rates of atrophy (p = 0.01 and p < 0.001).
  
  
  CONCLUSIONS
  Subjects with FTD with GRN mutations have a faster rate of whole brain atrophy than subjects with FTD with MAPT mutations, with similar rates of hippocampal atrophy. Rates of atrophy in both groups were associated with age. These findings are important for future treatment trials in FTD that use rates of atrophy as an outcome measure.
authors.affiliation: Department of Radiology, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA. Whitwell.jennifer@mayo.edu
authors.forename: J L
authors.initials: JL
authors.lastname: Whitwell
authors.forename: S D
authors.initials: SD
authors.lastname: Weigand
authors.forename: J L
authors.initials: JL
authors.lastname: Gunter
authors.forename: B F
authors.initials: BF
authors.lastname: Boeve
authors.forename: R
authors.initials: R
authors.lastname: Rademakers
authors.forename: M
authors.initials: M
authors.lastname: Baker
authors.forename: D S
authors.initials: DS
authors.lastname: Knopman
authors.forename: Z K
authors.initials: ZK
authors.lastname: Wszolek
authors.forename: R C
authors.initials: RC
authors.lastname: Petersen
authors.forename: C R
authors.initials: CR
authors.lastname: Jack
authors.forename: K A
authors.initials: KA
authors.lastname: Josephs
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001284:Atrophy / Q000473:pathology; D001921:Brain / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D057180:Frontotemporal Dementia / Q000235:genetics / Q000473:pathology*; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D016014:Linear Models; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000077153:Progranulins; D016875:tau Proteins / Q000235:genetics*
chemical_list: C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; C054369:MAPT protein, human; D000077153:Progranulins; D016875:tau Proteins