title: Age-related changes in the default mode network are more advanced in Alzheimer disease.
abstract: OBJECTIVE
  To investigate age-related default mode network (DMN) connectivity in a large cognitively normal elderly cohort and in patients with Alzheimer disease (AD) compared with age-, gender-, and education-matched controls.
  
  
  METHODS
  We analyzed task-free-fMRI data with both independent component analysis and seed-based analysis to identify anterior and posterior DMNs. We investigated age-related changes in connectivity in a sample of 341 cognitively normal subjects. We then compared 28 patients with AD with 56 cognitively normal noncarriers of the APOE ε4 allele matched for age, education, and gender.
  
  
  RESULTS
  The anterior DMN shows age-associated increases and decreases in fontal lobe connectivity, whereas the posterior DMN shows mainly age-associated declines in connectivity throughout. Relative to matched cognitively normal controls, subjects with AD display an accelerated pattern of the age-associated changes described above, except that the declines in frontal lobe connectivity did not reach statistical significance. These changes survive atrophy correction and are correlated with cognitive performance.
  
  
  CONCLUSIONS
  The results of this study indicate that the DMN abnormalities observed in patients with AD represent an accelerated aging pattern of connectivity compared with matched controls.
authors.affiliation: Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: D T
authors.initials: DT
authors.lastname: Jones
authors.forename: M M
authors.initials: MM
authors.lastname: Machulda
authors.forename: P
authors.initials: P
authors.lastname: Vemuri
authors.forename: E M
authors.initials: EM
authors.lastname: McDade
authors.forename: G
authors.initials: G
authors.lastname: Zeng
authors.forename: M L
authors.initials: ML
authors.lastname: Senjem
authors.forename: J L
authors.initials: JL
authors.lastname: Gunter
authors.forename: S A
authors.initials: SA
authors.lastname: Przybelski
authors.forename: R T
authors.initials: RT
authors.lastname: Avula
authors.forename: D S
authors.initials: DS
authors.lastname: Knopman
authors.forename: B F
authors.initials: BF
authors.lastname: Boeve
authors.forename: R C
authors.initials: RC
authors.lastname: Petersen
authors.forename: C R
authors.initials: CR
authors.lastname: Jack
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000544:Alzheimer Disease / Q000473:pathology*; D001921:Brain / Q000098:blood supply / Q000473:pathology*; D001931:Brain Mapping; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000098:blood supply; D009434:Neural Pathways / Q000098:blood supply; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D011569:Psychiatric Status Rating Scales; D018709:Statistics, Nonparametric
chemical_list: D010100:Oxygen