title: Alzheimer disease family history impacts resting state functional connectivity.
abstract: OBJECTIVE
  Offspring whose parents have Alzheimer disease (AD) are at increased risk for developing dementia. Patients with AD typically exhibit disruptions in the default mode network (DMN). The aim of this study was to investigate the effect of a family history of late onset AD on DMN integrity in cognitively normal individuals. In particular, we determined whether a family history effect is detectable in apolipoprotein E (APOE) ε4 allele noncarriers.
  
  
  METHODS
  We studied a cohort of 348 cognitively normal participants with or without family history of late onset AD. DMN integrity was assessed by resting state functional connectivity magnetic resonance imaging.
  
  
  RESULTS
  A family history of late onset AD was associated with reduced resting state functional connectivity between particular nodes of the DMN, namely the posterior cingulate and medial temporal cortex. The observed functional connectivity reduction was not attributable to medial temporal structural atrophy. Importantly, we detected a family history effect on DMN functional connectivity in APOE ε4 allele noncarriers.
  
  
  CONCLUSIONS
  Unknown genetic factors, embodied in a family history of late onset AD, may affect DMN integrity prior to cognitive impairment.
authors.affiliation: Department of Neurology, Washington University in Saint Louis, Saint Louis, MO 63110, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Roe
authors.forename: Abraham Z
authors.initials: AZ
authors.lastname: Snyder
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Brier
authors.forename: Jewell B
authors.initials: JB
authors.lastname: Thomas
authors.forename: Chengjie
authors.initials: C
authors.lastname: Xiong
authors.forename: Tammie L
authors.initials: TL
authors.lastname: Benzinger
authors.forename: John C
authors.initials: JC
authors.lastname: Morris
authors.forename: Beau M
authors.initials: BM
authors.lastname: Ances
mesh_terms: D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D053327:Apolipoprotein E4 / Q000235:genetics; D003071:Cognition / Q000502:physiology; D004247:DNA / Q000235:genetics; D004522:Educational Status; D018728:Entorhinal Cortex / Q000473:pathology; D005190:Family; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000473:pathology / Q000503:physiopathology*; D009483:Neuropsychological Tests; D012146:Rest / Q000502:physiology; D013702:Temporal Lobe / Q000473:pathology
chemical_list: D053327:Apolipoprotein E4; D004247:DNA