title: Progressive regional atrophy in normal adults with a maternal history of Alzheimer disease.
abstract: OBJECTIVE
  Beyond age, having a family history is the most significant risk factor for Alzheimer disease (AD). This longitudinal brain imaging study examines whether there are differential patterns of regional gray matter atrophy in cognitively healthy elderly subjects with (FH+) and without (FH-) a family history of late-onset AD.
  
  
  METHODS
  As part of the KU Brain Aging Project, cognitively intact individuals with a maternal history (FHm, n = 11), paternal history (FHp, n = 10), or no parental history of AD (FH-, n = 32) similar in age, gender, education, and Mini-Mental State Examination (MMSE) score received MRI at baseline and 2-year follow-up. A custom voxel-based morphometry processing stream was used to examine regional differences in atrophy between FH groups, controlling for age, gender, and APOE ε4 (APOE4) status. We also analyzed APOE4-related atrophy.
  
  
  RESULTS
  Cognitively normal FH+ individuals had significantly increased whole-brain gray matter atrophy and CSF expansion compared to FH-. When FH+ groups were split, only FHm was associated with longitudinal measures of brain change. Moreover, our voxel-based analysis revealed that FHm subjects had significantly greater atrophy in the precuneus and parahippocampus/hippocampus regions compared to FH- and FHp subjects, independent of APOE4 status, gender, and age. Individuals with an ε4 allele had more regional atrophy in the frontal cortex compared to ε4 noncarriers.
  
  
  CONCLUSIONS
  We conclude that FHm individuals without dementia have progressive gray matter volume reductions in select AD-vulnerable brain regions, specifically the precuneus and parahippocampal gyrus. These data complement and extend reports of regional cerebral metabolic differences and increases in amyloid-β burden in FHm subjects, which may be related to a higher risk for developing AD.
authors.affiliation: Department of Neurology, University of Kansas School of Medicine, Kansas City, KS 66160, USA. rhonea@kumc.edu
authors.forename: Robyn A
authors.initials: RA
authors.lastname: Honea
authors.forename: Russell H
authors.initials: RH
authors.lastname: Swerdlow
authors.forename: Eric D
authors.initials: ED
authors.lastname: Vidoni
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Burns
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D053327:Apolipoprotein E4 / Q000235:genetics; D001284:Atrophy / Q000235:genetics / Q000473:pathology; D002540:Cerebral Cortex / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009035:Mothers; D020534:Parahippocampal Gyrus / Q000473:pathology; D012307:Risk Factors
chemical_list: D053327:Apolipoprotein E4