Reduced gray matter volume in normal adults with a maternal family history of Alzheimer disease

Neurology. 2010 Jan 12;74(2):113-20. doi: 10.1212/WNL.0b013e3181c918cb.


Objective: A consistently identified risk factor for Alzheimer disease (AD) is family history of dementia, with maternal transmission significantly more frequent than paternal transmission. A history of maternal AD may be related to AD-like glucose consumption in cognitively healthy subjects. In this cross-sectional study, we tested whether cognitively healthy people with a family history of AD have less gray matter volume (GMV), an endophenotype for late-onset AD, than individuals with no family history, and whether decreases in GMV are different in subjects with a maternal family history.

Methods: As part of the Kansas University Brain Aging Project, 67 cognitively intact individuals with a maternal history of late-onset AD (FHm, n = 16), a paternal history of AD (FHp, n = 8), or no parental history of AD (FH-, n = 43), similar in age, gender, education, and Mini-Mental State Examination score, were scanned at 3 T. We used voxel-based morphometry to examine GMV differences between groups, controlling for age, gender, and apoE4.

Results: Cognitively healthy individuals with a family history of late-onset AD had significantly decreased GMV in the precuneus, middle frontal, inferior frontal, and superior frontal gyri compared with FH- individuals. FHm subjects had significantly smaller inferior frontal, middle frontal, precuneus, and lingual gyri compared with FH- and FHp subjects.

Conclusions: Overall, maternal family history of Alzheimer disease (AD) in cognitively normal individuals is associated with lower gray matter volume in AD-vulnerable brain regions. These data complement and extend reports of cerebral metabolic differences in subjects with a maternal family history.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Alzheimer Disease / diagnosis*
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / physiopathology
  • Apolipoprotein E4 / genetics
  • Atrophy / genetics*
  • Atrophy / pathology*
  • Atrophy / physiopathology
  • Brain / metabolism
  • Brain / pathology*
  • Brain / physiopathology
  • Brain Mapping
  • Cohort Studies
  • Cross-Sectional Studies
  • Early Diagnosis
  • Female
  • Genetic Predisposition to Disease / genetics
  • Genotype
  • Humans
  • Image Processing, Computer-Assisted
  • Inheritance Patterns / genetics*
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Mothers
  • Neuropsychological Tests
  • Risk Factors


  • Apolipoprotein E4