Gray matter network associated with risk for Alzheimer's disease in young to middle-aged adults

Gene E. Alexander, Kaitlin L. Bergfield, Kewei Chen, Eric M. Reiman, Krista D. Hanson, Lan Lin, Daniel Bandy, Richard John Caselli, James R. Moeller

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

The apolipoprotein E (APOE) ε4 allele increases the risk for late-onset Alzheimer's disease (AD) and age-related cognitive decline. We investigated whether ε4 carriers show reductions in gray matter volume compared with ε4 non-carriers decades before the potential onset of AD dementia or healthy cognitive aging. Fourteen cognitively normal ε4 carriers, aged 26 to 45 years, were compared with 10 age-matched, ε4 non-carriers using T1-weighted volumetric magnetic resonance imaging (MRI) scans. All had reported first- or second-degree family histories of dementia. Group differences in gray matter were tested using voxel-based morphometry (VBM) and a multivariate model of regional covariance, the Scaled Subprofile Model (SSM). A combination of the first two SSM MRI gray matter patterns distinguished the APOE ε4 carriers from non-carriers. This combined pattern showed gray matter reductions in bilateral dorsolateral and medial frontal, anterior cingulate, parietal, and lateral temporal cortices with covarying relative increases in cerebellum, occipital, fusiform, and hippocampal regions. With these gray matter differences occurring decades before the potential onset of dementia or cognitive aging, the results suggest longstanding, gene-associated differences in brain morphology that may lead to preferential vulnerability for the later effects of late-onset AD or healthy brain aging.

Original languageEnglish (US)
Pages (from-to)2723-2732
Number of pages10
JournalNeurobiology of Aging
Volume33
Issue number12
DOIs
StatePublished - Dec 2012

Fingerprint

Alzheimer Disease
Apolipoprotein E4
Dementia
Magnetic Resonance Imaging
Gyrus Cinguli
Brain
Temporal Lobe
Cerebellum
Alleles
Gray Matter
Genes
Cognitive Aging

Keywords

  • Apolipoprotein E
  • Gray matter volume
  • Late-onset Alzheimer's disease
  • Magnetic resonance imaging
  • Multivariate analysis
  • Voxel-based morphometry

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

Alexander, G. E., Bergfield, K. L., Chen, K., Reiman, E. M., Hanson, K. D., Lin, L., ... Moeller, J. R. (2012). Gray matter network associated with risk for Alzheimer's disease in young to middle-aged adults. Neurobiology of Aging, 33(12), 2723-2732. https://doi.org/10.1016/j.neurobiolaging.2012.01.014

Gray matter network associated with risk for Alzheimer's disease in young to middle-aged adults. / Alexander, Gene E.; Bergfield, Kaitlin L.; Chen, Kewei; Reiman, Eric M.; Hanson, Krista D.; Lin, Lan; Bandy, Daniel; Caselli, Richard John; Moeller, James R.

In: Neurobiology of Aging, Vol. 33, No. 12, 12.2012, p. 2723-2732.

Research output: Contribution to journalArticle

Alexander, GE, Bergfield, KL, Chen, K, Reiman, EM, Hanson, KD, Lin, L, Bandy, D, Caselli, RJ & Moeller, JR 2012, 'Gray matter network associated with risk for Alzheimer's disease in young to middle-aged adults', Neurobiology of Aging, vol. 33, no. 12, pp. 2723-2732. https://doi.org/10.1016/j.neurobiolaging.2012.01.014
Alexander, Gene E. ; Bergfield, Kaitlin L. ; Chen, Kewei ; Reiman, Eric M. ; Hanson, Krista D. ; Lin, Lan ; Bandy, Daniel ; Caselli, Richard John ; Moeller, James R. / Gray matter network associated with risk for Alzheimer's disease in young to middle-aged adults. In: Neurobiology of Aging. 2012 ; Vol. 33, No. 12. pp. 2723-2732.
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