Sex differences in grey matter atrophy patterns among AD and aMCI patients: Results from ADNI

Martha Skup, Hongtu Zhu, Yaping Wang, Kelly S. Giovanello, Ja an Lin, Dinggang Shen, Feng Shi, Wei Gao, Weili Lin, Yong Fan, Heping Zhang

Research output: Contribution to journalArticlepeer-review

82 Citations (Scopus)


We used longitudinal magnetic resonance imaging (MRI) data to determine whether there are any gender differences in grey matter atrophy patterns over time in 197 individuals with probable Alzheimer's disease (AD) and 266 with amnestic mild cognitive impairment (aMCI), compared with 224 healthy controls participating in the Alzheimer's Disease Neuroimaging Initiative (ADNI). While previous research has differentiated probable AD and aMCI groups from controls in brain atrophy, it is unclear whether and how sex plays a role in patterns of change over time. Using regional volumetric maps, we fit longitudinal models to the grey matter data collected at repeated occasions, seeking differences in patterns of volume change over time by sex and diagnostic group in a voxel-wise analysis. Additionally, using a region-of-interest approach, we fit longitudinal models to the global volumetric data of predetermined brain regions to determine whether this more conventional approach is sufficient for determining sex and group differences in atrophy. Our longitudinal analyses revealed that, of the various grey matter regions investigated, males and females in the AD group and the aMCI group showed different patterns of decline over time compared to controls in the bilateral precuneus, bilateral caudate nucleus, right entorhinal gyrus, bilateral thalamus, bilateral middle temporal gyrus, left insula, and right amygdala. As one of the first investigation to model more than two time points of structural MRI data over time, our findings add insight into how AD and aMCI males and females differ from controls and from each other over time.

Original languageEnglish
Pages (from-to)890-906
Number of pages17
Issue number3
Publication statusPublished - 2011 Jun 1

Bibliographical note

Funding Information:
M. Skup is supported in part by training grant T32 MH014235 from the National Institute on Mental Health . H. Zhu is supported in part by NSF grant BCS-08-26844 and NIH grants RR025747-01 , P01CA142538-01 , MH086633 , and AG03338 . Y. Fan is supported in part by the National Science Foundation of China grant 30970770 and by the Hundred Talents Programs, Chinese Academy of Sciences . W. Lin is supported in part by NIH grants R01NS055754 and R01EB5-34816.


  • Alzheimer's disease
  • GEE
  • Longitudinal MRI
  • Mild cognitive impairment
  • Sex differences

ASJC Scopus subject areas

  • Neurology
  • Cognitive Neuroscience


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