Subcortical brain structures and the risk of dementia in the Rotterdam Study

Isabelle F. van der Velpen, Vanja Vlasov, Tavia E. Evans, Mohammad Kamran Ikram, Boris A. Gutman, Gennady V. Roshchupkin, Hieab H. Adams, Meike W. Vernooij, Mohammad Arfan Ikram

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Introduction: Volumetric and morphological changes in subcortical brain structures are present in persons with dementia, but it is unknown if these changes occur prior to diagnosis. Methods: Between 2005 and 2016, 5522 Rotterdam Study participants (mean age: 64.4) underwent cerebral magnetic resonance imaging (MRI) and were followed for development of dementia until 2018. Volume and shape measures were obtained for seven subcortical structures. Results: During 12 years of follow-up, 272 dementia cases occurred. Mean volumes of thalamus (hazard ratio [HR] per standard deviation [SD] decrease 1.94, 95% confidence interval [CI]: 1.55–2.43), amygdala (HR 1.66, 95% CI: 1.44–1.92), and hippocampus (HR 1.64, 95% CI: 1.43–1.88) were strongly associated with dementia risk. Associations for accumbens, pallidum, and caudate volumes were less pronounced. Shape analyses identified regional surface changes in the amygdala, limbic thalamus, and caudate. Discussion: Structure of the amygdala, thalamus, hippocampus, and caudate is associated with risk of dementia in a large population-based cohort of older adults.

Original languageEnglish
Pages (from-to)646-657
Number of pages12
JournalAlzheimer's and Dementia
Issue number2
StatePublished - Feb 2023


  • brain
  • dementia
  • epidemiology
  • magnetic resonance imaging
  • morphology
  • subcortical


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