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Association of imaging-defined brain age with disease severity and adverse outcomes in CADASIL

Shao-Lun Hsu1,2, Pei-Lin Lee3, Kun-Hsien Chou3,4

  • 1Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|June 2, 2026
PubMed

Insights

Accelerated brain aging is evident in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL). The brain age gap (BAG) reflects disease severity and cumulative microvascular injury, impacting cognitive performance.

Area of Science:

  • Neurology
  • Neuroimaging
  • Genetics

Background:

  • Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a genetic disorder caused by NOTCH3 variants.
  • CADASIL leads to progressive neurological deficits, including cognitive impairment and stroke.

Purpose of the Study:

  • To investigate whether brain age is altered in CADASIL patients.
  • To determine the association between brain age gap (BAG) and disease severity, neuroimaging markers, and clinical outcomes in CADASIL.

Main Methods:

  • A brain-age prediction model was developed using MRI data from healthy individuals.
  • The model was applied to individuals with NOTCH3 variants (CADASIL) and controls to calculate BAG.
  • Associations between BAG, imaging markers (e.g., skeletonized mean diffusivity), and clinical performance were analyzed.

Main Results:

  • Individuals with CADASIL showed a significantly higher BAG compared to controls.
  • Higher BAG correlated with increased disease severity and specific neuroimaging markers.
  • BAG was associated with poorer cognitive performance and partially mediated the link between disease stage and cognition.

Conclusions:

  • Accelerated brain aging, indicated by BAG, is a feature of CADASIL.
  • BAG serves as a marker for cumulative microvascular injury burden in CADASIL.
  • BAG may play a role in the pathophysiology linking disease progression to cognitive decline.
Abstract

Keywords:
NOTCH3brain agebrain age gapcerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)cerebral small vessel disease

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