Alzheimer’s Research & Therapy (Sep 2022)

Imaging markers of cerebral amyloid angiopathy and hypertensive arteriopathy differentiate Alzheimer disease subtypes synergistically

  • Ting-Bin Chen,
  • Wei-Ju Lee,
  • Jun-Peng Chen,
  • Shiang-Yu Chang,
  • Chun-Fu Lin,
  • Hung-Chieh Chen

DOI
https://doi.org/10.1186/s13195-022-01083-8
Journal volume & issue
Vol. 14, no. 1
pp. 1 – 14

Abstract

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Abstract Background Both cerebral amyloid angiopathy (CAA) and hypertensive arteriopathy (HA) are related to cognitive impairment and dementia. This study aimed to clarify CAA- and HA-related small vessel disease (SVD) imaging marker associations with cognitive dysfunction and Alzheimer disease (AD) subtypes. Methods A sample of 137 subjects with clinically diagnosed late-onset AD identified from the dementia registry of a single center from January 2017 to October 2021 were enrolled. Semi-quantitative imaging changes (visual rating scale grading) suggestive of SVD were analyzed singularly and compositely, and their correlations with cognitive domains and AD subtypes were examined. Results Patients with typical and limbic-predominant AD subtypes had worse cognitive performance and higher dementia severity than minimal-atrophy subtype patients. Deep white matter hyperintensity (WMH) presence correlated inversely with short-term memory (STM) performance. The three composite SVD scores correlated with different cognitive domains and had distinct associations with AD subtypes. After adjusting for relevant demographic factors, multivariate logistic regression (using minimal-atrophy subtype as the reference condition) revealed the following: associations of the typical subtype with periventricular WMH [odds ratio (OR) 2.62; 95% confidence interval (CI), 1.23–5.57, p = 0.012], global SVD score (OR 1.67; 95%CI, 1.11–2.52, p = 0.009), and HA-SVD score (OR 1.93; 95%CI, 1.10–3.52, p = 0.034); associations of limbic-predominant subtype with HA-SVD score (OR 2.57; 95%CI, 1.23–5.37, p = 0.012) and most global and domain-specific cognitive scores; and an association of hippocampal-sparing subtype with HA-SVD score (OR 3.30; 95%CI, 1.58–6.85, p = 0.001). Conclusion Composite SVD imaging markers reflect overall CAA and/or HA severity and may have differential associations with cognitive domains and AD subtypes. Our finding supports the possibility that the clinical AD subtypes may reflect differing burdens of underlying CAA and HA microangiopathologies.

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