Intracranial internal carotid artery calcification is not predictive of future cognitive decline

Farzaneh Rahmani, Marina Nguyen, Charles D. Chen, Nicole McKay, Aylin Dincer, Nelly Joseph-Mathurin, Gengsheng Chen, Jingxia Liu, Hilary L.P. Orlowski, John C. Morris, Tammie L.S. Benzinger

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Background: Intracranial internal carotid artery (ICA) calcification is a common incidental finding in non-contrast head CT. We evaluated the predictive value of ICAC (ICAC) for future risk of cognitive decline and compared the results with conventional imaging biomarkers of dementia. Methods: In a retrospective observational cohort, we included 230 participants with a PET-CT scan within 18 months of a baseline clinical assessment and longitudinal imaging assessments. Intracranial ICAC was quantified on baseline CT scans using the Agatson calcium score, and the association between baseline ICA calcium scores and the risk of conversion from a CDR of zero in baseline to a persistent CDR > 0 at any follow-up visit, as well as longitudinal changes in cognitive scores, were evaluated through linear and mixed regression models. We also evaluated the association of conventional imaging biomarkers of dementia with longitudinal changes in cognitive scores and a potential indirect effect of ICAC on cognition through these biomarkers. Results: Baseline ICA calcium score could not distinguish participants who converted to CDR > 0. ICA calcium score was also unable to predict longitudinal changes in cognitive scores, imaging biomarkers of small vessel disease such as white matter hyperintensities (WMH) volume, or AD such as hippocampal volume, AD cortical signature thickness, and amyloid burden. Severity of intracranial ICAC increased with age and in men. Higher WMH volume and amyloid burden as well as lower hippocampal volume and AD cortical signature thickness at baseline predicted lower Mini-Mental State Exam scores at longitudinal follow-up. Baseline ICAC was indirectly associated with longitudinal cognitive decline, fully mediated through WMH volume. Conclusions: In elderly and preclinical AD populations, atherosclerosis of large intracranial vessels as demonstrated through ICAC is not directly associated with a future risk of cognitive impairment, or progression of imaging biomarkers of AD or small vessel disease.

Original languageEnglish
Article number32
JournalAlzheimer's Research and Therapy
Issue number1
StatePublished - Dec 2022


  • 11C-Pittsburgh compound B
  • Calcification
  • Centiloid
  • Clinical Dementia Rating
  • Internal carotid artery
  • Mini-Mental State Exam
  • PiB
  • White matter hyperintensities


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