Abstract
BackgroundIntracranial 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.MethodsIn 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.ResultsBaseline 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.ConclusionsIn 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.
Highlights
Mineralization of the intimal layer of the vessel wall is an integral part of the atherosclerotic process [1]
No difference in internal carotid artery (ICA) calcification, white matter hyperintensities (WMH) volume, or Alzheimer disease (AD) imaging biomarkers between converters and controls Figure 1 demonstrates a flow diagram showing the initial number of potentially eligible participants; selection criteria for the control, converter, and impaired groups; and those excluded for different reasons
We identified no direct association between the presence or severity of ICAC and baseline or longitudinal cognitive scores (MMSE, Clinical Dementia Rating Scale (CDR)-SB, and Preclinical Alzheimer Cognitive Composite (PACC)), nor did we find any association with the risk of conversion to CDR above 0
Summary
Mineralization of the intimal layer of the vessel wall is an integral part of the atherosclerotic process [1]. The most common sites of calcification are the cavernous carotid and the carotid siphon where the severity of calcification is associated with the presence of small vessel disease and white matter lesions [5,6,7,8], both of which have been shown to adversely affect cognition in older adults [9]. Studies have demonstrated an inverse relationship between the severity of intracranial ICAC and cognitive performance in terms of memory, executive function, global cognition, and processing speed in healthy adults [10, 11], as well as a relationship between extracranial ICAC and the risk of dementia [12]. 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
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