Intracranial Arterial Calcification on Computed Tomography and Risk of Cognitive Impairment or Dementia: A Systematic Review and Meta-Analysis

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Abstract
Introduction: Coronary arterial calcification on computed tomography (CT), or CT-coronary artery calcification (CAC), is a widely studied risk factor for acute coronary events, but although intracranial arterial calcification on CT brain imaging (CT-IAC) is also a frequent finding in older individuals, there is no consensus on its prognostic significance, particularly whether its presence, severity, or site predict cognitive impairment or dementia. Given the clinical and mechanistic importance of any associations, we did a systematic review and meta-analysis. Methods: Studies published before 30 January 2026 were identified from bibliographic databases, reference lists, and forward or backward screening. Inclusion criteria were: (1) studies of adults linking CT-IAC/CAC with later cognitive impairment or dementia; (2) reporting adjusted effect measures with 95% confidence interval or p values (or calculable); (3) calcification assessed by CT/CT angiography and cognition by recognised tests or expert evaluation. Studies were summarised qualitatively and pooled quantitatively depending on heterogeneity. Results: Six cross-sectional studies and three longitudinal studies reported data on CT-IAC and cognitive status. Among five studies that reported associations for presence vs. absence of CT-IAC, presence of calcification was weakly associated with cognitive impairment or dementia (three cross-sectional studies – pooled adjusted odds ratio [aOR] = 1.42, 0.88–2.28, p = 0.15; two longitudinal studies – aOR = 1.51, 1.03–2.22, p = 0.033; all studies – aOR = 1.48, 1.10–1.99, p = 0.01). Among five studies that reported associations for more severe vs. milder CT-IAC, severe calcification was more strongly associated with the cognitive outcome (two cross-sectional studies – pooled aOR = 2.29, 0.50–10.57, p = 0.29; three longitudinal studies – aOR = 1.84, 1.28–2.65, p = 0.001; all studies – aOR = 1.74, 1.28–2.36, p = 0.0004), including in two longitudinal cohorts in patients with stroke/transient ischaemic attack (pooled aOR = 1.73, 1.22–2.46, p = 0.002). In two longitudinal studies, severity of vertebrobasilar CT-IAC also predicted dementia (pooled aOR = 2.12, 1.06–4.21, p = 0.033), and severity of medial/internal elastic lamina (IEL) CT-IAC was a stronger predictor of dementia (pooled aOR = 2.35, 1.29–4.28, p = 0.005) than severity of intimal CT-IAC (pooled aOR = 1.29, 0.75–2.23, p = 0.36). For coronary CT-CAC, three longitudinal cohorts revealed weak associations with dementia (per standard deviation increase in calcification measures – pooled adjusted hazards ratio = 1.15, 1.02–1.30, p = 0.025). Conclusion: In longitudinal studies, presence and severity of CT-IAC are both independently associated with dementia, driven mainly by medial/IEL calcification, with weaker associations for intimal and coronary calcification. In cross-sectional studies, the associations for both CT-IAC measures were of a similar magnitude to the longitudinal analyses but were not statistically significant. Future studies should determine age- and dementia-subtype specific associations.

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