Coronary artery calcium is associated with cortical thinning in cognitively normal individuals

Abstract

To evaluate the association between coronary artery calcium (CAC) and cortical thickness in a large sample of cognitively normal individuals, with special emphasis in determining if the association thickness has regional brain specificity and if it is mediated by white matter hyperintensities (WMH). A total of 512 participants were included in this study. CAC scores were assessed by multi-detector computed tomography. Cortical thickness was measured using a surface-based method. Linear mixed models were used to assess the association between CAC scores and cortical thickness. In fully adjusted models, increased CAC scores were associated with cortical thinning across several brain regions, which generally overlapped with the distribution of default mode network. The association between CAC scores and cortical thickness was significantly stronger in participants with moderate or severe WMH compared to those with none or mild WMH, even though CAC scores were not associated with WMH. In cognitively normal adults, CAC was associated with cortical thinning in areas related to cognitive function. This association was evident after adjusting for multiple coronary artery disease risk factors and for WMH, suggesting that CAC may be more closely related to Alzheimer's Disease-type disease rather than to cerebral small vessel disease.

Figure 1

Average difference in cortical thickness in the (a) Global, (b) Frontal, (c) Temporal, (d) Parietal and (e) Occipital regions by coronary artery calcification scores. The curves were estimated using restricted cubic splines for CAC with knots at the 5^th, 25^th, 75^th and 95^th percentiles of the CAC score sample distributions. The reference value (diamond dot) was set at the 5th percentile (CAC score 0). Models were adjusted for age (continuous), sex, BMI (continuous), education (<high school, ≥high school), smoking status (never, past or current), alcohol intake (never, past or current), hypertension, diabetes, hyperlipidemia, ICV (continuous) and WMH (none or minimal, moderate or severe).

Figure 2. Three-dimensional reconstruction for correlation between coronary artery calcification scores and cortical thickness.

The association of higher CAC score with cortical thinning had regional specificity in the bilateral dorsolateral prefrontal, precuneus, superior parietal, and left medial prefrontal regions. The Q-value denotes the FDR-corrected P-value.

Figure 3. Adjusted average difference in cortical thickness in the frontal region per one unit increase in natural log (CAC score + 1) in clinically relevant subgroups.

Models were adjusted for age, sex, BMI, education (