Baseline demographic data for the study participants at the 6th examination cycle are shown in . There were no significant differences in clinical characteristics of subjects included and excluded from the present analysis. Hippocampal volume measurements were available in a subset of 787 participants (mean age 64years, 52% women) who were significantly older than those without hippocampal volume measurements, but did not differ in any of the other stroke risk factors. Carotid artery stenosis ≥25% was observed in 289 participants (14.7%) and carotid stenosis ≥50% in 35 participants (1.8%). In brain MRI we observed LWMH in 306 participants (15.5%), and SCI in 206 participants (11%). Mean TCBV (SD) was 0.78 (0.03) and the mean hippocampal volume (SD) was 0.31 (0.04). Performance in neuropsychological testing according to carotid atherosclerosis measures is shown in .
Characteristics of study sample, sex-specific subsamples and excluded subjects
Relation of carotid atherosclerosis measures, and MRI measures and Neuropsychological Factors performance
Relation of carotid atherosclerosis measures and brain MRI markers ()
Carotid stenosis ≥25% and ≥50% were both related to SCI and LWMH and inversely related to TCBV. Participants with ≥25% stenosis had a higher prevalence of SCI (Odds Ratio [OR] 1.64, 95% confidence interval [CI] 1.14–2.36, p=0.007), a higher prevalence of LWMH (OR 1.76, 95% CI 1.27–2.45, p <0.001) and lower brain volume (β −0.21 ± SE 0.05, p <0.001). After adjusting for vascular risk factors and the time between acquisition of carotid ultrasound and MRI and NP testing, the associations remained significant with LWMH (OR 1.77, 95% CI 1.25–2.53, p=0.001) and brain volume (β β − 0.11 ± SE 0.06, p=0.04), but not with SCI.
Carotid stenosis ≥50% was also associated with an increased prevalence of SCI (OR 3.07, 95% CI 1.46–6.42, p=0.003), and of LWMH (OR 2.26, 95% CI 1.06–4.80, p=0.03), and with lower brain volume (β −0.28 ± SE 0.14, p=0.047). After the full multivariable adjustment, carotid stenosis ≥50% was associated with SCI (OR 2.53, 95% CI 1.17 – 5.44, p=0.02), and with LWMH (OR 2.35, 95% CI 1.08–5.13, p=0.03).
We observed that ICA IMT was significantly associated with a higher prevalence of SCI (OR 1.33, 95% CI 1.14 – 1.55, p<0.001), and LWMH (OR 1.23, 95% CI 1.07 – 1.42, p=0.003) and with lower brain volume (β −0.10± SE 0.02, p<0.001). All of the associations above remained significant when using the full multivariable adjusted model, with the increase in odds of having LWMH for each increase of 1 SD age in log-transformed baseline ICA IMT value, OR=1.19 (95% CI 1.03 – 1.38) and with brain volume decreasing by 0.05 per 1SD increase in log-transformed baseline ICA IMT value (SE 0.02, p=0.02). Common carotid artery IMT was also associated with higher prevalence of SCI (OR 1.20, 95% CI 1.03 –1.41, p=0.02) and with lower brain volume (β −0.06 ± SE 0.02, p=0.003), but these associations were no longer significant in the full multivariable adjusted model.
Neither carotid stenosis, nor IMT were associated with hippocampal volume, possibly due to the smaller sample size (N=787) with available hippocampal volume measurements.
Relation of carotid atherosclerosis measures and NP Factors ( and )
Carotid stenosis ≥25% was associated with poorer performance on the executive function factor (β −0.08 ± SE 0.03, p=0.002) and non-verbal memory factor (β −09 ± SE 0.03, p=0.001) but not with the verbal memory factor. After full multivariable adjustment there was a trend for association with poorer performance on verbal memory and non-verbal memory factors, but the associations did not reach statistical significance. Carotid stenosis ≥ 50% was associated with poorer performance only on the executive function factor (β −0.42 ± SE 0.18, p=0.02). After the full multivariable adjustment, the association remained significant with persons with carotid stenosis ≥50% scoring a mean of 0.39 SD lower as compared to those with stenosis <50% (p<0.03). There was no significant association of carotid stenosis ≥ 50% with performance on verbal memory and non-verbal memory factors.
Higher ICA IMT was associated with poorer performance on the executive function factor (β −0.08 ± SE 0.03, p=0.002) and the non-verbal memory factor (β −0.09 ± SE 0.03, p=0.001). After full multivariable adjustment, the association became significant for the verbal memory factor (β −0.06± SE 0.03, p=0.047), remained significant for the non-verbal memory factor (β −0.08 ± SE 0.03, p=0.005), and was borderline for the executive function factor (β −0.05 ± SE 0.03; p=0.053). CCA IMT was not associated with any of the cognitive measures.
Additional adjustment for the MRI markers (SCI, LWMH, TCBV and hippocampal volume), which have been associated with cognitive impairment, did not alter the results (data not shown). We did not observe an effect of side (left versus right) in the association of carotid atherosclerosis measures and cognitive performance.
Carotid atherosclerosis measures and Neuropsychological Factors performance adjusted for MRI measures