Affiliations: [a] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands | [b] Image Sciences Institute, University Medical Center Utrecht, Utrecht, The Netherlands | [c] Department of Radiology, University Medical Center Utrecht, Utrecht, The Netherlands | [d] Department of Internal Medicine, VU University Medical Center Amsterdam, Amsterdam, The Netherlands | [e] Listed in Acknowledgments
Correspondence:
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Correspondence to: Mirjam I. Geerlings, PhD, Julius Center for Health Sciences and Primary Care, UMC Utrecht, Stratenum 6.131, PO BOX 85500, 3508 GA Utrecht, The Netherlands. Tel.: +31 88 755 9394; Fax: +31 88 755 5480; E-mail: [email protected].
Abstract: High levels of angiotensin-converting-enzyme (ACE) may increase the risk of dementia through blood pressure elevation and subsequent development of cerebral small-vessel disease. However, high ACE levels may also decrease this risk through amyloid degradation which prevents brain atrophy. Within the SMART-MR study, a prospective cohort study among patients with symptomatic atherosclerotic disease, serum ACE levels were measured at baseline and a 1.5 Tesla brain MRI was performed at baseline and after on average (range) 3.9 (3.0–5.8) years of follow-up in 682 persons (mean age 58 ± 10 years). Brain segmentation was used to quantify total, deep, and periventricular white matter lesion (WML) volume, and total brain, cortical gray matter and ventricular volume (%ICV). Lacunar infarcts were rated visually. Regression analyses were used to examine the prospective associations between serum ACE and brain measures. Patients with the highest serum ACE levels (>43.3 U/L) had borderline significantly more progression of deep WML volumes than patients with the lowest ACE levels (<21.8 U/L); mean difference (95% CI) in change was 0.20 (−0.02; 0.43) %ICV. On the contrary, patients with the highest serum ACE levels had significantly less progression of cortical brain atrophy than patients with the lowest ACE levels; mean difference (95% CI) in change was 0.78 (0.21; 1.36) %ICV. Serum ACE was not associated with subcortical atrophy, periventricular WML, or lacunar infarcts. Our results show that higher ACE activity is associated with somewhat more progression of deep WML volume, but with less progression of cortical brain atrophy. This suggests both detrimental and beneficial effects of high ACE levels on the brain.
Keywords: Brain infarction, cohort studies, magnetic resonance imaging, other cerebrovascular disorders, neurodegenerative diseases, renin-angiotensin system
