Effects of statins on cerebral blood velocity in older adults at risk for Alzheimer’s disease: Data from a phase II multisite clinical trial

Abstract

Reduced cerebral blood flow (CBF) along with vascular risk factors (e.g., dyslipidemia) are prevalent in Alzheimer's disease (AD) and related dementias. Considering the lack of disease-modifying therapies, targeting modifiable vascular risk factors is imperative. Statins are one of the most effective pharmacologic treatments for vascular risk reduction, which may increase CBF in individuals with an increased risk for AD. Despite widespread statin use in both sexes, sex specific statin effects on CBF is not completely understood. Cross-sectional analysis of 194 older adults with a family history of dementia. Heart rate via electrocardiogram, mean arterial pressure (MAP) via plethysmograph, end-tidal CO2 via capnograph, and CBF velocity at the middle cerebral artery (MCAv) via transcranial Doppler ultrasound were collected following 20-minutes of supine rest. Mean MCAv (cm/s) was measured within each cardiac cycle and averaged over an 8-minute duration. 114 females (68 ± 5 years; 49 statin) and 80 males (70 ± 6 years; 46 statin) were included in analyses. There were no significant differences between vasodilator medication use, heart rate, end-tidal CO2 , or MAP between sexes. MCAv was significantly higher in females compared to males. There was a significant interaction effect between statin use and sex (p = 0.03). Post-hoc analyses suggest that the female statin group had significantly higher MCAv than female non-statin group (59.0 ± 12.1 vs. 52.7 ± 12.1; p = 0.02) and female statin group had significantly higher MCAv than male statin group (59.0 ± 12.1 vs. 47.5 ± 10.4 cm/s; p < 0.001). Males were significantly older than females; however, we report that age was not a significant covariate in the model. Our findings suggest a sex specific statin effect on MCAv, with females having had a significantly higher MCAv from statin use. Further investigation is warranted into other components of cerebrovascular function, as differences between sexes may have implications for brain health and disease pathogenesis.