Hypertension and longitudinal changes in cerebral blood flow: The SMART-MR study

ArticleinAnnals of Neurology 71(6):825-33 · June 2012with20 Reads
DOI: 10.1002/ana.23554 · Source: PubMed
Cerebral hypoperfusion is among the mechanisms that may explain the association of high blood pressure (BP) with dementia. However, few data are available on the longitudinal association of hypertension and cerebral perfusion. We examined the longitudinal association of hypertension, BP, and antihypertensive drugs with change in parenchymal cerebral blood flow (pCBF) in 575 patients with manifest atherosclerotic disease (mean age, 57 ± 10 years) from the SMART-MR study. Total CBF was measured at baseline and at follow-up with magnetic resonance (MR) angiography and was expressed per 100ml brain volume as an indicator of cerebral perfusion. Automated brain segmentation was used to quantify brain tissue volumes and cerebrospinal fluid on MR imaging. Mean (standard deviation [SD]) baseline pCBF was 52.3 (9.8) ml/min/100ml and after 3.9 years (range, 3.0-5.8 years) of follow-up declined to 50.7 (10.3) ml/min/100ml. Regression analyses adjusted for age, sex, follow-up time, and vascular risk showed that untreated and poorly controlled hypertension and higher levels of systolic and diastolic BP (per SD) were significantly associated with a decline in pCBF; mean differences in decline (95% confidence interval) were -2.2 (-4.4 to 0.0), -1.0 (-1.8 to -0.1), and -1.0 (-1.8 to -0.2) ml/min/100ml. In addition, within hypertensive patients (n = 469), patients using angiotensin receptor blockers (ARBs) did not show a decline in pCBF, whereas patients using other antihypertensive drugs did show a decline in pCBF. Untreated hypertension, poorly controlled hypertension, and high BP levels are associated with a decline in pCBF. In addition, treatment with ARBs might result in less decline in pCBF than other antihypertensive treatment.
    • "Moreover, AD risk increases with the number of coexisting vascular risk factors present (Luchsinger et al. 2005). Studies investigating the link between vascular risk and CBF suggest that increased vascular risk factors are associated with a decrease in resting CBF over time, and with greater %D CBF in response to functional tasks (Bangen et al. 2009; Muller et al. 2012). Recent evidence also suggests that vascular risk burden might moderate the relationship between increasing age and reduced CBF, with a relationship between advancing age and reduced CBF only observed among those possessing multiple vascular risk factors. "
    [Show abstract] [Hide abstract] ABSTRACT: There is accumulating evidence suggesting that changes in brain perfusion are present long before the clinical symptoms of Alzheimer's disease (AD), perhaps even before amyloid-β accumulation or brain atrophy. This evidence, consistent with the vascular hypothesis of AD, implicates cerebral blood flow (CBF) in the pathogenesis of AD and suggests its utility as a biomarker of preclinical AD. The extended preclinical phase of AD holds particular significance for disease modification, as treatment would likely be most effective in this early asymptomatic stage of disease. This highlights the importance of identifying reliable and accurate biomarkers of AD that can differentiate normal aging from preclinical AD prior to clinical symptom manifestation. Cerebral perfusion, as measured by arterial spin labeling magnetic resonance imaging (ASL-MRI), has been shown to distinguish between normal controls and adults with AD. In addition to demonstrating diagnostic utility, CBF has shown usefulness as a tool for identifying those who are at risk for AD and for predicting subtle cognitive decline and conversion to mild cognitive impairment and AD. Taken together, this evidence not only implicates CBF as a useful biomarker for tracking disease severity and progression, but also suggests that ASL-measured CBF may be useful for identifying candidates for future AD treatment trials, especially in the preclinical, asymptomatic phases of the disease.
    Full-text · Article · Aug 2015
    • "The findings are based on cross-sectional data, for which we cannot infer causal direction. However, there is evidence from previous studies to suggest that VRF impair vasodilation and other components involved in hemodynamic response (Convit et al., 2003; Last et al., 2007; Wu et al., 2008; Muller et al., 2012). Different methodological aspects of the study may represent important factors with respect to interpretation of the results. "
    [Show abstract] [Hide abstract] ABSTRACT: Cumulating evidence from epidemiologic studies implicates cardiovascular health and cerebrovascular function in several brain diseases in late life. We examined vascular risk factors with respect to a cerebrovascular measure of brain functioning in subjects in mid-life, which could represent a marker of brain changes in later life. Breath-hold functional MRI (fMRI) was performed in 541 women and men (mean age 50.4 years) from the Coronary Artery Risk Development in Young Adults (CARDIA) Brain MRI sub-study. Cerebrovascular reactivity (CVR) was quantified as percentage change in blood-oxygen level dependent (BOLD) signal in activated voxels, which was mapped to a common brain template and log-transformed. Mean CVR was calculated for anatomic regions underlying the default-mode network (DMN) - a network implicated in AD and other brain disorders - in addition to areas considered to be relatively spared in the disease (e.g. occipital lobe), which were utilized as reference regions. Mean CVR was significantly reduced in the posterior cingulate/precuneus (β = -0.063, 95% CI: -0.106, -0.020), anterior cingulate (β = -0.055, 95% CI: -0.101, -0.010), and medial frontal lobe (β = -0.050, 95% CI: -0.092, -0.008) relative to mean CVR in the occipital lobe, after adjustment for age, sex, race, education, and smoking status, in subjects with pre-hypertension/hypertension compared to normotensive subjects. By contrast, mean CVR was lower, but not significantly, in the inferior parietal lobe (β = -0.024, 95% CI: -0.062, 0.014) and the hippocampus (β = -0.006, 95% CI: -0.062, 0.050) relative to mean CVR in the occipital lobe. Similar results were observed in subjects with diabetes and dyslipidemia compared to those without these conditions, though the differences were non-significant. Reduced CVR may represent diminished vascular functionality for the DMN for individuals with prehypertension/ hypertension in mid-life, and may serve as a preclinical marker for brain dysfunction in later life.
    Article · Jan 2015
    • "Individuals with greater exposure to vascular risk factors are at greater risk of clinically silent infarcts, identified on T1-and T2-weighted MRI (Das et al. 2008; Vermeer et al. 2007 ), as well as microhemorrhages visible on highly-sensitive T2*-weighted sequences such as susceptibility-weighted imaging (Cordonnier et al. 2007; Goos et al. 2010; Poels et al. 2010). Deficits in cerebral perfusion, measured using perfusion MRI with arterial spin labeling, have been demonstrated in elderly individuals possessing vascular risk factors, especially hypertension (Dai et al. 2008; Hajjar et al. 2010; Muller et al. 2012). Atheroslerosis of the blood vessels supplying the brain is most often measured at isolated locations, such as the carotid bifurcation, and is usually summarized in terms of univariate measures such as the carotid intima-media thickness based on ultrasound examination; however MRI sequences have the capability of providing more sensitive measures of plaque burden covering a greater extent of the vasculature . "
    [Show abstract] [Hide abstract] ABSTRACT: For some researchers, the relationship between prevalent cardiovascular risk factors and late-life cognitive decline is not worthy of further study. It is already known that effective treatment of vascular risk factors lowers risk of such major outcomes as stroke and heart attack, the argument goes; thus, any new information about the relationship between vascular risk factors and another major outcome - late-life cognitive decline-- is unlikely to have an impact on clinical practice. The purpose of this review is to probe the logic of this argument by focusing on what is known, and what is not known, about the relationship between vascular risk factors and late-life cognitive decline. The unknowns are substantial: in particular, there is relatively little evidence that current vascular risk factor treatment protocols are adequate to prevent late-life cognitive decline or the clinically silent brain injury that precedes it. In addition, there is relatively little understanding of which factors lead to differential vulnerability or resilience to the effects of vascular risk factors on silent brain injury. Differential effects of different classes of treatments are similarly unclear. Finally, there is limited understanding of the impact of clinically-silent neurodegenerative disease processes on cerebrovascular processes. Further study of the relationships among vascular risk factors, brain injury, and late-life cognitive decline could have a major impact on development of new vascular therapies and on clinical management of vascular risk factors, and there are promising avenues for future research in this direction.
    Full-text · Article · Aug 2014
Show more