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.
"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.
"Given these factors, ASL MRI may provide a sensitive technique for identifying at-risk individuals , monitoring changes in neural activity due to developing neuropathology, and assessing effectiveness of disease-modifying treatments. Although associations have been consistently found between aging and hypoperfusion and between vascular risk factors and hypoperfusion (Grolimund and Seiler, 1988; Bangen et al., 2009; Muller et al., 2012), the interaction between advanced age and vascular risk burden on CBF remains unclear. Furthermore, most studies have focused on individual vascular risk factors, however , multiple vascular risk factors often co-exist (Genest and Cohn, 1995) and have been shown to incrementally increase risk for AD (Luchsinger et al., 2005; Whitmer et al., 2005). "
[Show abstract][Hide abstract] ABSTRACT: Vascular risk factors and cerebral blood flow (CBF) reduction have been linked to increased risk of cognitive impairment and Alzheimer's disease (AD); however the possible moderating effects of age and vascular risk burden on CBF in late life remain understudied. We examined the relationships among elevated vascular risk burden, age, CBF, and cognition. Seventy-one non-demented older adults completed an arterial spin labeling MR scan, neuropsychological assessment, and medical history interview. Relationships among vascular risk burden, age, and CBF were examined in a priori regions of interest (ROIs) previously implicated in aging and AD. Interaction effects indicated that, among older adults with elevated vascular risk burden (i.e., multiple vascular risk factors), advancing age was significantly associated with reduced cortical CBF whereas there was no such relationship for those with low vascular risk burden (i.e., no or one vascular risk factor). This pattern was observed in cortical ROIs including medial temporal (hippocampus, parahippocampal gyrus, uncus), inferior parietal (supramarginal gyrus, inferior parietal lobule, angular gyrus), and frontal (anterior cingulate, middle frontal gyrus, medial frontal gyrus) cortices. Furthermore, among those with elevated vascular risk, reduced CBF was associated with poorer cognitive performance. Such findings suggest that older adults with elevated vascular risk burden may be particularly vulnerable to cognitive change as a function of CBF reductions. Findings support the use of CBF as a potential biomarker in preclinical AD and suggest that vascular risk burden and regionally-specific CBF changes may contribute to differential age-related cognitive declines.
"Hypertension may affect cerebral blood flow and increase vascular brain injury   ; there is also evidence from mice models and epidemiologic studies to suggest that hypertension interferes with b-amyloid clearance  . "
[Show abstract][Hide abstract] ABSTRACT: Lifestyle and health-related factors are critical components of the risk for cognitive aging among veterans. Because dementia has a prolonged prodromal phase, understanding effects across the life course could help focus the timing and duration of prevention targets. This perspective may be especially relevant for veterans and health behaviors. Military service may promote development and maintenance of healthy lifestyle behaviors, but the period directly after active duty has ended could be an important transition stage and opportunity to address some important risk factors. Targeting multiple pathways in one intervention may maximize efficiency and benefits for veterans. A recent review of modifiable risk factors for Alzheimer's disease estimated that a 25% reduction of a combination of seven modifiable risk factors including diabetes, hypertension, obesity, depression, physical inactivity, smoking, and education/cognitive inactivity could prevent up to 3 million cases worldwide and 492,000 cases in the United States. Lifestyle interventions to address cardiovascular health in veterans may serve as useful models with both physical and cognitive activity components, dietary intervention, and vascular risk factor management. Although the evidence is accumulating for lifestyle and health-related risk factors as well as military risk factors, more studies are needed to characterize these factors in veterans and to examine the potential interactions between them.
Alzheimer's and Dementia 06/2014; 10(3):S111–S121. DOI:10.1016/j.jalz.2014.04.010 · 12.41 Impact Factor
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