Lower Cerebral Vasoreactivity Research Articles

Factors associated with worse cerebrovascular function in aging women with and at risk for HIV.

Women may be disproportionately impacted by the negative effect of HIV on cerebrovascular risk. We examined the association of HIV, sex, menopause, and immune activation with cerebrovascular function among women with HIV (WWH) and at risk for HIV from the Women's Interagency HIV Study and men with HIV. Cross-sectional. Participants were aged at least 40 years with coronary heart disease or at least one cardiometabolic risk factor. All persons with HIV were on antiretroviral therapy with undetectable viral load. Cerebral vasoreactivity was assessed by the transcranial Doppler breath-holding test, with lower vasoreactivity corresponding to worse cerebrovascular function. Menopausal status was determined by anti-Müllerian hormone level. We used mixed effects linear regression to identify factors associated with cerebral vasoreactivity. Mean cerebral vasoreactivity was similar in WWH (n = 33) and women at risk for HIV (n = 16). A trend toward higher cerebral vasoreactivity in WWH compared with men with HIV (n = 37) was no longer present after excluding women on estrogen replacement therapy (n = 3). In women, menopausal status was not significantly associated with cerebral vasoreactivity. WWH with higher cardiovascular risk (-0.14 for each additional cardiometabolic risk factor, P = 0.038), sCD163 (-0.20 per doubling, P = 0.033), and proportion of CD4+CX3CR1+ T cells (-0.14 per doubling, P = 0.028) had lower cerebral vasoreactivity. Among older women at high cardiovascular risk, women with virologically suppressed HIV and women at risk for HIV had similar cerebrovascular function. Our findings, which must be interpreted in the context of the small sample, highlight the contribution of traditional cardiometabolic risk factors and immune activation to cerebrovascular risk in WWH.

Cerebrovascular Reactivity Impairment in Preclinical Alzheimer's Disease.

A substantial overlap exists between declines in cerebral vasoreactivity (CVR) and symptomatic Alzheimer's disease (AD). CVR can be quantified using transcranial Doppler (TCD) measurement of cerebral blood flow velocities (CBFV) in the middle cerebral artery (MCA) with CO2 as a vasodilatory stimulus. The breath-hold acceleration index (BHAI) is a new, more reliable measure of CVR developed recently in our laboratory. Our primary goal is to explore the possibility of using TCD for asymptomatic AD screening. A pilot study population was divided into three groups: 9 healthy control subjects, 8 subjects identified as preclinical AD, and 10 patients diagnosed with prodromal or mild AD. Control subjects had a Clinical Dementia Rating (CDR) score of 0 without elevated amyloid-β (Aβ) on amyloid positron emission tomography (PET) imaging, preclinical AD subjects had CDR = 0 with elevated Aβ, and prodromal to mild AD subjects had CDR scores≥.5 and elevated Aβ. CVR was calculated using two indices: the conventional breath-holding index (BHI) and the new BHAI. TCD parameters between the three groups were compared. BHAI was able to distinguish between 9 normal control subjects and 8 preclinical-AD subjects with high statistical significance (P<.001). BHI and pulsatility index were able only to distinguish AD from healthy and preclinical subjects (P<.001). In this exploratory pilot study, CVR was significantly decreased in preclinical, prodromal, and mild AD subjects as compared to the healthy group. Lower CVR in the preclinical AD group was detected using the new BHAI index but not the conventional BHI index.

Lower cerebral vasoreactivity as a predictor of gait speed decline in type 2 diabetes mellitus.

Gait speed is an indicator of overall functional health and is correlated with survival in older adults. We prospectively evaluated the long-term association between cerebral vasoreactivity and gait speed during normal walking (NW) and dual-task walking (DTW) in older adults with and without type 2 diabetes mellitus (T2DM). 40 participants (aged 67.3 ± 8.8 years, 20 with T2DM) completed a 2-year prospective study consisting of MRI, blood sampling, and gait assessments. The whole brain vasoreactivity was quantified using continuous arterial spin labeling MRI. Gait speed during DTW was assessed by subtracting serial sevens. Dual-task cost was calculated as the percent change in gait speed from NW to DTW. In the entire cohort, higher glycemic profiles were associated with a slower gait speed. In the diabetic group, lower vasoreactivity was associated with a slower gait speed during NW ([Formula: see text] = 0.30, p = 0.019) and DTW ([Formula: see text] = 0.35, p = 0.01) and a higher dual-task cost ([Formula: see text] = 0.69, p = 0.009) at 2-year follow-up. The participants with T2DM and lower cerebral vasoreactivity had a greater decrease in gait speed during NW and DTW after the 2-year follow-up ([Formula: see text] = 0.17, p = 0.04 and [Formula: see text] = 0.28, p = 0.03, respectively). Longer diabetes duration was associated with a higher dual-task cost ([Formula: see text] = 0.19, p = 0.04) and a greater decrease in gait speed during NW ([Formula: see text] = 0.17, p = 0.02). These findings indicate that in older adults with type 2 diabetes, gait performance is highly dependent on the integrity of cerebrovascular regulation.

Relationship Between HIV Infection, Antiretroviral Therapy, Inflammatory Markers, and Cerebrovascular Endothelial Function Among Adults in Urban China.

Cerebrovascular risk is increased in people living with HIV infection compared with age-matched uninfected individuals. Cerebrovascular endothelial dysfunction related to antiretroviral therapy (ART) and inflammation may contribute to higher stroke risk in HIV infection. We compared cerebral vasoreactivity-a measure of cerebrovascular endothelial function assessed by the breath-holding index (BHI) using transcranial Doppler ultrasound-between virologically suppressed Chinese HIV-infected individuals followed in an HIV clinic in Beijing, China, and uninfected controls. We constructed mixed-effects models to evaluate the association of HIV, ART, and inflammatory markers with cerebral vasoreactivity. In an unadjusted model, HIV infection was associated with a trend toward lower cerebral vasoreactivity (BHI 1.08 versus 1.26, P = 0.079). In multivariable analyses, cholesterol modified the association between HIV infection and cerebral vasoreactivity (P = 0.015 for interaction). At a lower total cholesterol of 4.15 mmol/L, HIV was associated with lower cerebral vasoreactivity (BHI -0.28, P = 0.019), whereas at a cholesterol of 5.15 mmol/L, the reduction in cerebral vasoreactivity associated with HIV was no longer statistically significant (BHI -0.05, P = 0.64). Among HIV-infected individuals, use of lopinavir/ritonavir compared with efavirenz was associated with lower cerebral vasoreactivity (BHI -0.24, P = 0.040). We did not find a significant association between inflammatory markers and cerebral vasoreactivity. Cerebrovascular endothelial dysfunction associated with HIV infection may be most relevant for individuals with less traditional vascular risk, such as those with lower cholesterol. Further study of the impact of ART on cerebrovascular endothelial function is warranted to aid with ART selection in individuals at high cerebrovascular risk.

Cerebral vasoreactivity is impaired in treated, virally suppressed HIV-infected individuals.

To compare cerebral vasoreactivity, a measure of cerebrovascular endothelial function, between treated, virally suppressed HIV-infected individuals and HIV-uninfected controls and to evaluate the effect of HIV-specific factors on cerebral vasoreactivity. Cross-sectional study of 65 antiretroviral therapy-treated, virally suppressed HIV-infected individuals and 28 HIV-uninfected controls. Participants underwent noninvasive assessment of cerebral vasoreactivity using transcranial Doppler ultrasound and inhaled carbon dioxide (CO2). We used mixed effects multivariable linear regression to determine the association of HIV infection and HIV-specific factors with cerebral vasoreactivity. Mean age was 57.2 years for HIV-infected participants and 53.5 years for HIV-uninfected controls. Most participants (95%) were men. Twenty-six per cent of HIV-infected participants were nonwhite compared to 32% of controls. Among HIV-infected participants, mean CD4 cell count was 596 cells/μl, and mean duration of viral suppression was 7.8 years. Cerebral vasoreactivity in response to hypercapnia (cerebral VRhyper) was lower in HIV-infected individuals compared to uninfected controls (3.23 versus 3.81%, P = 0.010). After adjusting for demographic and vascular risk factors, HIV infection was independently associated with lower cerebral vasoreactivity (-0.86%, 95% CI -1.30 to -0.42%, P < 0.001). We did not find a statistically significant effect of recent or nadir CD4 cell count on cerebral vasoreactivity. There was a trend toward higher cerebral vasoreactivity for each additional year of viral suppression. Treated, virally suppressed HIV infection negatively impacted cerebral vasoreactivity even after adjustment for traditional vascular risk factors. These data highlight the potential contribution of cerebrovascular endothelial dysfunction to the elevated risk of stroke observed in HIV-infected individuals.

Ambient Temperature and Cerebrovascular Hemodynamics in the Elderly.

Background and PurposeSome prior studies have linked ambient temperature with risk of cerebrovascular events. If causal, the pathophysiologic mechanisms underlying this putative association remain unknown. Temperature-related changes in cerebral vascular function may play a role, but this hypothesis has not been previously evaluated.MethodsWe evaluated the association between ambient temperature and cerebral vascular function among 432 participants ≥65 years old from the MOBILIZE Boston Study with data on cerebrovascular blood flow, cerebrovascular resistance, and cerebrovascular reactivity in the middle cerebral artery. We used linear regression models to assess the association of mean ambient temperature in the previous 1 to 28 days with cerebrovascular hemodynamics adjusting for potential confounding factors.ResultsA 10°C increase in the 21-day moving average of ambient temperature was associated with a 10.1% (95% confidence interval [CI], 2.2%, 17.3%) lower blood flow velocity, a 9.0% (95% CI, 0.7%, 18.0%) higher cerebrovascular resistance, and a 15.3% (95%CI, 2.7%, 26.4%) lower cerebral vasoreactivity. Further adjustment for ozone and fine particulate matter (PM2.5) did not materially alter the results. However, we found statistically significant interactions between ambient temperature and PM2.5 such that the association between temperature and blood flow velocity was attenuated at higher levels of PM2.5.ConclusionsIn this elderly population, we found that ambient temperature was negatively associated with cerebral blood flow velocity and cerebrovascular vasoreactivity and positively associated with cerebrovascular resistance. Changes in vascular function may partly underlie the observed associations between ambient temperature and risk of cerebrovascular events.

Inflammation-associated declines in cerebral vasoreactivity and cognition in type 2 diabetes

The aim of this prospective study was to investigate the relationships between inflammation, cerebral vasoregulation, and cognitive decline in type 2 diabetes mellitus (T2DM) over a 2-year span. Sixty-five participants (aged 66 ± 9.2 years, 35 with T2DM, 33 women) were enrolled for this 2-year prospective study. Continuous arterial spin labeling at 3-tesla MRI was used to measure global and regional cerebral perfusion and vasoreactivity. Neuropsychological measures were evaluated at the beginning and completion of the study. The associations between serum inflammatory markers, regional cerebral vasoreactivity, and cognitive functions were examined using least squares models. After 2 years of follow-up, participants with T2DM had diminished global and regional cerebral vasoreactivity and a decline in multiple cognitive tasks compared with baseline (p < 0.0001-0.012). In the T2DM group, lower cerebral vasoreactivity was associated with a greater decrease in daily living activities score (r(2) adj = 0.35, p = 0.04), and lower global vasodilation was associated with a greater decline in executive function (r(2) adj = 0.6, p = 0.047). Higher serum soluble intercellular and vascular adhesion molecules, higher cortisol, and higher C-reactive protein levels at baseline were associated with greater decreases in cerebral vasoreactivity and vasodilation only in the T2DM group (r(2) adj = 0.16-0.53, p = 0.007-0.048), independent of diabetes control and 24-hour blood pressure. Higher glycated hemoglobin A1c levels were associated with a greater increase in vasoconstriction in the T2DM group. Inflammation may further impair cerebral vasoregulation, which consequently accelerates decline in executive function and daily activities performance in older people with T2DM.