Cerebral vasomotor reactivity during hypo- and hypercapnia across the adult lifespan.

Age is the strongest risk factor for cerebrovascular disease; however, age-related changes in cerebrovascular function are still not well understood. The objective of this study was to measure cerebral vasomotor reactivity (CVMR) during hypo- and hypercapnia across the adult lifespan. One hundred fifty-three healthy participants (21-80 years) underwent measurements of cerebral blood flow velocity (CBFV) via transcranial Doppler, mean arterial pressure (MAP) via plethysmograph, and end-tidal CO2 (EtCO2) via capnography during hyperventilation (hypocapnia) and a modified rebreathing protocol (hypercapnia). Cerebrovascular conductance (CVCi) and resistance (CVRi) indices were calculated from the ratios of CBFV and MAP. CVMRs were assessed by the slopes of CBFV and CVCi in response to changes in EtCO2. The baseline CBFV and CVCi decreased and CVRi increased with age. Advanced age was associated with progressive declines in CVMR during hypocapnia indicating reduced cerebral vasoconstriction, but increases in CVMR during hypercapnia indicating increased vasodilation. A negative correlation between hypo- and hypercapnic CVMRs was observed across all subjects (CBFV%/ EtCO2: r = -0.419, CVCi%/ EtCO2: r = -0.442, P < 0.0001). Collectively, these findings suggest that aging is associated with decreases in CBFV, increases in cerebrovascular resistance, reduced vasoconstriction during hypocapnia, but increased vasodilatory responsiveness during hypercapnia.

Exercise Training in Amnestic Mild Cognitive Impairment: A One-Year Randomized Controlled Trial.

BACKGROUND: The current evidence is inconclusive to support the benefits of aerobic exercise training (AET) for preventing neurocognitive decline in patients with amnestic mild cognitive impairment (aMCI). OBJECTIVE: To examine the effect of a progressive, moderate-to-high intensity AET program on memory and executive function, brain volume, and cortical amyloid-ß (Aß) plaque deposition in aMCI patients. METHODS: This is a proof-of-concept trial that randomized 70 aMCI patients to 12 months of AET or stretching and toning (SAT, active control) interventions. Primary neuropsychological outcomes were assessed by using the California Verbal Learning Test-second edition (CVLT-II) and the Delis-Kaplan Executive Function System (D-KEFS). Secondary outcomes were the global and hippocampal brain volumes and the mean cortical and precuneus Aß deposition. RESULTS: Baseline cognitive scores were similar between the groups. Memory and executive function performance improved over time but did not differ between the AET and SAT groups. Brain volume decreased and precuneus Aß plaque deposition increased over time but did not differ between the groups. Cardiorespiratory fitness was significantly improved in the AET compared with SAT group. In amyloid positive patients, AET was associated with reduced hippocampal atrophy when compared with the SAT group. CONCLUSION: The AET and SAT groups both showed evidence of slightly improved neuropsychological scores in previously sedentary aMCI patients. However, these interventions did not prevent brain atrophy or increases in cortical Aß deposition over 12 months. In amyloid positive patients, AET reduced hippocampal atrophy when compared with the SAT group.

Ambulatory pulse pressure, brain neuronal fiber integrity, and cerebral blood flow in older adults.

Ambulatory blood pressure (ABP) reflects the end-organ vascular stress in daily life; however, its influence on brain neuronal fiber integrity and cerebral blood flow (CBF) remains unclear. The objective of this study was to determine the associations among ABP, white matter (WM) neuronal fiber integrity, and CBF in older adults. We tested 144 participants via ABP monitoring and diffusion tensor imaging. The total level and pulsatile indices of CBF were measured by phase-contrast MRI and transcranial Doppler, respectively. Neuropsychological assessment was conducted in 72 participants. Among ambulatory and office BP measures, elevated 24-h pulse pressure (PP) was associated with the greatest number of WM skeleton voxels with decreased fractional anisotropy (FA) and increased mean diffusivity (MD). Furthermore, these associations remained significant after adjusting for age, antihypertensive use, aortic stiffness, WM lesion volume, and office PP. Radial diffusivity (RD) was elevated in the regions with decreased FA, while axial diffusivity was unaltered. The reduction in diastolic index explained a significant proportion of the individual variability in FA, MD, and RD. Executive function performance was correlated with WM fiber integrity. These findings suggest that elevated ambulatory PP may deteriorate brain neuronal fiber integrity via reduction in diastolic index.

Cardiorespiratory Fitness and White Matter Neuronal Fiber Integrity in Mild Cognitive Impairment.

BACKGROUND: Mounting evidence showed the self-reported levels of physical activity are positively associated with white matter (WM) integrity and cognitive performance in normal adults and patients with mild cognitive impairment (MCI). However, the objective measure of cardiorespiratory fitness (CRF) was not used in these studies. OBJECTIVE: To determine the associations of CRF measured by maximal oxygen uptake (VO2max) with WM fiber integrity and neurocognitive performance in older adults with MCI. METHODS: Eighty-one participants (age = 65±7 years, 43 women), including 26 cognitively normal older adults and 55 amnestic MCI patients, underwent VO2max test to measure CRF, diffusion tensor imaging (DTI) to assess WM fiber integrity, and neurocognitive assessment focused on memory and executive function. DTI data were analyzed by the tract-based spatial statistics and region-of-interest approach. RESULTS: Cognitively normal older adults and MCI patients were not different in global WM fiber integrity and VO2max. VO2max was associated positively with DTI metrics of fractional anisotropy in ∼54% WM fiber tracts, and negatively with mean and radial diffusivities in ∼46% and ∼56% of the WM fiber tracts. The associations of VO2max with DTI metrics remained statistically significant after adjustment of age, sex, body mass index, WM lesion burden, and MCI status. The DTI metrics obtained from the area that correlated to VO2max were associated with executive function performance in MCI patients. CONCLUSIONS: Higher levels of CRF are associated with better WM fiber integrity, which in turn is correlated with better executive function performance in MCI patients.

Arterial Pressure, Heart Rate, and Cerebral Hemodynamics Across the Adult Life Span.

Age-related alterations in systemic and cerebral hemodynamics are not well understood. The purpose of this study is to characterize age-related alterations in beat-to-beat oscillations in arterial blood pressure (BP), heart rate (HR), cerebral blood flow (CBF), cardiac baroreflex sensitivity, and dynamic cerebral autoregulation across the adult life span. We studied 136 healthy adults aged 21 to 80 years (60% women). Beat-to-beat BP, HR, and CBF velocity were measured at rest and during sit-stand maneuvers to mimic effects of postural changes on BP and CBF. Transfer function analysis was used to assess baroreflex sensitivity and dynamic cerebral autoregulation. Carotid-femoral pulse wave velocity was measured to assess central arterial stiffness. Advanced aging was associated with elevated carotid-femoral pulse wave velocity, systolic and pulse BP, cerebrovascular resistance, and CBF pulsatility, but reduced mean CBF velocity. Compared with the young and middle-aged, older adults had lower beat-to-beat BP, HR, and CBF variability in the low-frequency ranges at rest, but higher BP and CBF variability during sit-stand maneuvers. Baroreflex sensitivity was reduced, whereas dynamic cerebral autoregulation gain was elevated at rest in older adults. Multiple linear regression analysis indicated that systolic BP variability is correlated positively with carotid-femoral pulse wave velocity independent of HR variability. In conclusion, advanced aging is associated with elevated pulsatility in BP and CBF; reduced beat-to-beat low-frequency oscillations in BP, HR, and CBF; and impaired baroreflex sensitivity and dynamic cerebral autoregulation at rest. The augmented BP and CBF variability in older adults during sit-stand maneuvers indicate diminished cardiovascular regulatory capability and increased hemodynamic stress on the cerebral circulation with aging.

Distribution of cardiac output to the brain across the adult lifespan.

A widely accepted dogma is that about 15-20% of cardiac output is received by the brain in healthy adults under resting conditions. However, it is unclear if the distribution of cardiac output directed to the brain alters across the adult lifespan and is modulated by sex or other hemodynamic variables. We measured cerebral blood flow/cardiac output ratio index in 139 subjects (88 women, age 21-80 years) using phase-contrast magnetic resonance imaging and echocardiography. Body mass index, cardiac systolic function (eject fraction), central arterial stiffness (carotid-femoral pulse wave velocity), arterial pressure, heart rate, physical fitness (VO2 max), and total brain volume were measured to assess their effects on the cardiac output-cerebral blood flow relationship. Cerebral blood flow/cardiac output ratio index decreased by 1.3% per decade associated with decreases in cerebral blood flow ( P < 0.001), while cardiac output remained unchanged. Women had higher cerebral blood flow, lower cardiac output, and thus higher cerebral blood flow/cardiac output ratio index than men across the adult lifespan. Age, body mass index, carotid-femoral pulse wave velocity, and arterial pressure all had negative correlations with cerebral blood flow and cerebral blood flow/cardiac output ratio index ( P < 0.05). Multivariable analysis adjusted for sex, age showed that only body mass index was negatively associated with cerebral blood flow/cardiac output ratio index (ß = -0.33, P < 0.001). These findings demonstrated that cardiac output distributed to the brain has sex differences and decreases across the adult lifespan and is inversely associated with body mass index.

Amyloid burden and sleep blood pressure in amnestic mild cognitive impairment.

OBJECTIVE: To determine whether cortical ß-amyloid (Aß) deposition is associated with circadian blood pressure (BP) profiles and dynamic cerebral blood flow (CBF) regulation in patients with amnestic mild cognitive impairment (aMCI). METHODS: Forty participants with aMCI were included in this study. Cortical Aß depositions were measured by (18)F-florbetapir PET and expressed as the standardized uptake value ratio (SUVR) relative to the cerebellum. Circadian BP profiles were measured by 24-hour ambulatory monitoring during awake and sleep periods. The dipping status of sleep BP (i.e., the percent changes from the awake BP) was calculated and dichotomized into the dipper (≥10%) and nondipper (<10%) groups. Dynamic CBF regulation was assessed by a transfer function analysis between beat-to-beat changes in BP and CBF velocity measured from the middle cerebral artery during a repeated sit-stand maneuver. RESULTS: Age was positively correlated with a greater Aß deposition in the posterior cingulate, precuneus, and mean cortex. Accounting for the age effect, attenuated reductions in sleep systolic BP were associated with higher levels of posterior cingulate SUVR. Consistently, the nondippers exhibited a higher SUVR in the posterior cingulate than the dippers. Transfer function gain between changes in BP and CBF velocity was diminished in the nondippers, and moreover those individuals with a lower gain exhibited a higher SUVR in the posterior cingulate. CONCLUSIONS: Attenuated reductions in sleep BP are associated with a greater Aß burden in the posterior cingulate and altered dynamic CBF regulation in patients with aMCI.