Vera Novak

The relationship between blood pressure and cognitive function

The relationship between blood pressure (BP) and cognitive outcomes in elderly adults has implications for global health care. Both hypertension and hypotension affect brain perfusion and worsen cognitive outcomes. The presence of hypertension and other vascular risk factors has been associated with decreased performance in executive function and attention tests. Cerebrovascular reserve has emerged as a potential biomarker for monitoring pressure–perfusion–cognition relationships. A decline in vascular reserve capacity can lead to impaired neurovascular coupling and decreased cognitive ability. Endothelial dysfunction, microvascular disease, and mascrovascular disease in midlife could also have an important role in the manifestations and severity of multiple medical conditions underlying cognitive decline late in life. However, questions remain about the role of antihypertensive therapies for long-term prevention of cognitive decline. In this Review, we address the underlying pathophysiology and the existing evidence supporting the role of vascular factors in late-life cognitive decline.

Hypocapnia and cerebral hypoperfusion in orthostatic intolerance

BACKGROUND AND PURPOSE Orthostatic and other stresses trigger tachycardia associated with symptoms of tremulousness, shortness of breath, dizziness, blurred vision, and, often, syncope. It has been suggested that paradoxical cerebral vasoconstriction during head-up tilt might be present in patients with orthostatic intolerance. We chose to study middle cerebral artery (MCA) blood flow velocity (BFV) and cerebral vasoregulation during tilt in patients with orthostatic intolerance (OI). METHODS Beat-to-beat BFV from the MCA, heart rate, CO2, blood pressure (BP), and respiration were measured in 30 patients with OI (25 women and 5 men; age range, 21 to 44 years; mean age, 31.3+/-1.2 years) and 17 control subjects (13 women and 4 men; age range, 20 to 41 years; mean age, 30+/-1.6 years); ages were not statistically different. These indices were monitored during supine rest and head-up tilt (HUT). We compared spontaneous breathing and hyperventilation and evaluated the effect of CO2 rebreathing in these 2 positions. RESULTS The OI group had higher supine heart rates (P<0.001) and cardiac outputs (P<0.01) than the control group. In response to HUT, OI patients underwent a greater heart rate increment (P<0.001) and greater reductions in pulse pressure (P<0.01) and CO2 (P<0.001), but total systemic resistance failed to show an increment. Among the cerebrovascular indices, all BFVs (systolic, diastolic, and mean) decreased significantly more, and cerebrovascular resistance (CVR) was increased in OI patients (P<0.01) compared with control subjects. In both groups, hyperventilation induced mild tachycardia (P<0.001), a significant reduction of BFV, and a significant increase of CVR associated with a fall in CO2. Hyperventilation during HUT reproduced hypocapnia, BFV reduction, and tachycardia and worsened symptoms of OI; these symptoms and indices were improved within 2 minutes of CO2 rebreathing. The relationships between CO2 and BFV and heart rate were well described by linear regressions, and the slope was not different between control subjects and patients with OI. CONCLUSIONS Cerebral vasoconstriction occurs in OI during orthostasis, which is primarily due to hyperventilation, causing significant hypocapnia. Hypocapnia and symptoms of orthostatic hypertension are reversible by CO2 rebreathing.

Physiological complexity and system adaptability: evidence from postural control dynamics of older adults

The degree of multiscale complexity in human behavioral regulation, such as that required for postural control, appears to decrease with advanced aging or disease. To help delineate causes and functional consequences of complexity loss, we examined the effects of visual and somatosensory impairment on the complexity of postural sway during quiet standing and its relationship to postural adaptation to cognitive dual tasking. Participants of the MOBILIZE Boston Study were classified into mutually exclusive groups: controls [intact vision and foot somatosensation, n = 299, 76 ± 5 (SD) yr old], visual impairment only (<20/40 vision, n = 81, 77 ± 4 yr old), somatosensory impairment only (inability to perceive 5.07 monofilament on plantar halluxes, n = 48, 80 ± 5 yr old), and combined impairments (n = 25, 80 ± 4 yr old). Postural sway (i.e., center-of-pressure) dynamics were assessed during quiet standing and cognitive dual tasking, and a complexity index was quantified using multiscale entropy analysis. Postural sway speed and area, which did not correlate with complexity, were also computed. During quiet standing, the complexity index (mean ± SD) was highest in controls (9.5 ± 1.2) and successively lower in the visual (9.1 ± 1.1), somatosensory (8.6 ± 1.6), and combined (7.8 ± 1.3) impairment groups (P = 0.001). Dual tasking resulted in increased sway speed and area but reduced complexity (P < 0.01). Lower complexity during quiet standing correlated with greater absolute (R = -0.34, P = 0.002) and percent (R = -0.45, P < 0.001) increases in postural sway speed from quiet standing to dual-tasking conditions. Sensory impairments contributed to decreased postural sway complexity, which reflected reduced adaptive capacity of the postural control system. Relatively low baseline complexity may, therefore, indicate control systems that are more vulnerable to cognitive and other stressors.

Enhanced gray and white matter contrast of phase susceptibility-weighted images in ultra-high-field magnetic resonance imaging

To evaluate if magnetic susceptibility sensitive phase postprocessed images can be used to enhance the inherent brain/gray white matter contrast in gradient echo (GE) images at 8‐Tesla (T) magnetic resonance (MR).

Foot Pressure Distribution During Walking in Young and Old Adults

BackgroundMeasurement of foot pressure distribution (FPD) is clinically useful for evaluation of foot and gait pathologies. The effects of healthy aging on FPD during walking are not well known. This study evaluated FPD during normal walking in healthy young and elderly subjects.MethodsWe studied 9 young (30 ± 5.2 years), and 6 elderly subjects (68.7 ± 4.8 years). FPD was measured during normal walking speed using shoe insoles with 99 capacitive sensors. Measured parameters included gait phase characteristics, mean and maximum pressure and force, and relative load.Time-series measurements of each variable for all sensors were grouped into 9 anatomical masks.ResultsElderly subjects had lower normalized maximum pressure for the medial and lateral calcaneal masks, and for all medial masks combined. In the medial calcaneus mask, the elderly group also had a lower absolute maximum and lower mean and normalized mean pressures and forces, compared to young subjects. Elderly subjects had lower maximum force and normalized maximum force and lower mean force and normalized mean forces in the medial masks as well.ConclusionFPD differences between the young and elderly groups were confined to the calcaneus and hallux regions and to the medial side of the foot. In elderly subjects, weight bearing on the lateral side of the foot during heel touch and toe-off phases may affect stability during walking.

Time-frequency mapping of R-R interval during complex partial seizures of temporal lobe origin.

BACKGROUND Activation of autonomic nervous system is common with seizures. No reliable biological markers of impending seizures have been found. Evaluation of autonomic changes might help elucidate the transition from interictal to ictal states. METHODS We studied twelve patients (eight females, four males), from 19 to 62 years old with temporal lobe complex partial seizures (CPS). Dynamics of autonomic functions from oscillations in R-R interval (RRI) using time-frequency mapping based upon a Wigner distribution during pre-ictal, ictal and post-ictal periods. Oscillations in RRI at respiratory frequencies (RF) (> 0.1 Hz) are parasympathetically mediated and at nonrespiratory frequencies (NONRF) (0.01-0.09 Hz) are under combined sympathetic and parasympathetic influence. RESULTS CPS evoked marked autonomic imbalance and tachycardia. Spectral powers at both RF_RRI and NONRF_RRI increased over the pre-ictal period. RF_RRI power then fell rapidly over the 30 s before seizure onset and remained markedly reduced during seizure (P < 0.004). NONRF_RRI power reached a maximum at seizure onset and declined to a minimum before the seizure cessation (P < 0.05). CONCLUSION Time-frequency analysis revealed that autonomic activation hallmarks clinical seizure onset for several minutes. After combined parasympathetic and sympathetic activation, rapid parasympathetic withdrawal occurred approximately 30 s before the seizure, and sympathetic activation peaks at seizure onset. Therefore, the transition from interictal to ictal states is relatively long and associated with subclinical autonomic changes.

Effect of step-synchronized vibration stimulation of soles on gait in Parkinson's disease: a pilot study

BackgroundPrevious studies have suggested that impaired proprioceptive processing in the striatum may contribute to abnormal gait in Parkinsons disease (PD).MethodsThis pilot study assessed the effects of enhanced proprioceptive feedback using step-synchronized vibration stimulation of the soles (S-VS) on gait in PD. S-VS was used in 8 PD subjects (3 women and 5 men, age range 44–79 years, on medication) and 8 age-matched healthy subjects (5 women and 3 men). PD subjects had mild or moderate gait impairment associated with abnormal balance, but they did not have gait freezing. Three vibratory devices (VDs) were embedded in elastic insoles (one below the heel and two below the forefoot areas) inserted into the shoes. Each VD operates independently and has a pressure switch that activates the underlying vibratory actuator. The VD delivered the 70-Hz suprathreshold vibration pulse upon touch by the heel or forefoot, and the vibration pulse was deactivated upon respective push-offs. Six-minute hallway walking was studied with and without S-VS. Gait characteristics were measured using the force-sensitive foot switches. The primary outcome was the stride variability expressed as a coefficient of variation (CV), a measure of gait steadiness. Secondary outcome measures were walking distance and speed, stride length and duration, cadence, stance, swing and double support duration, and respective CVs (if applicable).ResultsThe walking speed (p < 0.04) and the CV of the stride interval (p < 0.02) differed between the groups and S-VS conditions. In the PD group, S-VS decreased stride variability (p < 0.002), increased walking speed (p < 0.0001), stride duration (p < 0.01), stride length (p < 0.0002), and cadence (p < 0.03). In the control group, S-VS decreased stride variability (p < 0.006) and increased gait speed (p < 0.03), but other locomotion parameters were not significantly altered.ConclusionAugmented sensory feedback improves parkinsonian gait steadiness in the short-term setting. Because the suprathreshold stimulation prevented blinding of subjects, the learning effect and increased attention can be a confounding factor underlying results. Long-term studies are needed to establish the clinical value of the S-VS.

Enhancement of Vasoreactivity and Cognition by Intranasal Insulin in Type 2 Diabetes

OBJECTIVE To determine acute effects of intranasal insulin on regional cerebral perfusion and cognition in older adults with type 2 diabetes mellitus (DM). RESEARCH DESIGN AND METHODS This was a proof-of-concept, randomized, double-blind, placebo-controlled intervention evaluating the effects of a single 40-IU dose of insulin or saline on vasoreactivity and cognition in 15 DM and 14 control subjects. Measurements included regional perfusion, vasodilatation to hypercapnia with 3-Tesla MRI, and neuropsychological evaluation. RESULTS Intranasal insulin administration was well tolerated and did not affect systemic glucose levels. No serious adverse events were reported. Across all subjects, intranasal insulin improved visuospatial memory (P ≤ 0.05). In the DM group, an increase of perfusion after insulin administration was greater in the insular cortex compared with the control group (P = 0.0003). Cognitive performance after insulin administration was related to regional vasoreactivity. Improvements of visuospatial memory after insulin administration in the DM group (R2adjusted = 0.44, P = 0.0098) and in the verbal fluency test in the control group (R2adjusted = 0.64, P = 0.0087) were correlated with vasodilatation in the middle cerebral artery territory. CONCLUSIONS Intranasal insulin administration appears safe, does not affect systemic glucose control, and may provide acute improvements of cognitive function in patients with type 2 DM, potentially through vasoreactivity mechanisms. Intranasal insulin-induced changes in cognitive function may be related to vasodilatation in the anterior brain regions, such as insular cortex that regulates attention-related task performance. Larger studies are warranted to identify long-term effects and predictors of positive cognitive response to intranasal insulin therapy.

Multimodal pressure-flow method to assess dynamics of cerebral autoregulation in stroke and hypertension

BackgroundThis study evaluated the effects of stroke on regulation of cerebral blood flow in response to fluctuations in systemic blood pressure (BP). The autoregulatory dynamics are difficult to assess because of the nonstationarity and nonlinearity of the component signals.MethodsWe studied 15 normotensive, 20 hypertensive and 15 minor stroke subjects (48.0 ± 1.3 years). BP and blood flow velocities (BFV) from middle cerebral arteries (MCA) were measured during the Valsalva maneuver (VM) using transcranial Doppler ultrasound.ResultsA new technique, multimodal pressure-flow analysis (MMPF), was implemented to analyze these short, nonstationary signals. MMPF analysis decomposes complex BP and BFV signals into multiple empirical modes, representing their instantaneous frequency-amplitude modulation. The empirical mode corresponding to the VM BP profile was used to construct the continuous phase diagram and to identify the minimum and maximum values from the residual BP (BPR) and BFV (BFVR) signals. The BP-BFV phase shift was calculated as the difference between the phase corresponding to the BPR and BFVR minimum (maximum) values. BP-BFV phase shifts were significantly different between groups. In the normotensive group, the BFVR minimum and maximum preceded the BPR minimum and maximum, respectively, leading to large positive values of BP-BFV shifts.ConclusionIn the stroke and hypertensive groups, the resulting BP-BFV phase shift was significantly smaller compared to the normotensive group. A standard autoregulation index did not differentiate the groups. The MMPF method enables evaluation of autoregulatory dynamics based on instantaneous BP-BFV phase analysis. Regulation of BP-BFV dynamics is altered with hypertension and after stroke, rendering blood flow dependent on blood pressure.

Altered cerebral vasoregulation in hypertension and stroke

Background: Autoregulation of blood flow that maintains steady perfusion over the range of systemic blood pressure is compromised by stroke. Objectives: To determine whether cerebral vasoregulation is impaired in stroke during orthostatic stress. Methods: Subjects included 30 control subjects, 30 with hypertension, and 20 with minor stroke and were studied using transcranial Doppler. Bilateral blood flow velocities (BFVs) from middle cerebral arteries, heart rate, blood pressure (BP), and CO2 were obtained during hyperventilation and CO2 rebreathing during supine rest and tilt at 80°. Side-to-side BFV difference, vasomotor range (VMR), and cerebrovascular resistance (CVR) were calculated during normo-, hypo-, and hypercapnia. Results: Mean BFVs were similar between groups in supine position but differed during tilt. BFV diminished on the stroke side during tilt with hyperventilation and CO2 rebreathing (p < 0.0001). CVR increased (p < 0.0001) and VMR decreased (p < 0.01) on the stroke side. Vasoregulation was preserved on the normal side. BFV asymmetry differentiated patients with stroke from the other groups (p < 0.0001). BFV difference between the normal vs stroke side was the largest in stroke-normotensive (n = 7) compared with stroke-hypertensive (n = 13) patients and the two other groups (p < 0.0001). BFV asymmetry in stroke was associated with lower orthostatic BP (p < 0.0001). Conclusions: Cerebral vasoregulation is impaired with minor stroke, and cerebral blood flow depends on blood pressure. Decline of blood flow velocities during orthostatic stress may pose a risk of silent hypoperfusion.