Dynamic cerebral autoregulation measurement using rapid changes in head positioning: experiences in acute ischemic stroke and healthy control populations

The ideal technique for dynamic cerebral autoregulation (dCA) assessment in critically ill patients should provide considerable variability in blood pressure (BP) but without the need for patient cooperation. We proposed using rapid head positioning (RHP) over spontaneous BP fluctuations for dCA assessment in patients with acute ischemic stroke (AIS). Cerebral blood velocity (transcranial Doppler), beat-to-beat BP (Finometer), and end-tidal CO2 (capnography) were recorded during 5-min baseline and RHP in 16 controls (8 women and 8 men, mean age: 57 ± 16 yr) and 15 patients with AIS (7 women and 8 men, mean age: 69 ± 8 yr) at two (12 ± 8 days) and three visits (13.3 ± 6.9 h, 4.8 ± 3.2 days, and 93.9 ± 11.5 days from the symptom onset), respectively. All participants were able to complete the RHP protocol without difficulty. Compared with controls, patients with AIS were hypocapnic (all visits, P < 0.0024) and hypertensive ( visit 1, P = 0.011), although BP gradually reduced after the acute phase. RHP demonstrated greater beat-to-beat BP variability (BPV) in controls ( visits 1 and 2, P < 0.001) but not in patients with AIS at any visit. Compared with controls, a reduced autoregulation index (ARI) was demonstrated in patients with AIS, at visit 2 for the baseline recording but not at other visits or during RHP. The area under the receiver-operating curve was 0.53 and 0.54 for baseline and RHP, respectively. The RHP paradigm required minimal patient cooperation and could be considered a feasible alternative for assessing dCA, mainly in conditions leading to increased BPV. The lack of BPV increase in AIS with RHP deserves further investigation. NEW & NOTEWORTHY This study used rapid head positioning (RHP) to enhance blood pressure (BP) variability (BPV) to improve BP signal-to-noise ratio and reliability of dynamic cerebral autoregulation (dCA). RHP was well accepted by controls and acute ischemic stroke (AIS); the increased BPV induced in controls was not observed in AIS, suggesting BPV at rest was already elevated. RHP did not improve detection of impaired CA in AIS; further work is needed to understand the different responses observed

Inter-subject analysis of transfer function coherence in studies of dynamic cerebral autoregulation

Objective: The gain and phase of the arterial blood pressure (BP)-cerebral blood flow velocity (CBFV) relationship, assessed by transfer function analysis (TFA), are widely used dynamic cerebral autoregulation (CA) metrics, but their reliability depend on the statistical significance of the magnitude squared coherence (MSC) function. We tested a new approach, based on inter-subject data, to estimate the confidence limits of MSC. Approach: Five minute beat-to-beat time series of mean arterial BP (MAP, Finometer) and CBFV (transcranial Doppler) were used for intra-subject (MAP and CBFV from same subject) and inter-subject (BP and CBFV swapped between subjects) estimates of MSC. The 95% confidence limit of MSC was obtained by non-parametric methods for the cases of single frequency harmonics in the range [0.02-0.50 Hz], and also from the mean value of all possible frequency intervals in this range. Main results: Intra-subject estimates of MSC were obtained from 100 healthy subjects (48 female, age range: 21-82 years old) allowing calculation of 9,900 inter-subject estimates, with 95% confidence limits in excellent agreement with classical values derived from surrogate random data. Confidence limits of MSC, derived from mean values, decreased asymptotically to around 0.16 with the increasing number of harmonics averaged. Significance: Replacing estimates of MSC at a single frequency harmonic by the mean calculated over the range [0.02-0.30 Hz] could lead to more robust studies of dynamic CA with greater acceptance of recordings, an important consideration in clinical studies where measurements tend to be more susceptible to noise and artefacts.

Reproducibility of task activation using the Addenbrooke's cognitive examination in healthy controls: A functional Transcranial Doppler ultrasonography study

Introduction Cerebral blood flow velocity (CBFv) changes occurring with cognitive stimulation can be measured by Transcranial Doppler ultrasonography (TCD). The aim of this study was to assess the reproducibility of CBFv changes to the Addenbrooke's cognitive examination (ACE-III). New method 13 volunteers underwent bilateral TCD (middle cerebral artery), continuous heart rate (HR, 3-lead ECG, Finometer), beat-to-beat mean arterial pressure (MAP, Finometer), and end-tidal CO2 (ETCO2, capnography). After 5 min baseline, all ACE-III tasks were performed in 3 domains (A/B/C). Data presented are population CBFv peak normalised changes and area under the curve (AUC). Statistical analysis was by 2-way repeated measures (ANOVA), intra-class correlation coefficient (ICC), standard error of measurement (SEM) and coefficient of variation (CV). Results 12 bilateral data sets were obtained (10 right hand dominant, 6 female). Baseline parameters (MAP, HR, ETCO2) did not differ between visits. All tasks increased CBFv. Only domain A on AUC analysis differed significantly on ANOVA, and one task on post hoc testing (p < 0.05). ICC values were poor (<0.4) for most tasks, but 3 tasks produced more consistent results on AUC and peak CBFv analysis (range ICC: 0.15–0.73, peak CV: 16.2–56.1(%), AUC CV: 23.2–60.2(%), peak SEM: 2.5–6.0 (%), AUC SEM: 21.8–135.8 (%*s). Comparison with existing methods This is the first study to examine reproducibility of CBFv changes to a complete cognitive assessment tool. Conclusions Reproducibility of CBFv measurements to the ACE-III was variable. AUC may provide more reliable estimates than peak CBFv responses. These data need validating in patient populations

How many squat-stand manoeuvres to assess dynamic cerebral autoregulation?

PURPOSE: Squat-stand manoeuvres (SSMs) have been used to induce blood pressure (BP) changes for the reliable assessment of dynamic cerebral autoregulation. However, they are physically demanding and thus multiple manoeuvres can be challenging for older subjects. This study aimed to determine the minimum number of SSMs required to obtain satisfactory coherence, thus minimising the subjects' workload. METHOD: 20 subjects performed SSMs at a frequency of 0.05 Hz. End-tidal CO2, cerebral blood flow velocity, heart rate, continuous BP and the depth of the squat were measured. 11 subjects returned for a repeat visit. The time points at which subjects had performed 3, 6, 9, 12 and 15 SSMs were determined. Transfer function analysis was performed on files altered to the required length to obtain estimates of coherence and the autoregulation index (ARI). RESULTS: After three SSMs, coherence (0.05 Hz) was 0.93 ± 0.05, and peaked at 0.95 ± 0.02 after 12 manoeuvres. ARI decreased consecutively with more manoeuvres. ARI was comparable across the two visits (p = 0.92), but coherence was significantly enhanced during the second visit (p < 0.01). The intra-subject coefficients of variation (CoV) for ARI remained comparable as the number of manoeuvres varied. CONCLUSIONS: This analysis can aid those designing SSM protocols, especially where participants are unable to tolerate a standard 5-min protocol or when a shorter protocol is needed to accommodate additional tests. We emphasise that fewer manoeuvres should only be used in exceptional circumstances, and where possible a full set of manoeuvres should be performed. Furthermore, these results need replicating at 0.10 Hz to ensure their applicability to different protocols

The Assessment of Cerebrovascular Response to a Language Task from the Addenbrooke's Cognitive Examination in Cognitive Impairment: A Feasibility Functional Transcranial Doppler Ultrasonography Study

Background: The incidence of dementia is predicted to rise rapidly, but sensitive diagnostic tests remain elusive. Changes in cerebral blood flow velocity (CBFv) can occur at an early stage of cognitive decline, and can be measured by transcranial Doppler ultrasonography (TCD). Objective: The aim of this study was to characterize the CBFv changes that occur in healthy older adults (HC), mild cognitive impairment (MCI), and Alzheimer's disease (AD), in response to a language task from the Addenbrooke's cognitive examination (ACE-III). Methods: Participants underwent bilateral TCD, continuous heart rate (ECG), end-tidal CO2 (capnography, ETCO2), and beat-to-beat blood pressure (Finometer, MAP), monitoring, during a 5-minute baseline, followed by cognitive tasks from the ACE-III. Data are presented for a language task (repeating words and phrases aloud), as peak percentage change in CBFv, HR, MAP, and ETCO2 from a normalized baseline. Results: 30 participants (mean age 73.2 years, 20% female) were recruited; HC (n = 10), MCI (n = 10), AD (n = 10). Language scores did not differ between groups (p = 0.16). Peak percentage change in CBFv differed between groups with the language task (HC: 15.9 (7.5)%, MCI: 6.7 (4.5)%, AD: 0.1 (7.1)%; p < 0.005). However, changes in MAP (HC: 7.9 (4.6)%, MCI: -0.1 (0.9)%, AD: 0.9 (4.4)%; p < 0.005), HR (HC: 8.8 (8.2)%, MCI: 0.7 (4.3)%, AD: -0.5 (5.6)%; p = 0.005), and ETCO2 (HC: -0.9 (3.2)%, MCI: 0.9 (3.2)%, AD: -5.2 (5.7)%; p = 0.006), also occurred. Conclusions: TCD measured CBFv changes to a language task from the ACE-III was feasible in a cognitively impaired population, further work is required in a larger population

Neurovascular coupling response to cognitive examination in healthy controls: a multivariate analysis.

Cognitive testing with transcranial Doppler ultrasonography (TCD) has been used to assess neurovascular coupling (NVC), but few studies address its multiple contributions. Subcomponent analysis considers the relative myogenic (resistance area product, RAP) and metabolic (critical closing pressure (CrCP)) contributors. The aim of this study was to investigate the changes in subcomponents that occur with cognitive stimulation with the Addenbrooke's Cognitive Examination (ACE-III) in healthy controls. Healthy volunteers underwent continuous recording of bilateral TCD, heart rate (HR, three-lead ECG), end-tidal CO2 (ETCO2 , capnography), and mean arterial pressure (MAP, Finometer). The study comprised a 5-min baseline recording, followed by all 20 paradigms from the ACE-III. The cerebral blood flow velocity (CBFv) response was decomposed into the relative contributions (subcomponents); VBP (MAP), VCrCP (CrCP), and VRAP (RAP). Data are presented as peak population normalized mean changes from baseline, and median area under the curve (AUC). Forty bilateral datasets were obtained (27 female, 37 right hand dominant). VBP increased at task initiation in all paradigms but differed between tasks (range (SD): 4.06 (8.92)-16.04 (12.23) %, P < 0.05). HR, but not ETCO2 , also differed significantly (P < 0.05). Changes in VRAP reflected changes in MAP, but in some paradigms atypical responses were seen. VCrCP AUC varied significantly within paradigm sections (range [SD]: 18.4 [24.17] to 244.21 [243.21] %*s, P < 0.05). All paradigms demonstrated changes in subcomponents with cognitive stimulation, and can be ranked based on their relative presumed metabolic demand. The integrity of NVC requires further investigation in patient populations

Increased blood pressure variability following acute stroke is associated with poor long-term outcomes: a systematic review.

BACKGROUND: Blood pressure variability (BPV) in acute ischemic stroke (AIS) may be of prognostic significance. However, methodological heterogeneity of studies may contribute to inconsistent findings, and study findings are therefore not readily comparable. We investigated study methodologies which have assessed the long-term outcomes (≥7 days) of BPV post-AIS. MATERIALS AND METHODS: The literature search was conducted in OVID Medline, Embase, The Cochrane Library, and Web of Science following a predefined search strategy. Two reviewers independently assessed study eligibility and quality, and source data were extracted. RESULTS: Of 2044 studies identified, 19 observational studies and one case-control study were included; seven studies were additionally included. Twenty-two studies obtained good risk of bias ratings. Key findings were methodological heterogeneity and significant variability in the reporting of key criteria. Twenty-four studies reported intervals between blood pressure assessments; although 19 studies reported the monitoring device used, only eight studies reported the number of blood pressure measurements taken per visit. The majority measured supine blood pressure (n=13), and eight studies reported whether this was in the hemiparetic or unaffected arm. Sixteen studies defined BPV using SD and seven studies used only a single blood pressure parameter to quantify BPV. Increased BPV was associated with poorer neurological and functional outcomes, and death (n=23); other unfavorable outcomes included irregularly shaped lacunar infarcts, and impaired cognition (n=3). CONCLUSION: Methodological heterogeneity is frequently observed in studies, primarily because of incomplete study reporting. However, increased BPV is associated with adverse long-term outcomes. There is a need for prospective studies investigating BPV post-AIS to report full methodologies according to standardized criteria

Addenbrooke's Cognitive Examination III (ACE-III) and mini-ACE for the detection of dementia and mild cognitive impairment

This is a protocol for a Cochrane Review (Diagnostic test accuracy). The objectives are as follows: To assess the diagnostic test accuracy of the Addenbrooke's Cognitive Examination-III (ACE-III) and the mini-ACE, for the screening of all-cause dementia, dementia subtypes (Alzheimer's disease, vascular dementia, frontotemporal dementia, Lewy body dementia), and mild cognitive impairment, across all healthcare settings at all prespecified thresholds

Polypharmacy in older vascular surgery inpatients

Introduction: Polypharmacy is common in older people and is associated with mortality and hospital readmission. The prevalence of polypharmacy in vascular patients is not well described. Methods: Retrospective audit of all patients aged >65 years admitted to a single vascular surgery unit for ≥24 hours during a 10-week study period (20/4/17 – 28/6/17). Data collected included age, gender, admission type, diagnoses, medications and length of stay (LoS). Results: 87 admissions were included. Mean age was 78 [±7.6], 67 [77.0%] patients were male, 63 [72.4%] had unplanned admissions and 40 [46.0%] were admitted with severe limb ischaemia. Median number of medications on admission was 8 [IQR:6-10]. Excessive polypharmacy (defined as ≥10 medications) was present in 27 [31.0%] patients and was not associated with age, gender, admission type or diagnosis (binary logistic regression analysis). Overall, median LoS was 6 days [IQR:3-11.5] and was similar in patients with and without excessive polypharmacy (7 days [IQR:2.5-11.5] vs 6 days [IQR:3-11.25] respectively). 40 [46.0%] patients were discharged on ≥1 more medications than admission; only 9 [10.3%] patients were discharged on ≥1 fewer medications. 33 [37.9%] patients were discharged on more than three high-risk medications, with the only associated patient factor being number of high-risk medications on admission [OR=15.80; 95%CI=3.03-34.80; p<.001] (ordinal logistic regression analysis). Conclusion: Polypharmacy, including prescription of multiple high-risk medications, is highly prevalent amongst older vascular surgery inpatients. Further research is needed to understand the association of polypharmacy on outcomes and determine strategies to reduce the prescribing of unnecessary medications. Take-home message: Polypharmacy is common amongst older vascular surgery inpatients although more research is needed to understand its associations with outcomes from vascular surgery

The Effects of Healthy Ageing on Cerebral Blood Flow Responses to Cognitive Testing.

Background Transcranial Doppler Ultrasonography (TCD) can be utilised to measure the tight coupling of cerebral blood flow velocity (CBFv) in response to cognitive demand by task activation, termed neurovascular coupling. AIMS: To investigate the differences in neurovascular coupling between healthy older (>50 years) and younger (18-49 years) adults in response to cognitive testing. METHODS: Fifty-four older (n=25) and younger (n=29) adults underwent continuous bilateral TCD, beat-to-beat blood pressure (MAP; Finapres), heart rate (HR; electrocardiogram), and end-tidal CO2 (ETCO2; capnography) monitoring. After a 5-min baseline period, memory (M1-4: recalling three learnt words, learning a name and address, recalling US presidents and UK prime ministers, and recalling the previously learnt name and address) and visuospatial (V1-4: drawing a cube and infinity diagram, drawing a clock face, counting dots, and recognising obscured letters) tasks from the Addenbrooke's Cognitive Examination (ACE-III) were performed. Data are mean (standard deviation). RESULTS: In the memory paradigms, peak percentage change in CBFv differed significantly between younger and older groups only in the dominant hemisphere during the M1 task, (2.17 (9.16)% vs. 8.38 (9.27)%, respectively, p=0.017). In the visuospatial paradigm, there were also significant differences in peak percentage change in CBFv between younger and older groups in the V1 (5.87 (8.32)% vs. 11.89 (6.60)%, p=0.005) and V2 tasks (6.30 (8.72)% vs. 11.30 (7.77)%, p=0.032). Conclusions Healthy older adults demonstrate augmented cerebrovascular physiology in response to cognitive challenge compared to younger adults. The impact of abnormal ageing on cerebrovascular physiology, for example related to cognitively impaired states, requires further investigation