Determinants of cerebral blood flow velocity change during squat-stand maneuvers.

The large changes in mean arterial blood pressure (MABP) and cerebral blood flow velocity (CBFV) induced by squat-stand maneuvers (SSM) make this approach particularly suited for studying dynamic cerebral autoregulation (CA). However, the role of other systemic determinants of CBFV has not been described and could provide alternative physiological interpretations of SSM results. In 32 healthy subjects (16 female), continuous recordings of MABP (Finometer), bilateral CBFV (transcranial Doppler, MCA), end-tidal CO2 (EtCO2; capnography), and heart rate (HR; electrocardiogram) were performed for 5 min standing at rest, and during 15 SSM at the frequency of 0.05 Hz. A time-domain, multivariate dynamic model estimated the CBFV variance explained by different inputs, corresponding to significant contributions from MABP (P < 0.00001), EtCO2 (P < 0.0001), and HR (P = 0.041). The autoregulation index (ARI; range 0-9) was estimated from the CBFV response to a step change in MABP. At rest, ARI values (typically 5.7) were independent of the number of model inputs, but during SSM, ARI was reduced compared with baseline (P < 0.0001), and the three input model yielded lower values for the right and left MCA (3.4 ± 1.2, 3.1 ± 1.3) when compared with the single-input MABP-CBFV model (4.1 ± 1.1, 3.9 ± 1.0; P < 0.0001). The high coherence of the MABP-CBFV transfer function at 0.05 Hz (typically 0.98) was considerably reduced (around 0.71-0.73; P < 0.0001) when the contribution of CBFV covariates was taken into account. Not taking into consideration other determinants of CBFV, in addition to MABP, could be misleading and introduce biases in physiological and clinical studies.

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

BACKGROUND: The number of new cases of dementia is projected to rise significantly over the next decade. Thus, there is a pressing need for accurate tools to detect cognitive impairment in routine clinical practice. The Addenbrooke's Cognitive Examination III (ACE-III), and the mini-ACE are brief, bedside cognitive screens that have previously reported good sensitivity and specificity. The quality and quantity of this evidence has not, however, been robustly investigated. OBJECTIVES: To assess the diagnostic test accuracy of the ACE-III and mini-ACE for the detection of dementia, dementia sub-types, and mild cognitive impairment (MCI) at published thresholds in primary, secondary, and community care settings in patients presenting with, or at high risk of, cognitive decline. SEARCH METHODS: We performed the search for this review on 13 February 2019. We searched MEDLINE (OvidSP), Embase (OvidSP), BIOSIS Previews (ISI Web of Knowledge), Web of Science Core Collection (ISI Web of Knowledge), PsycINFO (OvidSP), and LILACS (BIREME). We applied no language or date restrictions to the electronic searches; and to maximise sensitivity we did not use methodological filters. The search yielded 5655 records, of which 2937 remained after we removed duplicates. We identified a further four articles through PubMed 'related articles'. We found no additional records through reference list citation searching, or grey literature. SELECTION CRITERIA: Cross-sectional studies investigating the accuracy of the ACE-III or mini-ACE in patients presenting with, or at high risk of, cognitive decline were suitable for inclusion. We excluded case-control, delayed verification and longitudinal studies, and studies which investigated a secondary cause of dementia. We did not restrict studies by language; and we included those with pre-specified thresholds (88 and 82 for the ACE-III, and 21 or 25 for the mini-ACE). DATA COLLECTION AND ANALYSIS: We extracted information on study and participant characteristics and used information on dementia and MCI prevalence, sensitivity, specificity, and sample size to generate 2×2 tables in Review Manager 5. We assessed methodological quality of included studies using the QUADAS-2 tool; and we assessed the quality of study reporting with the STARDdem tool. Due to significant heterogeneity in the included studies and an insufficient number of studies, we did not perform meta-analyses. MAIN RESULTS: This review identified seven studies (1711 participants in total) of cross-sectional design, four examining the accuracy of the ACE-III, and three of the mini-ACE. Overall, the majority of studies were at low or unclear risk of bias and applicability on quality assessment. Studies were at high risk of bias for the index test (n = 4) and reference standard (n = 2). Study reporting was variable across the included studies. No studies investigated dementia sub-types. The ACE-III had variable sensitivity across thresholds and patient populations (range for dementia at 82 and 88: 82% to 97%, n = 2; range for MCI at 88: 75% to 77%, n = 2), but with more variability in specificity (range for dementia: 4% to 77%, n = 2; range for MCI: 89% to 92%, n = 2). Similarly, sensitivity of the mini-ACE was variable (range for dementia at 21 and 25: 70% to 99%, n = 3; range for MCI at 21 and 25: 64% to 95%, n = 3) but with more variability specificity (range for dementia: 32% to 100%, n = 3; range for MCI: 46% to 79%, n = 3). We identified no studies in primary care populations: four studies were conducted in outpatient clinics, one study in an in-patient setting, and in two studies the settings were unclear. AUTHORS' CONCLUSIONS: There is insufficient information in terms of both quality and quantity to recommend the use of either the ACE-III or mini-ACE for the screening of dementia or MCI in patients presenting with, or at high risk of, cognitive decline. No studies were conducted in a primary care setting so the accuracy of the ACE-III and mini-ACE in this setting are not known. Lower thresholds (82 for the ACE-III, and 21 for the mini-ACE) provide better specificity with acceptable sensitivity and may provide better clinical utility. The ACE-III and mini-ACE should only be used to support the diagnosis as an adjunct to a full clinical assessment. Further research is needed to determine the utility of the ACE-III and mini-ACE for the detection of dementia, dementia sub-types, and MCI. Specifically, the optimal thresholds for detection need to be determined in a variety of settings (primary care, secondary care (inpatient and outpatient), and community services), prevalences, and languages.

Directional sensitivity of dynamic cerebral autoregulation during spontaneous fluctuations in arterial blood pressure at rest.

Directional sensitivity, the more efficient response of cerebral autoregulation to increases, compared to decreases, in mean arterial pressure (MAP), has been demonstrated with repeated squat-stand maneuvers (SSM). In 43 healthy subjects (26 male, 23.1 ± 4.2 years old), five min. recordings of cerebral blood velocity (bilateral Doppler ultrasound), MAP (Finometer), end-tidal CO2 (capnograph), and heart rate (ECG) were obtained during sitting (SIT), standing (STA) and SSM. A new analytical procedure, based on autoregressive-moving average models, allowed distinct estimates of the autoregulation index (ARI) by separating the MAP signal into its positive (MAP+D) and negative (MAP-D) derivatives. ARI+D was higher than ARI-D (p < 0.0001), SIT: 5.61 ± 1.58 vs 4.31 ± 2.16; STA: 5.70 ± 1.24 vs 4.63 ± 1.92; SSM: 4.70 ± 1.11 vs 3.31 ± 1.53, but the difference ARI+D-ARI-D was not influenced by the condition. A bootstrap procedure determined the critical number of subjects needed to identify a significant difference between ARI+D and ARI-D, corresponding to 24, 37 and 38 subjects, respectively, for SSM, STA and SIT. Further investigations are needed on the influences of sex, aging and other phenotypical characteristics on the phenomenon of directional sensitivity of dynamic autoregulation.

Age-related differences in cerebrovascular responses to cognitive stimulation using a novel method.

Aging is associated with a number of alterations to cerebrovascular function. We aimed to investigate the effect of age on cerebrovascular responses to cognitive stimulation using an objective two-parameter method.Previously derived from a large data-set (135 healthy participants) were applied to a task-activated dataset of 69 healthy participants in five different task conditions. Cumulative response rate (CRR) was calculated as the sum of responses across tasks and hemispheres.There was a significant effect of age (adjusted odds ratio: 1.02 (95% confidence interval: 1.01, 1.04), p = 0.016). There was also a significant effect of task (p = 0.002), but there was no significant interaction between age and task (p = 0.37). Increasing age was associated with increased CRR (adjusted odds ratio: 1.04 (95% confidence interval: 1.01, 1.07), p = 0.009).Using an objective two-parameter method, healthy older adults had increased cerebrovascular responses to cognitive testing.

Does depth of squat-stand maneuver affect estimates of dynamic cerebral autoregulation?

Repeated squat-stand maneuvers (SSM) are an effective way of measuring dynamic cerebral autoregulation (dCA), but the depth of SSM required to improve dCA estimations has never been studied. We compared beat-to-beat cerebral hemodynamic parameters between maximal depth SSM (SSMD ) and a shallower alternative (SSMS ) in two age groups (younger [20-34 years] vs. older [50-71 years]) at a frequency of 0.05 Hz. Cerebral blood flow velocity, continuous blood pressure (BP) and end-tidal CO2 (EtCO2 ) were measured using transcranial Doppler ultrasound, the Finometer device, and capnography, respectively. Coherence (at 0.05 Hz) was significantly higher in both SSM recordings compared to spontaneous BP oscillations at baseline standing (BS ). Median (IQR) autoregulation index (ARI) was reduced during SSMD (4.46 [4.03-5.22], p < .01) compared to SSMS (5.96 [5.40-6.69]) and BS (6.03 [5.20-6.49], p < .01) with similar relative differences also observed for phase (at 0.05 Hz). End-tidal CO2 was increased in SSMD (38.3 ± 3.7 mmHg, p < .01) compared to both SSMS (36.6 ± 3.6 mmHg) and BS (35.5 ± 3.2 mmHg). The older group demonstrated significantly lower ARI and phase estimates during SSM and found SSMS more effortful than SSMD . In conclusion, both SSMD and SSMS are effective at estimating dCA, and dCA appears to be less efficient during maximal depth SSM compared to baseline rest or a shallower alternative.

An objective method to identify non-responders in neurovascular coupling testing.

BACKGROUND: Neurovascular coupling (NVC) can be assessed using transcranial Doppler (TCD) measured task-activation of cerebral blood flow velocity (CBFv). However, not all individuals show consistent responses. The aim of this study was to develop a robust, objective, method to identify non-responders to task-activation. NEW METHOD: Using five-minute seated resting (non-stimulated), bilateral CBFv data from 135 healthy participants, the cross-correlation function peak (CCF) between the population coherent average and each individual was obtained for a randomly selected segment of data (40 s) for both hemispheres (n = 270). The variance ratio (VR) was calculated by comparing the variance in CBFv data pre- and post-random mark. The 90th percentile for non-stimulated data was used to determine the upper confidence limit of normal variation in the CCF peak value (0.53), and VR (2.59). These criteria were then applied to task-activated CBFv from 69 healthy participants for five cognitive tasks (attention, verbal fluency, language, visuospatial, memory). RESULTS: Data were accepted as responders if either CCF ≥ 0.53 or VR ≥ 2.59. The number of cases accepted as responders for each task were as follows: attention, 54-59 (78-86 %); verbal fluency, 42-48 (60-70 %); language, 51-53 (74-77 %); visuospatial, 54 (78 %); memory, 40-47 (58-68 %). COMPARISON WITH EXISTING METHOD: Currently, there are no objective criteria for the identification of non-responders in studies of NVC. This is a new method to objectively classify non-responders to task-activation. CONCLUSIONS: Using a large sample of resting CBFv data, we have set objective criteria to differentiate between responders and non-responders in task activation protocols.