Principal component analysis to identify the major contributors to task-activated neurovascular responses

Background: Consensus on the optimal metrics for neurovascular coupling (NVC) is lacking. The aim of this study was to use principal component analysis (PCA) to determine the most significant contributors to NVC responses in healthy adults (HC), Alzheimer's disease (AD), and mild cognitive impairment (MCI). New method: PCA was applied to three datasets: 1) 69 HC, 2) 30 older HC, 34 AD, and 22 MCI, 3) 1&2 combined. Data were extracted on peak percentage change in cerebral blood flow velocity (CBFv), variance ratio (VR), cross-correlation function peak (CCF), and blood pressure, for five cognitive tasks. An equamax rotation was applied and factors were significant where the eignevalue was ≥1. Rotated factor loadings ≥0.4 determined significant NVC variables. Results: PCA identified 12 significant factors accounting for 78% of variance (all datasets). Contributing variables loaded differently on the factors across the datasets. In datasets 1&2, peak percentage change in CBFv contributed to factors explaining the most variance (45–58%), whereas cognitive test scores, fluency and memory domains contributed the least (15–37%). In the combined dataset, CBFv, CCF and fluency domain contributed the majority (33–43%), whereas VR and attention the least (6–24%). Conclusions: Peak percentage change in CBFv and the visuospatial task consistently accounted for a large proportion of the variance, suggesting these are robust NVC markers for future studies

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

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

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