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.

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 learned words, learning a name and address, recalling US presidents and UK prime ministers, and recalling the previously learned 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, the 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). CONCLUSION: 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.

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 assessment of neurovascular coupling with the Addenbrooke's Cognitive Examination: a functional transcranial Doppler ultrasonographic study.

Cerebrovascular dysfunction occurs early in dementia and can be identified by transcranial Doppler ultrasonography (TCD). Few studies have examined cerebral blood flow velocity (CBFv) responses to a detailed cognitive battery. This study aimed to characterize all CBFv responses, and the effect of hemispheric dominance, to the Addenbrooke's Cognitive Examination (ACE-III) in healthy volunteers. Forty volunteers 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, all tasks from the ACE-III were performed in 3 sections (A: attention, fluency, memory; B: language; C: visuospatial, memory). Data are population mean normalized percentage (PM%) change from a 20-s baseline period before task initiation. Forty bilateral data sets were obtained (27 women, 37 right-hand dominant). All paradigms produced a sharp increase in CBFv in both dominant (PM% range: 3.29 to 9.70%) and nondominant (PM% range: 4.34 to 11.63%) hemispheres at task initiation, with associated increases in MAP (PM% range: 3.06 to 16.04%). ETCO2 did not differ significantly at task initiation (PM% range: -1.1 to 2.4%, P > 0.05). HR differed significantly across A and C tasks at initiation (PM% range: -1.1 to 2.4%, P < 0.05), but not B tasks. In conclusion, all tasks resulted in increases in CBFv, differing significantly between paradigms. These results require further investigation in a cognitively impaired population. NEW & NOTEWORTHY This study is the first to provide a normative data set of cerebral blood flow velocity (CBFv) responses to a complete cognitive assessment (Addenbrooke's Cognitive Examination, ACE-III) in a large sample ( n = 40) of healthy volunteers. All tasks produced peak and sustained increases in CBFv to different extents. The ACE-III is a feasible tool to assess neurovascular coupling with transcranial Doppler ultrasonography. These data can be used to inform the most appropriate cognitive task to elicit CBFv responses for future studies.