Challenging neurovascular coupling through complex and variable duration cognitive paradigms: A subcomponent analysis

A similar pattern of cerebral blood velocity (CBv) response has been observed for neurovascular coupling (NVC) assessment with cognitive tasks of varying complexity and duration. This lack of specificity could result from parallel changes in arterial blood pressure (BP) and PaCO2, which could confound the estimates of NVC integrity. Healthy participants (n = 16) underwent recordings at rest (5 min sitting) and during randomized paradigms of different complexity (naming words (NW) beginning with P-, R-, V- words and serial subtractions (SS) of 100–2, 100–7, 1000–17, with durations of 5, 30 and 60 s). Bilateral CBv (middle cerebral arteries, transcranial Doppler), end-tidal CO2 (EtCO2, capnography), blood pressure (BP, Finapres) and heart rate (HR, ECG) were recorded continuously. The bilateral CBv response to all paradigms was classified under objective criteria to select only responders, then the repeated data were averaged between visits. Bilateral CBv change to tasks was decomposed into the relative contributions (subcomponents) of arterial BP (VBP; neurogenic), critical closing pressure (VCrCP; metabolic) and resistance area product (VRAP; myogenic). A temporal effect was demonstrated in bilateral VBP and VRAP during all tasks (p<0.002), increased VBP early (between 0 and 10 s) and followed by decreases of VRAP late (25–35 s) in the response. VCrCP varied by complexity and duration (p<0.046). The main contributions to CBv responses to cognitive tasks of different complexity and duration were VBP and VRAP, whilst a smaller contribution from VCrCP would suggest sensitivity to metabolic demands. Further studies are needed to assess the influence of different paradigms, ageing and cerebrovascular conditions

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

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

Diagnostic test accuracy of remote, multidomain cognitive assessment (telephone and video call) for dementia

Background: Remote cognitive assessments are increasingly needed to assist in the detection of cognitive disorders, but the diagnostic accuracy of telephone- and video-based cognitive screening remains unclear. Objectives: To assess the test accuracy of any multidomain cognitive test delivered remotely for the diagnosis of any form of dementia. To assess for potential differences in cognitive test scoring when using a remote platform, and where a remote screener was compared to the equivalent face-to-face test. Search methods: We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group Specialized Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, LILACS, and ClinicalTrials.gov (www.clinicaltrials.gov/) databases on 2 June 2021. We performed forward and backward searching of included citations. Selection criteria: We included cross-sectional studies, where a remote, multidomain assessment was administered alongside a clinical diagnosis of dementia or equivalent face-to-face test. Data collection and analysis: Two review authors independently assessed risk of bias and extracted data; a third review author moderated disagreements. Our primary analysis was the accuracy of remote assessments against a clinical diagnosis of dementia. Where data were available, we reported test accuracy as sensitivity and specificity. We did not perform quantitative meta-analysis as there were too few studies at individual test level. For those studies comparing remote versus in-person use of an equivalent screening test, if data allowed, we described correlations, reliability, differences in scores and the proportion classified as having cognitive impairment for each test. Main results: The review contains 31 studies (19 differing tests, 3075 participants), of which seven studies (six telephone, one video call, 756 participants) were relevant to our primary objective of describing test accuracy against a clinical diagnosis of dementia. All studies were at unclear or high risk of bias in at least one domain, but were low risk in applicability to the review question. Overall, sensitivity of remote tools varied with values between 26% and 100%, and specificity between 65% and 100%, with no clearly superior test. Across the 24 papers comparing equivalent remote and in-person tests (14 telephone, 10 video call), agreement between tests was good, but rarely perfect (correlation coefficient range: 0.48 to 0.98). Authors' conclusions: Despite the common and increasing use of remote cognitive assessment, supporting evidence on test accuracy is limited. Available data do not allow us to suggest a preferred test. Remote testing is complex, and this is reflected in the heterogeneity seen in tests used, their application, and their analysis. More research is needed to describe accuracy of contemporary approaches to remote cognitive assessment. While data comparing remote and in-person use of a test were reassuring, thresholds and scoring rules derived from in-person testing may not be applicable when the equivalent test is adapted for remote use

The role of the autonomic nervous system in cerebral blood flow regulation in dementia: A review

In this review we will examine the role of the autonomic nervous system in the control of cerebral blood flow (CBF) in dementia. Worldwide, 55 million people currently live with dementia, and this figure will increase as the global population ages. Understanding the changes in vascular physiology in dementia could pave the way for novel therapeutic approaches. Reductions in CBF have been demonstrated in multiple dementia sub-types, in addition to increased cerebrovascular resistance and reduced vasoreactivity. Cerebral autoregulation (CA) is a key mechanism for the maintenance of cerebral perfusion, but remains largely intact in cognitive disorders, despite reductions in global and regional CBF. However, the tight coupling between neuronal activity and CBF (neurovascular coupling - NVC) is lost in dementia, which may be a key driver of cognitive dysfunction. Despite numerous studies investigating disturbances in the control of CBF in dementia, less is known about the specific mechanisms responsible for the observed changes. Disturbances could be related to one of a number of pathways and mechanisms including disruption of the autonomic component. In this review we will explore clinical and animal studies, which specifically investigated the autonomic component of CBF control in dementia, drawing on the clinical implications and potential for novel biomarker and therapeutic targets

The role of the autonomic nervous system in cerebral blood flow regulation in stroke: A review

Stroke is a pathophysiological condition which results in alterations in cerebral blood flow (CBF). The mechanism by which the brain maintains adequate CBF in presence of fluctuating cerebral perfusion pressure (CPP) is known as cerebral autoregulation (CA). Disturbances in CA may be influenced by a number of physiological pathways including the autonomic nervous system (ANS). The cerebrovascular system is innervated by adrenergic and cholinergic nerve fibers. The role of the ANS in regulating CBF is widely disputed owing to several factors including the complexity of the ANS and cerebrovascular interactions, limitations to measurements, variation in methods to assess the ANS in relation to CBF as well as experimental approaches that can or cannot provide insight into the sympathetic control of CBF. CA is known to be impaired in stroke however the number of studies investigating the mechanisms by which this occurs are limited. This literature review will focus on highlighting the assessment of the ANS and CBF via indices derived from the analyses of heart rate variability (HRV), and baroreflex sensitivity (BRS), and providing a summary of both clinical and animal model studies investigating the role of the ANS in influencing CA in stroke. Understanding the mechanisms by which the ANS influences CBF in stroke patients may provide the foundation for novel therapeutic approaches to improve functional outcomes in stroke patients