Abstract

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 CO 2 (ETCO 2, 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); V BP (MAP), V CrCP (CrCP), and V RAP (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). V BP 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 ETCO 2, also differed significantly (P < 0.05). Changes in V RAP reflected changes in MAP, but in some paradigms atypical responses were seen. V CrCP 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.

Highlights

  • As the population ages, the world prevalence of dementia is expected to reach 131 million by 2050, with limited diagnostics and therapeutics presently available (Prince et al 2015; Alzheimer’s-society 2016)

  • Forty-eight volunteers were recruited to the study, of whom 40 participants had good quality bilateral data suitable for analysis

  • The mean ACE-III score for volunteers was high (98), with no participant falling below the cut-off for mild cognitive impairment (MCI) and dementia

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Summary

Introduction

The world prevalence of dementia is expected to reach 131 million by 2050, with limited diagnostics and therapeutics presently available (Prince et al 2015; Alzheimer’s-society 2016). Identifying an early, sensitive marker that can distinguish dementia from normal aging is of paramount importance to facilitate early intervention with novel therapeutics (Alzheimer’ssociety 2016). Transcranial Doppler ultrasonography (TCD) is a noninvasive technique which uses ultrasound to measure cerebral blood flow velocity (CBFv) in the intracranial arteries, including the middle cerebral artery (MCA) (van Beek et al 2008). It is advantaged by its portability, acceptability to patients, lack of ionizing radiation, and relative ease with which to train operators

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