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Introduction: Neurovascular coupling (NVC) is an important mechanism for the regulation of cerebral perfusion during intensive cognitive activity. Thus, it should be examined in terms of its effects on the regulation dynamics of cerebral perfusion and its possible alterations during cognitive impairment. The dynamic dependence of continuous changes in cerebral blood velocity (CBv), which can be measured noninvasively using transcranial Doppler upon fluctuations in arterial blood pressure (ABP) and CO2 tension, using end-tidal CO2 (EtCO2) as a proxy, can be quantified via data-based dynamic modeling to yield insights into two key regulatory mechanisms: the dynamic cerebral autoregulation (dCA) and dynamic vasomotor reactivity (DVR), respectively. Methods: Using the Laguerre Expansion Technique (LET), this study extracted such models from data in supine resting vs cognitively active conditions (during attention, fluency, and memory tasks from the Addenbrooke's Cognitive Examination III, ACE-III) to elucidate possible changes in dCA and DVR due to cognitive stimulation of NVC. Healthy volunteers (n = 39) were recruited at the University of Leicester and continuous measurements of CBv, ABP, and EtCO2 were recorded. Results: Modeling analysis of the dynamic ABP-to-CBv and CO2-to-CBv relationships showed significant changes in dCA, but not DVR, under cognitively active conditions compared to resting state. Discussion: Interpretation of these changes through Principal Dynamic Mode (PDM) analysis is discussed in terms of possible associations between stronger NVC stimulation during cognitive tasks and enhanced sympathetic activation. [ABSTRACT FROM AUTHOR]

Prior studies have identified variable effects of aging on neurovascular coupling (NVC). Carbon dioxide (CO2) affects both cerebral blood velocity (CBv) and NVC, but the effects of age on NVC under different CO2 conditions are unknown. Therefore, we investigated the effects of aging on NVC in different CO2 states during cognitive paradigms. Seventy-eight participants (18–78 yr), with well-controlled comorbidities, underwent continuous recordings of CBv by bilateral insonation of middle (MCA) and posterior (PCA) cerebral arteries (transcranial Doppler), blood pressure, end-tidal CO2, and heart rate during poikilocapnia, hypercapnia (5% CO2 inhalation), and hypocapnia (paced hyperventilation). Neuroactivation via visuospatial (VS) and attention tasks (AT) was used to stimulate NVC. Peak percentage and absolute change in MCAv/PCAv, were compared between CO2 conditions and age groups (≤30, 31–60, and >60 yr). For the VS task, in poikilocapnia, younger adults had a lower NVC response compared with older adults [mean difference (MD): −7.92% (standard deviation (SD): 2.37), P = 0.004], but comparable between younger and middle-aged groups. In hypercapnia, both younger [MD: −4.75% (SD: 1.56), P = 0.009] and middle [MD: −4.58% (SD: 1.69), P = 0.023] age groups had lower NVC responses compared with older adults. Finally, in hypocapnia, both older [MD: 5.92% (SD: 2.21), P = 0.025] and middle [MD: 5.44% (SD: 2.27), P = 0.049] age groups had greater NVC responses, compared with younger adults. In conclusion, the magnitude of NVC response suppression from baseline during hyper- and hypocapnia, did not differ significantly between age groups. However, the middle age group demonstrated a different NVC response while under hypercapnic conditions, compared with hypocapnia. NEW & NOTEWORTHY: This study describes the effects of age on neurovascular coupling under altered CO2 conditions. We demonstrated that both hypercapnia and hypocapnia suppress neurovascular coupling (NVC) responses. Furthermore, that middle age exhibits an NVC response comparable with younger adults under hypercapnia, and older adults under hypocapnia. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Cognitive training (CT) may be beneficial in delaying the onset or slowing dementia progression. CT has been evaluated quantitatively and qualitatively, but none have used mixed methods approaches.Objective: The aim of this study was to use a mixed methods approach to identify those who may selectively benefit from CT.Methods: This was an explanatory sequential mixed methods study involving a quantitative randomized trial of 12 weeks multi-domain CT in healthy older adults (HC, n = 20), and people living with mild cognitive impairment (MCI; n = 12) and dementia (n = 24). Quantitative outcomes included: cognition, mood, quality of life, and activities of daily living. 28 (10 HC, 6 MCI, 12 dementia) training participants completed semi-structured interviews with their carer. Quantitative and qualitative data were integrated using joint displays.Results: Three participants dropped out from the training early-on, leaving 25 participants with follow-up data for full integration (10 HC, 6 MCI, 9 dementia). Dropouts and lower adherence to training were more common in dementia participants with greater non-modifiable barriers. High adherers were more resilient to negative emotions, and poorer or fluctuating performance. Integrated analysis found the majority of participants (n = 24) benefited across outcomes, with no clear profile of individuals who benefited more than others. Participants made a number of key recommendations to improve adherence and minimize dropout to CT.Conclusion: Reasons for dropout and low adherence were identified, with recommendations provided for the design of CT for dementia. An individual approach to training should be adopted and low adherence should not preclude engagement with CT. [ABSTRACT FROM AUTHOR]

The origin of the directional sensitivity (DS) of dynamic cerebral autoregulation (dCA) is not known. In 140 healthy participants (67 male, 27.5 ± 6.1 years old), middle cerebral artery velocity (MCAv, transcranial Doppler), arterial blood pressure (ABP, Finometer), and end-tidal CO2 (EtCO 2 , capnography) were recorded at rest. Critical closing pressure (CrCP) and resistance-area product (RAP) were obtained for each cardiac cycle, as well as mean MCAv and ABP (MAP). The integrated positive and negative derivatives of MAP (MAP ‫D , MAP -D ) were used as simultaneous inputs to an autoregressive moving average model to generate two distinct MCAv step responses. Similar models allowed estimation of corresponding MAP-CrCP and MAP-RAP responses to step changes in MAP ‫D and MAP -D . The strength of directional sensitivity (ΔDS) was expressed by the difference in mean values of the step responses for the time interval 12-18 s. ΔDS was significant for MCAv (8.5 ± 46.9% vs 26.7 ± 42.0%, p<0.001) and RAP (-93.9 ± 48.1 vs -74.5 ± 43.0%, p<0.001), respectively for MAP ‫D and MAP -D inputs, but not for CrCP (2.2 ± 48.1% vs 0.72 ± 42.9%, p=0.76). Compared to males, female participants had higher MCAv (63.9 ± 15.6 cm/s vs 55.4 ± 12.9 cm/s, p<0.001), but lower EtCO 2 (p<0.001) and RAP (p=0.015). Sex did not influence ΔDS for any of the three step responses. The presence of directional sensitivity in the RAP, but not in the CrCP transfer function, suggests the origin could be solely myogenic, without metabolic involvement.

Introduction Frailty is a clinical syndrome of increased vulnerability to stressors. Frailty is associated with adverse outcomes after stroke, but frailty and transient ischaemic attack (TIA) are less well described. Methods Retrospective analysis of patients referred by the emergency department (ED) to TIA clinic (01/01/2016-12/03/2022), linked to hospital records for electronic follow-up. Only those with Clinical Frailty Scale (CFS) recorded within two weeks of clinic were included. Prevalence of frailty was determined based on CFS score >4. Hazard ratios (HR) for mortality were determined through Cox proportional hazard regression, adjusted for prognostic factors. Where repeat CFS data were available, temporal change in frailty was recorded (~15 months). Results Of 1185 patients included, 53.5% (n=634) had frailty. Patients with frailty tended to be older (median age 81 vs 74 years, p<0.001) and female (53.9% vs 39.9% p<0.001). Of 335 diagnosed with TIA following review, 61.2% (n=205) were frail. Prevalence of frailty by clinic diagnosis was: TIA 61.2% (205/335); stroke 46.7% (128/274); other diagnoses 52.3% (301/575). In TIA patients and the whole cohort (WC), frailty (TIA:HR:2.69 [95%CI:1.23-5.87, p=0.013], WC:2.58 [95%CI:1.64-4.08, p<0.001]) and increasing age [HR:1.07 95%CI:1.04-1.12], were predictive of mortality. In stroke patients, only increasing age was predictive of death (HR:1.11 [95%CI:1.04-1.19, p=0.003]). Of 414 patients with repeat CFS, median interval 15 months, median change was +1 point (IQR:0-2). Conclusion Frailty is common in TIA and becomes more common following TIA. Strength of association of frailty with poor outcome was greater for TIA patients than for those with stroke. Routine assessment of frailty may be a useful addition to TIA services., (S. Karger AG, Basel.)

Prior studies have identified variable effects of aging on neurovascular coupling (NVC). Carbon dioxide (CO 2 ) affects both cerebral blood velocity (CBv) and NVC, but the effects of age on NVC under different CO 2 conditions are unknown. Therefore, we investigated the effects of aging on NVC in different CO 2 states during cognitive paradigms. Seventy-eight participants (18-78 yr), with well-controlled comorbidities, underwent continuous recordings of CBv by bilateral insonation of middle (MCA) and posterior (PCA) cerebral arteries (transcranial Doppler), blood pressure, end-tidal CO 2 , and heart rate during poikilocapnia, hypercapnia (5% CO 2 inhalation), and hypocapnia (paced hyperventilation). Neuroactivation via visuospatial (VS) and attention tasks (AT) was used to stimulate NVC. Peak percentage and absolute change in MCAv/PCAv, were compared between CO 2 conditions and age groups (≤30, 31-60, and >60 yr). For the VS task, in poikilocapnia, younger adults had a lower NVC response compared with older adults [mean difference (MD): -7.92% (standard deviation (SD): 2.37), P = 0.004], but comparable between younger and middle-aged groups. In hypercapnia, both younger [MD: -4.75% (SD: 1.56), P = 0.009] and middle [MD: -4.58% (SD: 1.69), P = 0.023] age groups had lower NVC responses compared with older adults. Finally, in hypocapnia, both older [MD: 5.92% (SD: 2.21), P = 0.025] and middle [MD: 5.44% (SD: 2.27), P = 0.049] age groups had greater NVC responses, compared with younger adults. In conclusion, the magnitude of NVC response suppression from baseline during hyper- and hypocapnia, did not differ significantly between age groups. However, the middle age group demonstrated a different NVC response while under hypercapnic conditions, compared with hypocapnia. NEW & NOTEWORTHY This study describes the effects of age on neurovascular coupling under altered CO 2 conditions. We demonstrated that both hypercapnia and hypocapnia suppress neurovascular coupling (NVC) responses. Furthermore, that middle age exhibits an NVC response comparable with younger adults under hypercapnia, and older adults under hypocapnia.