The effect of CO2 on the age dependence of neurovascular coupling.

Prior studies have identified variable effects of healthy 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 in healthy controls during cognitive paradigms. 78 healthy participants (18-78 years) 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) augmented CBv. Peak percentage change in MCAv/PCAv, were compared between CO2 conditions and age groups (< 30, 31-60, and >60 years). For the VS task, in normocapnia, younger adults had a lower NVC response compared to 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 to 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 to younger adults. In conclusion, the middle-aged adults demonstrated a variable NVC response, comparable to younger adults under hypercapnia, and older adults under hypocapnia. This may owe to a more cognitively favourable profile while under hypercapnic conditions, compared to hypocapnia.

Determinants of the dynamic cerebral critical closing pressure response to changes in mean arterial pressure.

Objective. Cerebral critical closing pressure (CrCP) represents the value of arterial blood pressure (BP) where cerebral blood flow (CBF) becomes zero. Its dynamic response to a step change in mean BP (MAP) has been shown to reflect CBF autoregulation, but robust methods for its estimation are lacking. We aim to improve the quality of estimates of the CrCP dynamic response.Approach. Retrospective analysis of 437 healthy subjects (aged 18-87 years, 218 males) baseline recordings with measurements of cerebral blood velocity in the middle cerebral artery (MCAv, transcranial Doppler), non-invasive arterial BP (Finometer) and end-tidal CO2(EtCO2, capnography). For each cardiac cycle CrCP was estimated from the instantaneous MCAv-BP relationship. Transfer function analysis of the MAP and MCAv (MAP-MCAv) and CrCP (MAP-CrCP) allowed estimation of the corresponding step responses (SR) to changes in MAP, with the output in MCAv (SRVMCAv) representing the autoregulation index (ARI), ranging from 0 to 9. Four main parameters were considered as potential determinants of the SRVCrCPtemporal pattern, including the coherence function, MAP spectral power and the reconstruction error for SRVMAP, from the other three separate SRs.Main results. The reconstruction error for SRVMAPwas the main determinant of SRVCrCPsignal quality, by removing the largest number of outliers (Grubbs test) compared to the other three parameters. SRVCrCPshowed highly significant (p< 0.001) changes with time, but its amplitude or temporal pattern was not influenced by sex or age. The main physiological determinants of SRVCrCPwere the ARI and the mean CrCP for the entire 5 min baseline period. The early phase (2-3 s) of SRVCrCPresponse was influenced by heart rate whereas the late phase (10-14 s) was influenced by diastolic BP.Significance. These results should allow better planning and quality of future research and clinical trials of novel metrics of CBF regulation.

The Effect of Translation and Cultural Adaptations on Diagnostic Accuracy and Test Performance in Dementia Cognitive Screening Tools: A Systematic Review.

Background: The current cognitive tests have been developed based on and standardized against Western constructs and normative data. With older people of minority ethnic background increasing across Western countries, there is a need for cognitive screening tests to address factors which influence performance bias and timely diagnostic dementia accuracy. The diagnostic accuracy in translated and culturally adapted cognitive screening tests and their impact on test performance in diverse populations have not been well addressed to date. Objective: This review aims to highlight considerations relating to the adaptation processes, language, cultural influences, impact of immigration, and level of education to assess for dementia in non-Western and/or non-English speaking populations. Methods: We conducted a systematic search for studies addressing the effects of translation and cultural adaptations of cognitive screening tests (developed in a Western context) upon their diagnostic accuracy and test performance across diverse populations. Four electronic databases and manual searches were conducted, using a predefined search strategy. A narrative synthesis of findings was conducted. Results: Search strategy yielded 2,890 articles, and seventeen studies (4,463 participants) met the inclusion criteria. There was variability in the sensitivity and specificity of cognitive tests, irrespective of whether they were translated only, culturally adapted only, or both. Cognitive test performance was affected by education, linguistic ability, and aspects of acculturation. Conclusions: We highlight the importance of translating and culturally adapting tests that have been developed in the Western context. However, these findings should be interpreted with caution as results varied due to the broad selection of included cognitive tests.

Statistical Complexity Analysis of Neurovascular Coupling with Cognitive Stimulation in Healthy Subjects.

Neurovascular coupling (NVC) is the tight relationship between changes in cerebral blood flow and neural activation. NVC can be evaluated non-invasively using transcranial Doppler ultrasound (TCD)-measured changes in brain activation (cerebral blood velocity [CBv]) using different cognitive tasks and stimuli. This study used a novel approach to analyzing CBv changes occurring in response to 20 tasks from the Addenbrooke's Cognitive Examination III in 40 healthy individuals. The novel approach compared various information entropy families (permutation, Tsallis, and Rényi entropy) and statistical complexity measures based on disequilibrium. Using this approach, we found the majority of the attention, visuospatial, and memory tasks from the Addenbrooke's Cognitive Examination III that showed lower statistical complexity values when compared with the resting state. On the entropy-complexity (HC) plane, a receiver operating characteristic curve was used to distinguish between baseline and cognitive tasks using the area under the curve. Best area under the curve values were 0.91 ± 0.04, p = .001, to distinguish between resting and cognitively active states. Our findings show that brain hemodynamic signals captured with TCD can be used to distinguish between resting state (baseline) and cognitive effort (stimulation paradigms) using entropy and statistical complexity as an alternative method to traditional techniques such as coherent averaging of CBv signals. Further work should directly compare these analysis methods to identify the optimal method for analyzing TCD-measured changes in NVC.

Individual Patient Data Meta-Analysis of Dynamic Cerebral Autoregulation and Functional Outcome After Ischemic Stroke.

BACKGROUND: The relationship between dynamic cerebral autoregulation (dCA) and functional outcome after acute ischemic stroke (AIS) is unclear. Previous studies are limited by small sample sizes and heterogeneity. METHODS: We performed a 1-stage individual patient data meta-analysis to investigate associations between dCA and functional outcome after AIS. Participating centers were identified through a systematic search of the literature and direct invitation. We included centers with dCA data within 1 year of AIS in adults aged over 18 years, excluding intracerebral or subarachnoid hemorrhage. Data were obtained on phase, gain, coherence, and autoregulation index derived from transfer function analysis at low-frequency and very low-frequency bands. Cerebral blood velocity, arterial pressure, end-tidal carbon dioxide, heart rate, stroke severity and sub-type, and comorbidities were collected where available. Data were grouped into 4 time points after AIS: <24 hours, 24 to 72 hours, 4 to 7 days, and >3 months. The modified Rankin Scale assessed functional outcome at 3 months. Modified Rankin Scale was analyzed as both dichotomized (0 to 2 versus 3 to 6) and ordinal (modified Rankin Scale scores, 0-6) outcomes. Univariable and multivariable analyses were conducted to identify significant relationships between dCA parameters, comorbidities, and outcomes, for each time point using generalized linear (dichotomized outcome), or cumulative link (ordinal outcome) mixed models. The participating center was modeled as a random intercept to generate odds ratios with 95% CIs. RESULTS: The sample included 384 individuals (35% women) from 7 centers, aged 66.3±13.7 years, with predominantly nonlacunar stroke (n=348, 69%). In the affected hemisphere, higher phase at very low-frequency predicted better outcome (dichotomized modified Rankin Scale) at <24 (crude odds ratios, 2.17 [95% CI, 1.47-3.19]; P<0.001) hours, 24-72 (crude odds ratios, 1.95 [95% CI, 1.21-3.13]; P=0.006) hours, and phase at low-frequency predicted outcome at 3 (crude odds ratios, 3.03 [95% CI, 1.10-8.33]; P=0.032) months. These results remained after covariate adjustment. CONCLUSIONS: Greater transfer function analysis-derived phase was associated with improved functional outcome at 3 months after AIS. dCA parameters in the early phase of AIS may help to predict functional outcome.

Tratamiento antiagregante plaquetario oral para el ictus isquémico agudo: una revisión Cochrane / Oral antiplatelet therapy for acute ischaemic stroke: a Cochrane review

Pregunta de la revisión. Queríamos comparar la seguridad y la eficacia del tratamiento antiplaquetario oral frente a placebo o ningún tratamiento en personas con ictus isquémico agudo para ver si los antiplaquetarios orales reducían el número de muertes y mejoraban los resultados a largo plazo en los supervivientes. Fundamento. La mayoría de los ictus están causados por una obstrucción repentina de una arteria del cerebro que suele deberse a un coágulo de sangre (lo que se denomina ictus isquémico). El tratamiento inmediato con antiagregantes plaquetarios, como la aspirina, puede evitar la formación de nuevos coágulos y mejorar así la recuperación tras el ictus. Sin embargo, los antiagregantes plaquetarios también pueden provocar hemorragias cerebrales, lo que podría anular sus efectos beneficiosos. Características del estudio. Se identificaron 11 estudios, hasta agosto de 2020, para su inclusión en la revisión. Estos estudios incluyeron 42.226 participantes. Tres eran nuevos ensayos desde la última actualización. Como en la versión anterior de esta revisión, dos estudios aportaron el 96% de los datos. La mayoría de los participantes en la revisión eran ancianos, con una proporción significativa de más de 70 años. Los hombres y las mujeres estaban representados casi por igual en los ensayos. Parecía haber alguna variación en la gravedad del accidente cerebrovascular entre los ensayos incluidos. La duración programada del tratamiento varió de 5 días a 3 meses y el periodo de seguimiento programado varió de 10 días a 6 meses. Resultados clave. La aspirina, en dosis de 160 mg a 300 mg diarios, iniciada en las 48 horas siguientes a la aparición de los síntomas del ictus, salvó vidas y redujo el riesgo de que se produjera un nuevo ictus en las dos primeras semanas... (AU)

Depression of dynamic cerebral autoregulation during neural activation: The role of responders and non-responders.

Neurovascular coupling (NVC) interaction with dynamic cerebral autoregulation (dCA) remains unclear. We investigated the effect of task complexity and duration on the interaction with dCA. Sixteen healthy participants (31.6 ± 11.6 years) performed verbal fluency (naming-words (NW)) and serial subtraction (SS) paradigms, of varying complexity, at durations of 05, 30 and 60 s. The autoregulation index (ARI), was estimated from the bilateral middle cerebral artery blood velocity (MCAv) step response, calculated by transfer function analysis (TFA), for each paradigm during unstimulated (2 min) and neuroactivated (1 min) segments. Intraclass correlation (ICC) and coefficient of variation (CV) determined reproducibility for two visits and objective criteria were applied to classify responders (R) and non-responders (NoR) to task-induced MCAv increase. ICC values demonstrated fair reproducibility in all tasks. ARI decreased in right (RH) and left (LH) hemispheres, irrespective of paradigm complexity and duration (p < 0.0001). Bilateral ARI estimates were significantly decreased during NW for the R group only (p < 0.0001) but were reduced in both R (p < 0.0001) and NoR (p = 0.03) groups for SS tasks compared with baseline. The reproducible attenuation of dCA efficiency due to paradigm-induced NVC response, its interaction, and different behaviour in R and NoR, warrant further research in different physiological and clinical conditions.

Culture-Fair Cognitive Screening Tools for Assessment of Cognitive Impairment: A Systematic Review.

Background: Cognitive screening tools are important in the detection of dementia, including Alzheimer's disease; however, they may contain cultural biases. Objective: This review examines culture-fair cognitive screening tools and evaluates their screening accuracy, strengths, and limitations. Methods: Medline, Embase, PsychINFO and CINAHL were searched. The protocol was registered on PROSPERO (CRD42021288776). Included studies used a culture-fair tool to assess cognition in older adults from varying ethnicities. Narrative synthesis was conducted. Results: 28 studies were included assessing eleven different tools. The Rowland Universal Dementia Assessment Scale (RUDAS) was as accurate as the Mini-Mental State Examination (MMSE) (AUC 0.62-0.93), with a similar sensitivity (52-94%) and better specificity (70-98%), and the Multicultural Cognitive Examination (MCE) had improved screening accuracy (AUC 0.99) compared to RUDAS (AUC 0.92). The Visual Cognitive Assessment Test (VCAT) was equivalent to MMSE (AUC 0.84-0.91). The Kimberley Indigenous Cognitive Assessment tool (KICA) had AUC of 0.93-0.95; sensitivity of 90.6%, specificity 92.6%. Conclusions: The RUDAS, KICA and VCAT were superior to MMSE for screening dementia in ethnic minorities. Other tools also showed good screening accuracy. Further research should be done to validate tools in different populations.

Tratamiento antiagregante plaquetario oral para el ictus isquémico agudo: una revisión Cochrane / Oral antiplatelet therapy for acute ischaemic stroke: a Cochrane review

Pregunta de la revisión. Queríamos comparar la seguridad y la eficacia del tratamiento antiplaquetario oral frente a placebo o ningún tratamiento en personas con ictus isquémico agudo para ver si los antiplaquetarios orales reducían el número de muertes y mejoraban los resultados a largo plazo en los supervivientes. Fundamento. La mayoría de los ictus están causados por una obstrucción repentina de una arteria del cerebro que suele deberse a un coágulo de sangre (lo que se denomina ictus isquémico). El tratamiento inmediato con antiagregantes plaquetarios, como la aspirina, puede evitar la formación de nuevos coágulos y mejorar así la recuperación tras el ictus. Sin embargo, los antiagregantes plaquetarios también pueden provocar hemorragias cerebrales, lo que podría anular sus efectos beneficiosos. Características del estudio. Se identificaron 11 estudios, hasta agosto de 2020, para su inclusión en la revisión. Estos estudios incluyeron 42.226 participantes. Tres eran nuevos ensayos desde la última actualización. Como en la versión anterior de esta revisión, dos estudios aportaron el 96% de los datos. La mayoría de los participantes en la revisión eran ancianos, con una proporción significativa de más de 70 años. Los hombres y las mujeres estaban representados casi por igual en los ensayos. Parecía haber alguna variación en la gravedad del accidente cerebrovascular entre los ensayos incluidos. La duración programada del tratamiento varió de 5 días a 3 meses y el periodo de seguimiento programado varió de 10 días a 6 meses. Resultados clave. La aspirina, en dosis de 160 mg a 300 mg diarios, iniciada en las 48 horas siguientes a la aparición de los síntomas del ictus, salvó vidas y redujo el riesgo de que se produjera un nuevo ictus en las dos primeras semanas... (AU)

The effect of hypercapnia on the directional sensitivity of dynamic cerebral autoregulation and the influence of age and sex.

The cerebral circulation responds differently to increases in mean arterial pressure (MAP), compared to reductions in MAP. We tested the hypothesis that this directional sensitivity is reduced by hypercapnia. Retrospective analysis of 104 healthy subjects (46 male (44%), age range 19-74 years), with five minute recordings of middle cerebral blood velocity (MCAv, transcranial Doppler), non-invasive MAP (Finometer) and end-tidal CO2 (capnography) at rest, during both poikilocapnia and hypercapnia (5% CO2 breathing in air) produced MCAv step responses allowing estimation of the classical Autoregulation Index (ARIORIG), and corresponding values for both positive (ARI+D) and negative (ARI-D) changes in MAP. Hypercapnia led to marked reductions in ARIORIG, ARI+D and ARI-D (p < 0.0001, all cases). Females had a lower value of ARIORIG compared to males (p = 0.030) at poikilocapnia (4.44 ± 1.74 vs 4.74 ± 1.48) and hypercapnia (2.44 ± 1.93 vs 3.33 ± 1.61). The strength of directional sensitivity (ARI+D-ARI-D) was not influenced by hypercapnia (p = 0.46), sex (p = 0.76) or age (p = 0.61). During poikilocapnia, ARI+D decreased with age in females (p = 0.027), but not in males. Directional sensitivity was not affected by hypercapnia, suggesting that its origins are more likely to be inherent to the mechanics of vascular smooth muscle than to myogenic pathways.

The effect of relative hypotension on 30-day mortality in older people receiving emergency care.

Research has observed increased mortality among older people attending the emergency department (ED) who had systolic pressure > 7 mmHg lower than baseline primary care values. This study aimed to (1) assess feasibility of identifying this 'relative hypotension' using readily available ED data, (2) externally validate the 7 mmHg threshold, and (3) refine a threshold for clinically important relative hypotension. A single-centre retrospective cohort study linked year 2019 data for ED attendances by people aged over 64 to hospital discharge vital signs within the previous 18 months. Frailty and comorbidity scores were calculated. Previous discharge ('baseline') vital signs were subtracted from initial ED values to give individuals' relative change. Cox regression analysis compared relative hypotension > 7 mmHg with mean time to mortality censored at 30 days. The relative hypotension threshold was refined using a fully adjusted risk tool formed of logistic regression models. Receiver operating characteristics were compared to NEWS2 models with and without incorporation of relative systolic. 5136 (16%) of 32,548 ED attendances were linkable with recent discharge vital signs. Relative hypotension > 7 mmHg was associated with increased 30-day mortality (HR 1.98; 95% CI 1.66-2.35). The adjusted risk tool (AUC: 0.69; sensitivity: 0.61; specificity: 0.68) estimated each 1 mmHg relative hypotension to increase 30-day mortality by 2% (OR 1.02; 95% CI 1.02-1.02). 30-day mortality prediction was marginally better with NEWS2 (AUC: 0.73; sensitivity: 0.59; specificity: 0.78) and NEWS2 + relative systolic (AUC: 0.74; sensitivity: 0.63; specificity: 0.75). Comparison of ED vital signs with recent discharge observations was feasible for 16% individuals. The association of relative hypotension > 7 mmHg with 30-day mortality was externally validated. Indeed, any relative hypotension appeared to increase risk, but model characteristics were poor. These findings are limited to the context of older people with recent hospital admissions.

Dynamic cerebral autoregulation in Alzheimer's disease and mild cognitive impairment: A systematic review.

Dynamic cerebral autoregulation (dCA) is a key mechanism that regulates cerebral blood flow (CBF) in response to transient changes in blood pressure (BP). Impairment of dCA could increase vulnerability to hypertensive vascular damage, but also to BP lowering effects of antihypertensive treatment. The literature remains conflicted on whether dCA is altered in Alzheimer's disease (AD) and mild cognitive impairment (MCI). We summarized available data on dCA in AD and MCI, by searching PubMed, Embase, PsycINFO and Web of Science databases (inception-January 2022). Eight studies (total n = 443) were included in the qualitative synthesis of which seven were eligible for meta-analysis. All studies used Transcranial Doppler (TCD) ultrasonography and transfer function analysis or the autoregulatory index to assess dCA during spontaneous or induced BP fluctuations. Meta-analysis indicated no significant difference between AD, MCI and healthy controls in dCA parameters for spontaneous fluctuations. For induced fluctuations, the available data were limited, but indicative of at least preserved and possibly better autoregulatory functioning in AD and MCI compared to controls. In summary, current evidence does not suggest poorer dCA efficiency in AD or MCI. Further work is needed to investigate dCA in dementia with induced fluctuations controlling for changes in end-tidal carbon dioxide.

Cognitive testing following transient ischaemic attack: A systematic review of clinical assessment tools.

Cognitive deficits are prevalent after transient ischaemic attack (TIA) and result in loss of function, poorer quality of life and increased risks of dependency and mortality. This systematic review aimed to synthesise the available evidence on cognitive assessment in TIA patients to determine the prevalence of cognitive deficits, and the optimal tests for cognitive assessment. Medline, Embase, PsychINFO and CINAHL databases were searched for relevant articles. Articles were screened by title and abstract. Full-text analysis and quality assessment was performed using the National Institute of Health Tool. Data were extracted on study characteristics, prevalence of TIA deficits, and key study findings. Due to significant heterogeneity, meta-analysis was not possible. Twenty-five full-text articles met the review inclusion criteria. There was significant heterogeneity in terms of cognitive tests used, definitions of cognitive impairment and TIA, time points post-event, and analysis methods. The majority of studies used the Mini-Mental State Examination (MMSE) or Montreal Cognitive Assessment (MoCA) (n = 23). Prevalence of cognitive impairment ranged from 2% to 100%, depending on the time-point and cognitive domain studied. The MoCA was more sensitive than the MMSE for identifying cognitive deficits. Deficits were common in executive function, attention, and language. No studies assessed diagnostic test accuracy against a reference standard diagnosis of cognitive impairment. Recommendations on cognitive testing after TIA are hampered by significant heterogeneity between studies, as well as a lack of diagnostic test accuracy studies. Future research should focus on harmonising tools, definitions, and time-points, and validating tools specifically for the TIA population.

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.

Three-dimensional simulations of embolic stroke and an equation for sizing emboli from imaging.

Stroke simulations are needed to run in-silico trials, develop hypotheses for clinical studies and to interpret ultrasound monitoring and radiological imaging. We describe proof-of-concept three-dimensional stroke simulations, carrying out in silico trials to relate lesion volume to embolus diameter and calculate probabilistic lesion overlap maps, building on our previous Monte Carlo method. Simulated emboli were released into an in silico vasculature to simulate 1000 s of strokes. Infarct volume distributions and probabilistic lesion overlap maps were determined. Computer-generated lesions were assessed by clinicians and compared with radiological images. The key result of this study is development of a three-dimensional simulation for embolic stroke and its application to an in silico clinical trial. Probabilistic lesion overlap maps showed that the lesions from small emboli are homogeneously distributed throughout the cerebral vasculature. Mid-sized emboli were preferentially found in posterior cerebral artery (PCA) and posterior region of the middle cerebral artery (MCA) territories. For large emboli, MCA, PCA and anterior cerebral artery (ACA) lesions were comparable to clinical observations, with MCA, PCA then ACA territories identified as the most to least probable regions for lesions to occur. A power law relationship between lesion volume and embolus diameter was found. In conclusion, this article showed proof-of-concept for large in silico trials of embolic stroke including 3D information, identifying that embolus diameter could be determined from infarct volume and that embolus size is critically important to the resting place of emboli. We anticipate this work will form the basis of clinical applications including intraoperative monitoring, determining stroke origins, and in silico trials for complex situations such as multiple embolisation.

Ethnic Variations in Patient Outcomes in a Memory Clinic Setting Between 2013 and 2021.

BACKGROUND: The incidence of dementia in Black and Asian populations in the UK is set to rise. There is concern surrounding differences in services provided for different ethnic groups. OBJECTIVE: This study aimed to examine ethnic variations in survival, services accessed, and medication use across White, Black, and Asian groups in routine memory clinic setting. METHODS: We retrospectively examined referrals to a memory service between 2013 and 2021. A random sample of 104 White, 99 Asian, and 74 Black patients were analyzed for differences in support services, voluntary services, medication use, and survival rate. RESULTS: There were statistically significant differences in survival of the Asian compared to the White group (Hazard ratio (HR = 2.17,95% confidence interval (CI) 1.23-3.85, p = 0.008)) following adjustment for age, gender, diagnosis, cognitive impairment, severity, access to support and voluntary services, and use of cholinesterase inhibitors, N-methyl-D-aspartate antagonists, and antipsychotics. The Asian group showed a statistically significantly reduction in access to support services compared to the White group (HR = 0.05, 95% CI 0.01-0.37, p = 0.003). In contrast, the survival rate was similar between the White and Black dementia patients. CONCLUSION: We found significantly reduced survival and reduced access to support services in Asian compared to White patients with dementia. Further research is needed to investigate the generalizability of our results, and determine the cause, and consequent remedies of these associations in ethnic minority groups.

International research priority setting exercises in stroke: A systematic review.

BACKGROUND: Agreeing on priority topics for stroke research can help make best use of limited funding, people, and time. Formal priority-setting exercises collate stakeholders' opinions to reach consensus on the most important research questions. Several stroke research priority setting exercises have been published. Exploring commonalities and differences between these exercises could bring a better understanding of priority research topics. AIM: We collated and compared published stroke research priority setting exercises across international healthcare systems. SUMMARY OF REVIEW: Multidisciplinary, electronic literature databases were searched from 2000 to 2021, using a validated search syntax. Inclusion criteria were: full article; stroke focus (any subtype); prioritization method described; and lists priorities for research. Priorities were extracted, coded, and assigned to categories using thematic analysis. The Nine Common Themes of Good Practice and the Reporting guideline for priority setting of health research checklists were used to assess methodological and reporting quality respectively. From 623 titles assessed, 14 studies were eligible for inclusion, including 2410 participants and describing 165 priorities. The majority of priority setting exercises were conducted in high-income countries (86%, n = 12 articles), published between 2011 and 2021 (64%, n = 9), and included views of healthcare professionals (57%, n = 8), and stroke survivors (50%, n = 7). Caregivers (n = 3, 21%) were under-represented. The James Lind Alliance priority setting method was most commonly used (50%, n = 7). Priorities were grouped into 10 thematic categories. Rehabilitation and follow-up was the most common priority theme (15%, n = 25 priorities), followed by psychological recovery (14%, n = 23), pathology (14%, n = 23), and caregivers and support (14%, n = 23). Priorities differed by year and case-mix (stakeholder group and demographics) of respondents. No article was judged high quality for all aspects of method or reporting. Common limitations were around inclusiveness and evaluation of the exercise. CONCLUSION: Stroke research priorities are dynamic and context-specific. However, there was a common theme of prioritizing research that considered life after stroke. Future priority settings should consider the inclusion of nonindustrialized countries and stroke survivors with a range of impairments.

Antihypertensives in dementia: Good or bad for the brain?

Hypertension is associated with both ageing and dementia. Despite this, optimal blood pressure targets in dementia remain unclear. Both high and low blood pressure are associated with poorer cognition. Changes in vascular physiology in dementia may increase the vulnerability of the brain to hypoperfusion associated with antihypertensives. We discuss the potential risks of antihypertensives in the context of altered cerebral haemodynamics, and evidence from antihypertensive trials in dementia. We suggest that individualised blood pressure targets should be the focus for antihypertensive therapy in dementia, rather than strict control to uniform targets extrapolated from trials in cognitively healthy individuals.