Introduction Increased mortality has been demonstrated in older adults with COVID-19, but the effect of frailty has been unclear. Methods This multi-centre cohort study involved patients aged 18 years and older hospitalised with COVID-19, using routinely collected data. We used Cox regression analysis to assess the impact of age, frailty, and delirium on the risk of inpatient mortality, adjusting for sex, illness severity, inflammation, and co-morbidities. We used ordinal logistic regression analysis to assess the impact of age, Clinical Frailty Scale (CFS), and delirium on risk of increased care requirements on discharge, adjusting for the same variables. Results Data from 5,711 patients from 55 hospitals in 12 countries were included (median age 74, IQR 54–83; 55.2% male). The risk of death increased independently with increasing age (>80 vs 18–49: HR 3.57, CI 2.54–5.02), frailty (CFS 8 vs 1–3: HR 3.03, CI 2.29–4.00) inflammation, renal disease, cardiovascular disease, and cancer, but not delirium. Age, frailty (CFS 7 vs 1–3: OR 7.00, CI 5.27–9.32), delirium, dementia, and mental health diagnoses were all associated with increased risk of higher care needs on discharge. The likelihood of adverse outcomes increased across all grades of CFS from 4 to 9. Conclusions Age and frailty are independently associated with adverse outcomes in COVID-19. Risk of increased care needs was also increased in survivors of COVID-19 with frailty or older age.

Despite small sample sizes and heterogeneity, meta-analyses demonstrate clear abnormalities in cerebral hemodynamic and oxygenation parameters, even at an early stage of cognitive decline. Further work is required to investigate the use of cerebral hemodynamic and oxygenation parameters as a sensitive biomarker for dementia.

Dynamic cerebral autoregulation (dCA) has been shown to be impaired in cerebrovascular diseases, but there is a lack of consistency across different studies and the different metrics that have been proposed for assessment. We performed a systematic review and meta-analyses involving assessment of dCA in ischemic and hemorrhagic stroke. Thirty-three articles describing assessment of dCA with transfer function analysis (TFA) were included, with meta-analyses performed for derived parameters of gain, phase and autoregulation index (ARI). A total of 1233 patients were pooled from 12 studies on acute ischemic stroke (AIS) and two studies on intracerebral hemorrhage (ICH). In comparison with controls, TFA phase of AIS was significantly reduced (nine studies), in both hemispheres ( P < 0.0001). TFA gain provided inconsistent results, with reduced values in relation to controls, for both hemispheres. The ARI (six studies) was reduced compared to controls, in both hemispheres ( P < 0.005). In ICH, gain showed higher values compared to controls for the unaffected ( P = 0.01), but not for the affected hemisphere. Meta-analyses in AIS have demonstrated that phase and the ARI index can show highly significant differences in comparison with healthy controls, while ICH have been limited by the scarcity of studies and the diversity of units adopted for gain.

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 CO (ETCO; 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%). ETCO 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.

Background: In older age, the benefits of antihypertensive treatment (AHT) become less evident, with greater associated risk. Of particular concern is compromising cerebral blood flow (CBF), especially in those with cognitive impairment. Methods: We created a synthesis of the published evidence by searching multiple electronic databases from 1970 to May 2021. Included studies had participants with mean age ≥50 years, hypertension and cognitive impairment, and assessed CBF before and after initiating AHT. Two authors independently determined eligibility and extracted data. Study quality was assessed using The Risk of Bias in Nonrandomized Studies of Interventions tool. We summarized study characteristics (qualitative synthesis) and performed random-effects meta-analyses (quantitative synthesis). Results: Thirty-two studies (total n=1306) were included, of which 23 were eligible for meta-analysis. In line with the qualitative synthesis, the meta-analysis indicated no effect of AHT initiation on CBF (standardized mean difference, 0.08 [95% CI, −0.07 to 0.22]; P =0.31, I 2 =42%). This was consistent across subgroups of acute versus chronic AHT, drug class, study design, and CBF measurement. Subgroups by age demonstrated an increase in CBF after AHT in those aged >70 years (standardized mean difference, 4.15 [95% CI, 0.16–8.15]; P =0.04, I 2 =42%), but not in those aged 50 to 65 and 65 to 70 years (standardized mean difference, 0.18 [95% CI,−2.02 to 2.38]; P =0.87, I 2 =49%; standardized mean difference, 1.22 [95% CI, −0.45 to 2.88]; P =0.15, I 2 =68%). Overall, risk of bias was moderate-to-high and quality of evidence (Grading of Recommendations Assessment, Development and Evaluation) was very low, reflecting the observational nature of the data. Conclusions: Accepting the observed limitations, current evidence does not suggest a harmful effect of AHT on CBF. Concerns over CBF should not preclude treatment of hypertension.

The population is ageing worldwide, thus increasing the burden of common age-related disorders to the individual, society and economy. Cerebrovascular diseases (stroke, dementia) contribute a significant proportion of this burden and are associated with high morbidity and mortality. Thus, understanding and promoting healthy vascular brain ageing are becoming an increasing priority for healthcare systems. In this review, we consider the effects of normal ageing on two major physiological processes responsible for vascular brain function: Cerebral autoregulation (CA) and neurovascular coupling (NVC). CA is the process by which the brain regulates cerebral blood flow (CBF) and protects against falls and surges in cerebral perfusion pressure, which risk hypoxic brain injury and pressure damage, respectively. In contrast, NVC is the process by which CBF is matched to cerebral metabolic activity, ensuring adequate local oxygenation and nutrient delivery for increased neuronal activity. Healthy ageing is associated with a number of key physiological adaptations in these processes to mitigate age-related functional and structural declines. Through multiple different paradigms assessing CA in healthy younger and older humans, generating conflicting findings, carbon dioxide studies in CA have provided the greatest understanding of intrinsic vascular anatomical factors that may mediate healthy ageing responses. In NVC, studies have found mixed results, with reduced, equivalent and increased activation of vascular responses to cognitive stimulation. In summary, vascular and haemodynamic changes occur in response to ageing and are important in distinguishing “normal” ageing from disease states and may help to develop effective therapeutic strategies to promote healthy brain ageing.

Background and purpose Although poor prognosis after intracerebral hemorrhage relates to risk factors and hematoma characteristics, there is limited evidence for the effect of race–ethnicity. Methods Data from 1011 patients with intracerebral hemorrhage enrolled into hyperacute trials and randomized to control were obtained from the Virtual International Stroke Trials Archive and Efficacy of Nitric Oxide in Stroke Trial. Clinical characteristics and functional outcome were compared among three racial groups – Asians, Blacks, and Caucasians. Results The majority of patients were Caucasian (78.1%) followed by Asians (14.5%) and Blacks (5.5%). At baseline, Caucasians were older and had larger hematoma volumes; Blacks had lower Glasgow Coma Scale and higher systolic blood pressure (all p < 0.05). Although the primary outcome of modified Rankin Scale did not differ at 90 days (p = 0.14), there were significant differences in mortality (p < 0.0001) and quality of life (EQ-5D p < 0.0001; EQ-VAS p 0.015). In test of multiple comparisons, Caucasians were more likely to die (p = 0.0003) and had worse quality of life (EQ-5D p = 0.003; EQ-VAS p < 0.0001) as compared to Asians. Conclusion Race–ethnicity appears to explain some of the variation in clinical characteristics and outcomes after acute intracerebral hemorrhage. Factors that explain this variation need to be identified.

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