Oral antiplatelet therapy for acute ischaemic stroke.

BACKGROUND: In people with acute ischaemic stroke, platelets become activated and can cause blood clots to form and block an artery in the brain, resulting in damage to part of the brain. Such damage gives rise to the symptoms of stroke. Antiplatelet therapy might reduce the volume of brain damaged by ischaemia and also reduce the risk of early recurrent ischaemic stroke, thereby reducing the risk of early death and improving long-term outcomes in survivors. However, antiplatelet therapy might also increase the risk of fatal or disabling intracranial haemorrhage. OBJECTIVES: To assess the efficacy and safety of immediate oral antiplatelet therapy (i.e. started as soon as possible and no later than two weeks after stroke onset) in people with acute presumed ischaemic stroke. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register, CENTRAL, MEDLINE Ovid, Embase Ovid, and two trials registers, and performed forward reference/cited reference searching in August 2020. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing oral antiplatelet therapy (started within 14 days of the stroke) with control in people with definite or presumed ischaemic stroke. DATA COLLECTION AND ANALYSIS: Two review authors independently applied the inclusion criteria and assessed trial quality. For the included trials, they extracted and cross-checked the data. They assessed risk of bias of each study using the Risk of Bias 1 (RoB1) tool and overall certainty of the evidence for each outcome using the GRADE approach. MAIN RESULTS: We included 11 studies involving 42,226 participants. Three new trials have been added since the last update (743 participants). As per the previous version of this review, two trials testing aspirin 160 mg to 300 mg once daily, started within 48 hours of onset, contributed 96% of the data. The risk of bias was low. The maximum follow-up was six months. With treatment, there was a decrease in death or dependency at the end of follow-up (odds ratio (OR) 0.95, 95% confidence interval (CI) 0.91 to 0.99; 7 RCTs, 42,034 participants; moderate-certainty evidence). For every 1000 people treated with aspirin, 13 people would avoid death or dependency (number needed to treat for an additional beneficial outcome 79). AUTHORS' CONCLUSIONS: Antiplatelet therapy with aspirin 160 mg to 300 mg daily, given orally (or by nasogastric tube or per rectum in people who cannot swallow) and started within 48 hours of onset of presumed ischaemic stroke, significantly decreased death and dependency, and reduced the risk of early recurrent ischaemic stroke without a major risk of early haemorrhagic complications; long-term outcomes were improved.

Vascular and haemodynamic issues of brain ageing.

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.

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.

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.

Association Between Maternal Postnatal Depression and Offspring Anxiety and Depression in Adolescence and Young Adulthood: A Meta-Analysis.

OBJECTIVE: Postnatal depression (PND) is common, with an incidence of 10% to 20% in new mothers. Studies have identified an association between maternal PND and adverse childhood effects. Fewer studies have explored the risk of psychiatric disorders in adolescence and adulthood. METHODS: MEDLINE, PubMed, PsycINFO, Embase, and EmCare were searched. Studies evaluating the association between maternal PND and offspring anxiety or depression in adolescence or adulthood were included. Five prospective cohort studies met the inclusion criteria. The odds ratios were pooled using a random effects model, and heterogeneity and publication bias were assessed. RESULTS: Anxiety: The 4 relevant studies were composed of 273 mothers with PND and 916 controls, followed up for 12 to 23 years. The pooled odds ratio (OR) was 2.19 (1.33-3.61), p = 0.002, with no heterogeneity (I2 = 0.00, p = 0.49). Depression: The 5 studies were composed of 937 mothers with PND and 3099 controls, followed up from 12 to 23 years. The pooled OR was 1.92 (1.08-3.42), p = 0.026, with heterogeneity (I2 = 62.89, p = 0.03). CONCLUSION: Offspring of mothers with PND are twice as likely to suffer from anxiety and almost twice as likely to suffer from depression than those without exposure. This evidence heightens the importance of detection and treatment of postnatal depression. Furthermore, early assessment and support could be provided to the high-risk group of offspring.

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.

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.

Age-related differences in cerebrovascular responses to cognitive stimulation using a novel method.

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.

Investigating the association between depression and cerebral haemodynamics-A systematic review and meta-analysis.

BACKGROUND: Vascular mechanisms may play a role in depression. The aim of this review is to summarise the evidence on alterations in cerebral haemodynamics in depression. METHODS: MEDLINE (1946- present), Embase (1947-present), Web of Science (1970-present), PsycINFO (1984-present), CINAHL (1976-present) and CENTRAL were searched using a predefined search strategy. A meta-analysis was conducted in four groups: 1) global cerebral blood flow (CBF) in ml/min/100 g, 2) CBF velocity (CBFv) in cm/s (maximum flow of left middle cerebral artery, 3) combined CBF and CBFv, 4) Ratio of uptake of Tc 99 m HMPAO (region of interest compared to whole brain). Data are presented as mean difference or standardised mean difference and 95% confidence interval (95% CI). A narrative synthesis of the remaining studies was performed. RESULTS: 87 studies were included. CBF was significantly reduced in depressed patients compared to HC [15 studies, 538 patients, 416 HC, MD: -2.24 (95% CI -4.12, -0.36), p = 0.02, I2 = 64%]. There were no statistically significant differences in other parameters. The narrative synthesis revealed variable changes in CBF in depressed patients, particularly affecting the anterior cingulate and prefrontal cortices. LIMITATIONS: There were various sources of heterogeneity including the severity of depression, use of antidepressant medication, imaging modality used and reporting of outcomes. All of these factors made direct comparisons between studies difficult. CONCLUSIONS: The reduction in CBF in depressed patients compared to HCs may indicate a role for assessment and CBF altering interventions in high-risk groups. However, results were inconsistent across studies, warranting further work to investigate specific subgroups.