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Background: \ud Cerebral small vessel disease is a progressive disease of the brain's deep perforating blood vessels. It is usually diagnosed based on lesions seen on brain imaging. Cerebral small vessel disease is a common cause of stroke but can also cause a progressive cognitive decline. As antithrombotic therapy is an established treatment for stroke prevention, we sought to determine whether antithrombotic therapy might also be effective in preventing cognitive decline in people with small vessel disease.\ud \ud Objectives: \ud To assess the effects of antithrombotic therapy for prevention of cognitive decline in people with small vessel disease on neuroimaging but without dementia.\ud \ud Search methods: \ud We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Review Group's Specialised Register, and the Cochrane Stroke Group's Specialised Register; the most recent search was on 21 July 2021. We also searched MEDLINE, Embase, four other databases and two trials registries. We searched the reference lists of the articles retrieved from these searches. As trials with a stroke focus may include relevant subgroup data, we complemented these searches with a focussed search of all antithrombotic titles in the Cochrane Stroke Group database. \ud \ud Selection criteria: \ud We included randomised controlled trials (RCT) of people with neuroimaging evidence of at least mild cerebral small vessel disease (defined here as white matter hyperintensities, lacunes of presumed vascular origin and subcortical infarcts) but with no evidence of dementia. The trials had to compare antithrombotic therapy of minimum 24 weeks' duration to no antithrombotic therapy (either placebo or treatment as usual), or compare different antithrombotic treatment regimens. Antithrombotic therapy could include antiplatelet agents (as monotherapy or combination therapy), anticoagulants or a combination.\ud \ud Data collection and analysis: \ud Two review authors independently screened all the titles identified by the searches. We assessed full texts for eligibility for inclusion according to our prespecified selection criteria, extracted data to a proforma and assessed risk of bias using the Cochrane tool for RCTs. We evaluated the certainty of evidence using GRADE. Due to heterogeneity across included participants, interventions and outcomes of eligible trials, it was not possible to perform meta‐analyses.\ud \ud Main results: \ud We included three RCTs (3384 participants). One study investigated the effect of antithrombotic therapy in participants not yet on antithrombotic therapy; two studies investigated the effect of additional antithrombotic therapy, one in a population already taking a single antithrombotic agent and one in a mixed population (participants on an antithrombotic drug and antithrombotic‐naive participants). Intervention and follow‐up durations varied from 24 weeks to four years.\ud \ud Jia 2016 was a placebo‐controlled trial assessing 24 weeks of treatment with DL‐3‐n‐butylphthalide (a compound with multimodal actions, including a putative antiplatelet effect) in 280 Chinese participants with vascular cognitive impairment caused by subcortical ischaemic small vessel disease, but without dementia. There was very low‐certainty evidence for a small difference in cognitive test scores favouring treatment with DL‐3‐n‐butylphthalide, as measured by the 12‐item Alzheimer’s Disease Assessment Scale‐Cognitive subscale (adjusted mean difference −1.07, 95% confidence interval (CI) −2.02 to −0.12), but this difference may not be clinically relevant. There was also very low‐certainty evidence for greater proportional improvement measured with the Clinician Interview‐Based Impression of Change‐Plus Caregiver Input (57% with DL‐3‐n‐butylphthalide versus 42% with placebo; P = 0.01), but there was no difference in other measures of cognition (Mini‐Mental State Examination and Clinical Dementia Rating) or function. There was no evidence of a difference in adverse events between treatment groups.\ud \ud The SILENCE RCT compared antithrombotic therapy (aspirin) and placebo during four years of treatment in 83 participants with 'silent brain infarcts' who were on no prior antithrombotic therapy. There was very low‐certainty evidence for no difference between groups across various measures of cognition and function, rates of stroke or adverse events.\ud \ud The Secondary Prevention of Subcortical Stroke Study (SPS3) compared dual antiplatelet therapy (clopidogrel plus aspirin) to aspirin alone in 3020 participants with recent lacunar stroke. There was low‐certainty evidence of no effect on cognitive outcomes as measured by the Cognitive Abilities Screening Instruments (CASI) assessed annually over five years. There was also low‐certainty evidence of no difference in the annual incidence of mild cognitive decline between the two treatment groups (9.7% with dual antiplatelet therapy versus 9.9% with aspirin), or the annual stroke recurrence rate (2.5% with dual antiplatelet therapy versus 2.7% with aspirin). Bleeding risk may be higher with dual antiplatelet therapy (hazard ratio (HR) 2.15, 95% CI 1.49 to 3.11; low certainty evidence), but there may be no significant increase in intracerebral bleeding risk (HR 1.52, 95% CI 0.79 to 2.93; low‐certainty evidence).\ud \ud None of the included trials assessed the incidence of new dementia.\ud \ud Authors' conclusions: \ud We found no convincing evidence to suggest any clinically relevant cognitive benefit of using antithrombotic therapy in addition to standard treatment in people with cerebral small vessel disease but without dementia, but there may be an increased bleeding risk with this approach. There was marked heterogeneity across the trials and the certainty of the evidence was generally poor.

BackgroundRegular participation in resistance exercise is known to have broad-ranging health benefits and for this reason is prominent in the current physical activity guidelines. Recovery after such exercise is important for several populations across the age range and nutritional strategies to enhance recovery and modulate post-exercise physiological processes are widely studied, yet effective strategies remain elusive. Vitamin K2 supplementation has emerged as a potential candidate, and the aim of the current study, therefore, is to test the hypothesis that vitamin K2 supplementation can accelerate recovery, via modulation of the underlying physiological processes, following a bout of resistance exercise in young and older adults.MethodsThe current study is a two-arm randomised controlled trial which will be conducted in 80 (40 young (≤40 years) and 40 older (≥65 years)) adults to compare post-exercise recovery in those supplemented with vitamin K2 or placebo for a 12-week period. The primary outcome is muscle strength with secondary outcomes including pain-free range of motion, functional abilities, surface electromyography (sEMG) and markers of inflammation and oxidative stress.DiscussionEthical approval has been granted by the College of Medical Veterinary and Life Sciences Ethical Committee at the University of Glasgow (Project No 200190189) and recruitment is ongoing. Study findings will be disseminated through a presentation at scientific conferences and in scientific journals.Trial registrationClinicialTrials.gov NCT04676958. Prospectively registered on 21 December 2020.

Medications with anticholinergic properties are commonly prescribed to older adults with a pre-existing diagnosis of dementia or cognitive impairment. The cumulative anticholinergic effect of all the medications a person takes is referred to as the anticholinergic burden because of its potential to cause adverse effects. It is possible that a high anticholinergic burden may be a risk factor for further cognitive decline or neuropsychiatric disturbances in people with dementia. Neuropsychiatric disturbances are the most frequent complication of dementia that require hospitalisation, accounting for almost half of admissions; hence, identification of modifiable prognostic factors for these outcomes is crucial. There are various scales available to measure anticholinergic burden but agreement between them is often poor.Our primary objective was to assess whether anticholinergic burden, as defined at the level of each individual scale, was a prognostic factor for further cognitive decline or neuropsychiatric disturbances in older adults with pre-existing diagnoses of dementia or cognitive impairment. Our secondary objective was to investigate whether anticholinergic burden was a prognostic factor for other adverse clinical outcomes, including mortality, impaired physical function, and institutionalisation.We searched these databases from inception to 29 November 2021: MEDLINE OvidSP, Embase OvidSP, PsycINFO OvidSP, CINAHL EBSCOhost, and ISI Web of Science Core Collection on ISI Web of Science.We included prospective and retrospective longitudinal cohort and case-control observational studies, with a minimum of one-month follow-up, which examined the association between an anticholinergic burden measurement scale and the above stated adverse clinical outcomes, in older adults with pre-existing diagnoses of dementia or cognitive impairment. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, and undertook data extraction, risk of bias assessment, and GRADE assessment. We summarised risk associations between anticholinergic burden and all clinical outcomes in a narrative fashion. We also evaluated the risk association between anticholinergic burden and mortality using a random-effects meta-analysis. We established adjusted pooled rates for the anticholinergic cognitive burden (ACB) scale; then, as an exploratory analysis, established pooled rates on the prespecified association across scales. MAIN RESULTS: We identified 18 studies that met our inclusion criteria (102,684 older adults). Anticholinergic burden was measured using five distinct measurement scales: 12 studies used the ACB scale; 3 studies used the Anticholinergic Risk Scale (ARS); 1 study used the Anticholinergic Drug Scale (ADS); 1 study used the Anticholinergic Effect on Cognition (AEC) Scale; and 2 studies used a list developed by Tune and Egeli. Risk associations between anticholinergic burden and adverse clinical outcomes were highly heterogenous. Four out of 10 (40%) studies reported a significantly increased risk of greater long-term cognitive decline for participants with an anticholinergic burden compared to participants with no or minimal anticholinergic burden. No studies investigated neuropsychiatric disturbance outcomes. One out of four studies (25%) reported a significant association with reduced physical function for participants with an anticholinergic burden versus participants with no or minimal anticholinergic burden. No study (out of one investigating study) reported a significant association between anticholinergic burden and risk of institutionalisation. Six out of 10 studies (60%) found a significantly increased risk of mortality for those with an anticholinergic burden compared to those with no or minimal anticholinergic burden. Pooled analysis of adjusted mortality hazard ratios (HR) measured anticholinergic burden with the ACB scale, and suggested a significantly increased risk of death for those with a high ACB score relative to those with no or minimal ACB scores (HR 1.153, 95% confidence interval (CI) 1.030 to 1.292; 4 studies, 48,663 participants). An exploratory pooled analysis of adjusted mortality HRs across anticholinergic burden scales also suggested a significantly increased risk of death for those with a high anticholinergic burden (HR 1.102, 95% CI 1.044 to 1.163; 6 studies, 68,381 participants). Overall GRADE evaluation of results found low- or very low-certainty evidence for all outcomes. AUTHORS' CONCLUSIONS: There is low-certainty evidence that older adults with dementia or cognitive impairment who have a significant anticholinergic burden may be at increased risk of death. No firm conclusions can be drawn for risk of accelerated cognitive decline, neuropsychiatric disturbances, decline in physical function, or institutionalisation.

Background C-reactive protein (CRP) is a non-specific acute phase reactant elevated in infection or inflammation. Higher levels indicate more severe infection and have been used as an indicator of COVID-19 disease severity. However, the evidence for CRP as a prognostic marker is yet to be determined. The aim of this study is to examine the CRP response in patients hospitalized with COVID-19 and to determine the utility of CRP on admission for predicting inpatient mortality. Methods Data were collected between 27 February and 10 June 2020, incorporating two cohorts: the COPE (COVID-19 in Older People) study of 1564 adult patients with a diagnosis of COVID-19 admitted to 11 hospital sites (test cohort) and a later validation cohort of 271 patients. Admission CRP was investigated, and finite mixture models were fit to assess the likely underlying distribution. Further, different prognostic thresholds of CRP were analysed in a time-to-mortality Cox regression to determine a cut-off. Bootstrapping was used to compare model performance [Harrell’s C statistic and Akaike information criterion (AIC)]. Results The test and validation cohort distribution of CRP was not affected by age, and mixture models indicated a bimodal distribution. A threshold cut-off of CRP ≥40 mg/L performed well to predict mortality (and performed similarly to treating CRP as a linear variable). Conclusions The distributional characteristics of CRP indicated an optimal cut-off of ≥40 mg/L was associated with mortality. This threshold may assist clinicians in using CRP as an early trigger for enhanced observation, treatment decisions and advanced care planning.

Introduction Resistance training (RT) is the most effective way to increase muscle mass and function in older adults both with/without sarcopenia/frailty. In younger adults, when RT is performed to muscle failure the load lifted does not mediate the magnitude of response, but there are no studies in older adults. We aimed to determine the feasibility of recruitment to a RT intervention working to muscle failure at different loads in frail and healthy older adults. Methods We performed an 8-week randomised feasibility trial of lower limb RT to volitional muscular failure, at high and low load. Participants were recruited via hospital outpatient clinics and newspaper advertisements. Outcomes included: frailty assessment (Fried criteria); muscle strength (maximum voluntary contraction/one-repetition maximum); functional abilities (Short Physical Performance Battery); safety/adverse events were recorded via a log, and patient experiences from focus groups. Results 110 people were assessed for eligibility, and 58 randomised (frail n = 6, prefrail n = 20, robust n = 32) to either high (n = 30) or low load (n = 28) groups. Mean age of participants was 72 years (range 65–93), 36 were female, 22 male. Session attendance was 95% (high load) and 90.4% (low load). Most participants were recruited via advertisements. All participants reported feeling safe and reassured in the RT sessions. Two participants had a serious adverse event, one related to RT (hypotension) and several had adverse events (three intervention-related). Pain was reported at both loads (high n = 9, low n = 8) yet all completed. There were no differences (P > 0.05) in effects of RT outcome variables between low and high load groups. Conclusion In this feasibility trial the recruitment of frail patients via clinics was limited. Performing supervised RT to muscle failure in older adults was safe/acceptable and the load at which RT was performed did not influence its efficacy. Future research into the effectiveness of such RT is warranted.

Introduction Detection of delirium in hospitalised older adults is recommended in national and international guidelines. The 4 ‘A’s Test (4AT; www.the4AT.com) is a short ( Methods We searched the following electronic databases through Ovid: MEDLINE, Embase, and PsycINFO. Additional databases were searched: CINAHL (EBSCOhost), clinicaltrials.gov and Cochrane Central Register of Controlled Trials from 2011 (4AT publication) until 21 December 2019. Inclusion criteria: older adults (≥65) across any setting of care except critical care; validation study of the 4AT against a delirium reference standard (standard diagnostic criteria or validated tool). Two reviewers independently screened abstracts and papers and performed the data extraction. Pooled estimates of sensitivity and specificity were generated from a bivariate random effects model. Results 17 studies (n = 3,701 observations) were included. Various settings including acute medicine, surgery, stroke wards and the emergency department were represented. The overall prevalence of delirium was 24.2% (95% CI 17.8–32.1%; range 10.5–61.9%). The pooled sensitivity was 0.88 (95% CI 0.80–0.93) and the pooled specificity was 0.88 (95% CI 0.82–0.92). The methodological quality of studies was mostly good. Conclusions The 4AT is now supported by a substantial evidence base comparable to other well-studied tools such as the Confusion Assessment Method (CAM). The strong pooled sensitivity and specificity findings for the 4AT in this meta-analysis along with its brevity and lack of need for specific training provide support for its use as an effective assessment tool for delirium.

Background:\ud Remote cognitive assessments are increasingly needed to assist in the detection of cognitive disorders, but the diagnostic accuracy of telephone‐ and video‐based cognitive screening remains unclear.\ud \ud Objectives:\ud To assess the test accuracy of any multidomain cognitive test delivered remotely for the diagnosis of any form of dementia.\ud \ud To assess for potential differences in cognitive test scoring when using a remote platform, and where a remote screener was compared to the equivalent face‐to‐face test.\ud \ud Search methods:\ud We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group Specialized Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, LILACS, and ClinicalTrials.gov (www.clinicaltrials.gov/) databases on 2 June 2021. We performed forward and backward searching of included citations.\ud \ud Selection criteria:\ud We included cross‐sectional studies, where a remote, multidomain assessment was administered alongside a clinical diagnosis of dementia or equivalent face‐to‐face test.\ud \ud Data collection and analysis:\ud Two review authors independently assessed risk of bias and extracted data; a third review author moderated disagreements. Our primary analysis was the accuracy of remote assessments against a clinical diagnosis of dementia. Where data were available, we reported test accuracy as sensitivity and specificity. We did not perform quantitative meta‐analysis as there were too few studies at individual test level.\ud \ud For those studies comparing remote versus in‐person use of an equivalent screening test, if data allowed, we described correlations, reliability, differences in scores and the proportion classified as having cognitive impairment for each test.\ud \ud Main results:\ud The review contains 31 studies (19 differing tests, 3075 participants), of which seven studies (six telephone, one video call, 756 participants) were relevant to our primary objective of describing test accuracy against a clinical diagnosis of dementia. All studies were at unclear or high risk of bias in at least one domain, but were low risk in applicability to the review question. Overall, sensitivity of remote tools varied with values between 26% and 100%, and specificity between 65% and 100%, with no clearly superior test.\ud \ud Across the 24 papers comparing equivalent remote and in‐person tests (14 telephone, 10 video call), agreement between tests was good, but rarely perfect (correlation coefficient range: 0.48 to 0.98).\ud \ud Authors' conclusions:\ud Despite the common and increasing use of remote cognitive assessment, supporting evidence on test accuracy is limited. Available data do not allow us to suggest a preferred test. Remote testing is complex, and this is reflected in the heterogeneity seen in tests used, their application, and their analysis. More research is needed to describe accuracy of contemporary approaches to remote cognitive assessment. While data comparing remote and in‐person use of a test were reassuring, thresholds and scoring rules derived from in‐person testing may not be applicable when the equivalent test is adapted for remote use.

Standard methods for the meta-analysis of medical tests, without assuming a gold standard, are limited to dichotomous data. Multivariate probit models are used to analyze correlated dichotomous data, and can be extended to model ordinal data. Within the context of an imperfect gold standard, they have previously been used for the analysis of dichotomous and ordinal test data from a single study, and for the meta-analysis of dichotomous tests. However, they have not previously been used for the meta-analysis of ordinal tests.\ud \ud In this paper, we developed a Bayesian multivariate probit latent class model for the simultaneous meta-analysis of ordinal and dichotomous tests without assuming a gold standard, which also allows one to obtain summary estimates of joint test accuracy. We fitted the models using the software Stan, which uses a state-of-the-art Hamiltonian Monte Carlo algorithm, and we applied the models to a dataset in which studies evaluated the accuracy of tests, and test combinations, for deep vein thrombosis. We demonstrate the issues with dichotomising ordinal test accuracy data in the presence of an imperfect gold standard, before applying and comparing several variations of our proposed model which do not require the data to be dichotomised.\ud \ud The models proposed will allow researchers to more appropriately meta-analyse ordinal and dichotomous tests without a gold standard, potentially leading to less biased estimates of test accuracy. This may lead to a better understanding of which tests, and test combinations, should be used for any given medical condition.

The values of Newton’s constant of gravitation, G, reported by determinations at the International Bureau of Weights and Measures (BIPM) in Quinn et al (2001 Phys. Rev. Lett. 87 111101/1–111101/4) and in Quinn et al (2013 Phil. Trans. R. Soc. A 372 2–28) are some 200 parts per million (ppm) larger than the value of 6.67430 × 10 − 11 m3 kg−1 s−2 which was recommended by CODATA in Tiesinga et al (2018 J. Phys. Chem. Ref. Data 50 033105). The CODATA value has an assigned uncertainty of 22 ppm and the reported uncertainties in the BIPM values were 41 ppm and 25 ppm, respectively. The discrepancy therefore amounts to about seven times the combined uncertainty of the latest BIPM and CODATA values. We examine experimentally the hypothesis that the difference is due to a bias produced by stray alternating (AC) magnetic fields in the vicinity of the experiment. Whilst the BIPM torsion balance was located at the University of Birmingham a coil, having a similar scale to the balance, was used to generate AC magnetic fields of magnitude approximately 1 μT which in turn produced torques of magnitude approximately 0.2 % of the gravity torque. The magnitudes of these torques were compared with simple analytical models and finite element analyses. Measurements in the laboratory in Birmingham and, more recently, at BIPM give a very conservative upper limit on the rms magnitude of ambient AC magnetic fields of 100 nT. As the torque was demonstrated to vary with the square of the ambient field, these observations and our analyses suggest an upper limit to the possible bias in the BIPM determinations of the order of 20 ppm. It is therefore unlikely that torques due to ambient magnetic fields could have significantly biased values of G determined at BIPM.

Background\ud \ud Delirium is an acute neuropsychological disorder that is common in hospitalised patients. It can be distressing to patients and carers and it is associated with serious adverse outcomes. Treatment options for established delirium are limited and so prevention of delirium is desirable. Non‐pharmacological interventions are thought to be important in delirium prevention. \ud \ud \ud \ud Objectives\ud \ud To assess the effectiveness of non‐pharmacological interventions designed to prevent delirium in hospitalised patients outside intensive care units (ICU).\ud \ud \ud \ud Search methods\ud \ud We searched ALOIS, the specialised register of the Cochrane Dementia and Cognitive Improvement Group, with additional searches conducted in MEDLINE, Embase, PsycINFO, CINAHL, LILACS, Web of Science Core Collection, ClinicalTrials.gov and the World Health Organization Portal/ICTRP to 16 September 2020. There were no language or date restrictions applied to the electronic searches, and no methodological filters were used to restrict the search.\ud \ud \ud \ud Selection criteria\ud \ud We included randomised controlled trials (RCTs) of single and multicomponent non‐pharmacological interventions for preventing delirium in hospitalised adults cared for outside intensive care or high dependency settings. We only included non‐pharmacological interventions which were designed and implemented to prevent delirium. \ud \ud Data collection and analysis\ud \ud Two review authors independently examined titles and abstracts identified by the search for eligibility and extracted data from full‐text articles. Any disagreements on eligibility and inclusion were resolved by consensus. We used standard Cochrane methodological procedures. The primary outcomes were: incidence of delirium; inpatient and later mortality; and new diagnosis of dementia. We included secondary and adverse outcomes as pre‐specified in the review protocol. We used risk ratios (RRs) as measures of treatment effect for dichotomous outcomes and between‐group mean differences for continuous outcomes. The certainty of the evidence was assessed using GRADE. A complementary exploratory analysis was undertaker using a Bayesian component network meta‐analysis fixed‐effect model to evaluate the comparative effectiveness of the individual components of multicomponent interventions and describe which components were most strongly associated with reducing the incidence of delirium.\ud \ud \ud \ud Main results\ud \ud We included 22 RCTs that recruited a total of 5718 adult participants. Fourteen trials compared a multicomponent delirium prevention intervention with usual care. Two trials compared liberal and restrictive blood transfusion thresholds. The remaining six trials each investigated a different non‐pharmacological intervention. Incidence of delirium was reported in all studies. \ud \ud Using the Cochrane risk of bias tool, we identified risks of bias in all included trials. All were at high risk of performance bias as participants and personnel were not blinded to the interventions. Nine trials were at high risk of detection bias due to lack of blinding of outcome assessors and three more were at unclear risk in this domain. \ud \ud Pooled data showed that multi‐component non‐pharmacological interventions probably reduce the incidence of delirium compared to usual care (10.5% incidence in the intervention group, compared to 18.4% in the control group, risk ratio (RR) 0.57, 95% confidence interval (CI) 0.46 to 0.71, I2 = 39%; 14 studies; 3693 participants; moderate‐certainty evidence, downgraded due to risk of bias). \ud \ud There may be little or no effect of multicomponent interventions on inpatient mortality compared to usual care (5.2% in the intervention group, compared to 4.5% in the control group, RR 1.17, 95% CI 0.79 to 1.74, I2 = 15%; 10 studies; 2640 participants; low‐certainty evidence downgraded due to inconsistency and imprecision). \ud \ud No studies of multicomponent interventions reported data on new diagnoses of dementia. \ud \ud Multicomponent interventions may result in a small reduction of around a day in the duration of a delirium episode (mean difference (MD) ‐0.93, 95% CI ‐2.01 to 0.14 days, I2 = 65%; 351 participants; low‐certainty evidence downgraded due to risk of bias and imprecision). The evidence is very uncertain about the effect of multicomponent interventions on delirium severity (standardised mean difference (SMD) ‐0.49, 95% CI ‐1.13 to 0.14, I2=64%; 147 participants; very low‐certainty evidence downgraded due to risk of bias and serious imprecision). Multicomponent interventions may result in a reduction in hospital length of stay compared to usual care (MD ‐1.30 days, 95% CI ‐2.56 to ‐0.04 days, I2=91%; 3351 participants; low‐certainty evidence downgraded due to risk of bias and inconsistency), but little to no difference in new care home admission at the time of hospital discharge (RR 0.77, 95% CI 0.55 to 1.07; 536 participants; low‐certainty evidence downgraded due to risk of bias and imprecision). Reporting of other adverse outcomes was limited. \ud \ud Our exploratory component network meta‐analysis found that re‐orientation (including use of familiar objects), cognitive stimulation and sleep hygiene were associated with reduced risk of incident delirium. Attention to nutrition and hydration, oxygenation, medication review, assessment of mood and bowel and bladder care were probably associated with a reduction in incident delirium but estimates included the possibility of no benefit or harm. Reducing sensory deprivation, identification of infection, mobilisation and pain control all had summary estimates that suggested potential increases in delirium incidence, but the uncertainty in the estimates was substantial. \ud \ud Evidence from two trials suggests that use of a liberal transfusion threshold over a restrictive transfusion threshold probably results in little to no difference in incident delirium (RR 0.92, 95% CI 0.62 to 1.36; I2 = 9%; 294 participants; moderate‐certainty evidence downgraded due to risk of bias). \ud \ud Six other interventions were examined, but evidence for each was limited to single studies and we identified no evidence of delirium prevention. \ud \ud \ud \ud Authors' conclusions\ud \ud There is moderate‐certainty evidence regarding the benefit of multicomponent non‐pharmacological interventions for the prevention of delirium in hospitalised adults, estimated to reduce incidence by 43% compared to usual care. We found no evidence of an effect on mortality. There is emerging evidence that these interventions may reduce hospital length of stay, with a trend towards reduced delirium duration, although the effect on delirium severity remains uncertain. Further research should focus on implementation and detailed analysis of the components of the interventions to support more effective, tailored practice recommendations.

This is a protocol for a Cochrane Review (prognosis). The objectives are as follows: Primary objective To assess whether anticholinergic burden, as defined at the level of each individual scale, is a prognostic factor for further cognitive decline or neuropsychiatric disturbances in people with mild cognitive impairment (MCI) or dementia. Secondary objective To compare the prognostic validity of different anticholinergic burden scales. To examine the effect of type of dementia and severity of dementia on the association between anticholinergic burden and rate of cognitive decline or neuropsychiatric disturbances. To examine the effect of setting (care home versus non‐care home) on the association between anticholinergic burden and rate of cognitive decline or neuropsychiatric disturbances. To examine whether anticholinergic burden is a prognostic factor for other clinical outcomes in people with MCI or dementia.

Regular participation in resistance exercise is known to have broad-ranging health benefits and for this reason is prominent in the current physical activity guidelines. Recovery after such exercise is important for several populations across the age range and nutritional strategies to enhance recovery and modulate post-exercise physiological processes are widely studied, yet effective strategies remain elusive. Vitamin K2 supplementation has emerged as a potential candidate, and the aim of the current study, therefore, is to test the hypothesis that vitamin K2 supplementation can accelerate recovery, via modulation of the underlying physiological processes, following a bout of resistance exercise in young and older adults.The current study is a two-arm randomised controlled trial which will be conducted in 80 (40 young (≤40 years) and 40 older (≥65 years)) adults to compare post-exercise recovery in those supplemented with vitamin K2 or placebo for a 12-week period. The primary outcome is muscle strength with secondary outcomes including pain-free range of motion, functional abilities, surface electromyography (sEMG) and markers of inflammation and oxidative stress.Ethical approval has been granted by the College of Medical Veterinary and Life Sciences Ethical Committee at the University of Glasgow (Project No 200190189) and recruitment is ongoing. Study findings will be disseminated through a presentation at scientific conferences and in scientific journals.ClinicialTrials.gov NCT04676958. Prospectively registered on 21 December 2020.

BACKGROUND: The diagnosis of dementia relies on the presence of new-onset cognitive impairment affecting an individual's functioning and activities of daily living. The Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) is a questionnaire instrument, completed by a suitable 'informant' who knows the patient well, designed to assess change in functional performance secondary to cognitive change; it is used as a tool to identifying those who may have dementia.In secondary care there are two specific instances where patients may be assessed for the presence of dementia. These are in the general acute hospital setting, where opportunistic screening may be undertaken, or in specialist memory services where individuals have been referred due to perceived cognitive problems. To ensure an instrument is suitable for diagnostic use in these settings, its test accuracy must be established. OBJECTIVES: To determine the diagnostic accuracy of the informant-based questionnaire IQCODE, for detection of all-cause (undifferentiated) dementia in adults presenting to secondary-care services. SEARCH METHODS: We searched the following sources on the 28th of January 2013: ALOIS (Cochrane Dementia and Cognitive Improvement Group), MEDLINE (Ovid SP), EMBASE (Ovid SP), PsycINFO (Ovid SP), BIOSIS Previews (Thomson Reuters Web of Science), Web of Science Core Collection (includes Conference Proceedings Citation Index) (Thomson Reuters Web of Science), CINAHL (EBSCOhost) and LILACS (BIREME). We also searched sources specific to diagnostic test accuracy: MEDION (Universities of Maastricht and Leuven); DARE (Database of Abstracts of Reviews of Effects - via the Cochrane Library); HTA Database (Health Technology Assessment Database via the Cochrane Library) and ARIF (Birmingham University). We also checked reference lists of relevant studies and reviews, used searches of known relevant studies in PubMed to track related articles, and contacted research groups conducting work on IQCODE for dementia diagnosis to try to find additional studies. We developed a sensitive search strategy; search terms were designed to cover key concepts using several different approaches run in parallel and included terms relating to cognitive tests, cognitive screening and dementia. We used standardised database subject headings such as MeSH terms (in MEDLINE) and other standardised headings (controlled vocabulary) in other databases, as appropriate. SELECTION CRITERIA: We selected those studies performed in secondary-care settings, which included (not necessarily exclusively) IQCODE to assess for the presence of dementia and where dementia diagnosis was confirmed with clinical assessment. For the 'secondary care' setting we included all studies which assessed patients in hospital (e.g. acute unscheduled admissions, referrals to specialist geriatric assessment services etc.) and those referred for specialist 'memory' assessment, typically in psychogeriatric services. DATA COLLECTION AND ANALYSIS: We screened all titles generated by electronic database searches, and reviewed abstracts of all potentially relevant studies. Two independent assessors checked full papers for eligibility and extracted data. We determined quality assessment (risk of bias and applicability) using the QUADAS-2 tool, and reporting quality using the STARD tool. MAIN RESULTS: From 72 papers describing IQCODE test accuracy, we included 13 papers, representing data from 2745 individuals (n = 1413 (51%) with dementia). Pooled analysis of all studies using data presented closest to a cut-off of 3.3 indicated that sensitivity was 0.91 (95% CI 0.86 to 0.94); specificity 0.66 (95% CI 0.56 to 0.75); the positive likelihood ratio was 2.7 (95% CI 2.0 to 3.6) and the negative likelihood ratio was 0.14 (95% CI 0.09 to 0.22).There was a statistically significant difference in test accuracy between the general hospital setting and the specialist memory setting (P = 0.019), suggesting that IQCODE performs better in a 'general' setting.We found no significant differences in the test accuracy of the short (16-item) versus the 26-item IQCODE, or in the language of administration.There was significant heterogeneity in the included studies, including a highly varied prevalence of dementia (10.5% to 87.4%). Across the included papers there was substantial potential for bias, particularly around sampling of included participants and selection criteria, which may limit generalisability. There was also evidence of suboptimal reporting, particularly around disease severity and handling indeterminate results, which are important if considering use in clinical practice. AUTHORS'CONCLUSIONS: The IQCODE can be used to identify older adults in the general hospital setting who are at risk of dementia and require specialist assessment; it is useful specifically for ruling out those without evidence of cognitive decline. The language of administration did not affect test accuracy, which supports the cross-cultural use of the tool. These findings are qualified by the significant heterogeneity, the potential for bias and suboptimal reporting found in the included studies.

BackgroundThe long-term psychological consequences of stroke and how cognitive problems change over time after the first-year following stroke remain unclear. Particularly, trajectories of domain-specific and domain-general cognitive functions and how cognition interacts with mood, fatigue, and quality of life are not well described.AimsTo determine the prevalence, trajectories and wider impact of domain specific cognitive impairment in long term stroke survivors, in relation to mood, fatigue, and quality of life.MethodsParticipants who previously took part in the Oxford Cognitive Screening study, completed the 6-month follow up with cognitive, mood, fatigue, and quality of life assessments and agreed to be contacted for future research will be recruited into OX-CHRONIC. The eligible cohort is between 2- and 9-years post stroke. Cognition will be assessed with a detailed neuropsychological battery, alongside questionnaire measures of mood, fatigue, activities of daily life and quality of life measures at two timepoints, one year apart. Additionally, medical records will be accessed to extract further clinical information about the stroke and patients may opt-in to wear an activity monitor for one week to provide fine-grained measures of sleep and activity. The study protocol and study materials were approved by the national ethics committee (REC Ref:19/SC/0520).Planned outputsOX-CHRONIC will provide detailed data on the evolving cognitive profiles of stroke survivors over several years post-stroke. Estimates of long-term prevalence as well as the effect of changes in cognitive profiles on mood, fatigue and quality of life will be examined. This Study is funded by a Priority Programme Grant from the Stroke Association (SA PPA 18/100032).

This is a protocol for a Cochrane Review (prognosis). The objectives are as follows: PRIMARY OBJECTIVE: Identify all available multi‐domain prognostic models (that is, models involving two or more modifiable risk factors for dementia) used in middle‐aged adults (45 to 65 years) for the prediction of subsequent dementia. SECONDARY OBJECTIVES: Descriptively summarise the characteristics of these prognostic models. Appraise the predictive accuracy (discrimination and calibration) in the development and validation studies of these models. Identify implications of the use of dementia prognostic models for the management of people at risk of dementia or populations. THE OBJECTIVE IN PICOTS FORMAT: INVESTIGATION OF SOURCES OF HETEROGENEITY BETWEEN STUDIES: The expected sources of heterogeneity are: measurement of candidate predictors in the model; type of dementia (e.g. early‐ versus late‐onset dementia, Alzheimer's disease versus other forms of dementia); the country where the study was conducted; and method of diagnosis of dementia.

Background: \ud Medications with anticholinergic properties are commonly prescribed to older adults. The cumulative anticholinergic effect of all the medications a person takes is referred to as the 'anticholinergic burden' because of its potential to cause adverse effects. It is possible that high anticholinergic burden may be a risk factor for development of cognitive decline or dementia. There are various scales available to measure anticholinergic burden but agreement between them is often poor.\ud \ud Objectives: \ud To assess whether anticholinergic burden, as defined at the level of each individual scale, is a prognostic factor for future cognitive decline or dementia in cognitively unimpaired older adults.\ud \ud Search methods: \ud We searched the following databases from inception to 24 March 2021: MEDLINE (OvidSP), Embase (OvidSP), PsycINFO (OvidSP), CINAHL (EBSCOhost), and ISI Web of Science Core Collection (ISI Web of Science).\ud \ud Selection criteria: \ud We included prospective and retrospective longitudinal cohort and case‐control observational studies with a minimum of one year' follow‐up that examined the association between an anticholinergic burden measurement scale and future cognitive decline or dementia in cognitively unimpaired older adults.\ud \ud Data collection and analysis: \ud Two review authors independently assessed studies for inclusion, and undertook data extraction, assessment of risk of bias, and GRADE assessment. We extracted odds ratios (OR) and hazard ratios, with 95% confidence intervals (CI), and linear data on the association between anticholinergic burden and cognitive decline or dementia. We intended to pool each metric separately; however, only OR‐based data were suitable for pooling via a random‐effects meta‐analysis. We initially established adjusted and unadjusted pooled rates for each available anticholinergic scale; then, as an exploratory analysis, established pooled rates on the prespecified association across scales. We examined variability based on severity of anticholinergic burden.\ud \ud Main results: \ud We identified 25 studies that met our inclusion criteria (968,428 older adults). Twenty studies were conducted in the community care setting, two in primary care clinics, and three in secondary care settings. Eight studies (320,906 participants) provided suitable data for meta‐analysis. The Anticholinergic Cognitive Burden scale (ACB scale) was the only scale with sufficient data for 'scale‐based' meta‐analysis. Unadjusted ORs suggested an increased risk for cognitive decline or dementia in older adults with an anticholinergic burden (OR 1.47, 95% CI 1.09 to 1.96) and adjusted ORs similarly suggested an increased risk for anticholinergic burden, defined according to the ACB scale (OR 2.63, 95% CI 1.09 to 6.29). Exploratory analysis combining adjusted ORs across available scales supported these results (OR 2.16, 95% CI 1.38 to 3.38), and there was evidence of variability in risk based on severity of anticholinergic burden (ACB scale 1: OR 2.18, 95% CI 1.11 to 4.29; ACB scale 2: OR 2.71, 95% CI 2.01 to 3.56; ACB scale 3: OR 3.27, 95% CI 1.41 to 7.61); however, overall GRADE evaluation of certainty of the evidence was low.\ud \ud Authors' conclusions: \ud There is low‐certainty evidence that older adults without cognitive impairment who take medications with anticholinergic effects may be at increased risk of cognitive decline or dementia.

BackgroundVascular cognitive impairment (VCI) describes a broad spectrum of cognitive impairments caused by cerebrovascular disease, ranging frommild cognitive impairment to dementia. There are currently no pharmacological treatments recommended for improving either cognitionor function in people with VCI. Three cholinesterase inhibitors (donepezil, galantamine, and rivastigmine) are licenced for the treatmentof dementia due to Alzheimer's disease. They are thought to work by compensating for reduced cholinergic neurotransmission, which isalso a feature of VCI. Through pairwise comparisons with placebo and a network meta-analysis, we sought to determine whether thesemedications are eEective in VCI and whether there are diEerences between them with regard to eEicacy or adverse events.Objectives(1) To assess the eEicacy and safety of cholinesterase inhibitors in the treatment of adults with vascular dementia and other VCI.(2) To compare the eEects of diEerent cholinesterase inhibitors on cognition and adverse events, using network meta-analysis.Search methodsWe searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's register, MEDLINE (OvidSP), Embase (OvidSP), PsycINFO(OvidSP), CINAHL (EBSCOhost), Web of Science Core Collection (ISI Web of Science), LILACS (BIREME), ClinicalTrials.gov, and the WorldHealth Organization International Clinical Trials Registry Platform on 19 August 2020.Selection criteriaWe included randomised controlled trials in which donepezil, galantamine, or rivastigmine was compared with placebo or in which thedrugs were compared with each other in adults with vascular dementia or other VCI (excluding cerebral autosomal dominant arteriopathywith subcortical infarcts and leukoencephalopathy (CADASIL)). We included all drug doses and routes of administration.Data collection and analysisTwo review authors independently identified eligible trials, extracted data, assessed risk of bias, and applied the GRADE approach to assessthe certainty of the evidence. The primary outcomes were cognition, clinical global impression, function (performance of activities of dailyliving), and adverse events. Secondary outcomes were serious adverse events, incidence of development of new dementia, behavioural disturbance, carer burden, institutionalisation, quality of life and death. For the pairwise analyses, we pooled outcome data at similar timepoints using random-eEects methods. We also performed a network meta-analysis using Bayesian methods.Main resultsWe included eight trials (4373 participants) in the review. Three trials studied donepezil 5 mg or 10 mg daily (n= 2193); three trials studiedrivastigmine at a maximum daily dose of 3 to 12 mg (n= 800); and two trials studied galantamine at a maximum daily dose of 16 to 24 mg(n= 1380). The trials included participants with possible or probable vascular dementia or cognitive impairment following stroke. Meanages were between 72.2 and 73.9 years. All of the trials were at low or unclear risk of bias in all domains, and the evidence ranged fromvery low to high level of certainty.For cognition, the results showed that donepezil 5 mg improves cognition slightly, although the size of the eEect is unlikely to be clinicallyimportant (mean diEerence (MD) −0.92 Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) points (range 0 to 70), 95%confidence interval (CI) −1.44 to −0.40; high-certainty evidence). Donepezil 10 mg (MD −2.21 ADAS-Cog points, 95% CI −3.07 to −1.35;moderate-certainty evidence) and galantamine 16 to 24 mg (MD −2.01 ADAS-Cog point, 95%CI −3.18 to −0.85; moderate-certainty evidence)probably also improve cognition, although the larger eEect estimates still may not be clinically important. With low certainty, there maybe little to no eEect of rivastigmine 3 to 12 mg daily on cognition (MD 0.03 ADAS-Cog points, 95% CI −3.04 to 3.10; low-certainty evidence).Adverse events reported in the studies included nausea and/or vomiting, diarrhoea, dizziness, headache, and hypertension. The resultsshowed that there was probably little to no diEerence between donepezil 5 mg and placebo in the number of adverse events (odds ratio(OR) 1.22, 95% CI 0.94 to 1.58; moderate-certainty evidence), but there were slightly more adverse events with donepezil 10 mg than withplacebo (OR 1.95, 95% CI 1.20 to 3.15; high-certainty evidence). The eEect of rivastigmine 3 to 12 mg on adverse events was very uncertain(OR 3.21, 95% CI 0.36 to 28.88; very low-certainty evidence). Galantamine 16 to 24 mg is probably associated with a slight excess of adverseevents over placebo (OR 1.57, 95% CI 1.02 to 2.43; moderate-certainty evidence).In the network meta-analysis (NMA), we included cognition to represent benefit, and adverse events to represent harm. All drugs rankedabove placebo for cognition and below placebo for adverse events. We found donepezil 10 mg to rank first in terms of benefit, but thirdin terms of harms, when considering the network estimates and quality of evidence. Galantamine was ranked second in terms of bothbenefit and harm. Rivastigmine had the lowest ranking of the cholinesterase inhibitors in both benefit and harm NMA estimates, but thismay reflect possibly inadequate doses received by some trial participants and small trial sample sizes.Authors' conclusionsWe found moderate- to high-certainty evidence that donepezil 5 mg, donepezil 10 mg, and galantamine have a slight beneficial eEect oncognition in people with VCI, although the size of the change is unlikely to be clinically important. Donepezil 10 mg and galantamine 16 to24 mg are probably associated with more adverse events than placebo. The evidence for rivastigmine was less certain.The data suggest that donepezil 10 mg has the greatest eEect on cognition, but at the cost of adverse eEects. The eEect is modest, butin the absence of any other treatments, people living with VCI may still wish to consider the use of these agents. Further research into rivastigmine is needed, including the use of transdermal patches.

Background Dementia is a syndrome that comprises many differing pathologies, including Alzheimer's disease dementia (ADD), vascular dementia (VaD) and frontotemporal dementia (FTD). People may benefit from knowing the type of dementia they live with, as this could inform prognosis and may allow for tailored treatment. Beta-amyloid (1-42) (ABeta42) is a protein which decreases in both the plasma and cerebrospinal fluid (CSF) of people living with ADD, when compared to people with no dementia. However, it is not clear if changes in ABeta42 are specific to ADD or if they are also seen in other types of dementia. It is possible that ABeta42 could help differentiate ADD from other dementia subtypes. Objectives To determine the accuracy of plasma and CSF ABeta42 for distinguishing ADD from other dementia subtypes in people who meet the criteria for a dementia syndrome. Search methods We searched MEDLINE, and nine other databases up to 18 February 2020. We checked reference lists of any relevant systematic reviews to identify additional studies. Selection criteria We considered cross-sectional studies that differentiated people with ADD from other dementia subtypes. Eligible studies required measurement of participant plasma or CSF ABeta42 levels and clinical assessment for dementia subtype. Data collection and analysis Seven review authors working independently screened the titles and abstracts generated by the searches. We collected data on study characteristics and test accuracy. We used the second version of the 'Quality Assessment of Diagnostic Accuracy Studies' (QUADAS-2) tool to assess internal and external validity of results. We extracted data into 2 x 2 tables, cross-tabulating index test results (ABeta42) with the reference standard (diagnostic criteria for each dementia subtype). We performed meta-analyses using bivariate, random-effects models. We calculated pooled estimates of sensitivity, specificity, positive predictive values, positive and negative likelihood ratios, and corresponding 95% confidence intervals (CIs). In the primary analysis, we assessed accuracy of plasma or CSF ABeta42 for distinguishing ADD from other mixed dementia types (non-ADD). We then assessed accuracy of ABeta42 for differentiating ADD from specific dementia types: VaD, FTD, dementia with Lewy bodies (DLB), alcohol-related cognitive disorder (ARCD), Creutzfeldt-Jakob disease (CJD) and normal pressure hydrocephalus (NPH). To determine test-positive cases, we used the ABeta42 thresholds employed in the respective primary studies. We then performed sensitivity analyses restricted to those studies that used common thresholds for ABeta42. Main results We identified 39 studies (5000 participants) that used CSF ABeta42 levels to differentiate ADD from other subtypes of dementia. No studies of plasma ABeta42 met the inclusion criteria. No studies were rated as low risk of bias across all QUADAS-2 domains. High risk of bias was found predominantly in the domains of patient selection (28 studies) and index test (25 studies). The pooled estimates for differentiating ADD from other dementia subtypes were as follows: ADD from non-ADD: sensitivity 79% (95% CI 0.73 to 0.85), specificity 60% (95% CI 0.52 to 0.67), 13 studies, 1704 participants, 880 participants with ADD; ADD from VaD: sensitivity 79% (95% CI 0.75 to 0.83), specificity 69% (95% CI 0.55 to 0.81), 11 studies, 1151 participants, 941 participants with ADD; ADD from FTD: sensitivity 85% (95% CI 0.79 to 0.89), specificity 72% (95% CI 0.55 to 0.84), 17 studies, 1948 participants, 1371 participants with ADD; ADD from DLB: sensitivity 76% (95% CI 0.69 to 0.82), specificity 67% (95% CI 0.52 to 0.79), nine studies, 1929 participants, 1521 participants with ADD. Across all dementia subtypes, sensitivity was greater than specificity, and the balance of sensitivity and specificity was dependent on the threshold used to define test positivity. Authors' conclusions Our review indicates that measuring ABeta42 levels in CSF may help differentiate ADD from other dementia subtypes, but the test is imperfect and tends to misdiagnose those with non-ADD as having ADD. We would caution against the use of CSF ABeta42 alone for dementia classification. However, ABeta42 may have value as an adjunct to a full clinical assessment, to aid dementia diagnosis.

UK care home residents are invisible in national datasets. The COVID-19 pandemic has exposed data failings that have hindered service development and research for years. Fundamental gaps, in terms of population and service demographics coupled with difficulties identifying the population in routine data are a significant limitation. These challenges are a key factor underpinning the failure to provide timely and responsive policy decisions to support care homes. In this commentary we propose changes that could address this data gap, priorities include: (1) Reliable identification of care home residents and their tenure; (2) Common identifiers to facilitate linkage between data sources from different sectors; (3) Individual-level, anonymised data inclusive of mortality irrespective of where death occurs; (4) Investment in capacity for large-scale, anonymised linked data analysis within social care working in partnership with academics; (5) Recognition of the need for collaborative working to use novel data sources, working to understand their meaning and ensure correct interpretation; (6) Better integration of information governance, enabling safe access for legitimate analyses from all relevant sectors; (7) A core national dataset for care homes developed in collaboration with key stakeholders to support integrated care delivery, service planning, commissioning, policy and research. Our suggestions are immediately actionable with political will and investment. We should seize this opportunity to capitalise on the spotlight the pandemic has thrown on the vulnerable populations living in care homes to invest in data-informed approaches to support care, evidence-based policy making and research.

Background Many millions of people living with dementia around the world are not diagnosed, which has a negative impact both on their access to care and treatment and on rational service planning. Telehealth - the use of information and communication technology (ICT) to provide health services at a distance - may be a way to increase access to specialist assessment for people with suspected dementia, especially those living in remote or rural areas. It has also been much used during the COVID-19 pandemic. It is important to know whether diagnoses made using telehealth assessment are as accurate as those made in conventional, face-to-face clinical settings. Objectives Primary objective: to assess the diagnostic accuracy of telehealth assessment for dementia and mild cognitive impairment. Secondary objectives: to identify the quality and quantity of the relevant research evidence; to identify sources of heterogeneity in the test accuracy data; to identify and synthesise any data on patient or clinician satisfaction, resource use, costs or feasibility of the telehealth assessment models in the included studies. Search methods We searched multiple databases and clinical trial registers on 4 November 2020 for published and 'grey' literature and registered trials. We applied no search filters and no language restrictions. We screened the retrieved citations in duplicate and assessed in duplicate the full texts of papers considered potentially relevant. Selection criteria We included in the review cross-sectional studies with 10 or more participants who had been referred to a specialist service for assessment of a suspected cognitive disorder. Within a period of one month or less, each participant had to undergo two clinical assessments designed to diagnose dementia or mild cognitive impairment (MCI): a telehealth assessment (the index test) and a conventional face-to-face assessment (the reference standard). The telehealth assessment could be informed by some data collected face-to-face, e.g. by nurses working in primary care, but all contact between the patient and the specialist clinician responsible for synthesising the information and making the diagnosis had to take place remotely using ICT. Data collection and analysis Two review authors independently extracted data from included studies. Data extracted covered study design, setting, participants, details of index test and reference standard, and results in the form of numbers of participants given diagnoses of dementia or MCI. Data were also sought on dementia subtype diagnoses and on quantitative measures of patient or clinician satisfaction, resource use, costs and feasibility. We assessed risk of bias and applicability of each included study using QUADAS-2. We entered the results into 2x2 tables in order to calculate the sensitivity and specificity of telehealth assessment for the diagnosis of all-cause dementia, MCI, and any cognitive syndrome (combining dementia and MCI). We presented the results of included studies narratively because there were too few studies to derive summary estimates of sensitivity and specificity. Main results Three studies with 136 participants were eligible for inclusion. Two studies (20 and 100 participants) took place in community settings in Australia and one study (16 participants) was conducted in veterans' homes in the USA. Participants were referred from primary care with undiagnosed cognitive symptoms or were identified as being at high risk of having dementia on a screening test in the care homes. Dementia and MCI were target conditions in the larger study; the other studies targeted dementia diagnosis only. Only one small study used a 'pure' telehealth model, i.e. not involving any elements of face-to-face assessment. The studies were generally well-conducted. We considered two studies to be at high risk of incorporation bias because a substantial amount of information collected face-to-face by nurses was used to inform both index test and reference standard assessments. One study was at unclear risk of selection bias. For the diagnosis of all-cause dementia, sensitivity of telehealth assessment ranged from 0.80 to 1.00 and specificity from 0.80 to 1.00. We considered this to be very low-certainty evidence due to imprecision, inconsistency between studies and risk of bias. For the diagnosis of MCI, data were available from only one study (100 participants) giving a sensitivity of 0.71 (95% CI 0.54 to 0.84) and a specificity of 0.73 (95% CI 0.60 to 0.84). We considered this to be low-certainty evidence due to imprecision and risk of bias. For diagnosis of any cognitive syndrome (dementia or MCI), data from the same study gave a sensitivity of 0.97 (95% CI 0.91 to 0.99) and a specificity of 0.22 (95% CI 0.03 to 0.60). The majority of diagnostic disagreements concerned the distinction between MCI and dementia, occurring approximately equally in either direction. There was also a tendency for patients identified as cognitively healthy at face-to-face assessment to be diagnosed with MCI at telehealth assessment (but numbers were small). There were insufficient data to make any assessment of the accuracy of dementia subtype diagnosis. One study provided a small amount of data indicating a good level of clinician and especially patient satisfaction with the telehealth model. There were no data on resource use, costs or feasibility. Authors' conclusions We found only very few eligible studies with a small number of participants. An important difference between the studies providing data for the analyses was whether the target condition was dementia only (two studies) or dementia and MCI (one study). The data suggest that telehealth assessment may be highly sensitive and specific for the diagnosis of all-cause dementia when assessed against a reference standard of conventional face-to-face assessment, but the estimates are imprecise due to small sample sizes and between-study heterogeneity, and may apply mainly to telehealth models which incorporate a considerable amount of face-to-face contact with healthcare professionals other than the doctor responsible for making the diagnosis. For the diagnosis of MCI by telehealth assessment, best estimates of both sensitivity and specificity were somewhat lower, but were based on a single study. Errors occurred at the cognitively healthy/MCI and the MCI/dementia boundaries. However, there is no evidence that diagnostic disagreements were more frequent than would be expected due to the known variation between clinicians' opinions when assigning a dementia diagnosis.

Background Robust diagnosis of dementia requires an understanding of the accuracy of the available diagnostic tests. Informant questionnaires are frequently used to assess for dementia in clinical practice. Recent systematic reviews have sought to establish the diagnostic test accuracy of various dementia informant screening tools. However, most reviews to date have focused on a single diagnostic tool and this does not address which tool is ‘best’. A key aim of the overview of systematic reviews is to present a disparate evidence base in a single, easy to access platform. Methods We will conduct an overview of systematic reviews in which we ‘review the systematic reviews’ of diagnostic test accuracy studies evaluating informant questionnaires for dementia. As an overview of systematic reviews of test accuracy is a relatively novel approach, we will use this review to explore methods for visual representation of complex data, for highlighting evidence gaps and for indirect comparative analyses. We will create a list of informant tools by consulting with dementia experts. We will search 6 databases (EMBASE (OVID); Health and Psychosocial Instruments (OVID); Medline (OVID); CINAHL (EBSCO); PSYCHinfo (EBSCO) and the PROSPERO registry of review protocols) to identify systematic reviews that describe the diagnostic test accuracy of informant questionnaires for dementia. We will assess review quality using the AMSTAR-2 (Assessment of Multiple Systematic Reviews) and assess reporting quality using PRISMA-DTA (Preferred Reporting Items for Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies) checklists. We will collate the identified reviews to create an ‘evidence map’ that highlights where evidence does and does not exist in relation to informant questionnaires. We will pool sensitivity and specificity data via meta-analysis to generate a diagnostic test accuracy summary statistic for each informant questionnaire. If data allow, we will perform a statistical comparison of the diagnostic test accuracy of each informant questionnaire using a network approach. Discussion Our overview of systematic reviews will provide a concise summary of the diagnostic test accuracy of informant tools and highlight areas where evidence is currently lacking in this regard. It will also apply network meta-analysis techniques to a new area.

Background Post-operative delirium is an important, yet under-researched complication of surgery. Patients undergoing urological surgery may be at especially high risk of POD, as they are often older, and interventions can be associated with conditions that trigger delirium. The main aim of this systematic review was to evaluate the available evidence for risk factors in this patient group. Methods Five databases were searched (MEDLINE, Web of Science, EMBASE, CINAHL and PsychInfo) between January 1987 and June 2019. The Newcastle–Ottawa Scale was used to assess for risk of bias. Pooled odds ratio or mean difference (MD) for individual risk factors were estimated using the Mantel–Haenzel and inverse variance methods. Results Seven articles met the inclusion criteria, giving a total population of 1937. The incidence of POD ranged from 5 to 29%. Three studies were deemed low risk of bias and four at a high risk of bias. Nine risk factors were suitable for meta-analysis, with age (MD 4.314 95% CI 1.597, 7.032 p = 0.002) and the clock drawing test (MD − 2.443 95% CI − 3.029, − 1.857 p Conclusion Delirium is common in urological patients. This review has identified a lack of studies in this surgical population, with wide heterogeneity and high risk of bias. It also highlights a number of potential risk factors for post-operative delirium, of which some are modifiable. However, the strength of evidence is weak at present and so future research should focus on assessing comparable risk factors in this patient group in order to inform future clinical practice. Review registration The review protocol was prospectively registered with the PROSPERO database (reference CRD42017054613)

ObjectivesThis is a protocol for a Cochrane Review (diagnostic). The objectives are as follows:Our main objective is to assess the test accuracy of any multidomain cognitive test delivered remotely for the diagnosis of any form of dementia.Our review will not be limited to a particular healthcare setting or a particular threshold score of index test.Secondary objectives To describe the degree of agreement between a remotely delivered cognitive test and the same or a closely related test delivered in‐person when neither is assessed against a clinical dementia reference standard. To identify the quality and quantity of the research evidence describing test accuracy of remote testing. To identify sources of heterogeneity in the test accuracy described. To identify gaps in the evidence where further research is required.Investigation of sources of heterogeneityHeterogeneity is often seen in clinical test accuracy reviews (Deeks 2001). Important potential sources of heterogeneity will include the case‐mix of the population being assessed; clinical setting; person performing the assessment; platform used to administer the test (e.g. standard telephone versus video call); threshold scores used to define test positivity; and the quality of the included papers. We will collect data on all of these factors, and if data allow will explore their effect using subgroup and sensitivity analyses as appropriate.

Introduction Delirium is associated with a wide range of adverse patient safety outcomes, yet it remains consistently under-diagnosed. We undertook a systematic review of studies describing delirium in adult medical patients in secondary care. We investigated if changes in healthcare complexity were associated with trends in reported delirium over the last four decades. Methods We used identical criteria to a previous systematic review, only including studies using internationally accepted diagnostic criteria for delirium (the Diagnostic and Statistical Manual of Mental Disorders and the International Statistical Classification of Diseases). Estimates were pooled across studies using random effects meta-analysis, and we estimated temporal changes using meta-regression. We investigated publication bias with funnel plots. Results We identified 15 further studies to add to 18 studies from the original review. Overall delirium occurrence was 23% (95% CI 19–26%) (33 studies) though this varied according to diagnostic criteria used (highest in DSM-IV, lowest in DSM-5). There was no change from 1980 to 2019, nor was case-mix (average age of sample, proportion with dementia) different. Overall, risk of bias was moderate or low, though there was evidence of increasing publication bias over time. Discussion The incidence and prevalence of delirium in hospitals appears to be stable, though publication bias may have masked true changes. Nonetheless, delirium remains a challenging and urgent priority for clinical diagnosis and care pathways.

Background Dementia is a worldwide concern. Its global prevalence is increasing. At present, there is no medication licensed to prevent or delay the onset of dementia. Inflammation has been suggested as a key factor in dementia pathogenesis. Therefore, medications with anti-inflammatory properties could be beneficial for dementia prevention. Objectives To evaluate the effectiveness and adverse effects of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) for the primary or secondary prevention of dementia. Search methods We searched ALOIS, the specialised register of the Cochrane Dementia and Cognitive Improvement Group up to 9 January 2020. ALOIS contains records of clinical trials identified from monthly searches of several major healthcare databases, trial registries and grey literature sources. We ran additional searches across MEDLINE (OvidSP), Embase (OvidSP) and six other databases to ensure that the searches were as comprehensive and up-to-date as possible. We also reviewed citations of reference lists of included studies. Selection criteria We searched for randomised controlled trials (RCTs) and controlled clinical trials (CCTs) comparing aspirin or other NSAIDs with placebo for the primary or secondary prevention of dementia. We included trials with cognitively healthy participants (primary prevention) or participants with mild cognitive impairment (MCI) or cognitive complaints (secondary prevention). Data collection and analysis We used standard methodological procedures according to the Cochrane Handbook for Systematic Reviews of Interventions. We rated the strength of evidence for each outcome using the GRADE approach. Main results We included four RCTs with 23,187 participants. Because of the diversity of these trials, we did not combine data to give summary estimates, but presented a narrative description of the evidence. We identified one trial (19,114 participants) comparing low-dose aspirin (100 mg once daily) to placebo. Participants were aged 70 years or older with no history of dementia, cardiovascular disease or physical disability. Interim analysis indicated no significant treatment effect and the trial was terminated slightly early after a median of 4.7 years' follow-up. There was no evidence of a difference in incidence of dementia between aspirin and placebo groups (risk ratio (RR) 0.98, 95% CI 0.83 to 1.15; high-certainty evidence). Participants allocated aspirin had higher rates of major bleeding (RR 1.37, 95% CI 1.17 to 1.60, high-certainty evidence) and slightly higher mortality (RR 1.14, 95% CI 1.01 to 1.28; high-certainty evidence). There was no evidence of a difference in activities of daily living between groups (RR 0.84, 95% CI 0.70 to 1.02; high-certainty evidence). We identified three trials comparing non-aspirin NSAIDs to placebo. All three trials were terminated early due to adverse events associated with NSAIDs reported in other trials. One trial (2528 participants) investigated the cyclo-oxygenase-2 (COX-2) inhibitor celecoxib (200 mg twice daily) and the non-selective NSAID naproxen (220 mg twice daily) for preventing dementia in cognitively healthy older adults with a family history of Alzheimer's disease (AD). Median follow-up was 734 days. Combining both NSAID treatment arms, there was no evidence of a difference in the incidence of AD between participants allocated NSAIDs and those allocated placebo (RR 1.91, 95% CI 0.89 to 4.10; moderate-certainty evidence). There was also no evidence of a difference in rates of myocardial infarction (RR 1.21, 95% CI 0.61 to 2.40), stroke (RR 1.82, 95% CI 0.76 to 4.37) or mortality (RR 1.37, 95% CI 0.78 to 2.43) between treatment groups (all moderate-certainty evidence). One trial (88 participants) assessed the effectiveness of celecoxib (200 mg or 400 mg daily) in delaying cognitive decline in participants aged 40 to 81 years with mild age-related memory loss but normal memory performance scores. Mean duration of follow-up was 17.6 months in the celecoxib group and 18.1 months in the placebo group. There was no evidence of a difference between groups in test scores in any of six cognitive domains. Participants allocated celecoxib experienced more gastrointestinal adverse events than those allocated placebo (RR 2.66, 95% CI 1.05 to 6.75; low-certainty evidence). One trial (1457 participants) assessed the effectiveness of the COX-2 inhibitor rofecoxib (25 mg once daily) in delaying or preventing a diagnosis of AD in participants with MCI. Median duration of study participation was 115 weeks in the rofecoxib group and 130 weeks in the placebo group. There was a higher incidence of AD in the rofecoxib than the placebo group (RR 1.32, 95% CI 1.01 to 1.72; moderate-certainty evidence). There was no evidence of a difference between groups in cardiovascular adverse events (RR 1.07, 95% CI 0.68 to 1.66; moderate-certainty evidence) or mortality (RR 1.62, 95% CI 0.85 to 3.05; moderate-certainty evidence). Participants allocated rofecoxib had more upper gastrointestinal adverse events (RR 3.53, 95% CI 1.17 to 10.68; moderate-certainty evidence). Reported annual mean difference scores showed no evidence of a difference between groups in activities of daily living (year 1: no data available; year 2: 0.0, 95% CI -0.1 to 0.2; year 3: 0.1, 95% CI -0.1 to 0.3; year 4: 0.1, 95% CI -0.1 to 0.4; moderate-certainty evidence). Authors' conclusions There is no evidence to support the use of low-dose aspirin or other NSAIDs of any class (celecoxib, rofecoxib or naproxen) for the prevention of dementia, but there was evidence of harm. Although there were limitations in the available evidence, it seems unlikely that there is any need for further trials of low-dose aspirin for dementia prevention. If future studies of NSAIDs for dementia prevention are planned, they will need to be cognisant of the safety concerns arising from the existing studies.

This paper gives a brief account of the history of time standards and timekeeping beginning with John Harrison's seagoing clocks for navigation up to today's optical frequency standards and prospects for the future definition of the second.

BACKGROUND: The number of new cases of dementia is projected to rise significantly over the next decade. Thus, there is a pressing need for accurate tools to detect cognitive impairment in routine clinical practice. The Addenbrooke's Cognitive Examination III (ACE‐III), and the mini‐ACE are brief, bedside cognitive screens that have previously reported good sensitivity and specificity. The quality and quantity of this evidence has not, however, been robustly investigated. OBJECTIVES: To assess the diagnostic test accuracy of the ACE‐III and mini‐ACE for the detection of dementia, dementia sub‐types, and mild cognitive impairment (MCI) at published thresholds in primary, secondary, and community care settings in patients presenting with, or at high risk of, cognitive decline. SEARCH METHODS: We performed the search for this review on 13 February 2019. We searched MEDLINE (OvidSP), Embase (OvidSP), BIOSIS Previews (ISI Web of Knowledge), Web of Science Core Collection (ISI Web of Knowledge), PsycINFO (OvidSP), and LILACS (BIREME). We applied no language or date restrictions to the electronic searches; and to maximise sensitivity we did not use methodological filters. The search yielded 5655 records, of which 2937 remained after we removed duplicates. We identified a further four articles through PubMed 'related articles'. We found no additional records through reference list citation searching, or grey literature. SELECTION CRITERIA: Cross‐sectional studies investigating the accuracy of the ACE‐III or mini‐ACE in patients presenting with, or at high risk of, cognitive decline were suitable for inclusion. We excluded case‐control, delayed verification and longitudinal studies, and studies which investigated a secondary cause of dementia. We did not restrict studies by language; and we included those with pre‐specified thresholds (88 and 82 for the ACE‐III, and 21 or 25 for the mini‐ACE). DATA COLLECTION AND ANALYSIS: We extracted information on study and participant characteristics and used information on dementia and MCI prevalence, sensitivity, specificity, and sample size to generate 2×2 tables in Review Manager 5. We assessed methodological quality of included studies using the QUADAS‐2 tool; and we assessed the quality of study reporting with the STARDdem tool. Due to significant heterogeneity in the included studies and an insufficient number of studies, we did not perform meta‐analyses. MAIN RESULTS: This review identified seven studies (1711 participants in total) of cross‐sectional design, four examining the accuracy of the ACE‐III, and three of the mini‐ACE. Overall, the majority of studies were at low or unclear risk of bias and applicability on quality assessment. Studies were at high risk of bias for the index test (n = 4) and reference standard (n = 2). Study reporting was variable across the included studies. No studies investigated dementia sub‐types. The ACE‐III had variable sensitivity across thresholds and patient populations (range for dementia at 82 and 88: 82% to 97%, n = 2; range for MCI at 88: 75% to 77%, n = 2), but with more variability in specificity (range for dementia: 4% to 77%, n = 2; range for MCI: 89% to 92%, n = 2). Similarly, sensitivity of the mini‐ACE was variable (range for dementia at 21 and 25: 70% to 99%, n = 3; range for MCI at 21 and 25: 64% to 95%, n = 3) but with more variability specificity (range for dementia: 32% to 100%, n = 3; range for MCI: 46% to 79%, n = 3). We identified no studies in primary care populations: four studies were conducted in outpatient clinics, one study in an in‐patient setting, and in two studies the settings were unclear. AUTHORS' CONCLUSIONS: There is insufficient information in terms of both quality and quantity to recommend the use of either the ACE‐III or mini‐ACE for the screening of dementia or MCI in patients presenting with, or at high risk of, cognitive decline. No studies were conducted in a primary care setting so the accuracy of the ACE‐III and mini‐ACE in this setting are not known. Lower thresholds (82 for the ACE‐III, and 21 for the mini‐ACE) provide better specificity with acceptable sensitivity and may provide better clinical utility. The ACE‐III and mini‐ACE should only be used to support the diagnosis as an adjunct to a full clinical assessment. Further research is needed to determine the utility of the ACE‐III and mini‐ACE for the detection of dementia, dementia sub‐types, and MCI. Specifically, the optimal thresholds for detection need to be determined in a variety of settings (primary care, secondary care (inpatient and outpatient), and community services), prevalences, and languages.

AimsTo investigate the effect of serum urate on blood pressure and cardiovascular disease (CVD) risk by updating evidence from Mendelian randomization (MR) analysis and meta-analysis of randomized controlled trials (RCTs).Methods and ResultsUsing recently available data from the Million Veterans Program and UK Biobank, the main MR analyses showed that every 1-standard deviation increase in genetically predicted serum urate was associated with an increased risk of coronary heart disease (odds ratio 1.19, 95% confidence interval 1.10-1.30,P=4×10−5), peripheral artery disease (1.12, 95%CI 1.03 to 1.21,P=9×10−3), and stroke (1.11, 95%CI 1.05 to 1.18,P=2×10−4). In MR mediation analyses, SBP was estimated to mediate approximately one third the effect of urate on CVD risk. Systematic review and meta-analysis of RCTs showed a favorable effect of urate-lowering treatment on SBP (mean difference -2.55mmHg, 95%CI -4.06 to -1.05,P=1×10−3) and major adverse cardiovascular events (MACE) in those with previous CVD (OR 0.40, 95%CI 0.22 to 0.73,P=3×10−3), but no significant effect on MACE in all individuals (OR 0.73, 95%CI 0.48 to 1.09,P=0.12).ConclusionMR and clinical trial data support an effect of higher serum urate on increasing blood pressure, which may mediate a consequent effect on CVD risk. High-quality trials are necessary to provide definitive evidence on the specific clinical contexts where urate-lowering may be of cardiovascular benefit.

Background: Changing population demographics have led to an increasing number of functionally dependent older people who require care and medical treatment. In many countries, government policy aims to shift resources into the community from institutional care settings with the expectation that this will reduce costs and improve the quality of care compared. Objectives: To assess the effects of long‐term home or foster home care versus institutional care for functionally dependent older people. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Library, MEDLINE, Embase, CINAHL, and two trials registers to November 2015. Selection criteria: We included randomised and non‐randomised trials, controlled before‐after studies and interrupted time series studies complying with the EPOC study design criteria and comparing the effects of long‐term home care versus institutional care for functionally dependent older people. Data collection and analysis: Two reviewers independently extracted data and assessed the risk of bias of each included study. We reported the results narratively, as the substantial heterogeneity across studies meant that meta‐analysis was not appropriate. Main results: We included 10 studies involving 16,377 participants, all of which were conducted in high income countries. Included studies compared community‐based care with institutional care (care homes). The sample size ranged from 98 to 11,803 (median N = 204). There was substantial heterogeneity in the healthcare context, interventions studied, and outcomes assessed. One study was a randomised trial (N = 112); other included studies used designs that had potential for bias, particularly due lack of randomisation, baseline imbalances, and non‐blinded outcome assessment. Most studies did not select (or exclude) participants for any specific disease state, with the exception of one study that only included patients if they had a stroke. All studies had methodological limitations, so readers should interpret results with caution. It is uncertain whether long‐term home care compared to nursing home care decreases mortality risk (2 studies, N = 314, very‐low certainty evidence). Estimates ranged from a nearly three‐fold increased risk of mortality in the homecare group (risk ratio (RR) 2.89, 95% confidence interval (CI) 1.57 to 5.32) to a 62% relative reduction (RR 0.38, 95% CI 0.17 to 0.61). We did not pool data due to the high degree of heterogeneity (I2 = 94%). It is uncertain whether the intervention has a beneficial effect on physical function, as the certainty of evidence is very low (5 studies, N = 1295). Two studies reported that participants who received long‐term home care had improved activities of daily living compared to those in a nursing home, whereas a third study reported that all participants performed equally on physical function. It is uncertain whether long‐term home care improves happiness compared to nursing home care (RR 1.97, 95% CI 1.27 to 3.04) or general satisfaction because the certainty of evidence was very low (2 studies, N = 114). The extent to which long‐term home care was associated to more or fewer adverse health outcomes than nursing home care was not reported. It is uncertain whether long‐term home care compared to nursing home care decreases the risk of hospital admission (very low‐certainty evidence, N = 14,853). RR estimates ranged from 2.75 (95% CI 2.59 to 2.92), showing an increased risk for those receiving care at home, to 0.82 (95% CI 0.72 to 0.93), showing a slightly reduced risk for the same group. We did not pool data due to the high degree of heterogeneity (I2 = 99%). Authors' conclusions: There are insufficient high‐quality published data to support any particular model of care for functionally dependent older people. Community‐based care was not consistently beneficial across all the included studies; there were some data suggesting that community‐based care may be associated with improved quality of life and physical function compared to institutional care. However, community alternatives to institutional care may be associated with increased risk of hospitalisation. Future studies should assess healthcare utilisation, perform economic analysis, and consider caregiver burden.

Background:\ud \ud The diagnosis of Alzheimer's disease dementia and other dementias relies on clinical assessment. There is a high prevalence of cognitive disorders, including undiagnosed dementia in secondary care settings. Short cognitive tests can be helpful in identifying those who require further specialist diagnostic assessment; however, there is a lack of consensus around the optimal tools to use in clinical practice. The Mini‐Cog is a short cognitive test comprising three‐item recall and a clock‐drawing test that is used in secondary care settings.\ud Objectives:\ud \ud The primary objective was to determine the diagnostic accuracy of the Mini‐Cog for detecting Alzheimer's disease dementia and other dementias in a secondary care setting. The secondary objectives were to investigate the heterogeneity of test accuracy in the included studies and potential sources of heterogeneity. These potential sources of heterogeneity will include the baseline prevalence of dementia in study samples, thresholds used to determine positive test results, the type of dementia (Alzheimer's disease dementia or all causes of dementia), and aspects of study design related to study quality.\ud Search methods:\ud \ud We searched the following sources in September 2012, with an update to 12 March 2019: Cochrane Dementia Group Register of Diagnostic Test Accuracy Studies, MEDLINE (OvidSP), Embase (OvidSP), BIOSIS Previews (Web of Knowledge), Science Citation Index (ISI Web of Knowledge), PsycINFO (OvidSP), and LILACS (BIREME). We made no exclusions with regard to language of Mini‐Cog administration or language of publication, using translation services where necessary.\ud Selection criteria:\ud \ud We included cross‐sectional studies and excluded case‐control designs, due to the risk of bias. We selected those studies that included the Mini‐Cog as an index test to diagnose dementia where dementia diagnosis was confirmed with reference standard clinical assessment using standardised dementia diagnostic criteria. We only included studies in secondary care settings (including inpatient and outpatient hospital participants).\ud Data collection and analysis:\ud \ud We screened all titles and abstracts generated by the electronic database searches. Two review authors independently checked full papers for eligibility and extracted data. We determined quality assessment (risk of bias and applicability) using the QUADAS‐2 tool. We extracted data into two‐by‐two tables to allow calculation of accuracy metrics for individual studies, reporting the sensitivity, specificity, and 95% confidence intervals of these measures, summarising them graphically using forest plots.\ud Main results:\ud \ud Three studies with a total of 2560 participants fulfilled the inclusion criteria, set in neuropsychology outpatient referrals, outpatients attending a general medicine clinic, and referrals to a memory clinic. Only n = 1415 (55.3%) of participants were included in the analysis to inform evaluation of Mini‐Cog test accuracy, due to the selective use of available data by study authors. There were concerns related to high risk of bias with respect to patient selection, and unclear risk of bias and high concerns related to index test conduct and applicability. In all studies, the Mini‐Cog was retrospectively derived from historic data sets. No studies included acute general hospital inpatients. The prevalence of dementia ranged from 32.2% to 87.3%. The sensitivities of the Mini‐Cog in the individual studies were reported as 0.67 (95% confidence interval (CI) 0.63 to 0.71), 0.60 (95% CI 0.48 to 0.72), and 0.87 (95% CI 0.83 to 0.90). The specificity of the Mini‐Cog for each individual study was 0.87 (95% CI 0.81 to 0.92), 0.65 (95% CI 0.57 to 0.73), and 1.00 (95% CI 0.94 to 1.00). We did not perform meta‐analysis due to concerns related to risk of bias and heterogeneity.\ud Authors' conclusions:\ud \ud This review identified only a limited number of diagnostic test accuracy studies using Mini‐Cog in secondary care settings. Those identified were at high risk of bias related to patient selection and high concerns related to index test conduct and applicability. The evidence was indirect, as all studies evaluated Mini‐Cog differently from the review question, where it was anticipated that studies would conduct Mini‐Cog and independently but contemporaneously perform a reference standard assessment to diagnose dementia. The pattern of test accuracy varied across the three studies. Future research should evaluate Mini‐Cog as a test in itself, rather than derived from other neuropsychological assessments. There is also a need for evaluation of the feasibility of the Mini‐Cog for the diagnosis of dementia to help adequately determine its role in the clinical pathway.

Background:\ud Dementia assessment often involves initial screening, using a brief tool, followed by more detailed assessment where required. The AD‐8 is a short questionnaire, completed by a suitable 'informant' who knows the person well. AD‐8 is designed to assess change in functional performance secondary to cognitive change.\ud \ud Objectives:\ud To determine the diagnostic accuracy of the informant‐based AD‐8 questionnaire, in detection of all‐cause (undifferentiated) dementia in adults. Where data were available, we described the following: the diagnostic accuracy of the AD‐8 at various predefined threshold scores; the diagnostic accuracy of the AD‐8 for each healthcare setting and the effects of heterogeneity on the reported diagnostic accuracy of the AD‐8.\ud \ud Search Methods:\ud We searched the following sources on 27 May 2014, with an update to 7 June 2018: ALOIS (Cochrane Dementia and Cognitive Improvement Group), MEDLINE (Ovid SP), Embase (Ovid SP), PsycINFO (Ovid SP), BIOSIS Previews (Thomson Reuters Web of Science), Web of Science Core Collection (includes Conference Proceedings Citation Index) (Thomson Reuters Web of Science), CINAHL (EBSCOhost) and LILACS (BIREME). We checked reference lists of relevant studies and reviews, used searches of known relevant studies in PubMed to track related articles, and contacted research groups conducting work on the AD‐8 to try to find additional studies. We developed a sensitive search strategy and used standardised database subject headings as appropriate. Foreign language publications were translated.\ud \ud Selection Criteria:\ud We selected those studies which included the AD‐8 to assess for the presence of dementia and where dementia diagnosis was confirmed with clinical assessment. We only included those studies where the AD‐8 was used as an informant assessment. We made no exclusions in relation to healthcare setting, language of AD‐8 or the AD‐8 score used to define a 'test positive' case.\ud \ud Data Collection and Analysis:\ud We screened all titles generated by electronic database searches, and reviewed abstracts of potentially relevant studies. Two independent assessors checked full papers for eligibility and extracted data. We extracted data into two‐by‐two tables to allow calculation of accuracy metrics for individual studies. We then created summary estimates of sensitivity, specificity and likelihood ratios using the bivariate approach and plotting results in receiver operating characteristic (ROC) space. We determined quality assessment (risk of bias and applicability) using the QUADAS‐2 tool.\ud \ud Main Results:\ud From 36 papers describing AD‐8 test accuracy, we included 10 papers. We utilised data from nine papers with 4045 individuals, 1107 of whom (27%) had a clinical diagnosis of dementia. Pooled analysis of seven studies, using an AD‐8 informant cut‐off score of two, indicated that sensitivity was 0.92 (95% confidence interval (CI) 0.86 to 0.96); specificity was 0.64 (95% CI 0.39 to 0.82); the positive likelihood ratio was 2.53 (95% CI 1.38 to 4.64); and the negative likelihood ratio was 0.12 (95% CI 0.07 to 0.21). Pooled analysis of five studies, using an AD‐8 informant cut‐off score of three, indicated that sensitivity was 0.91 (95% CI 0.80 to 0.96); specificity was 0.76 (95% CI 0.57 to 0.89); the positive likelihood ratio was 3.86 (95% CI 2.03 to 7.34); and the negative likelihood ratio was 0.12 (95% CI 0.06 to 0.24).\ud \ud Four studies were conducted in community settings; four were in secondary care (one in the acute hospital); and one study was in primary care. The AD‐8 has a higher relative sensitivity (1.11, 95% CI 1.02 to 1.21), but lower relative specificity (0.51, 95% CI 0.23 to 1.09) in secondary care compared to community care settings.\ud \ud There was heterogeneity across the included studies. Dementia prevalence rate varied from 12% to 90% of included participants. The tool was also used in various different languages. Among all the included studies there was evidence of risk of bias. Issues included the selection of participants, conduct of index test, and flow of assessment procedures.\ud \ud Authors' Conclusions:\ud The high sensitivity of the AD‐8 suggests it can be used to identify adults who may benefit from further specialist assessment and diagnosis, but is not a diagnostic test in itself. This pattern of high sensitivity and lower specificity is often suited to a screening test. Test accuracy varies by setting, however data in primary care and acute hospital settings are limited. This review identified significant heterogeneity and risk of bias, which may affect the validity of its summary findings.