New horizons in the diagnosis and management of Alzheimer's Disease in older adults.

Alzheimer's Disease (ad) is the most common cause of dementia, and in addition to cognitive decline, it directly contributes to physical frailty, falls, incontinence, institutionalisation and polypharmacy in older adults. Increasing availability of clinically validated biomarkers including cerebrospinal fluid and positron emission tomography to assess both amyloid and tau pathology has led to a reconceptualisation of ad as a clinical-biological diagnosis, rather than one based purely on clinical phenotype. However, co-pathology is frequent in older adults which influence the accuracy of biomarker interpretation. Importantly, some older adults with positive amyloid or tau pathological biomarkers may never experience cognitive impairment or dementia. These strides towards achieving an accurate clinical-biological diagnosis are occurring alongside recent positive phase 3 trial results reporting statistically significant effects of anti-amyloid Disease-Modifying Therapies (DMTs) on disease severity in early ad. However, the real-world clinical benefit of these DMTs is not clear and concerns remain regarding how trial results will translate to real-world clinical populations, potential adverse effects (including amyloid-related imaging abnormalities), which can be severe and healthcare systems readiness to afford and deliver potential DMTs to appropriate populations. Here, we review recent advances in both clinical-biological diagnostic classification and future treatment in older adults living with ad. Advocating for access to both more accurate clinical-biological diagnosis and potential DMTs must be done so in a holistic and gerontologically attuned fashion, with geriatricians advocating for enhanced multi-component and multi-disciplinary care for all older adults with ad. This includes those across the ad severity spectrum including older adults potentially ineligible for emerging DMTs.

Barriers and motivators to undertaking physical activity in adults over 70-a systematic review of the quantitative literature.

BACKGROUND: Physical activity (PA) has multiple benefits for older adults (≥70 years old). Despite this many older adults do not undertake the World Health Organisation guideline recommended amount of PA. This systematic review examines barriers and motivators to PA in adults aged ≥70 years. METHODS: We analysed the quantitative literature, including observational studies and baseline data from randomised controlled trials. Studies examining specific diseases (e.g. cognitive impairment), or care home residents were excluded. Database searches of ASSIA, CINAHL, Embase, Medline, PsycINFO and Web of Science were undertaken on 7 March 2023. Quality assessment was performed using the ROBANS tool. We synthesised the results using the socioecological model. The protocol was registered on PROSPERO (CRD42021160503). RESULTS: We identified 37 papers, n = 26,961, age 70-101 years (median 78), 62% female. We undertook a narrative review; meta-analysis was not possible. Overall risk of bias was low. A total of 23 studies addressed barriers, seven motivators, seven both. The most cited barriers were: concern about physical health/fitness (14 studies), lack of motivation/interest (13 studies), fear of falls/history of falling (11 studies) and environmental barriers (10 studies). Key motivators were: support from family/friends (five studies), social interaction (five studies), personal benefits (five studies) and outside facilities (five studies). Results varied across gender, age, functional ability and geographical location. DISCUSSION: To maximise PA in older adults, important modifiable factors identified in this review should be targeted: support from healthcare professionals; reducing fear of falls; and prioritising ease of access and safety of outdoor facilities. When considering future policy, a person-centred, age group appropriate approach will have the most impact.

Commentary on: physical activity and exercise for mild cognitive impairment and dementia: a collaborative international guideline.

Physical inactivity is an important, but potentially reversible risk factor for dementia and mild cognitive impairment (MCI). There is literature about physical activity and exercise for the prevention and management of dementia and MCI, but this had not been previously synthesized into specific guidelines about this topic. A recent guideline on physical activity and exercise in MCI and dementia was published, authored by several international societies, including lay representatives. In this commentary, we discuss the implications of this guidance for healthcare professionals, caregivers, and lay representatives involved in the care of people with MCI and dementia.The guidelines highlight the importance of physical activity and exercise in cognitively healthy persons and for dementia and MCI, at different stages of these conditions. For primary prevention of dementia, physical activity may be suggested in cognitively healthy persons. In people with MCI, mind-body interventions, such as yoga, have the greatest evidence, whilst the role of physical activity and exercise requires more evidence from high-quality randomized controlled trials. In people living with moderately severe dementia, exercise may be useful for maintaining physical and cognitive function. There are benefits of physical activity and exercise separate from their impact on cognitive outcomes. The guidelines also proposed some questions for future research. In conclusion, there is limited evidence on the beneficial role of physical activity and exercise in preserving cognitive functions in subjects with normal cognition, MCI or dementia. The guidelines support the promotion of physical activity based on the beneficial effects on almost all facets of health.

Neurogranin in Alzheimer's disease and ageing: A human post-mortem study.

Neurogranin (Ng), a post-synaptic protein involved in memory formation, has been investigated as a biomarker in the cerebrospinal fluid (CSF) in Alzheimer's disease (AD) and ageing. CSF Ng levels are elevated in AD relative to healthy controls and correlate with cognition; however, few studies have focused on Ng abundance in the brain. Synapse loss in the brain correlates closely with cognitive decline in AD making synaptic biomarkers potentially important for tracking disease progression, but the links between synaptic protein changes in CSF and brain remain incompletely understood. In the current study, Ng abundance was examined in post-mortem human brain tissue across AD, healthy ageing (HA), and mid-life (ML) cohorts. Ng levels were quantified in three brain regions associated with cognitive change found during ageing and neurodegenerative diseases, namely the middle temporal gyrus, primary visual cortex and the posterior hippocampus using immunohistochemistry. To support immunohistochemical analysis, total homogenate and biochemically enriched synaptic fractions from available temporal gyrus tissues were examined by immunoblot. Finally, we examined whether Ng is associated with lifetime cognitive ageing. Ng levels were significantly reduced in AD relative to HA and ML cases across all regions. Additionally Ng was significantly reduced in HA in comparison to ML in the primary visual cortex. Immunoblotting confirms reduced Ng levels in AD cases supporting immunohistochemical results. Interestingly, there was also a significant reduction of synapse-associated Ng in our group who had lifetime cognitive decline in comparison to the group with lifetime cognitive resilience indicating loss of neurogranin in remaining synapses during ageing is associated with cognitive decline. Our findings indicate that increases in CSF Ng reflect loss of brain neurogranin and support the use of CSF Ng as a biomarker of AD and potentially of cognitive decline in healthy ageing.

A systematic review of studies reporting on neuropsychological and functional domains used for assessment of recovery from delirium in acute hospital patients.

OBJECTIVES: Assessing for recovery in delirium is essential in guiding ongoing investigation and treatment. Yet, there is little scrutiny and no research or clinical consensus on how recovery should be measured. We reviewed studies which used tests of neuropsychological domains and functional ability to track recovery of delirium longitudinally in acute hospital settings. METHODS/DESIGN: We systematically searched databases (MEDLINE, PsycInfo, CINAHL, Embase, ClinicalTrials.gov, Cochrane Central Register of Controlled Trials), from inception to October 14th , 2022. Inclusion criteria were: adult acute hospital patients (≥18 years) diagnosed with delirium by a validated tool; 1+ repeat assessment using an assessment tool measuring domains of delirium/functional recovery ≤7 days from baseline. Two reviewers independently screened articles, performed data extraction, and assessed risk of bias. A narrative data synthesis was completed. RESULTS: From 6533 screened citations, we included 39 papers (reporting 32 studies), with 2370 participants with delirium. Studies reported 21 tools with an average of four repeat assessments including baseline (range 2-10 assessments within ≤7 days), measuring 15 specific domains. General cognition, functional ability, arousal, attention and psychotic features were most commonly assessed for longitudinal change. Risk of bias was moderate to high for most studies. CONCLUSIONS: There was no standard approach for tracking change in specific domains of delirium. The methodological heterogeneity of studies was too high to draw firm conclusions on the effectiveness of assessment tools to measure delirium recovery. This highlights the need for standardised methods for assessing recovery from delirium.

Seeing the forest (plot) for the trees-the importance of evidence synthesis in older adult care.

Systematically reviewing all the available evidence and then creating summary analyses of the pooled data is the foundation of evidence-based practice. Indeed, this evidence synthesis approach informs much of the care of older adults in hospital and community. It is perhaps no surprise that the journal Age and Ageing is a frequent platform for publishing research papers based on systematic review and synthesis. This research has evolved substantially from the early days of evidence-based medicine and the Cochrane Collaboration. The traditional approach would be a quantitative summary, calculated using pair-wise meta-analysis of randomised controlled trials of drug versus placebo, or a synthesis of observational studies to create summaries of prevalence, associations and outcomes. Methods have evolved and newer techniques such as scoping reviews, test accuracy meta-analysis and qualitative synthesis are all now available. The sophistication of these methods is driven in part by the increasingly complex decisions that need be made in contemporary older adult care. Age and Ageing continues to champion established and novel evidence synthesis approaches, and in the accompanying Collection exemplars of these differing methods are presented and described. Whilst there is marked heterogeneity in the techniques used, the consistent and defining feature of all these papers is the desire to comprehensively, and critically summarise the evidence in order to answer the most pertinent questions regarding older adult care.

Impact of MidMed, a general practitioner-led modified comprehensive geriatric assessment for patients with frailty.

INTRODUCTION: the identification and management of frailty occurs mostly in primary care. Several different models of care exist. This study aimed to assess the impact of a new General Practitioner (GP)-led modified Comprehensive Geriatric Assessment (CGA) on service delivery, healthcare utilisation and patient outcomes. METHOD: patients with moderate-severe frailty (electronic Frailty Index score > 0.24) in Newbattle Medical Practice, Scotland, were eligible for a novel intervention (MidMed) in which an additional GP performed a modified CGA and was directly accessible for appointments. The recruits to the intervention (MidMed) group were compared with those waiting to be enrolled (non-MidMed). Outcomes included unscheduled hospital admissions, primary care consultations, continuity of care (Usual Provider of Care (UPC) index), outpatient attendances and mortality. Adjusted rate ratios (aRR), for MidMed compared to non-MidMed, were estimated using regression models adjusting for demographics and healthcare utilisation histories. RESULTS: 510 patients were included: 290 MidMed (mean(SD) age 80.1(7.6)years; 59.6% female) and 220 non-MidMed (75.4(8.6)years; 57.7% female). Median follow-up was 396 days. aRR(95%CI) was 0.46(0.30-0.71) for >1 admission, 0.62(0.41-0.95) >1 Emergency Department (ED) attendance and 1.52(1.30-1.75) for use of primary care, with no difference in outpatient appointments or mortality. Continuity of care was better for the MidMed group (MidMed UPC 0.77(SD 0.19), non-MidMed 0.41(0.18), P < 0.001). CONCLUSION: this GP-led service for frail patients was associated with lower risk of hospital readmission/ED reattendance, greater use of primary care and improved continuity of care. More detailed evaluation of novel primary care frailty services, over longer time-periods, including robust randomised controlled trials, are needed.

Complex interventions for improving independent living and quality of life amongst community-dwelling older adults: a systematic review and meta-analysis.

BACKGROUND: community-based complex interventions for older adults have a variety of names, including Comprehensive Geriatric Assessment, but often share core components such as holistic needs assessment and care planning. OBJECTIVE: to summarise evidence for the components and effectiveness of community-based complex interventions for improving older adults' independent living and quality of life (QoL). METHODS: we searched nine databases and trial registries to February 2022 for randomised controlled trials comparing complex interventions to usual care. Primary outcomes included living at home and QoL. Secondary outcomes included mortality, hospitalisation, institutionalisation, cognitive function and functional status. We pooled data using risk ratios (RRs) or standardised mean differences (SMDs) with 95% confidence intervals (CIs). RESULTS: we included 50 trials of mostly moderate quality. Most reported using holistic assessment (94%) and care planning (90%). Twenty-seven (54%) involved multidisciplinary care, with 29.6% delivered mainly by primary care teams without geriatricians. Nurses were the most frequent care coordinators. Complex interventions increased the likelihood of living at home (RR 1.05; 95% CI 1.00-1.10; moderate-quality evidence) but did not affect QoL. Supported by high-quality evidence, they reduced mortality (RR 0.86; 95% CI 0.77-0.96), enhanced cognitive function (SMD 0.12; 95% CI 0.02-0.22) and improved instrumental activities of daily living (ADLs) (SMD 0.11; 95% CI 0.01-0.21) and combined basic/instrumental ADLs (SMD 0.08; 95% CI 0.03-0.13). CONCLUSIONS: complex interventions involving holistic assessment and care planning increased the chance of living at home, reduced mortality and improved cognitive function and some ADLs.

Factors that influence older adults' participation in physical activity: a systematic review of qualitative studies.

BACKGROUND: Despite the advantages of physical activity (PA), older adults are often insufficiently active to maximise health. Understanding factors that influence PA engagement will support well-designed interventions for older people. Our aim was to review the qualitative evidence exploring the factors affecting older adults' engagement in PA. METHODS: We searched six electronic databases for studies of community-dwelling older adults (≥70 years) including qualitative methods. We excluded studies of a single-disease group, individuals with cognitive impairment and care home residents. Methodological rigour was assessed with the Critical Appraisal Skills Programme, and framework synthesis was applied using the Capability Opportunity Motivation-Behaviour (COM-B) model, which hypothesises that behaviour is influenced by three factors: capability, opportunity and motivation. RESULTS: Twenty-five studies were included in the review (N = 4,978; mean 79 years) and 32 themes were identified. Older adults' capability was influenced by functional capacity (e.g. strength) and perceived risk of injury from PA (e.g. falls). Opportunity was impacted by the environment 'fit' (e.g. neighbourhood safety), the availability of social interaction and socio-cultural ageing stereotypes. PA was motivated by identifying as an 'exerciser', health gains and experiencing positive emotions (e.g. enjoyment), whereas negative sensations (e.g. pain) reduced motivation. CONCLUSIONS: The qualitative synthesis showcased a complex web of interacting factors influencing PA between the sub-domains of COM-B, pinpointing directions for intervention, including a focus on whole systems approaches. There was a lack of research exploring PA influences in the oldest old and in low-income countries. Future research should seek to involve under-served groups, including a wider diversity of older people.

Identifying dementia using medical data linkage in a longitudinal cohort study: Lothian Birth Cohort 1936.

BACKGROUND: The Lothian Birth Cohort 1936 (LBC1936) is a longitudinal study of ageing with well-characterised assessments, but until now, it has relied on self-report or proxies for dementia such as cognitive tests. Our aims were twofold: a) to describe a framework for identifying dementia in a cohort study. b) to report the age-specific incidence and prevalence of all-cause dementia and dementia subtypes in 865 individuals in the LBC1936. METHODS: Electronic Health Records (EHR) of all participants were reviewed, and relevant information was extracted to form case vignettes for everyone with any record of cognitive dysfunction. The EHR data sources include hospital and clinic letters, general practitioner and hospital referrals, prescribed medications, imaging and laboratory results. Death certificate data were obtained separately. Clinician assessments were performed when there was concern about a participant's cognition. A diagnosis of probable dementia, possible dementia, or no dementia was agreed upon by a consensus diagnostic review board, comprised of a multidisciplinary team of clinical dementia experts who reviewed case vignettes and clinician assessment letters. For those with probable dementia, a subtype was also determined, where possible. We compared the agreement between our newly ascertained dementia diagnoses with the existing self-reported dementia diagnoses. RESULTS: Self-reported dementia diagnoses were positive in only 17.8% of ascertained dementia diagnoses. The EHR review identified 163/865 (18.8%) individuals as having cognitive dysfunction. At the consensus diagnostic review board, 118/163 were diagnosed with probable all-cause dementia, a prevalence of 13.6%. Age-specific dementia prevalence increased with age from 0.8% (65-74.9 years) to 9.93% (85-89.9 years). Prevalence rates for women were higher in nearly all age groups. The most common subtype was dementia due to Alzheimer disease (49.2%), followed by mixed Alzheimer and cerebrovascular disease (17.0%), dementia of unknown or unspecified cause (16.1%), and dementia due to vascular disease (8.5%). CONCLUSIONS: We present a robust systematic framework and guide for other cohort teams wanting to ascertain dementia diagnoses. The newly ascertained dementia diagnosis provides vital data for further analyses of LBC1936 to allow exploration of lifecourse predictors of dementia.

Do prenatal factors shape the risk for dementia?: A systematic review of the epidemiological evidence for the prenatal origins of dementia.

PURPOSE: Prenatal factors such as maternal stress, infection and nutrition affect fetal brain development and may also influence later risk for dementia. The purpose of this systematic review was to provide an overview of all studies which investigated the association between prenatal factors and later risk for dementia. METHODS: We systematically searched MEDLINE and Embase for original human studies reporting on associations between prenatal factors and dementia from inception to 23 November 2022. Prenatal factors could be any factor assessed during pregnancy, at birth or postnatally, provided they were indicative of a prenatal exposure. Risk of bias was assessed using the Newcastle Ottawa Scale. We followed PRISMA guidelines for reporting. RESULTS: A total of 68 studies met eligibility criteria (including millions of individuals), assessing maternal age (N = 30), paternal age (N = 22), birth order (N = 15), season of birth (N = 16), place of birth (N = 13), prenatal influenza pandemic (N = 1) or Chinese famine exposure (N = 1), birth characteristics (N = 3) and prenatal hormone exposure (N = 4). We observed consistent results for birth in a generally less optimal environment (e.g. high infant mortality area) being associated with higher dementia risk. Lower and higher birth weight and prenatal famine exposure were associated with higher dementia risk. The studies on season of birth, digit ratio, prenatal influenza pandemic exposure, parental age and birth order showed inconsistent results and were hampered by relatively high risk of bias. CONCLUSION: Our findings suggest that some prenatal factors, especially those related to a suboptimal prenatal environment, are associated with an increased dementia risk. As these associations may be confounded by factors such as parental socioeconomic status, more research is needed to examine the potential causal role of the prenatal environment in dementia.

Early life predictors of late life cerebral small vessel disease in four prospective cohort studies.

Development of cerebral small vessel disease, a major cause of stroke and dementia, may be influenced by early life factors. It is unclear whether these relationships are independent of each other, of adult socio-economic status or of vascular risk factor exposures. We examined associations between factors from birth (ponderal index, birth weight), childhood (IQ, education, socio-economic status), adult small vessel disease, and brain volumes, using data from four prospective cohort studies: STratifying Resilience And Depression Longitudinally (STRADL) (n = 1080; mean age = 59 years); the Dutch Famine Birth Cohort (n = 118; mean age = 68 years); the Lothian Birth Cohort 1936 (LBC1936; n = 617; mean age = 73 years), and the Simpson's cohort (n = 110; mean age = 78 years). We analysed each small vessel disease feature individually and summed to give a total small vessel disease score (range 1-4) in each cohort separately, then in meta-analysis, adjusted for vascular risk factors and adult socio-economic status. Higher birth weight was associated with fewer lacunes [odds ratio (OR) per 100 g = 0.93, 95% confidence interval (CI) = 0.88 to 0.99], fewer infarcts (OR = 0.94, 95% CI = 0.89 to 0.99), and fewer perivascular spaces (OR = 0.95, 95% CI = 0.91 to 0.99). Higher childhood IQ was associated with lower white matter hyperintensity burden (OR per IQ point = 0.99, 95% CI 0.98 to 0.998), fewer infarcts (OR = 0.98, 95% CI = 0.97 to 0.998), fewer lacunes (OR = 0.98, 95% CI = 0.97 to 0.999), and lower total small vessel disease burden (OR = 0.98, 95% CI = 0.96 to 0.999). Low education was associated with more microbleeds (OR = 1.90, 95% CI = 1.33 to 2.72) and lower total brain volume (mean difference = -178.86 cm3, 95% CI = -325.07 to -32.66). Low childhood socio-economic status was associated with fewer lacunes (OR = 0.62, 95% CI = 0.40 to 0.95). Early life factors are associated with worse small vessel disease in later life, independent of each other, vascular risk factors and adult socio-economic status. Risk for small vessel disease may originate in early life and provide a mechanistic link between early life factors and risk of stroke and dementia. Policies investing in early child development may improve lifelong brain health and contribute to the prevention of dementia and stroke in older age.

Developing a care home data platform in Scotland: a mixed methods study of data routinely collected in care homes.

BACKGROUND: care homes collect extensive data about their residents, and their care, in multiple ways, for multiple purposes. We aimed to (i) identify what data are routinely collected and (ii) collate care home managers' views and experiences of collecting, using and sharing data. METHODS: we examined data collected in six care homes across Lothian, Scotland. We extracted the meta-data, cross-referenced definitions and assessed the degree of harmonisation between care homes and with data sets currently in use in Scotland and internationally. We interviewed care home managers about their views and experiences of collecting, using and sharing data. RESULTS: we identified 15 core data items used routinely, with significant heterogeneity in tools and assessments used, and very limited harmonisation. Two overarching themes were identified of importance to the development of a care home data platform: (i) the rationale for collecting data, including to (a) support person-centred care, (b) share information, (c) manage workforce and budget and (d) provide evidence to statutory bodies and (ii) the reality of collecting data, including data accuracy, and understanding data in context. DISCUSSION: considerable information is collected by care home staff, in varied formats, with heterogeneity of scope and definition, for range of reasons. We discuss the issues that should be considered to ensure that individual resident-level form the strong foundations for any data platform for care homes, which must also include, robust infrastructure and clear interoperability, with appropriate governance. It must be co-produced by academics, policy makers and sector representatives, with residents, their families and care staff.

Understanding Pathways into Care homes using Data (UnPiCD study): a retrospective cohort study using national linked health and social care data.

BACKGROUND: Pathways into care are poorly understood but important life events for individuals and their families. UK policy is to avoid moving-in to care homes from acute hospital settings. This assumes that moves from secondary care represent a system failure. However, those moving to care homes from community and hospital settings may be fundamentally different groups, each requiring differing care approaches. OBJECTIVE: To characterise individuals who move-in to a care home from hospital and compare with those moving-in from the community. DESIGN AND SETTING: A retrospective cohort study using cross-sectoral data linkage of care home data. METHODS: We included adults moving-in to care homes between 1/4/13 and 31/3/16, recorded in the Scottish Care Home Census. Care home data were linked to general and psychiatric hospital admissions, community prescribing and mortality records to ascertain comorbidities, significant diagnoses, hospital resource use, polypharmacy and frailty. Multivariate logistic regression identified predictors of moving-in from hospital compared to from community. RESULTS: We included 23,892 individuals moving-in to a care home, 13,564 (56.8%) from hospital and 10,328 (43.2%) from the community. High frailty risk adjusted Odds Ratio (aOR) 5.11 (95% Confidence Interval (CI): 4.60-5.68), hospital discharge with diagnosis of fracture aOR 3.91 (95%CI: 3.41-4.47) or stroke aOR 8.42 (95%CI: 6.90-10.29) were associated with moving-in from hospital. Discharge from in-patient psychiatry was also a highly significant predictor aOR 19.12 (95%CI: 16.26-22.48). CONCLUSIONS: Individuals moving-in to care homes directly from hospital are clinically distinct from those from the community. Linkage of cross-sectoral data can allow exploration of pathways into care at scale.

Informing Patients with Acute Stroke About their Risk of Dementia: A Survey of UK Healthcare Professionals.

OBJECTIVES: Cognitive problems following stroke are of key concern to stroke survivors. Discussing risk of dementia at the time of stroke could have implications for follow-up care. However, informing someone who has just had a stroke about risk of dementia could cause distress. This survey explored healthcare professionals' views on discussing risk of post-stroke dementia at the time of stroke. MATERIALS AND METHODS: This online survey was aimed at all UK healthcare professionals who care for patients with stroke. The survey was distributed via the mailing lists of seven professional stroke-related organisations and Twitter. Descriptive statistics were used to summarise findings. RESULTS: Sixty healthcare professionals completed the survey. Healthcare professionals were aware of the main risk factors associated with post-stroke dementia (e.g. previous stroke, age). Most respondents (N=34/60, 57%) thought that patients with acute stroke would benefit from knowing if they are at high risk of dementia, and 75% (N=45/60) agreed that carers would benefit. Despite this, the majority of healthcare professionals (N=47/53, 89%) who cared for patients with acute stroke in the past year said they rarely/never discussed dementia with their patients. Most respondents (N=46/60, 77%) thought risk of dementia should be discussed 1-6 months post-stroke. CONCLUSION: Although healthcare professionals felt it would be helpful to discuss risk of post-stroke dementia, in practice, most said that they rarely or never discussed this with their patients. Stroke survivors could benefit from a healthcare system that offers appropriate follow-up care and support to patients at high risk of dementia.

Predicting readmission and death after hospital discharge: a comparison of conventional frailty measurement with an electronic health record-based score.

BACKGROUND: frailty measurement may identify patients at risk of decline after hospital discharge, but many measures require specialist review and/or additional testing. OBJECTIVE: to compare validated frailty tools with routine electronic health record (EHR) data at hospital discharge, for associations with readmission or death. DESIGN: observational cohort study. SETTING: hospital ward. SUBJECTS: consented cardiology inpatients ≥70 years old within 24 hours of discharge. METHODS: patients underwent Fried, Short Physical Performance Battery (SPPB), PRISMA-7 and Clinical Frailty Scale (CFS) assessments. An EHR risk score was derived from the proportion of 31 possible frailty markers present. Electronic follow-up was completed for a primary outcome of 90-day readmission or death. Secondary outcomes were mortality and days alive at home ('home time') at 12 months. RESULTS: in total, 186 patients were included (79 ± 6 years old, 64% males). The primary outcome occurred in 55 (30%) patients. Fried (hazard ratio [HR] 1.47 per standard deviation [SD] increase, 95% confidence interval [CI] 1.18-1.81, P < 0.001), CFS (HR 1.24 per SD increase, 95% CI 1.01-1.51, P = 0.04) and EHR risk scores (HR 1.35 per SD increase, 95% CI 1.02-1.78, P = 0.04) were independently associated with the primary outcome after adjustment for age, sex and co-morbidity, but the SPPB and PRISMA-7 were not. The EHR risk score was independently associated with mortality and home time at 12 months. CONCLUSIONS: frailty measurement at hospital discharge identifies patients at risk of poorer outcomes. An EHR-based risk score appeared equivalent to validated frailty tools and may be automated to screen patients at scale, but this requires further validation.

Diagnostic accuracy of the 4AT for delirium detection in older adults: systematic review and meta-analysis.

OBJECTIVE: Detection of delirium in hospitalised older adults is recommended in national and international guidelines. The 4 'A's Test (4AT) is a short (<2 minutes) instrument for delirium detection that is used internationally as a standard tool in clinical practice. We performed a systematic review and meta-analysis of diagnostic test accuracy of the 4AT for delirium detection. METHODS: We searched MEDLINE, EMBASE, PsycINFO, CINAHL, clinicaltrials.gov and the Cochrane Central Register of Controlled Trials, from 2011 (year of 4AT release on the website www.the4AT.com) until 21 December 2019. Inclusion criteria were: older adults (≥65 years); diagnostic accuracy study of the 4AT index test when compared to delirium reference standard (standard diagnostic criteria or validated tool). Methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Pooled estimates of sensitivity and specificity were generated from a bivariate random effects model. RESULTS: Seventeen studies (3,702 observations) were included. Settings were acute medicine, surgery, a care home and the emergency department. Three studies assessed performance of the 4AT in stroke. 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). Excluding the stroke studies, the pooled sensitivity was 0.86 (95% CI 0.77-0.92) and the pooled specificity was 0.89 (95% CI 0.83-0.93). The methodological quality of studies varied but was moderate to good overall. CONCLUSIONS: The 4AT shows good diagnostic test accuracy for delirium in the 17 available studies. These findings support its use in routine clinical practice in delirium detection. PROSPERO REGISTRATION NUMBER: CRD42019133702.

Cholinesterase inhibitors for vascular dementia and other vascular cognitive impairments: a network meta-analysis.

BACKGROUND: Vascular cognitive impairment (VCI) describes a broad spectrum of cognitive impairments caused by cerebrovascular disease, ranging from mild cognitive impairment to dementia. There are currently no pharmacological treatments recommended for improving either cognition or function in people with VCI. Three cholinesterase inhibitors (donepezil, galantamine, and rivastigmine) are licenced for the treatment of dementia due to Alzheimer's disease. They are thought to work by compensating for reduced cholinergic neurotransmission, which is also a feature of VCI. Through pairwise comparisons with placebo and a network meta-analysis, we sought to determine whether these medications are effective in VCI and whether there are differences between them with regard to efficacy or adverse events. OBJECTIVES: (1) To assess the efficacy and safety of cholinesterase inhibitors in the treatment of adults with vascular dementia and other VCI. (2) To compare the effects of different cholinesterase inhibitors on cognition and adverse events, using network meta-analysis. SEARCH METHODS: We 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 World Health Organization International Clinical Trials Registry Platform on 19 August 2020. SELECTION CRITERIA: We included randomised controlled trials in which donepezil, galantamine, or rivastigmine was compared with placebo or in which the drugs were compared with each other in adults with vascular dementia or other VCI (excluding cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)). We included all drug doses and routes of administration. DATA COLLECTION AND ANALYSIS: Two review authors independently identified eligible trials, extracted data, assessed risk of bias, and applied the GRADE approach to assess the certainty of the evidence. The primary outcomes were cognition, clinical global impression, function (performance of activities of daily living), 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 time points using random-effects methods. We also performed a network meta-analysis using Bayesian methods. MAIN RESULTS: We included eight trials (4373 participants) in the review. Three trials studied donepezil 5 mg or 10 mg daily (n= 2193); three trials studied rivastigmine 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. Mean ages 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 from very low to high level of certainty. For cognition, the results showed that donepezil 5 mg improves cognition slightly, although the size of the effect is unlikely to be clinically important (mean difference (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 effect estimates still may not be clinically important. With low certainty, there may be little to no effect 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 results showed that there was probably little to no difference 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 with placebo (OR 1.95, 95% CI 1.20 to 3.15; high-certainty evidence). The effect 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 adverse events 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 ranked above placebo for cognition and below placebo for adverse events. We found donepezil 10 mg to rank first in terms of benefit, but third in terms of harms, when considering the network estimates and quality of evidence. Galantamine was ranked second in terms of both benefit and harm. Rivastigmine had the lowest ranking of the cholinesterase inhibitors in both benefit and harm NMA estimates, but this may reflect possibly inadequate doses received by some trial participants and small trial sample sizes. AUTHORS' CONCLUSIONS: We found moderate- to high-certainty evidence that donepezil 5 mg, donepezil 10 mg, and galantamine have a slight beneficial effect on cognition in people with VCI, although the size of the change is unlikely to be clinically important. Donepezil 10 mg and galantamine 16 to 24 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 effect on cognition, but at the cost of adverse effects. The effect is modest, but in 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.

Association between components of the delirium syndrome and outcomes in hospitalised adults: a systematic review and meta-analysis.

BACKGROUND: Delirium is a heterogeneous syndrome with inattention as the core feature. There is considerable variation in the presence and degree of other symptom domains such as altered arousal, psychotic features and global cognitive dysfunction. Delirium is independently associated with increased mortality, but it is unclear whether individual symptom domains of delirium have prognostic importance. We conducted a systematic review and meta-analysis of studies in hospitalised adults in general settings to identify the relationship between symptom domains of delirium and outcomes. (PROSPERO: CRD42018093935). METHODS: We searched MEDLINE, EMBASE, PsycINFO, CINAHL, clinicaltrials.gov and the Cochrane Central Register of Controlled Trials from inception to November 2019. We included studies of hospitalised adults that reported associations between symptom domains of delirium and 30-day mortality (primary outcome), and other outcomes including mortality at other time points, length of stay, and dementia. Reviewer pairs independently screened articles, extracted data, and assessed risk of bias (Risk of Bias Assessment tool for Non-randomized Studies) and quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation framework. We performed random-effects meta-analyses stratified by delirium domain where possible. RESULTS: From 7092 citations we included 6 studies (6002 patients, 1112 with delirium). Higher mortality (ranging from in-hospital to follow-up beyond 12 months) was associated with altered arousal (pooled Odds Ratio (OR) 2.80, 95% Confidence Interval (CI) 2.33-3.37; moderate-quality evidence), inattention (pooled OR 2.57, 95% CI 1.74-3.80; low-quality evidence), and in single studies with disorientation, memory deficits and disorganised thoughts. Risk of bias varied across studies but was moderate-to-high overall, mainly due to selection bias, lack of blinding of assessments and unclear risk of selective outcome reporting. We found no studies on the association between psychotic features, visuospatial deficits or affective disturbances in delirium and outcomes, or studies reporting non-mortality outcomes. CONCLUSIONS: Few studies have related symptom domains of delirium to outcomes, but the available evidence suggests that altered arousal and inattention in delirium are associated with higher mortality than normal arousal and attention in people with or without delirium. Measurable symptom domains of delirium may have value in predicting survival and stratifying patients for treatment. We recommend that future delirium studies report outcomes by symptom domain.

Research with older people in a world with COVID-19: identification of current and future priorities, challenges and opportunities.

Older people are disproportionately affected by the COVID-19 pandemic, which has had a profound impact on research as well as clinical service delivery. This commentary identifies key challenges and opportunities in continuing to conduct research with and for older people, both during and after the current pandemic. It shares opinions from responders to an international survey, a range of academic authors and opinions from specialist societies. Priorities in COVID-19 research include its specific presentation in older people, consequences for physical, cognitive and psychological health, treatments and vaccines, rehabilitation, supporting care homes more effectively, the impact of social distancing, lockdown policies and system reconfiguration to provide best health and social care for older people. COVID-19 research needs to be inclusive, particularly involving older people living with frailty, cognitive impairment or multimorbidity, and those living in care homes. Non-COVID-19 related research for older people remains of critical importance and must not be neglected in the rush to study the pandemic. Profound changes are required in the way that we design and deliver research for older people in a world where movement and face-to-face contact are restricted, but we also highlight new opportunities such as the ability to collaborate more widely and to design and deliver research efficiently at scale and speed.