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Alzheimer’s disease is a major cause of morbidity and mortality. Currently, there are no disease-modifying pharmacotherapies for this condition. Aducanumab, an amyloid beta-directed monoclonal antibody that targets aggregated forms of amyloid-beta in the brains of people with Alzheimer’s disease, has raised hopes that such a therapy has been discovered, but its approval by the US Food and Drug Administration has engendered a good deal of controversy. A similar application for approval has been submitted to Health Canada. In response to this, a group of Canadian clinical dementia experts representing a number of organizations, including the Canadian Geriatrics Society, was convened by the Canadian Consortium on Neurodegeneration in Aging (CCNA) to discuss the evidence currently available on this agent and seek consensus on what advice they would offer Health Canada on the application. There was wide-spread agreement that it would be premature for aducanumab to receive approval for the treatment of Alzheimer’s disease. It was also noted that the Canadian health-care system is poorly prepared at this time to deal with a disease-modifying therapeutic with targeting, administration, and monitoring characteristics like aducanumab. In this paper, the consensus reached is presented along with its underlying rationale.

Background The extent by which the degree of baseline frailty, as measured using standardized multidimensional health assessments before admission to hospital, predicts survival among older adults following admission to an intensive care unit (ICU) remains unclear. Research Question Is baseline frailty an independent predictor of survival among older adults receiving care in an ICU? Study Design and Methods Retrospective cohort study of community-dwelling older adults (age ≥65 years) receiving public home services that were admitted to any ICU in Ontario, Canada between April 1st, 2009 and March 31st, 2015. All individuals had an interRAI-Home Care (RAI-HC) assessment completed within 180 days of ICU admission; these assessments were linked to hospital discharge abstract records. Patients were categorized using frailty measures each calculated from the RAI-HC: a classification tree version of the Clinical Frailty Scale (CFS); the Frailty Index - Acute Care (FI-AC); and the Changes in Health, End-Stage Disease, Signs, and Symptoms Scale (CHESS). One-year survival models were used to compare their performance. Patients were stratified based on the receipt of mechanical ventilation in the ICU. Results Of 24,499 individuals admitted to an ICU within 180 days of a RAI-HC assessment, 26.4% (6,467) received mechanical ventilation. Overall, 43.0% (95% CI 42.4% - 43.6%) survived 365 days after ICU admission. In general, among the overall cohort and both mechanical ventilation sub-groups, mortality hazards increased with the severity of baseline frailty. Models predicting survival 30, 90 and 365 days after admission to an ICU that adjusted for one of the frailty measures were more discriminant than reference models that adjusted only for age, sex, major clinical category, and area income quintile. Interpretation Severity of baseline frailty is independently associated with survival after ICU admission and should be considered when determining goals-of-care and treatment plans for persons with critical illness.

Background Frailty is associated with poor outcomes in critical illness. However, it is unclear whether frailty screening on admission to the ICU can be conducted routinely at the population level and whether it has prognostic importance. Research Question Can population-scale frailty screening with the Clinical Frailty Scale (CFS) be implemented for critically ill adults in Australia and New Zealand (ANZ) and can it identify patients at risk of negative outcomes? Study Design and Methods We conducted a binational prospective cohort study of critically ill adult patients admitted between July 1, 2018, and June 30, 2020, in 175 ICUs in ANZ. We classified frailty with the CFS on admission to the ICU. The primary outcome was in-hospital mortality; secondary outcomes were length of stay (LOS), discharge destination, complications (delirium, pressure injury), and duration of survival. Results We included 234,568 critically ill patients; 45,245 (19%) were diagnosed as living with frailty before ICU admission. Patients with vs without frailty had higher in-hospital mortality (16% vs 5%; P Interpretation Large-scale population screening for frailty degree in critical illness was possible and prognostically important, with greater frailty (especially CFS score of ≥ 6) associated with worse outcomes, including among younger patients.

The comprehensive geriatric assessment (CGA) is the core tool used by geriatricians across diverse clinical settings to identify vulnerabilities and estimate physiologic reserve in older adults. In this paper, we demonstrate the iterative process at our institution to identify and develop a feasible, acceptable, and sustainable bedside CGA-based frailty index tool (FI-CGA) that not only quantifies and grades frailty but also provides a uniform way to efficiently communicate complex geriatric concepts such as reserve and vulnerability with other teams. We describe our incorporation of the FI-CGA into the electronic health record (EHR) and dissemination among clinical services. We demonstrate that an increasing number of patients have documented FI-CGA in their initial assessment from 2018 to 2020, while additional comanagement services were established (Figure 2). The acceptability and sustainability of the FI-CGA, and its routine use by geriatricians in our division, were demonstrated by a survey where the majority of clinicians report using the FI-CGA when assessing a new patient and that the FI-CGA informs their clinical management. Finally, we demonstrate how we refined and updated the FI-CGA, we provide examples of applications of the FI-CGA across the institution and describe areas of ongoing process improvement and challenges for the use of this tailored yet standardized tool across diverse inpatient and outpatient services. The process outlined can be used by other geriatric departments to introduce and incorporate an FI-CGA.

Frailty is a multiply determined, age-related state of increased risk for adverse health outcomes. We review how the degree of frailty conditions the development of late-life diseases and modifies their expression. The risks for frailty range from subcellular damage to social determinants. These risks are often synergistic—circumstances that favor damage also make repair less likely. We explore how age-related damage and decline in repair result in cellular and molecular deficits that scale up to tissue, organ and system levels, where they are jointly expressed as frailty. The degree of frailty can help to explain the distinction between carrying damage and expressing its usual clinical manifestations. Studying people—and animals—who live with frailty, including them in clinical trials and measuring the impact of the degree of frailty are ways to better understand the diseases of old age and to establish best practices for the care of older adults. Rockwood and colleagues discuss how measuring the degree of frailty helps us understand how aging gives rise to the diseases of aging, and aids translation from comprehensive geriatric assessment and individual care plans to geroscience and back.

In sporadic Alzheimer's disease (SpAD), acetylcholinesterase and butyrylcholinesterase, co-regulators of acetylcholine, are associated with β-amyloid plaques and tau neurofibrillary tangles in patterns suggesting a contribution to neurotoxicity. This association has not been explored in early-onset familial Alzheimer's disease (FAD). We investigated whether cholinesterases are observed in the neuropathological hallmarks in FAD expressing the presenilin 1 Leu235Pro mutation. Brain tissues from three FAD cases and one early-onset SpAD case were stained and analyzed for β-amyloid, tau, α-synuclein, acetylcholinesterase and butyrylcholinesterase. AD pathology was prominent throughout the rostrocaudal extent of all 4 brains but α-synuclein-positive neurites were present in only one familial case. In FAD and SpAD cases, cholinergic activity was associated with plaques and tangles but not with α-synuclein pathology. Both cholinesterases showed similar or decreased plaque staining than detected with β-amyloid immunostaining but greater plaque deposition than observed with thioflavin-S histofluorescence. Acetylcholinesterase and butyrylcholinesterase are highly associated with AD pathology in inherited disease and both may represent specific diagnostic and therapeutic targets for all AD forms.

Older persons experiencing a longer length of stay (LOS) or delayed discharge (DD) may see a decline in their health and well-being, generating significant costs. This review aimed to identify evidence on the impact of cognitive impairment (CI) on acute care hospital LOS/DD. A scoping review of studies examining the association between CI and LOS/DD was performed. We searched six databases; two reviewers independently screened references until November 2019. A narrative synthesis was used to answer the research question; 58 studies were included of which 33 found a positive association between CI and LOS or DD, 8 studies had mixed results, 3 found an inverse relationship, and 14 showed an indirect link between CI-related syndromes and LOS/DD. Thus, cognitive impairment seemed to be frequently associated with increased LOS/DD. Future research should consider CI together with other risks for LOS/DD and also focus on explaining the association between the two.

The COVID-19 pandemic has disproportionately impacted frail older adults, especially residents of long-term care (LTC) facilities. This has appropriately led to prioritization of frail older adults and LTC residents, and those who care for them, in the vaccination effort against COVID-19. Older adults have distinct immunological, clinical, and practical complexity, which can be understood through a lens of frailty. Even so, frailty has not been considered in studies of COVID-19 vaccines to date, leading to concerns that the vaccines have not been optimally tailored for and evaluated in this population even as vaccination programs are being implemented. This is an example of how vaccines are often not tested in Phase 1/2/3 clinical trials in the people most in need of protection. We argue that geriatricians, as frailty specialists, have much to contribute to the development, testing and implementation of COVID-19 vaccines in older adults. We discuss roles for geriatricians in ten stages of the vaccine development process, covering vaccine design, trial design, trial recruitment, establishment and interpretation of illness definitions, safety monitoring, consideration of relevant health measures such as frailty and function, analysis methods to account for frailty and differential vulnerability, contributions in regulatory and advisory roles, post-marketing surveillance, and program implementation and public health messaging. In presenting key recommendations pertinent to each stage, we hope to contribute to a dialogue on how to push the field of vaccinology to embrace the complexity of frailty. Making vaccines that can benefit frail older adults will benefit everyone in the fight against COVID-19., Video abstract Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/kVCbo9QA9O4

Background Growing evidence supports the clinical importance of evaluating frailty in older adults, with its strong outcome relevance. We aimed to assess whether the Short Physical Performance Battery (SPPB) correlates with frailty status according to phenotype and deficit accumulation models and can be used as a link between these models. Methods We analyzed records of 1064 individuals from the Aging Study of Pyeongchang Rural Area, a population-based, prospective cohort from South Korea. Frailty was determined using the Cardiovascular Health Study (CHS) phenotype (phenotype model), 26- and 34-item frailty indices (deficit accumulation model). Associations of SPPB score and frailty with a composite outcome of mortality or long-term institutionalization were assessed. Crosswalks for SPPB, the CHS frailty phenotype, and the frailty index were created. Results The mean age of the study population was 76.0 years, and 583 (54.8%) were women. According to the CHS phenotype, 26- and 34-item frailty indices, 242 (22.7%), 161 (15.1%), and 280 (26.3%) participants, respectively, had frailty. Sensitivities/specificities for classifying CHS phenotype, 26- and 34-item frailty indices were 0.93/0.55, 0.71/0.84, and 0.80/0.83 by SPPB cut points of ≤9, ≤6, and ≤7, respectively. C-index of SPPB score (0.78) showed a predictive ability for the composite outcome that was comparable to that of CHS frailty phenotype (0.79), 26- (0.78), and 34-item frailty indices (0.79). Conclusions We could create a crosswalk linking frailty phenotype and frailty index from correlations between SPPB and frailty models. This result may facilitate clinical adoption of the frailty concept in a broader spectrum of older adults.

Objectives People with neurogenic bladder and/or bowel dysfunction experience diverse challenges that can be difficult to evaluate with standardized outcome measures. Goal attainment scaling (GAS) is an individualized, patient-centric outcome measure that enables patients/caregivers to identify and track their own treatment goals. Because creating goals de novo can be cumbersome, we aimed to develop a neurogenic bladder/bowel dysfunction goal menu to facilitate goal attainment scaling uptake and use. Methods We conducted a workshop with 6 expert clinicians to develop an initial menu. Individual interviews with 12 people living with neurogenic bladder and/or bowel dysfunction and 2 clinician panels with 5 additional experts aided us in refining the menu. A thematic framework analysis identified emergent themes for analysis and reporting. Results Interview participants were adults (median = 36 years, range 25-58), most with spinal cord injury (75%; 9/12). Of 24 goals identified initially, 2 (8%) were not endorsed and were removed, and 3 goals were added. Most participants listed “Impact on Life” goals (eg, Exercise, Emotional Well-Being) among their 5 most important goals (58%; 35/60). Three main themes emerged: challenges posed by incontinence, limitations on everyday life, and need for personalized care. Conclusions We developed a clinical outcome assessment tool following a multistep process of representative stakeholder engagement. This patient-centric tool consists of 25 goals specific to people living with neurogenic bladder and/or bowel dysfunction. Asking people what matters most to them can identify important constructs that clinicians might have overlooked.

Background As life expectancy of people with Down syndrome (DS) increases, so does the risk of Alzheimer’s disease (AD). Identifying symptoms and tracking disease progression is especially challenging whenever levels of function vary before the onset of dementia. Goal Attainment Scaling (GAS), an individualized patient-reported outcome, can aid in monitoring disease progression and treatment effectiveness in adults with DS. Here, with clinical input, a validated dementia symptom menu was revised to facilitate GAS in adults living with Down Syndrome-associated Alzheimer’s disease (DS-AD). Methods Four clinicians with expertise in DS-AD and ten caregivers of adults living with DS-AD participated in semi-structured interviews to review the menu. Each participant reviewed 9–15 goal areas to assess their clarity and comprehensiveness. Responses were systematically and independently coded by two researchers as ‘clear’, ‘modify’, ‘remove’ or ‘new’. Caregivers were encouraged to suggest additional items and recommend changes to clarify items. Results Median caregiver age was 65 years (range 54–77). Most were female (9/10) with ≥15 years of education (10/10). Adults with DS-AD had a median age of 58 years (range 52–61) and either a formal diagnosis (6/10) or clinical suspicion (4/10) of dementia. The initial symptom menu consisted of 67 symptoms each with 2–12 descriptors (589 total). The clinicians’ adaptation yielded 58 symptoms each with 4–17 descriptors (580 total). Of these 580 descriptors, caregivers identified 37 (6%) as unclear; these were reworded, and one goal area (4 descriptors) was removed. A further 47 descriptors and one goal area were added to include caregiver-identified concepts. The final menu contained 58 goal areas, each with 7–17 descriptors (623 total). Conclusions A comprehensive symptom menu for adults living with DS-AD was developed to facilitate GAS. Incorporating expert clinician opinion and input from caregivers of adults with DS-AD identified meaningful items that incorporate patient/caregiver perspectives.

Background Atrial fibrillation (AF) is common in older people and is associated with increased stroke risk that may be reduced by oral anticoagulation (OAC). Frailty also increases with increasing age, yet the extent of OAC prescription in older people according to extent of frailty in people with AF is insufficiently described. Methods An electronic health records study of 536,955 patients aged ≥65 years from ResearchOne in England (384 General Practices), over 15.4 months, last follow-up 11th April 2017. OAC prescription for AF with CHA2DS2-Vasc ≥2, adjusted (demographic and treatments) risk of all-cause mortality, and subsequent cerebrovascular disease, bleeding and falls were estimated by electronic frailty index (eFI) category of fit, mild, moderate and severe frailty. Results AF prevalence and mean CHA2DS2-Vasc for those with AF increased with increasing eFI category (fit 2.9%, 2.2; mild 11.2%, 3.2; moderate 22.2%, 4.0; and severe 31.5%, 5.0). For AF with CHA2DS2-Vasc ≥2, OAC prescription was higher for mild (53.2%), moderate (55.6%) and severe (53.4%) eFI categories than fit (41.7%). In those with AF and eligible for OAC, frailty was associated with increased risk of death (HR for severe frailty compared with fit 4.09, 95% confidence interval 3.43–4.89), gastrointestinal bleeding (2.17, 1.45–3.25), falls (8.03, 4.60–14.03) and, among women, stroke (3.63, 1.10–12.02). Conclusion Among older people in England, AF and stroke risk increased with increasing degree of frailty; however, OAC prescription approximated 50%. Given competing demands of mortality, morbidity and stroke prevention, greater attention to stratified stroke prevention is needed for this group of the population.

ObjectiveTo determine whether health-deficit accumulation is associated with the risks of mild cognitive impairment (MCI) and dementia independently of APOE genotype.MethodsA frailty index was calculated using the deficit-accumulation approach in participants aged 50 years and older from the National Alzheimer’s Coordinating Center. Cognitive status was determined by clinical evaluation. Using multistate transition models, we assessed the extent to which an increasing degree of frailty affected the probabilities of transitioning between not cognitively impaired (NCI), MCI, and dementia.ResultsParticipants (n=14 490) had a mean age of 72.2 years (SD=8.9 years; range=50–103 years). Among those NCI at baseline (n=9773), each 0.1 increment increase in the frailty index was associated with a higher risk of developing MCI and a higher risk of progressing to dementia. Among those with MCI at baseline (n=4717), higher frailty was associated with a higher risk of progressing to dementia, a lower probability of being reclassified as NCI, and a higher likelihood of returning to MCI in those that were reclassified as NCI. These risk effects were present and similar in both carriers and non-carriers of the APOE ε4 allele.ConclusionAmong older Americans, health-deficit accumulation affects the likelihood of progressive cognitive impairment and the likelihood of cognitive improvement independently of a strong genetic risk factor for dementia. Frailty represents an important risk factor for cognitive dysfunction and a marker of potential prognostic value.

ObjectiveThe Systemic Lupus International Collaborating Clinics (SLICC) frailty index (FI) predicts mortality and damage accrual in systemic lupus erythematosus (SLE), but its association with hospitalizations has not been described. Our objective was to estimate the association of baseline SLICC-FI values with future hospitalizations in the SLICC inception cohort.MethodsBaseline SLICC-FI scores were calculated. The number and duration of inpatient hospitalizations during follow-up were recorded. Negative binomial regression was used to estimate the association between baseline SLICC-FI values and the rate of hospitalizations per patient-year of follow-up. Linear regression was used to estimate the association of baseline SLICC-FI scores with the proportion of follow-up time spent in the hospital. Multivariable models were adjusted for relevant baseline characteristics.ResultsThe 1,549 patients with SLE eligible for this analysis were mostly female (88.7%), with a mean ± SD age of 35.7 ± 13.3 years and a median disease duration of 1.2 years (interquartile range 0.9-1.5) at baseline. Mean ± SD baseline SLICC-FI was 0.17 ± 0.08. During mean ± SD follow-up of 7.2 ± 3.7 years, 614 patients (39.6%) experienced 1,570 hospitalizations. Higher baseline SLICC-FI values (per 0.05 increment) were associated with more frequent hospitalizations during follow-up, with an incidence rate ratio of 1.21 (95% confidence interval [95% CI] 1.13-1.30) after adjustment for baseline age, sex, glucocorticoid use, immunosuppressive use, ethnicity/location, SLE Disease Activity Index 2000 score, SLICC/American College of Rheumatology Damage Index score, and disease duration. Among patients with ≥1 hospitalization, higher baseline SLICC-FI values predicted a greater proportion of follow-up time spent hospitalized (relative rate 1.09 [95% CI 1.02-1.16]).ConclusionThe SLICC-FI predicts future hospitalizations among incident SLE patients, further supporting the SLICC-FI as a valid health measure in SLE.

ObjectiveTo test the hypothesis that degree of frailty and neuropathologic burden independently contribute to global cognition and odds of dementia.MethodsThis was a secondary analysis of a prospective cohort study of older adults living in Illinois. Participants underwent an annual neuropsychological and clinical evaluation. We included 625 participants (mean age 89.7 ± 6.1 years; 67.5% female) who died and underwent autopsy. We quantified neuropathology using an index measure of 10 neuropathologic features: β-amyloid deposition, hippocampal sclerosis, Lewy bodies, tangle density, TDP-43, cerebral amyloid angiopathy, arteriolosclerosis, atherosclerosis, and gross and chronic cerebral infarcts. Clinical consensus determined dementia status, which we coded as no cognitive impairment, mild cognitive impairment, or dementia. A battery of 19 tests spanning multiple domains quantified global cognition. We operationalized frailty using a 41-item frailty index. We employed regression analyses to model relationships between neuropathology, frailty, and dementia.ResultsBoth frailty and a neuropathology index were independently associated with global cognition and dementia status. These results held after controlling for traditional pathologic measures in a sample of participants with Alzheimer clinical syndrome. Frailty improved the fit of the model for dementia status (χ2[2] 72.64; p < 0.0001) and explained an additional 11%–12% of the variance in the outcomes.ConclusionDementia is a multiply determined condition, to which both general health, as captured by frailty, and neuropathology significantly contribute. This integrative view of dementia and health has implications for prevention and therapy; specifically, future research should evaluate frailty as a means of dementia risk reduction.

Background Clinically meaningful change (CMC) for frailty index (FI) scores is little studied. We estimated the CMC by associating changes in FI scores with changes in the Clinical Frailty Scale (CFS) in hospitalized patients. Methods The Serious Outcomes Surveillance Network of the Canadian Immunization Research Network enrolled older adults (65+ years) admitted to hospital with acute respiratory illness (mean age = 79.6 ± 8.4 years; 52.7% female). Patients were assigned CFS and 39-item FI scores in-person at admission and via telephone at 1-month postdischarge. Baseline frailty state was assessed at admission using health status 2 weeks before admission. We classified those whose CFS scores remained unchanged (n = 1,534) or increased (n = 4,390) from baseline to hospital admission, and whose CFS scores remained unchanged (n = 1,565) or decreased (n = 2,546) from admission to postdischarge. For each group, the CMC was represented as the FI score change value that best predicted one level CFS change, having the largest Youden J value in comparison to no change. Results From baseline to admission, 74.1% increased CFS by ≥1 level. From admission to postdischarge, 61.9% decreased CFS by ≥1 levels. A change in FI score of 0.03 best predicted both one-level CFS increase (sensitivity = 70%; specificity = 69%) and decrease (sensitivity = 66%; specificity = 61%) in comparison to no change. Of those who changed CFS by ≥1 levels, 70.9% (baseline to admission) and 72.4% (admission to postdischarge) changed their FI score by at least 0.03. Conclusions A clinically meaningful change of 0.03 in the frailty index score holds promise as a benchmark for assessing the meaningfulness of frailty interventions.

The authors sought to examine how much sedentary time needs to be replaced by light or moderate–vigorous physical activity in order to reduce frailty and protect against mortality. The authors built isotemporal substitution models to assess the theoretical effect of replacing sedentary behavior with an equal amount of light or moderate–vigorous activity on frailty and mortality in community-based adults aged 50 years and older. Controlling for age, sex, body mass index, marital status, race, education, employment status, and National Health and Nutrition Examination Study cycle, replacing 1 hr of sedentary time with moderate–vigorous or light physical activity daily was associated with a lower frailty index. For mortality, results varied based on frailty level. Replacing sedentary behavior with moderate–vigorous exercise was associated with lower mortality risk in vulnerable individuals; however, replacing sedentary behavior with light activity was associated with lower mortality risk in frailer individuals.

BACKGROUND: Acutely ill and frail older adults have complex social and health care needs. It is important to understand how this complexity affects acute outcomes for admission to hospital. We validated a frailty index using routine admission laboratory tests with outcomes after patients were admitted to hospital. METHODS: In a prospective cohort of older adults admitted to a large tertiary hospital in the United Kingdom, we created a frailty index from routine admission laboratory investigations (FI-Laboratory) linked to data comprising hospital outcomes. We evaluated the association between the FI-Laboratory and total days spent in hospital, discharge to a higher level of care, readmission and mortality. RESULTS: Of 2552 admissions among 1750 older adults, we were able to generate FI-Laboratory values for 2254 admissions (88.3% of the cohort). More than half of admitted patients were women (55.3%) and the mean age was 84.6 (SD 14.0) years. We found that the FI-Laboratory correlated weakly with the Clinical Frailty Scale (CFS; r2 = 0.09). An increase in the CFS and the equivalent of 3 additional abnormal laboratory test results in the FI-Laboratory, respectively, were associated with an increased proportion of inpatient days (rate ratios [RRs] 1.43, 95% confidence interval [CI] 1.35–1.52; and 1.47, 95% CI 1.41–1.54), discharge to a higher level of care (odd ratios [ORs] 1.39, 95% CI 1.27–1.52; and 1.30, 95% CI 1.16–1.47) and increased readmission rate (hazard ratios [HRs] 1.26, 95% CI 1.17–1.37; and 1.18, 95% CI 1.11–1.26). Increases in the CFS and FI-Laboratory were associated with increased mortality HRs of 1.39 (95% CI 1.28–1.51) and 1.45 (95% CI 1.37–1.54), respectively. INTERPRETATION: We determined that FI-Laboratory, distinct from baseline frailty, could be used to predict risk of many adverse outcomes. The score is therefore a useful way to quantify the degree of acute illness in frail older adults.

Background Most people living with dementia want to remain living in their own homes and are supported to do so by family carers. No interventions have consistently demonstrated improvements to people with dementia’s life quality, functioning, or other indices of living as well as possible with dementia. We have co-produced, with health and social care professionals and family carers of people with dementia, a new intervention (NIDUS-family). To our knowledge, NIDUS-family is the first manualised intervention that can be tailored to personal goals of people living with dementia and their families and is delivered by facilitators without clinical training. The intervention utilizes components of behavioural management, carer support, psychoeducation, communication and coping skills training, enablement, and environmental adaptations, with modules selected to address dyads’ selected goals. We will evaluate the effect of NIDUS-family and usual care on goal attainment, as measured by Goal Attainment Scaling (GAS) rated by family carers, compared to usual care alone at 12-month follow-up. We will also determine whether NIDUS-family and usual care is more cost-effective than usual care alone over 12 months. Methods A randomised, two-arm, single-masked, multi-site clinical trial involving 297 people living with dementia-family carer dyads. Dyads will be randomised 2:1 to receive the NIDUS-family intervention with usual care (n = 199) or usual care alone (n = 98). The intervention group will be offered, over 1 year, via 6–8 video call or telephone sessions (or face to face if COVID-19 restrictions allow in the recruitment period) in the initial 6 months, followed by telephone follow-ups every 1–2 months to support implementation, with a trained facilitator. Discussion Increasing the time lived at home by people living with dementia is likely to benefit lives now and in the future. Our intervention, which we adapted to include remote delivery prior to trial commencement due to the COVID-19 pandemic, aims to address barriers to living as well and as independently as possible that distress people living with dementia, exacerbate family carer(s) stress, negatively affect relationships, lead to safety risks, and frequently precipitate avoidable moves to a care home. Trial registration International Standard Randomised Controlled Trials Number ISRCTN11425138. Registered on 7 October 2019

Background : Frailty is associated with a prodromal stage called pre-frailty, a potentially reversible and highly prevalent intermediate state before frailty becomes established. Despite being widely-used in the literature and increasingly in clinical practice, it is poorly understood. Objective : To establish consensus on the construct and approaches to diagnose and manage pre-frailty. Methods : We conducted a modified (electronic, two-round) Delphi consensus study. The questionnaire included statements concerning the concept, aspects and causes, types, mechanism, assessment, consequences, prevention and management of pre-frailty. Qualitative and quantitative analysis methods were employed. An agreement level of 70% was applied. Results : Twenty-three experts with different backgrounds from 12 countries participated. In total 70 statements were circulated in Round 1. Of these, 52.8% were accepted. Following comments, 51 statements were re-circulated in Round 2 and 92.1% were accepted. It was agreed that physical and non-physical factors including psychological and social capacity are involved in the development of pre-frailty, potentially adversely affecting health and health-related quality of life. Experts considered pre-frailty to be an age-associated multi-factorial, multi-dimensional, and non-linear process that does not inevitably lead to frailty. It can be reversed or attenuated by targeted interventions. Brief, feasible, and validated tools and multidimensional assessment are recommended to identify pre-frailty. Conclusions : Consensus suggests that pre-frailty lies along the frailty continuum. It is a multidimensional risk-state associated with one or more of physical impairment, cognitive decline, nutritional deficiencies and socioeconomic disadvantages, predisposing to the development of frailty. More research is needed to agree an operational definition and optimal management strategies.

Background: Indigenous populations experience high rates of age-related illness when compared to their non-Indigenous counterparts. Frailty is a challenging expression of aging and an important public health priority. The purpose of this review was to map what the existing literature reports around frailty in Indigenous populations and to highlight the current gaps in frailty research within the Indigenous landscape.Method: Scoping review of English language original research articles focusing on frailty within Indigenous adult populations in settler colonial countries (Australia, Canada, New Zealand and USA). Ten electronic databases and eight relevant institutional websites were searched from inception to October 2020.Results: Nine articles met our inclusion criteria, finding this population having a higher prevalence of frailty and frailty occurring at younger ages when compared to their non-Indigenous counterparts, but two did not use a formal frailty tool. Females presented with higher levels of frailty. No culturally specific frailty tool was identified, and the included articles did not assess strategies or interventions to manage or prevent frailty in Indigenous peoples.Conclusions: There was little definitive evidence of the true frailty prevalence, approaches to frailty screening and of potential points of intervention to manage or prevent the onset of frailty. Improvements in the quality of evidence are urgently needed, along with further research to determine the factors contributing to higher rates of frailty within Indigenous populations. Incorporation of Indigenous views of frailty, and instruments and programs that are led and designed by Indigenous communities, are crucial to address this public health priority.

The many changes that occur in the lives of older people put them at an increased risk of being socially isolated and lonely. Intergenerational programs for older adults and young children can potentially address this shortfall, because of the perceived benefit from generations interacting. This study explores whether there is an appetite in the community for intergenerational programs for community dwelling older adults. An online survey was distributed via social media, research team networks, and snowballing recruitment with access provided via QR code or hyperlink. Semi-structured interviews were undertaken with potential participants of a pilot intergenerational program planned for the Eastern Suburbs of Sydney, Australia in 2020. The interviews were thematically analyzed. Over 250 people completed the survey, and 21 interviews took place with older adults (10) and parents of young children (11). The data showed that participants were all in favor of intergenerational programs, but there were different perceptions about who benefits most and how. The study highlighted considerations to be addressed in the development of effective and sustainable intergenerational programs. For example, accessing people in the community who are most socially isolated and lonely was identified as a primary challenge. More evidence-based research is needed to support involvement of different cohorts, such as those who are frail, or living with physical or cognitive limitations.

Objective:To examine the relative contributions of frailty and neuropathology to dementia expression in a population-based cohort study.Design:Cross-sectional analysis of observational data.Setting:Population-representative clinicopathological cohort study.Participants:Adults aged 75+ recruited from general practice registries in Cambridge, UK, in 1985.Measurements:A 39-item frailty index and 15-item neuropathological index were used to operationalize frailty and neuropathology, respectively. Dementia status was ascertained by clinical consensus at time of death. Relationships were evaluated using logistic regression models in participants with autopsy records (n = 183). Model fit was assessed using change in deviance. Population attributable fraction for frailty was evaluated in relation to dementia incidence in a representative sample of the survey participants (n = 542).Results:Participants with autopsy were 92.3 ± 4.6 years at time of death, and mostly women (70%). Average frailty index value at last survey before death was 0.34 ± 0.16. People with dementia (63% of the sample) were frailer, had lower MMSE scores, and a higher burden of neuropathology. Frailty and neuropathological burden were significantly and independently associated with dementia status, without interaction; frailty explained an additional 3% of the variance in the model. Assuming a causal relationship and based on population-attributable fraction analyses, preventing severe frailty (Frailty Index ≥ 0.40) could have avoided 14.2% of dementia cases in this population-based cohort.Conclusions:In the very old, frailty contributes to the risk for dementia beyond its relationship with the burden of traditional dementia neuropathologies. Reducing frailty could have important implications for controlling the burden of dementia. Future research on frailty interventions should include dementia risk as a key outcome, public health interventions and policy decisions should consider frailty as a key risk factor for dementia, and biomedical research should focus on elucidating shared mechanisms of frailty and dementia development.

Background The SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus 2) has led to more than 165 million COVID-19 cases and >3.4 million deaths worldwide. Epidemiological analysis has revealed that the risk of developing severe COVID-19 increases with age. Despite a disproportionate number of older individuals and long-term care facilities being affected by SARS-CoV-2 and COVID-19, very little is understood about the immune responses and development of humoral immunity in the extremely old person after SARS-CoV-2 infection. Here we conducted a serological study to investigate the development of humoral immunity in centenarians following a SARS-CoV-2 outbreak in a long-term care facility. Methods Extreme aged individuals and centenarians who were residents in a long-term care facility and infected with or exposed to SARS-CoV-2 were investigated between April and June 2020 for the development of antibodies to SARS-CoV-2. Blood samples were collected from positive and bystander individuals 30 and 60 days after original diagnosis of SARS-CoV-2 infection. Plasma was used to quantify IgG, IgA, and IgM isotypes and subsequent subclasses of antibodies specific for SARS-CoV-2 spike protein. The function of anti-spike was then assessed by virus neutralization assays against the native SARS-CoV-2 virus. Findings Fifteen long-term care residents were investigated for SARS-CoV-2 infection. All individuals had a Clinical Frailty scale score ≥5 and were of extreme older age or were centenarians. Six women with a median age of 98.8 years tested positive for SARS-CoV-2. Anti-spike IgG antibody titers were the highest titers observed in our cohort with all IgG positive individuals having virus neutralization ability. Additionally, 5 out of the 6 positive participants had a robust IgA anti-SARS-CoV-2 response. In all 5, antibodies were detected after 60 days from initial diagnosis.

Frailty is associated with hospitalization and mortality among dialysis patients. To now, few studies have considered the degree of frailty as a predictor of hospitalization.We evaluated whetherRetrolective cohort study.Nova Scotia, Canada.Consecutive adult, chronic dialysis patients who initiated dialysis from January 1, 2009 to June 30, 2014, (last follow-up June, 2015).Frailty Severity, as determined by the 7-point Clinical Frailty Scale (CFS, ranging from 1 = very fit to 7 = severely frail), was measured at dialysis initiation and treated as continuous and in categories (CFS scores of 1-3, 4/5, and 6/7). Hospitalization was characterized by cumulative time admitted to hospital (proportion of days admitted/time at risk) and by the joint risk of hospitalization and death. Time at risk included time in hospital after dialysis initiation and patients were followed until transplantation or death.Of 647 patients (mean age: 62 ± 15), 564 (87%) had CFS scores. The mean CFS score was 4 ("corresponding to "vulnerable") ± 2 ("well" to "moderately frail"). In an adjusted negative binomial regression model, moderate-severely frail patients (CFS 6/7) had a2-fold increased risk of cumulative time admitted to hospital compared to the lowest CFS category (IRR = 2.18, 95% confidence interval [CI] = 1.31-3.63). In the joint model, moderate-severely frail patients had a 61% increase in the relative hazard for hospitalization (hazard ratio [HR] = 1.61, 95% CI = 1.29-2.02) and a 93% increase in the relative hazard for death compared to the lowest CFS category (HR = 1.93, 95% CI = 1.16-3.22).Potential unknown confounders may have affected the association between frailty severity and hospitalization given observational study design. The CFS is subjective and different clinicians may grade frailty severity differently or misclassify patients on the basis of limited availability.Among incident dialysis patients, a higher frailty severity as defined by the CFS is associated with both an increased risk of cumulative time admitted to hospital and joint risk of hospitalization and death.La fragilité est associée à davantage d’hospitalisations et de mortalité chez les patients qui suivent des traitements de dialyze. À l’heure actuelle, peu d’études se sont penchées sur le degré de fragilité comme facteur prédictif d’hospitalization.Nous avons évalué l’existence d’un lien entreÉtude de cohorte rétrospective.Nouvelle-Écosse, Canada.L’étude porte sur des patients adultes consécutifs sous dialyze chronique et ayant entrepris leur traitement entre le 1er janvier 2009 et le 30 juin 2014 (dernier suivi en juin 2015).L’échelle CFS (Clinical Frailty Scale) en 7 points (1 = très bonne forme physique; 7= gravement fragile) a été employée pour déterminer le niveau de gravité de la fragilité. Cette dernière a été évaluée à l’amorce de la dialyze et traitée en tant que mesure continue et selon trois niveaux d’atteinte (scores CFS de 1-3, de 4-5 et de 6-7). L’hospitalization a été caractérisée par la durée cumulative des hospitalisations (proportion de jours d’hospitalization/l’intervalle de risque) et par un risque conjoint d’hospitalization et de décès. L’intervalle de risque comprend le temps passé à l’hôpital depuis le début du traitement. Les patients ont été suivis jusqu’à la transplantation ou jusqu’au décès.Parmi les 647 patients admissibles (âge moyen: 62 ans ± 15), 564 patients (87 %) disposaient d’un score CFS. Le score CFS moyen était de 4 (correspondant à « apparence de vulnérabilité ») ± 2 (« bonne forme physique » à « modérément fragile »). Dans un modèle corrigé de régression binomiale négative, les patients jugés modérément à gravement fragiles (CFS 6/7) présentaient un risque cumulatif plus de 2 fois plus élevé d’être hospitalisés comparativement aux patients du groupe avec le score CFS le plus faible (RTI: 2,18; IC 95 %: 1,31 à 3,63). Dans le modèle conjoint, les patients jugés modérément à gravement fragiles ont présenté une augmentation de 61 % du risque relatif d’hospitalization (RR:1,61; IC 95 %: 1,29 à 2,02) et une augmentation de 93 % du risque relatif de décès comparativement aux patients avec le score CFS le plus faible (RR: 1,93; IC 95 %: 1,16 à 3,22).La méthodologie de l’étude (observationnelle) laisse supposer que de possibles facteurs confusionnels inconnus pourraient avoir eu une incidence sur le lien entre les hospitalisations et la gravité de la fragilité. Le score CFS est une mesure subjective. Il est possible que les cliniciens évaluent différemment la gravité de la fragilité ou classent les patients de façon erronée en raison d’une disponibilité limitée.Chez les patients dialysés, une plus grande fragilité, telle que définie par le score CFS, a été associée à la fois à un risque accru d’être hospitalisé sur une plus longue durée cumulative et à un risque conjoint d’hospitalization et de décès.

Introduction Older Canadians living with frailty are high users of healthcare services; however, the healthcare system is not well designed to meet the complex needs of many older adults. Older persons look to their primary care practitioners to assess their needs and coordinate their care. They may need care from a variety of providers and services, but often this care is not well coordinated. Older adults and their family caregivers are the experts in their own needs and preferences, but often do not have a chance to participate fully in treatment decisions or care planning. As a result, older adults may have health problems that are not properly assessed, managed or treated, resulting in poorer health outcomes and higher economic and social costs. We will be implementing enhanced primary healthcare approaches for older patients, including risk screening, patient engagement and shared decision making and care coordination. These interventions will be tailored to the needs and circumstances of the primary care study sites. In this article, we describe our study protocol for implementing and testing these approaches. Methods and analysis Nine primary care sites in three Canadian provinces will participate in a multi-phase mixed methods study. In phase 1, baseline information will be collected through questionnaires and interviews with patients and healthcare providers (HCPs). In phase 2, HCPs and patients will be consulted to tailor the evidence-based interventions to site-specific needs and circumstances. In phase 3, sites will implement the tailored care model. Evaluation of the care model will include measures of patient and provider experience, a quality of life measure, qualitative interviews and economic evaluation. Ethics and dissemination This study has received ethics clearance from the host academic institutions: University of Calgary (REB17-0617), University of Waterloo (ORE#22446) and Université Laval (#MP-13-2019-1500 and 2017-2018-12-MP). Results will be disseminated through traditional means, including peer-reviewed publications and conferences and through an extensive network of knowledge user partners. Trial registration number NCT03442426; Pre-results.

Background The Canadian Geriatrics Society (CGS) fosters the health and well-being of older Canadians and older adults worldwide. Although severe COVID-19 illness and significant mortality occur across the lifespan, the fatality rate increases with age, especially for people over 65 years of age. The dichotomization of COVID-19 patients by age has been proposed as a way to decide who will receive intensive care admission when critical care unit beds or ventilators are limited. We provide perspectives and evidence why alternatives approaches should be used Methods Practitioners and researchers in geriatric medicine and gerontology have led in the development of alternative approaches to using chronological age as the sole criterion for allocating medical resources. Evidence and ethical based recommendations are provided. Results Age alone should not drive decisions for health-care resource allocation during the COVID-19 pandemic. Decisions on health-care resource allocation should take into consideration the preferences of the patient and their goals of care, as well as patient factors like the Clinical Frailty Scale score based on their status two weeks before the onset of symptoms. Conclusions Age alone does not accurately capture the variability of functional capacities and physiological reserve seen in older adults. A threshold of 5 or greater on the Clinical Frailty Scale is recommended if this scale is utilized in helping to decide on access to limited health-care resources such as admission to a critical care unit and/or intubation during the COVID-19 pandemic.