Exploring the potential impact of multi-factor precision interventions in Alzheimer's disease with system dynamics.

Numerous clinical trials based on a single-cause paradigm have not resulted in efficacious treatments for Alzheimer's disease (AD). Recently, prevention trials that simultaneously intervened on multiple risk factors have shown mixed results, suggesting that careful design is necessary. Moreover, intensive pilot precision medicine (PM) trial results have been promising but may not generalize to a broader population. These observations suggest that a model-based approach to multi-factor precision medicine (PM) is warranted. We systematically developed a system dynamics model (SDM) of AD for PM using data from two longitudinal studies (N=3660). This method involved a model selection procedure in identifying interaction terms between the SDM components and estimating individualized parameters. We used the SDM to explore simulated single- and double-factor interventions on 14 modifiable risk factors. We quantified the potential impact of double-factor interventions over single-factor interventions as 1.5 [95% CI: 1.5-2.6] and of SDM-based PM over a one-size-fits-all approach as 3.5 [3.1, 3.8] ADAS-cog-13 points in 12 years. Although the model remains to be validated, we tentatively conclude that multi-factor PM could come to play an important role in AD prevention.

Digital resilience monitoring of informal caregivers of persons with dementia for early detection of overburden: Development and pilot testing.

OBJECTIVES: Informal caregiving is becoming increasingly important in dementia care, but causes a considerable burden on caregivers which impacts their wellbeing. We aimed to develop and pilot test a digital monitoring tool (REsilience Monitor for INformal caregivers in Dementia [REMIND]) for wellbeing and resilience of informal caregivers to provide timely support and thereby prevent their overburden and eventually crises admissions of persons with dementia. METHODS: A human-centered design method based on co-creation with informal caregivers and professionals was used to design REMIND. During co-creation meetings and in-between sprint sessions, a point of focus was formulated, and a prototype was created. Case manager-caregiver duos pilot-tested REMIND for 3 months. Semi-structured interviews were conducted to determine usability and acceptability. Thematic analysis was applied to the transcripts. RESULTS: Informal caregivers and professionals with varying backgrounds participated in three co-creation meetings. Defined point of focus was to develop a tool that is able to provide insight into the experienced burden of informal caregivers. The REMIND prototype consisted of weekly questions about wellbeing and resilience for informal caregivers and a dashboard with answers for case managers. Eight case managers and 13 informal caregivers considered REMIND easy-to-use. Informal caregivers mentioned that REMIND stimulated self-reflection. Case managers appreciated the tool's ability to gain insight in the actual wellbeing of informal caregivers. CONCLUSIONS: The REMIND tool developed in co-creation with end-users potentially increases insight in actual wellbeing of informal caregivers for both caregivers and case managers. A long-term (controlled) follow-up study is needed to evaluate REMIND's impact on caregiver burden and crisis admissions.

Determinants of quality of life in family caregivers in MCI: a comparison with mild dementia.

OBJECTIVES: The aim of the current study was to investigate the health-related quality of life (HRQol) of the family caregiver in MCI, explore possible determinants and study possible differences with mild dementia. METHODS: This secondary data analysis included 145 persons with MCI and 154 persons with dementia and their family caregivers from two Dutch cohort studies. HRQoL was measured with the VAS of the EuroQol-5D-3L version. Regressions analyses were conducted to examine potential demographic and clinical determinants of the caregiver's HRQoL. RESULTS: The mean EQ5D-VAS in family caregivers of persons with MCI was 81.1 (SD 15.7), and did not significantly differ from family caregivers in mild dementia (81.9 (SD 13.0)). In MCI, patient measurements were not significantly associated with caregiver mean EQ5D-VAS. Concerning caregiver characteristics, being a spouse and a lower educational level were associated with a lower mean EQ5D-VAS (in a multiple linear regression model: unstandardized B -8.075, p = 0.013 and unstandardized B -6.162, p = 0.037 resp.). In mild dementia, the NPI item irritability showed an association with caregiver EQ5D-VAS in bivariate linear regression analyses. CONCLUSION: Results indicate that especially family caregiver characteristics seem to influence family caregiver HRQoL in MCI. Future research should include other potential determinants such as burden, coping strategies and relationship quality.

DementiaNet facilitates a sustainable transition toward integrated primary dementia care: A long-term evaluation.

INTRODUCTION: Care integration is a promising strategy to achieve sustainable health-care systems. With DementiaNet, a 2-year program, we facilitated collaboration between primary health-care professionals. We studied changes in primary dementia care integration during and after DementiaNet participation. METHODS: A longitudinal follow-up study was performed. Networks started between 2015 and 2020; follow-up ended in 2021. Quantitative and quantitative data were collected annually to assess quality of care, network collaboration, and number of crisis admissions. Growth modeling was used to identify changes over time. RESULTS: Thirty-five primary care networks participated. Network collaboration and quality of care of newly formed networks increased significantly in the first 2 years (respectively, 0.35/year, P < .001; 0.29/year, P < .001) and thereafter stabilized. CONCLUSION: Primary care networks improved their collaboration and quality of care during DementiaNet participation, which persisted after the program ended. This indicates that DementiaNet facilitated a sustainable transition toward integrated primary dementia care.

Implementation of interprofessional digital communication tools in primary care for frail older adults: An interview study.

Communication and coordination between primary healthcare professionals and informal caregivers involved in the care for frail older adults is suboptimal and could benefit from interprofessional digital communication tools. Implementation in daily practice however frequently fails. We aim to identify generic barriers and facilitators experienced by healthcare professionals and informal caregivers during implementation of interprofessional communication tools to improve their long-term use. Qualitative content analysis using individual semi-structured interviews was used for evaluating three different digital communication tools used by interprofessional primary care networks for frail older adults by 28 professionals and 10 caregivers. After transcription and open coding, categories and themes were identified. Barriers and facilitators were related to: tool characteristics, context of use, involvement of professionals and caregivers. The tool improved availability, approachability and users' involvement. The large number of digital systems professionals simultaneously use, and different work agreements hampered tool use. The tools facilitated care coordination, and professionals declared to be better informed about patients' current situations. Overall, interprofessional digital communication tools can facilitate communication in networks for primary elderly care. However, integration between digital systems is needed to reduce the number of tools. Organizations and policy makers have an important role in realizing the tools' long-term use.

Older Adults' Views on Social Interactions and Online Socializing Games - A Qualitative Study.

Age-related difficulties and quarantine restrictions impede the possibilities to maintain contact with one's social network. Maintaining these contacts may be supported by digital games. To develop effective and feasible digital tools to foster social interaction, we aimed to explore what older adults find important in social contact and what barriers and enablers they foresee in digital gaming interventions as network support aids. Two focus groups and 20 semi-structured interviews (N = 29) with older adults (aged 55-87) were held to explore the research questions. Furthermore, a questionnaire was administered (N = 29) containing measures of loneliness, frailty, and social network size. Participants found 'reciprocity', 'in-person contact', and 'personal connection' important in contact with strong ties. Online games were not used much for socializing but may be used in the future, particularly by less mobile older adults. Future social gaming interventions should be challenging, user-friendly, and offer the possibility to communicate. Digital co-designed interventions that are feasible, challenging, intuitive, and trigger meaningful communication may strengthen social interactions in older adults. They may be a relevant social support tool in periods of interaction limitations due to functional impairment or social isolation.

A comparison of two approaches for modeling dementia progression in a changing patient context.

OBJECTIVES: To explain the heterogeneity in dementia disease trajectory, we studied the influence of changing patient characteristics on disease course by comparing the association of dementia progression with baseline comorbidity and frailty, and with time-varying comorbidity and frailty. METHODS: We used individual growth models to study baseline and time-varying associations in newly diagnosed dementia patients (n = 331) followed for 3 years. We measured cognition using the Mini-Mental State Examination (MMSE), daily functioning using the Disability Assessment for Dementia (DAD), frailty using the Fried criteria and comorbidity using the Cumulative Illness Rating Scale for Geriatrics (CIRS-G). RESULTS: Although baseline comorbidity and frailty were associated with decreased daily functioning at diagnosis, their effects clearly diminished over time. In contrast, when incorporating comorbidity and frailty as time-varying covariates, comorbidity was associated with lower daily functioning, and frailty with both lower cognition and daily functioning. Being frail was associated with a 0.9-point lower MMSE score (p = 0.03) and a 14.9-point lower DAD score (p < 0.01). A 1-point increase in CIRS-G score was associated with a 1.1-point lower DAD score (p < 0.01). CONCLUSIONS: Time-varying comorbidity and frailty were more consistently associated with dementia disease course than baseline comorbidity and frailty. Therefore, modeling only baseline predictors is insufficient for understanding the course of dementia in a changing patient context.

Implementation of prehabilitation in colorectal cancer surgery: qualitative research on how to strengthen facilitators and overcome barriers.

PURPOSE: Prehabilitation is increasingly offered to patients with colorectal cancer (CRC) undergoing surgery as it could prevent complications and facilitate recovery. However, implementation of such a complex multidisciplinary intervention is challenging. This study aims to explore perspectives of professionals involved in prehabilitation to gain understanding of barriers or facilitators to its implementation and to identify strategies to successful operationalization of prehabilitation. METHODS: In this qualitative study, semi-structured interviews were performed with healthcare professionals involved in prehabilitation for patients with CRC. Prehabilitation was defined as a preoperative program with the aim of improving physical fitness and nutritional status. Parallel with data collection, open coding was applied to the transcribed interviews. The Ottawa Model of Research Use (OMRU) framework, a comprehensive interdisciplinary model guide to promote implementation of research findings into healthcare practice, was used to categorize obtained codes and structure the barriers and facilitators into relevant themes for change. RESULTS: Thirteen interviews were conducted. Important barriers were the conflicting scientific evidence on (cost-)effectiveness of prehabilitation, the current inability to offer a personalized prehabilitation program, the complex logistic organization of the program, and the unawareness of (the importance of) a prehabilitation program among healthcare professionals and patients. Relevant facilitators were availability of program coordinators, availability of physician leadership, and involving skeptical colleagues in the implementation process from the start. CONCLUSIONS: Important barriers to prehabilitation implementation are mainly related to the intervention being complex, relatively unknown and only evaluated in a research setting. Therefore, physicians' leadership is needed to transform care towards more integration of personalized prehabilitation programs. IMPLICATIONS FOR CANCER SURVIVORS: By strengthening prehabilitation programs and evidence of their efficacy using these recommendations, it should be possible to enhance both the pre- and postoperative quality of life for colorectal cancer patients during survivorship.

Age and Ageing journal 50th anniversary commentary seriesWhy illness is more important than disease in old age.

Clinical reasoning and research in modern geriatrics often prioritises the disease concept. This is understandable as it has brought impressive advances in medicine (e.g. antibiotics, vaccines, successful cancer treatment and many effective surgeries). However, so far the disease framework has not succeeded in getting us to root causes of many age-related chronic diseases (e.g. Alzheimer's disease, diabetes, osteoarthritis). Moreover, in aging and disease constructs alone fail to explain the variability in illness presentations. Therefore, we propose to apply the underused illness concept in a new way by reconsidering the importance of common symptoms in the form of a dynamic network of symptoms as a complementary framework. We show that concepts and methods of complex system thinking now enable to fruitfully monitor and analyse the multiple interactions between symptoms in such in networks, offering new routes for prognosis and treatment. Moreover, close attention to the symptoms that bother older persons may also improve weighing the therapeutic objectives of well-being and survival and aligning treatment targets with the patients' priorities.

Functional co-activation of the default mode network in APOE ε4-carriers: A replication study.

Structural and functional alterations of the brain in persons genetically at-risk for Alzheimer's disease (AD) are crucial in unravelling AD development. Filippini et al. found that the default mode network (DMN) is already affected in young APOE ε4-carriers, with increased co-activation of the DMN during rest and increased hippocampal task activation. We aimed to replicate the early findings of Filippini et al, using the APOE gene, still the principal AD risk gene, and extended this with a polygenic risk score (PRS) analysis for AD, using the Human Connectome Project dataset (HCP). We included participants from the HCP S1200 dataset (age range: 22-36 years). We studied morphometric features, functional DMN co-activation and functional task activation of recollection performance. Permutation Analysis of Linear Models (PALM) was used to test for group differences between APOE ε4-carriers and non-carriers, and to test the association with PRS. PALM controls for biases induced by the family structure of the HCP sample. Results were family-wise error rate corrected at p < 0.05. Our primary analysis did not replicate the early findings of Filippini et al. (2009). However, compared with non-carriers, APOE ε4-carriers showed increased functional activation during the encoding of subsequently recollected items in areas related to facial recognition (p<0.05, t>756.11). This increased functional activation was also positively associated with PRS (APOE variants included) (p<0.05, t>647.55). Our results are supportive for none to limited genetic effects on brain structure and function in young adults. Taking the methodological considerations of replication studies into account, the true effect of APOE ε4-carriership is likely smaller than indicated in the Filippini paper. However, it still holds that we may not yet be able to detect already present measurable effects decades before a clinical expression of AD. Since the mechanistic pathway of AD is likely to encompass many different factors, further research should be focused on the interactions of genetic risk, biomarkers, aging and lifestyle factors over the life course. Sensitive functional neuroimaging as used here may help disentangling these complex interactions.

Dutch emergency physicians insufficiently educated in geriatric emergency medicine: results of a nationwide survey.

BACKGROUND: Emergency physicians (EPs) provide care to older adults with complex health problems. Treating these patients is challenging for many EPs, which might originate from modest geriatric education. OBJECTIVE: Our aim was to assess EPs' self-perceived needs regarding geriatric emergency medicine (GEM) education, factors determining these needs and the utilization of this education. Our secondary aim was to assess emergency department (ED) managers' view and support for GEM education. METHODS: All EPs and ED managers in the Netherlands received a survey by e-mail. The questionnaires focused on EPs' needs in GEM education, EPs' utilization of GEM education and managerial support for GEM education. We used descriptive statistics to analyse needs, utilization of- and support for GEM education. Regression analyses were used to identify factors associated with EPs' need for GEM education. RESULTS: EPs reported to need better training in diagnosing, treating and communicating with older adults. Seventy percent of EPs reported no GEM education program in their hospital, and 83% reported no utilization of GEM education outside their hospital. EPs working in EDs with a possibility for geriatric consultation, and EPs aware of actual GEM education programs, had lower educational needs. Of responding managers, 86.2% reported the care for older adults as an important topic; lack of finances and time were obstacles to provide GEM education for EPs. CONCLUSION: EPs in the Netherlands feel insufficiently educated to treat older adults. ED managers largely recognize this educational challenge. This nationwide survey underlines the need to prioritize GEM education for EPs.

Quantifying resilience of humans and other animals.

All life requires the capacity to recover from challenges that are as inevitable as they are unpredictable. Understanding this resilience is essential for managing the health of humans and their livestock. It has long been difficult to quantify resilience directly, forcing practitioners to rely on indirect static indicators of health. However, measurements from wearable electronics and other sources now allow us to analyze the dynamics of physiology and behavior with unsurpassed resolution. The resulting flood of data coincides with the emergence of novel analytical tools for estimating resilience from the pattern of microrecoveries observed in natural time series. Such dynamic indicators of resilience may be used to monitor the risk of systemic failure across systems ranging from organs to entire organisms. These tools invite a fundamental rethinking of our approach to the adaptive management of health and resilience.

Determinants of Cross-Sectional and Longitudinal Health-Related Quality of Life in Memory Clinic Patients Without Dementia.

OBJECTIVE: To identify determinants within 3 different domains (ie, somatic comorbidities, cognitive functioning, and neuropsychiatric symptoms [NPS]) of health-related quality of life (HRQoL) over time in memory clinic patients without dementia. METHODS: This longitudinal multicenter cohort study with a 3-year observation period recruited 315 individuals (age: 69.8 ± 8.6, 64.4% males, Mini-Mental State Examination score 26.9 ± 2.6). A multivariable explanatory model was built using linear mixed effects models (forward selection per domain) to select determinants for self-perceived HRQoL over time, as measured by the EuroQoL-5D visual analogue scale (EQ VAS). RESULTS: Mean HRQoL at study entry was 69.4 ± 15.6. The presence of agitation, appetite and eating abnormalities, and eyes/ears/nose (ie, sensory impairment) comorbidities were associated with a change in HRQoL over time. Agitation was most strongly associated with HRQoL over time. CONCLUSIONS: The association of somatic comorbidities and NPS in memory clinic patients with course of HRQoL shows that these should receive more awareness, detection, and monitoring by clinicians.

Frailty as a predictor of mortality in older adults within 5 years of psychiatric admission.

OBJECTIVES: Older adults with psychiatric disorders have a substantially lower life expectancy than age-matched controls. Knowledge of risk factors may lead to targeting treatment and interventions to reduce this gap in life expectancy. In this study, we investigated whether frailty independently predicts mortality in older patients following an acute admission to a geriatric psychiatry hospital. METHODS: Clinical cohort study with a 5-year follow-up of 120 older patients admitted to a psychiatric hospital between February 2009 and September 2010. On admission, we assessed frailty with a frailty index (FI). We applied Cox regression analyses with time to death as the dependent variable, to examine whether the FI was a predictor for mortality, adjusted for age, sex, level of education, multimorbidity (Cumulative Illness Rating Scale for Geriatrics, CIRS-G scores), functional status (Barthel Index), neuropsychiatric symptoms (NPS), and severity of psychiatric symptoms at admission (Clinical Global Impressions Scale of Severity). RESULTS: Of the 120 patients, 63 (53%) patients were frail (FI ≥ 0.25), and 59 (49%) had died within 5 years. The FI predicted mortality with a hazard ratio (HR) of 1.78 (95% CI, 1.06-2.98) per 0.1 point increase, independent of the covariates. Co-morbidity measured by the CIRS-G and functional status measured by the Barthel Index were not significantly associated. CONCLUSIONS: Frailty was a strong predictor of mortality, independent of age, gender, multimorbidity, and functional status. This implies that frailty may be helpful in targeting inpatient psychiatric treatment and aftercare according to patients' life expectancy.

Pathways to care for people with dementia: An international multicentre study.

OBJECTIVE: The aim of the present study was to characterize the clinical pathways that people with dementia (PwD) in different countries follow to reach specialized dementia care. METHODS: We recruited 548 consecutive clinical attendees with a standardized diagnosis of dementia, in 19 specialized public centres for dementia care in 15 countries. The WHO "encounter form," a standardized schedule that enables data concerning basic socio-demographic, clinical, and pathways data to be gathered, was completed for each participant. RESULTS: The median time from the appearance of the first symptoms to the first contact with specialist dementia care was 56 weeks. The primary point of access to care was the general practitioners (55.8%). Psychiatrists, geriatricians, and neurologists represented the most important second point of access. In about a third of cases, PwD were prescribed psychotropic drugs (mostly antidepressants and tranquillizers). Psychosocial interventions (such as psychological counselling, psychotherapy, and practical advice) were delivered in less than 3% of situations. The analyses of the "pathways diagram" revealed that the path of PwD to receiving care is complex and diverse across countries and that there are important barriers to clinical care. CONCLUSIONS: The study of pathways followed by PwD to reach specialized care has implications for the subsequent course and the outcome of dementia. Insights into local differences in the clinical presentations and the implementation of currently available dementia care are essential to develop more tailored strategies for these patients, locally, nationally, and internationally.

A Guiding Nightlight Decreases Fear of Falling and Increases Sleep Quality of Community-Dwelling Older People: A Quantitative and Qualitative Evaluation.

BACKGROUND: Even though poor lighting at nighttime is an important risk factor for falls (and most falls occur during the night), lighting interventions to improve nightly lighting from bed to bathroom are rarely evaluated for fall prevention. OBJECTIVE: We tested the hypothesis that an automated guiding light would reduce nightly fear of falling (FOF) and increase sleep quality of community-dwelling older people. METHODS: This study had a pragmatic uncontrolled before-after design, including participants during a period of 8 months if they (i) were aged at least 65 years, (ii) ambulated independently at night, and (iii) had no cognitive or audiovisual impairments obstructing outcome measurement. Automated LED strips (GightTM) were installed in the participants' homes. The primary outcome measure was overnight FOF on a scale of 0-10. Secondary outcome measures included sleep quality on a scale of 0-10 and fall rate. Additionally, a sample of participants was interviewed about their experiences with Gight. RESULTS: Sixty-four participants were included (mean age: 80.8 ± 8.1 years; 89% living independently). Mean study length was 118 days (range: 30-231). In the intention-to-treat analysis, overnight FOF declined from 5.5 ± 3.0 to 3.8 ± 3.2 (p = 0.001), and sleep quality increased from 6.7 ± 2.4 to 7.4 ± 1.7 (p = 0.012). The fall rate during the study was too low to detect changes. Participants appreciated Gight (8.4 ± 0.8 on a scale of 10), and the majority (57%) reported a subjective decrease in FOF. CONCLUSION: Gight shows promising results for overnight FOF and sleep quality, but the effect of lighting interventions on fall rate should be evaluated further before widespread implementation.

Frailty, multimorbidity and functional status as predictors for health outcomes of acute psychiatric hospitalisation in older adults.

Objectives: Frailty, multimorbidity and functional decline predict adverse health outcomes in community dwelling older people and older patients in general hospitals. This study investigates whether these characteristics separately are independent predictors of health outcomes of acute psychiatric hospitalization.Methods: Observational study in a prospectively sampled cohort of older patients, consecutively admitted to a psychiatric hospital. On admission we assessed frailty (Frailty Index and walking speed); multimorbidity (Cumulative Index Rating Scale Geriatrics (CIRS-G)) and functional status (Barthel Index). We used the Clinical Global Impressions of Improvement scale (CGI-I) as the psychiatric outcome measure, and dichotomized discharge destination as overall outcome measure: favourable (able to return home or previous care level) or adverse (death, or move to higher level of residential care).Results: We included 120 patients, 74.6 years (±7.8). 52.5% of the patients was frail (FI ≥0.25). The mean level of the CIRS-G was 13.5 (5.4). Mean CGI-I at discharge was 2.8 (± 1.0), indicating moderate improvement in the psychiatric outcome. Neither FI, CIRS-G, nor Barthel scores were, independent of age, sex and diagnosis, associated with the CGI-I. FI was predictive for adverse discharge destination (OR 1.91, 95%CI 1.09-3.37 per 0.1), as were higher CIRS-G (OR 1.19 95%CI 1.06-1.34, per point) and lower walking speed (OR 1.35 95%CI 1.06-1.72 per 0.1 m/s).Conclusions: Half of our patients were frail and had a high level of multimorbidity. The FI, walking speed and multimorbidity did not predict improvement of psychiatric symptoms at discharge, but independently helped to predict adverse discharge destination.

Physical Exercise Training Improves Quality of Life in Healthy Older Adults: A Meta-Analysis.

The current meta-analysis first aimed to quantify the overall effect of physical exercise training on the quality of life (QoL) in healthy older adults. Second, the effects on the social, physical, and psychological QoL were assessed. In total, 16 randomized controlled trials were included. The primary analysis showed a medium effect of physical exercise training on QoL in healthy older adults (standard mean difference [SMD] = 0.38, confidence interval, CI, [0.18, 0.59], p < .05). The secondary analyses showed a positive medium effect of physical exercise training on the physical component of QoL (SMD = 0.39, CI [0.17, 0.60], p < .05), and a positive medium effect of physical exercise training on the psychological component of QoL (SMD = 0.348, CI [0.125, 0.570], p < .05), and no significant effect of physical exercise training on the social component of QoL was observed (SMD = 0.16, CI [-0.07, 0.38], p = .17). These findings warrant implementation efforts pertaining to exercise training for older adults to improve the QoL in our aging societies.