Effectiveness of integrated person-centered interventions for older people's care: Review of Swedish experiences and experts' perspective.

Older adults have multiple medical and social care needs, requiring a shift toward an integrated person-centered model of care. Our objective was to describe and summarize Swedish experiences of integrated person-centered care by reviewing studies published between 2000 and 2023, and to identify the main challenges and scientific gaps through expert discussions. Seventy-three publications were identified by searching MEDLINE and contacting experts. Interventions were categorized using two World Health Organization frameworks: (1) Integrated Care for Older People (ICOPE), and (2) Integrated People-Centered Health Services (IPCHS). The included 73 publications were derived from 31 unique and heterogeneous interventions pertaining mainly to the micro- and meso-levels. Among publications measuring mortality, 15% were effective. Subjective health outcomes showed improvement in 24% of publications, morbidity outcomes in 42%, disability outcomes in 48%, and service utilization outcomes in 58%. Workshop discussions in Stockholm (Sweden), March 2023, were recorded, transcribed, and summarized. Experts emphasized: (1) lack of rigorous evaluation methods, (2) need for participatory designs, (3) scarcity of macro-level interventions, and (4) importance of transitioning from person- to people-centered integrated care. These challenges could explain the unexpected weak beneficial effects of the interventions on health outcomes, whereas service utilization outcomes were more positively impacted. Finally, we derived a list of recommendations, including the need to engage care organizations in interventions from their inception and to leverage researchers' scientific expertise. Although this review provides a comprehensive snapshot of interventions in the context of Sweden, the findings offer transferable perspectives on the real-world challenges encountered in this field.

Cholinergic white matter pathways along the Alzheimer's disease continuum.

Previous studies have shown that the cholinergic nucleus basalis of Meynert and its white matter projections are affected in Alzheimer's disease dementia and mild cognitive impairment. However, it is still unknown whether these alterations can be found in individuals with subjective cognitive decline, and whether they are more pronounced than changes found in conventional brain volumetric measurements. To address these questions, we investigated microstructural alterations of two major cholinergic pathways in individuals along the Alzheimer's disease continuum using an in vivo model of the human cholinergic system based on neuroimaging. We included 402 participants (52 Alzheimer's disease, 66 mild cognitive impairment, 172 subjective cognitive decline and 112 healthy controls) from the Deutsches Zentrum für Neurodegenerative Erkrankungen Longitudinal Cognitive Impairment and Dementia Study. We modelled the cholinergic white matter pathways with an enhanced diffusion neuroimaging pipeline that included probabilistic fibre-tracking methods and prior anatomical knowledge. The integrity of the cholinergic white matter pathways was compared between stages of the Alzheimer's disease continuum, in the whole cohort and in a CSF amyloid-beta stratified subsample. The discriminative power of the integrity of the pathways was compared to the conventional volumetric measures of hippocampus and nucleus basalis of Meynert, using a receiver operating characteristics analysis. A multivariate model was used to investigate the role of these pathways in relation to cognitive performance. We found that the integrity of the cholinergic white matter pathways was significantly reduced in all stages of the Alzheimer's disease continuum, including individuals with subjective cognitive decline. The differences involved posterior cholinergic white matter in the subjective cognitive decline stage and extended to anterior frontal white matter in mild cognitive impairment and Alzheimer's disease dementia stages. Both cholinergic pathways and conventional volumetric measures showed higher predictive power in the more advanced stages of the disease, i.e. mild cognitive impairment and Alzheimer's disease dementia. In contrast, the integrity of cholinergic pathways was more informative in distinguishing subjective cognitive decline from healthy controls, as compared with the volumetric measures. The multivariate model revealed a moderate contribution of the cholinergic white matter pathways but not of volumetric measures towards memory tests in the subjective cognitive decline and mild cognitive impairment stages. In conclusion, we demonstrated that cholinergic white matter pathways are altered already in subjective cognitive decline individuals, preceding the more widespread alterations found in mild cognitive impairment and Alzheimer's disease. The integrity of the cholinergic pathways identified the early stages of Alzheimer's disease better than conventional volumetric measures such as hippocampal volume or volume of cholinergic nucleus basalis of Meynert.

Long-term effects of cholinesterase inhibitors and memantine on cognitive decline, cardiovascular events, and mortality in dementia with Lewy bodies: An up to 10-year follow-up study.

INTRODUCTION: We aimed to assess the impact of cholinesterase inhibitors (ChEIs) and memantine on cognition, major adverse cardiovascular events (MACE) and mortality in dementia with Lewy bodies (DLB). METHODS: A total of 1,095 incident DLB patients from the Swedish Registry on cognitive/dementia disorders were included. Using an inverse probability of treatment weighting, the effect of initiating ChEI or memantine within 90 days of DLB diagnosis and nonuse was evaluated on cognitive trajectories and risks of MACE and death. RESULTS: The use of ChEIs significantly slowed cognitive decline at follow-ups (Mini-Mental State Examination [MMSE] -0.39 points/y; 95% confidence interval [CI], -0.96 to 0.18) compared to memantine (-2.49 points/y; -4.02 to -0.97) and nonuse (-2.50 points/y; -4.28 to -0.73). Treatment groups did not differ in MACE events. ChEI use was associated with lower risk of death in the first year after DLB diagnosis (adjusted hazard ratio [HR] 0.66, 95% CI 0.46, 0.94). DISCUSSION: Our findings illuminate the potential benefits of ChEI treatment in DLB patients. HIGHLIGHTS: Cholinesterase inhibitors slow cognitive decline over a 5-year follow-up period when compared to both memantine treatment and nonuse in patients with dementia with Lewy bodies. Cholinesterase Inhibitors reduce risk of mortality within the initial year, but this effect is not sustained after 1 year in patients with dementia with Lewy bodies.

Predicting sojourn times across dementia disease stages, institutionalization, and mortality.

INTRODUCTION: Inferring the timeline from mild cognitive impairment (MCI) to severe dementia is pivotal for patients, clinicians, and researchers. Literature is sparse and often contains few patients. We aim to determine the time spent in MCI, mild-, moderate-, severe dementia, and institutionalization until death. METHODS: Multistate modeling with Cox regression was used to obtain the sojourn time. Covariates were age at baseline, sex, amyloid status, and Alzheimer's disease (AD) or other dementia diagnosis. The sample included a register (SveDem) and memory clinics (Amsterdam Dementia Cohort and Memento). RESULTS: Using 80,543 patients, the sojourn time from clinically identified MCI to death across all patient groups ranged from 6.20 (95% confidence interval [CI]: 5.57-6.98) to 10.08 (8.94-12.18) years. DISCUSSION: Generally, sojourn time was inversely associated with older age at baseline, males, and AD diagnosis. The results provide key estimates for researchers and clinicians to estimate prognosis.

Association between cholinesterase inhibitors and kidney function decline in patients with Alzheimer's dementia.

Preclinical evidence shows that activation of the cholinergic anti-inflammatory pathway (CAP) may have direct and indirect beneficial effects on the kidney. Cholinesterase inhibitors (ChEIs) are specific Alzheimer's dementia (AD) therapies that block the action of cholinesterases and activate CAP. Here, we explored a plausible effect of ChEIs on slowing kidney function decline by comparing the risk of CKD progression among patients with newly diagnosed AD that initiated ChEI or not within 90 days. Using complete information of routine serum creatinine tests, we evaluated changes in estimated glomerular filtration rate (eGFR) and defined the outcome of chronic kidney disease (CKD) progression as the composite of an eGFR decline of over 30%, initiation of dialysis/transplant or death attributed to CKD. A secondary outcome was death. Inverse probability of treatment-weighted Cox regression was used to estimate hazard ratios. Among 11, 898 patients, 6,803 started on ChEIs and 5,095 did not. Mean age was 80 years (64% women) and the mean eGFR was 68 ml/min/1.73m2. During a median 3.0 years of follow-up, and compared to non-use, ChEI use was associated with 18% lower risk of CKD progression (1,231 events, adjusted hazard ratio 0.82; 95% confidence interval 0.71-0.96) and a 21% lower risk of death (0.79; 0.72-0.86). Results were consistent across subgroups, ChEI subclasses and after accounting for competing risks. Thus, in patients with AD undergoing routine care, use of ChEI (vs no-use) was associated with lower risk of CKD progression.

Cerebrospinal Fluid Profile of Lipid Mediators in Alzheimer's Disease.

Alzheimer's disease (AD) develops into dementia over a period of several years, during which subjective cognitive impairment (SCI) and mild cognitive impairment (MCI) can be used as intermediary diagnoses of increasing severity. Chronic neuroinflammation resulting from insufficient resolution is involved in the pathogenesis of AD and is associated with cognitive impairment. Specialized pro-resolving lipid mediators (LMs) that promote the resolution of inflammation may be valuable markers in AD diagnosis and as therapeutic targets. Liquid chromatography-tandem mass spectrometry was used to analyze pro-resolving and pro-inflammatory LMs in cerebrospinal fluid (CSF) from patients with cognitive impairment ranging from subjective impairment to a diagnosis of AD and correlated to cognition, CSF tau, and ß-amyloid. Resolvin (Rv) D4, RvD1, neuroprotectin D1 (NPD1), maresin 1 (MaR1), and RvE4 were lower in AD and/or MCI compared to SCI. The pro-inflammatory LTB4 and 15-HETE were higher in AD and MCI, respectively, while PGD2, PGE2, and PGF2a were decreased in AD, compared to SCI. RvD4 was also negatively correlated to AD tangle biomarkers, and positive correlations to cognitive test scores were observed for both pro-resolving LMs and their precursor fatty acids. In this exploratory study of the lipidome in CSF of AD, MCI, and SCI, the results indicate a shift in the LM profile from pro-resolving to pro-inflammatory in progression to AD, suggesting that it may be of use as a biomarker when followed by confirmation by replication studies.

Two Years with COVID-19: The Electronic Frailty Index Identifies High-Risk Patients in the Stockholm GeroCovid Study.

INTRODUCTION: Frailty, a measure of biological aging, has been linked to worse COVID-19 outcomes. However, as the mortality differs across the COVID-19 waves, it is less clear whether a medical record-based electronic frailty index (eFI) that we have previously developed for older adults could be used for risk stratification in hospitalized COVID-19 patients. OBJECTIVES: The aim of the study was to examine the association of frailty with mortality, readmission, and length of stay in older COVID-19 patients and to compare the predictive accuracy of the eFI to other frailty and comorbidity measures. METHODS: This was a retrospective cohort study using electronic health records (EHRs) from nine geriatric clinics in Stockholm, Sweden, comprising 3,980 COVID-19 patients (mean age 81.6 years) admitted between March 2020 and March 2022. Frailty was assessed using a 48-item eFI developed for Swedish geriatric patients, the Clinical Frailty Scale, and the Hospital Frailty Risk Score. Comorbidity was measured using the Charlson Comorbidity Index. We analyzed in-hospital mortality and 30-day readmission using logistic regression, 30-day and 6-month mortality using Cox regression, and the length of stay using linear regression. Predictive accuracy of the logistic regression and Cox models was evaluated by area under the receiver operating characteristic curve (AUC) and Harrell's C-statistic, respectively. RESULTS: Across the study period, the in-hospital mortality rate decreased from 13.9% in the first wave to 3.6% in the latest (Omicron) wave. Controlling for age and sex, a 10% increment in the eFI was significantly associated with higher risks of in-hospital mortality (odds ratio = 2.95; 95% confidence interval = 2.42-3.62), 30-day mortality (hazard ratio [HR] = 2.39; 2.08-2.74), 6-month mortality (HR = 2.29; 2.04-2.56), and a longer length of stay (ß-coefficient = 2.00; 1.65-2.34) but not with 30-day readmission. The association between the eFI and in-hospital mortality remained robust across the waves, even after the vaccination rollout. Among all measures, the eFI had the best discrimination for in-hospital (AUC = 0.780), 30-day (Harrell's C = 0.733), and 6-month mortality (Harrell's C = 0.719). CONCLUSION: An eFI based on routinely collected EHRs can be applied in identifying high-risk older COVID-19 patients during the continuing pandemic.

Few geriatric heart failure patients investigated according to clinical guidelines: a retrospective review of patient records.

BACKGROUND: Research on heart failure (HF) has often focused on younger patients. The aim of this study was to analyze extent of investigation and treatment among older patients prior to referral to inpatient geriatric care for worsening of HF. METHODS: Data on etiology, ejection fraction (EF) by echocardiography (ECHO), level of functioning according to New York Heart Association (NYHA), analysis of N-terminal-pro-brain natriuretic peptide (NT-Pro-BNP), ongoing treatment, adherence to guidelines, and information from previous caregiver were collected from patient records prior to admission from a sample of 134 patients. RESULTS: Few patients had been examined by a cardiologist (14%) during the year prior to referral. EF assessment had been performed in 78% (n = 105). The patients were categorized as having HF with reduced (HFrEF 28%), preserved (HFpEF 53%) or mid-range (HFmrEF 19%) EF. HFpEF patients had older EF assessments (mean 517 days) than those with HFrEF (385 days). In 61% (n = 82) at least one assessment with NT-Pro-BNP had been performed, being older among patients with HFpEF (290 days vs 16 days). There was a strong positive correlation (OR 4.9, p = 0.001) between having recent assessments of EF and NT-Pro-BNP (n = 30, 21%) and being presented with etiology in the referral, adjusted for EF, age, sex, and comorbidity. Among the HFrEF patients, 78% were treated with ACEI/ARB and BB according to ESC guidelines but reaching only half of target doses. In the HFpEF group the corresponding treatment was 46%. Among patients with EF ≤ 35% only 14% were treated with mineral receptor antagonists, ie low adherence to guidelines. CONCLUSIONS: HF care in this population of older individuals showed deficiencies. There was little contact with cardiologists, lack of information of etiology in referrals and low adherence to treatment guidelines. Improving adherence to HF guidelines regarding investigation and treatment for HF in older people is therefore urgent and calls for more collaboration between specialists in cardiology and geriatric medicine.

Calcified carotid artery atheromas in individuals with cognitive dysfunction.

OBJECTIVE: The aim of this case-control study was to investigate whether cognitively impaired individuals have a higher burden of calcified carotid artery atheroma (CCAA) than controls without cognitive impairment. MATERIAL AND METHODS: The study included 154 cases with Alzheimer's disease (n = 52), mild cognitive impairment (n = 51), or subjective cognitive decline (n = 51) diagnosed at a university memory clinic. Seventy-six cognitively healthy controls were sampled through the Swedish population register. All participants underwent clinical oral and panoramic radiographic examinations. Two oral and maxillofacial radiologists performed blinded analyses of the panoramic radiographs for signs of CCAA, which was registered as absent or present and, if present, unilateral or bilateral. Consensus assessment was used for all statistical analyses. RESULTS: CCAA was common (40%) in this middle-aged and older Swedish population. We found no differences in the prevalence of CCAA between cases and controls (40% vs. 42%). CONCLUSION: Cognitively impaired patients do not have a higher burden of CCAA than matched controls without cognitive impairment.

Cognitive impairment in people with physical frailty using the phenotype model: A systematic review and meta analysis.

OBJECTIVE: We performed a systematic review and meta-analysis to study the relationship between cognitive functioning and phenotypic frailty status. METHODS: We searched Pubmed, Cochrane Library and Epistemonikos from 2000 until March 2022, and used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Samples included both sexes, age ≥55 years, assessed with standardized measures of the different cognitive domains and the frailty phenotype model and analyzing the relationship between the frailty subtypes pre-frail, frail and robust and specific cognitive function. RESULTS: Eleven studies published from 2008 until March 2022 fulfilled the inclusion criteria, and 10 were included in our meta-analyses. Sample sizes varied from 104 to 4649 individuals. Mean Mini-Mental State Examination (MMSE) scores ranged from 17.0 to 27.6, with mean difference (MD) of -2.55 (95% confidence interval [CI] -3.32, -1.78) in frail compared to robust, MD -1.64 (95% CI -2.21, -1.06) in frail compared to prefrail and MD -0.68 (95% CI -0.94, -0.43) in prefrail compared to robust. In subgroup analyses, frail persons had lower scores in the memory domain with standardized mean difference (SMD) -1.01 (95% CI -1.42, -0.59). CONCLUSION: MMSE scores were significantly lower in frail compared to robust and prefrail persons and in prefrail compared to robust persons. Subgroup analysis of memory revealed significantly poorer scores in frail compared to robust. The results indicate a strong relationship between physical frailty and cognitive impairment suggesting incorporation of cognitive function in frailty assessments.