Micronutrients, Frailty, and Cognitive Impairment: Design and Preliminary Results from the CogLife 2.0 Study.

Background: Among preventive strategies against dementia, nutrition is considered a powerful one and the recently established "nutritional cognitive neuroscience of aging" is a highly active research field. Objective: The present study was designed to deeply characterize older adults across the continuum from cognitive integrity to mild cognitive impairment (MCI) and better elucidate the prognostic role of lipophilic micronutrients within their lipidomic signature. Methods: 123 participants older than 65 years across the continuum from cognitive integrity to MCI were included [49 with subjective cognitive impairment, 29 women, 72.5±5.4 years, 26 MCI, 9 women, 74.5±5.8 years and 50 without cognitive impairment, 21 women, 70.8±4.3 years]. All participants underwent neuropsychological and nutritional examination as well as comprehensive geriatric assessment with calculation of the Multidimensional Prognostic Index (MPI) as a proxy of frailty and biological age and blood withdrawal for the analyses of lipophilic micronutrients, metabolomics and oxylipidomics. One year after the evaluation, same tests are ongoing. Results: After adjustment for age, sex, daily fruit and vegetable intake and cholesterol, we found a significant positive correlation between lutein and the number of correct words in category fluency (p = 0.016). Conclusions: This result supports the importance of carotenoids as robust biomarkers of cognitive performance independent of the nutritional status and frailty of the participants, as the entire present study collective was robust (MPI 0-0.33). The complete analyses of the metabolome and the oxylipidome will hopefully shed light on the metabolic and prognostic signature of cognitive decline in the rapidly growing population at risk of frailty.

Profiles of Geriatric Syndromes and Resources in Older Patients with Atrial Fibrillation.

Objective: Older patients with nonvalvular atrial fibrillation (AF) are at high risk for frailty and geriatric syndromes (GSs), which modulate their individual prognosis and are therefore relevant for further management. Because few studies have evaluated the geriatric profile of older AF patients, this secondary analysis aims to further characterize the patterns of GSs and geriatric resources (GRs) in AF patients and their association with anticoagulation use. Methods: Data from 362 hospitalized patients aged 65 years and older with AF (n = 181, 77.8 ± 5.8 years, 38% female) and without AF (non-AF [NAF]; n = 181, 77.5 ± 5.9 years, 40% female) admitted to an internal medicine and nephrology ward of a large university hospital in Germany were included. All patients underwent usual care plus a comprehensive geriatric assessment (CGA) including calculation of the Multidimensional Prognostic Index (MPI) and collection of 17 GSs and 10 GRs. Patients were followed up by telephone 6 and 12 months after discharge to collect data on their health status. Results: The mean MPI score of 0.47 indicated an average risk of poor outcome, and patients with AF had a significantly higher MPI than those without AF (p = 0.040). After adjustment for chronological age, biological sex, Cumulative Illness Rating Scale (CIRS) for relevant chronic diagnoses and MPI as a proxy for biological age, AF patients had significantly more mnestic resources (63.5% vs. 33.1%, p < 0.001), a tendency for less age-appropriate living conditions (56.4% vs. 72.9%, p = 0.051) and more sensory impairment (78.5% vs. 52.5%, p < 0.001) than NAF patients. They also had a higher number of GSs (p = 0.046). AF patients on oral anticoagulants (OACs, n = 91) had less age-appropriate living conditions (48.4% vs. 64.4%, p < 0.05) and mnestic resources (36.3% vs. 54.4%, p < 0.01), but more emotional resources (80.2% vs. 65.6%, p < 0.05) and chronic pain (56% vs. 40%, p < 0.05) than patients without OACs (n = 90). Overall, mortality at 1 year was increased in patients with a higher MPI (p < 0.009, adjusted for age, sex and CIRS), with a diagnosis of AF (p = 0.007, adjusted for age, sex, CIRS and MPI), with of male sex (p = 0.008, adjusted for age, CIRS and MPI) and those with AF and treated with hemodialysis (p = 0.022, compared to AF patients without dialysis treatment). Conclusions: Patients with AF and patients with AF and OACs show differences in their multidimensional frailty degree as well as GR and GS profiles compared to patients without AF or with AF not treated with OACs. Mortality after 1 year is increased in AF patients with a higher MPI and dialysis, independently from OAC use and overall burden of chronic disease as assessed per CIRS. GRs and GSs, especially age-appropriate living conditions, emotional resources, sensory impairment and chronic pain, can be considered as factors that may modify the individual impact of frailty, underscoring the relevance of these parameters in the management of older patients.

The multidimensional prognostic index in hospitalized older adults: practicability with regard to time needs.

BACKGROUND: Comprehensive Geriatric Assessment (CGA) is decisive in patient-centered medicine of the aged individual, yet it is not systematically used. AIM: The aim of this study was to provide precise practice-relevant time expenditure data for the Multidimensional Prognostic Index (MPI), a questionnaire-based frailty assessment tool. METHODS: MPI was determined in ninety older multimorbid adults in three geriatric departments (cohorts 1, 2 and 3). The time needed to perform the MPI (tnpMPI) was recorded in minutes. Follow-up data were collected after 6 months. RESULTS: The median tnpMPI was 15.0 min (IQR 7.0) in the total collective. In the last visited cohort 3, the median was 10.0 min and differed significantly from cohorts 1 and 2 with medians of 15.5 and 15.0 (p < 0.001). CONCLUSION: These findings indicate, that MPI, as a highly informative frailty tool of individualized medicine, can be performed in an adequately practicable time frame.

Prognostic Signature of Chronic Kidney Disease in Advanced Age: Secondary Analysis from the InGAH Study with One-Year Follow-Up.

The negative impact of chronic kidney disease (CKD) on health status and quality of life in older patients has been well documented. However, data on frailty trajectories and long-term outcomes of older CKD patients undergoing structured Comprehensive Geriatric Assessment (CGA) with multidimensional frailty evaluation are sparse. Here, we analysed records from 375 CKD patients admitted to our university hospital (mean age 77.5 (SD 6.1) years, 36% female) who had undergone a CGA-based calculation of the frailty score with the multidimensional prognostic index (MPI) as well as follow-up evaluations at 3, 6 and 12 months after discharge. Based on the MPI score at admission, 21% of the patients were frail and 56% were prefrail. MPI values were significantly associated with KDIGO CKD stages (p = 0.003) and rehospitalisation after 6 months (p = 0.027) and mortality at 3, 6 and 12 months (p = 0.001), independent of chronological age. Kidney transplant recipients (KTR) showed a significantly lower frailty compared to patients with renal replacement therapy (RRT, p = 0.028). The association between frailty and mortality after 12 months appeared particularly strong for KTR (mean MPI 0.43 KTR vs. 0.52 RRT, p < 0.001) and for patients with hypoalbuminemia (p < 0.001). Interestingly, RRT was per se not significantly associated with mortality during follow up. However, compared to patients on RRT those with KTR had a significantly lower grade of care (p = 0.031) and lower rehospitalisation rates at 12 months (p = 0.010). The present analysis shows that the large majority of older CKD inpatients are prefrail or frail and that the risk for CKD-related adverse outcomes on the long term can be accurately stratified by CGA-based instruments. Further studies are needed to explore the prognostic and frailty-related signature of laboratory biomarkers in CKD.

Influence of a 12-Month Structured Exercise Program on the Micronutrient-Cognitive Fitness-Physical Association Profiles in Mild Cognitive Impairment.

Background: Preventive lifestyle strategies have shown promise to slow down or prevent age-related cognitive decline. However, evidence on the reciprocal longitudinal relationships between nutrition biomarkers and cognitive and physical performance is lacking. Studying nutritional, cognitive, and physical profiles over time may help to overcome this knowledge gap. Objective: To investigate the relationship of plasma levels of the robust nutritional- and antioxidant defense-related biomarkers carotenoids and tocopherols with both indicators of cognitive and physical performance in persons with mild cognitive impairment (MCI) participating in a structured exercise program. Methods: Data from 40 participants with MCI of the NeuroExercise study were analyzed. Participants had undergone a blood withdrawal for the analysis of plasma concentrations of six carotenoids, two tocopherols and retinol prior to and after one-year of structured exercise. All participants had undergone a broad spectrum of cognitive and physical performance tests. Results: Significant associations between lipophilic micronutrients and cognitive/physical measures were observed that were previously found to play a role in cognitive and physical frailty. In particular, lutein, zeaxanthin, and lycopene are confirmed as robust, reliable, and stable indicators of nutritional defense. Importantly, these micronutrients were associated with cognitive measures prior to the physical training program and to a more prominent extent with indicators of motoric function after the physical exercise program. Conclusion: Specific profiles of lipophilic micronutrients are associated to cognitive performance measures and, especially after a structured exercise program, to indicators of physical performance.

Role of a multidimensional prognosis in-hospital monitoring for older patients with prolonged stay.

OBJECTIVES: The Multidimensional Prognostic Index (MPI) is a prognostic tool-amongst others-validated for mortality, length of hospital stay (LHS) and rehospitalisation risk assessment. Like the Comprehensive Geriatric Assessment (CGA), the MPI is usually obtained at hospital admission and discharge, not during the hospital stay. The aim of the present study was to address the role of an additional CGA-based MPI measurement during hospitalisation as an indicator of "real-time" in-hospital changes. STUDY DESIGN AND MAIN OUTCOME MEASURES: Two-hundred consecutive multimorbid patients (128 M, 72 F, median age 75 (78-82)) admitted to an internal medicine ward of a German metropolitan university hospital prospectively underwent a CGA and a prognosis calculation using the MPI on admission and discharge. Seven to 10 days later, an intermediate assessment (IA) was performed for patients needing a longer stay. RESULTS: The median LHS was 10 (6-19) days. As expected, patients who received an IA had poorer prognosis as measured by higher MPI values (P = .037) and a worse functional status at admission than patients who had a shorter stay (P = .025). In case of prolonged hospitalisation, significant changes in the MPI were detected between admission and IA, both in terms of improvement and deterioration (P < .001). Different overtime courses were observed during prolonged hospitalisation according to the severity of prognosis (P < .001). CONCLUSION: A CGA-based MPI evaluation during hospitalisation can be used as an objective instrument to detect changes in multidimensional health course. Prompt identification of the latter may enable quick tailored interventions to ensure overall better outcomes at and after discharge.

The impact of oral health on prognosis of older multimorbid inpatients: the 6-month follow up MPI oral health study (MPIOH).

PURPOSE: There is clear evidence for an association between oral health and systemic illnesses, geriatric syndromes, and mortality. Frail and multimorbid older people often suffer from insufficient oral health care, but standardized dental examinations are not routinely performed in clinical settings. The aim of this study was to verify the practicability of in-hospital oral health examinations and to identify their association with patients' prognosis as assessed by means of the Comprehensive Geriatric Assessment (CGA)-based Multidimensional Prognostic Index (MPI). METHODS: One hundred hospitalized patients aged 65 years and older (mean age 76.9 years (SD 6.4); 58.2% male, 41.8% female) underwent a CGA-based MPI calculation at discharge with subdivision into three mortality risk groups (MPI-1, low risk, score 0-0.33; MPI-2, moderate risk, score 0.34-0.66; MPI-3, high risk, score 0.67-1). To identify the current oral health status and the Oral Health-related Quality of Life (OHRQoL), three oral health examinations were performed. Information on survival, the incidence of oral diseases, dental appointments, and treatments up to 6 months after discharge were collected. RESULTS: All oral health examinations were feasible during hospitalization and were associated with MPI prognosis, even though they were not associated with 6-month mortality. The MPI could not predict the use of dental health care or treatment, as, irrespective of MPI and oral health examinations, dental services were underutilized during follow up. CONCLUSION: Besides MPI evaluation, oral health examinations should be implemented into an inhospital course to improve clinical decision-making as well as secondary and tertiary prevention of oral health- and related systemic diseases. TRIAL REGISTRATION NUMBER: German Clinical Trials Register: DRKS00013607 (07.02.2019, retrospectively registered).

The prognostic signature of health-related quality of life in older patients admitted to the emergency department: a 6-month follow-up study.

BACKGROUND: The management of older and multimorbid patients with complex care requires a personalised and comprehensive approach. The main diagnosis is often registered as the cause of hospitalisation, yet poor health-related quality of life (HRQoL) as well as multimorbidity may represent the underlying cause and markedly influence prognosis. AIMS: To analyse the association of HRQoL and clinical prognosis over time as assessed by a Comprehensive Geriatric Assessment (CGA)-based Multidimensional Prognostic Index (MPI) in older patients admitted to the emergency department (ED). METHODS: We used data from the prospective MPI-HOPE (Influence of the MPI on the Hospitalisation of Older Patients admitted to the Emergency department) study. Data from 165 patients (≥ 75 years) admitted to the ED of the University Hospital of Cologne, Germany, between Oct 2017 and Jan 2018 were included. Clinical prognosis was calculated by the MPI and HRQoL by the EQ5D-5L. Follow-up interviews assessed HRQoL up to 6 months after discharge. RESULTS: Most patients were multimorbid and presented with several geriatric syndromes. At admission, HRQoL was highest in patients with the best clinical prognosis. The MPI showed a negative correlation with the EQ-Index at admission (rs(86) = - 0.50, p < 0.0001) and follow-up assessments after 3 and 6 months (rs(86) = - 0.55 and rs(86) = - 0.47, p < 0.0001). DISCUSSION: Our results suggest that patients' self-perceived HRQoL in the ED is related to functional health status and clinical prognosis. CONCLUSION: The MPI as a multidimensional snapshot provides information on clinical health indicators and informs about subjective HRQoL, thereby helping in identifying patients who would benefit from a specific treatment within the frame of a patient-centered, value-based care strategy geriatric treatment.

[Strategies to prevent age-related cognitive decline]. / Präventive Geriatrie: kognitiven Abbau verhindern.

The increasing aging demographics never seen before is associated with the enormous challenge of dementia epidemics which urgently needs a paradigm shift in the approach to cognitive functions in health and disease. If on one hand the achievement or maintenance of a healthy lifestyle should be a medical priority, the early recognition of cognitive disturbances is mandatory. Cognitive impairment is not only associated with disability and lack of compliance and adherence, but also with dangerous geriatric syndromes such as instability, falls, and delirium. The evaluation of cognitive performance, particularly in older patients and especially in those hospitalized for other reasons, should be performed in all cases. While the National Institute of Aging and Alzheimer Association established new criteria for the diagnosis of Alzheimer's disease, the large majority of dementia cases are assigned to a multifactorial syndrome presenting as a long-lasting continuum from organ/function integrity to dementia. While the monoclonal antibody aducanumab is under careful evaluation for release on the market as the first curative drug, current anti-Alzheimer medication strategies remain symptomatic. In spite of the previous distinction between neurodegenerative and vascular forms of dementia, it is now accepted that control of vascular risk factors and comorbidities strongly affects the prevention of all types of cognitive impairment. The WHO has published in May 2019 an official guideline document for reducing dementia risk. The guidelines provide recommendations on the major modifiable lifestyle factors and chronic diseases. The best way to prevent cognitive impairment and its worsening include vascular risk control and a healthy diet including a balanced natural nutrition (without nutritional supplements for which scientific evidence is lacking), physical exercise (preferably aerobic), enough social participation, interaction and conviviality as well as cognitive exercise (focusing on general cognitive function, executive function and working memory) While the activation of all domains of lifestyle are critical for the achievement of the best preventive effects, these should be implemented 1) in a personalized, goal-oriented fashion (the so called tailored interventions) and 2) with the ultimate goal of maintaining the care of personal interests and functions along with quality of life and wellbeing.For an effective prevention of cognitive decline, resources from all domains of lifestyle (nutrition, exercise, rest, social participation, cognitive activity) should be used, however in a personalized way. The Comprehensive Geriatric Assessment (CGA), evaluating the physical, psychosocial and functional aspects of young-old, old-old and oldest-old persons, can be used to detect early cognitive impairment and factors associated with its course in order to modulate them.