Can geroscience be translated into healthcare?

As an introduction to this special issue on geroscience, the present work focuses on the complexity of disentangling biomolecular mechanisms of aging from biopsychosocial causes of accelerated aging. Due to this complexity, the biomolecular aging hallmarks of frailty and multimorbidity as predominant aging phenotypes in geriatrics reflect single aspects of the aging process. A possible approach to facilitate the integration of geroscience into healthcare might be to consider aging as the dynamic ratio between damage accumulation at the molecular and cellular level and resilience as strategies that prevent or repair such damage. There is a large body of evidence to show that geroscience has the potential to change healthcare; however, reaching a consensus and translating the best tool to measure aging needs more research on 1) the sensitivity of biomarkers to interventions and 2) the relationship between changes in biomarkers and changes in health trajectories.

Definitions and symptoms of the post-COVID syndrome: an updated systematic umbrella review.

Post-COVID syndrome (PCS) describes a persistent complex of symptoms following a COVID-19 episode, lasting at least 4 to 12 weeks, depending on the specific criteria used for its definition. It is often associated with moderate to severe impairments of daily life and represents a major burden for many people worldwide. However, especially during the first two years of the COVID-19 pandemic, therapeutic and diagnostic uncertainties were prominent due to the novelty of the disease and non-specific definitions that overlooked functional deficits and lacked objective assessment. The present work comprehensively examines the status of PCS definitions as depicted in recent reviews and meta-analyses, alongside exploring associated symptoms and functional impairments. We searched the database Pubmed for reviews and meta-analysis evaluating PCS in the period between May 31, 2022, to December 31, 2023. Out of 95 studies, 33 were selected for inclusion in our analyses. Furthermore, we extended upon prior research by systematically recording the symptoms linked with PCS as identified in the studies. We found that fatigue, neurological complaints, and exercise intolerance were the most frequently reported symptoms. In conclusion, over the past eighteen months, there has been a notable increase in quantity and quality of research studies on PCS. However, there still remains a clear need for improvement, particularly with regard to the definition of the symptoms necessary for diagnosing this syndrome. Enhancing this aspect will render future research more comparable and precise, thereby advancing and understanding PCS.

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.

Long-term effects of a telemedically-assisted lifestyle intervention on glycemic control in patients with type 2 diabetes - A two-armed randomised controlled trial in Germany.

Purpose: Diabetes is considered one of the fastest growing diseases worldwide. Especially in the treatment of type 2 diabetes, lifestyle interventions have proven to be effective. However, long-term studies in real-world contexts are rare, which is why further research is needed. The aim of the present study is to investigate whether effects achieved in the context of a long-term lifestyle intervention can be sustained by patients in the long term. Methods: In a two-arm randomized trial we compared diabetes care as usual to a lifestyle intervention combining telemedically support and individual needs-based telephone coaching. The study included 151 patients with type 2 diabetes randomized to either the intervention or control group. Intervention Group (IG; N = 86, 80.2% male, mean age: 59.7) received telemedical devices and telephone coaching over a period of 12 months, Control Group (CG; N = 65, 83.1% male, mean age: 58,8) received care as usual. The primary outcome was chance in HbA1c. A follow-up survey was conducted after 24 months. Results: The intervention group showed significantly better HbA1c- values compared to the control group at both 12 and 24 months (12 M: - 0.52 (-0.73; - 0.32), p < .000; 24 M: - 0.38 (-0.61; - 0.15), p = .001). The strongest change was seen in the first three months, with the best value obtained at 6 months and stable thereafter. Conclusion: Combined telephone coaching with telemedicine support could lead to better long-term glycemic control in people with type 2 diabetes. In the future, more long-term studies should be conducted in real-world settings and lifestyle interventions should be offered more widely.

Embracing complexity of (brain) aging.

Aging is a multifactorial process occurring in a pathophysiological continuum which leads to organ and system functional loss. While aging is not a disease, its pathophysiological continuum predisposes to illness and multimorbidity clusters which share common biomolecular mechanisms-the pillars of aging. Brain aging and neurodegeneration share many hallmarks with other age-related diseases. The central nervous system is often the weakest link susceptible to the aging process and its deterioration, resulting in cognitive impairment and other symptoms; the aging process is associated with proteostasis collapse, stem cell exhaustion, repair mechanisms, altered brain nutrient sensing, endothelial changes, inflammation, oxidative distress, and energy unbalance, as well as other disturbances. These mechanisms are highly interwoven, and considerable research is aimed at their disentanglement and detection of their clinically relevant impact, particularly in order to identify pharmacological and non-pharmacological preventive and therapeutic strategies.

The Multidimensional Prognostic Index predicts incident delirium among hospitalized older patients with COVID-19: a multicenter prospective European study.

PURPOSE: Incident delirium is a frequent complication among hospitalized older people with COVID-19, associated with increased length of hospital stay, higher morbidity and mortality rates. Although delirium is preventable with early detection, systematic assessment methods and predictive models are not universally defined, thus delirium is often underrated. In this study, we tested the role of the Multidimensional Prognostic Index (MPI), a prognostic tool based on Comprehensive Geriatric Assessment, to predict the risk of incident delirium. METHODS: Hospitalized older patients (≥ 65 years) with COVID-19 infection were enrolled (n = 502) from ten centers across Europe. At hospital admission, the MPI was administered to all the patients and two already validated delirium prediction models were computed (AWOL delirium risk-stratification score and Martinez model). Delirium occurrence during hospitalization was ascertained using the 4A's Test (4AT). Accuracy of the MPI and the other delirium predictive models was assessed through logistic regression models and the area under the curve (AUC). RESULTS: We analyzed 293 patients without delirium at hospital admission. Of them 33 (11.3%) developed delirium during hospitalization. Higher MPI score at admission (higher multidimensional frailty) was associated with higher risk of incident delirium also adjusting for the other delirium predictive models and COVID-19 severity (OR = 12.72, 95% CI = 2.11-76.86 for MPI-2 vs MPI-1, and OR = 33.44, 95% CI = 4.55-146.61 for MPI-3 vs MPI-1). The MPI showed good accuracy in predicting incident delirium (AUC = 0.71) also superior to AWOL tool, (AUC = 0.63) and Martinez model (AUC = 0.61) (p < 0.0001 for both comparisons). CONCLUSIONS: The MPI is a sensitive tool for early identification of older patients with incident delirium.

Which Comprehensive Geriatric Assessment (CGA) instruments are currently used in Germany: a survey.

BACKGROUND: The Comprehensive Geriatric Assessment (CGA) records geriatric syndromes in a standardized manner, allowing individualized treatment tailored to the patient's needs and resources. Its use has shown a beneficial effect on the functional outcome and survival of geriatric patients. A recently published German S1 guideline for level 2 CGA provides recommendations for the use of a broad variety of different assessment instruments for each geriatric syndrome. However, the actual use of assessment instruments in routine geriatric clinical practice and its consistency with the guideline and the current state of literature has not been investigated to date. METHODS: An online survey was developed by an expert group of geriatricians and sent to all licenced geriatricians (n = 569) within Germany. The survey included the following geriatric syndromes: motor function and self-help capability, cognition, depression, pain, dysphagia and nutrition, social status and comorbidity, pressure ulcers, language and speech, delirium, and frailty. Respondents were asked to report which geriatric assessment instruments are used to assess the respective syndromes. RESULTS: A total of 122 clinicians participated in the survey (response rate: 21%); after data cleaning, 76 data sets remained for analysis. All participants regularly used assessment instruments in the following categories: motor function, self-help capability, cognition, depression, and pain. The most frequently used instruments in these categories were the Timed Up and Go (TUG), the Barthel Index (BI), the Mini Mental State Examination (MMSE), the Geriatric Depression Scale (GDS), and the Visual Analogue Scale (VAS). Limited or heterogenous assessments are used in the following categories: delirium, frailty and social status. CONCLUSIONS: Our results show that the assessment of motor function, self-help capability, cognition, depression, pain, and dysphagia and nutrition is consistent with the recommendations of the S1 guideline for level 2 CGA. Instruments recommended for more frequent use include the Short Physical Performance Battery (SPPB), the Montreal Cognitive Assessment (MoCA), and the WHO-5 (depression). There is a particular need for standardized assessment of delirium, frailty and social status. The harmonization of assessment instruments throughout geriatric departments shall enable more effective treatment and prevention of age-related diseases and syndromes.

Focus on senescence: Clinical significance and practical applications.

The older population is increasing worldwide, and life expectancy is continuously rising, predominantly thanks to medical and technological progress. Healthspan refers to the number of years an individual can live in good health. From a gerontological viewpoint, the mission is to extend the life spent in good health, promoting well-being and minimizing the impact of aging-related diseases to slow the aging process. Biologically, aging is a malleable process characterized by an intra- and inter-individual heterogeneous and dynamic balance between accumulating damage and repair mechanisms. Cellular senescence is a key component of this process, with senescent cells accumulating in different tissues and organs, leading to aging and age-related disease susceptibility over time. Removing senescent cells from the body or slowing down the burden rate has been proposed as an efficient way to reduce age-dependent deterioration. In animal models, senotherapeutic molecules can extend life expectancy and lifespan by either senolytic or senomorphic activity. Much research shows that dietary and physical activity-driven lifestyle interventions protect against senescence. This narrative review aims to summarize the current knowledge on targeting senescent cells to reduce the risk of age-related disease in animal models and their translational potential for humans. We focused on studies that have examined the potential role of senotherapeutics in slowing the aging process and modifying age-related disease burdens. The review concludes with a general discussion of the mechanisms underlying this unique trajectory and its implications for future research.

Aging hallmarks, biomarkers, and clocks for personalized medicine: (re)positioning the limelight.

The rapidly increasing aging prevalence, complexity, and heterogeneity pose the scientific and medical communities in front of challenges. These are delivered by gaps between basic and translational research, as well as between clinical practice guidelines to improve survival and absence of evidence on personalized strategies to improve functions, wellbeing and quality of life. The triumphs of aging science sheding more and more light on mechanisms of aging as well as those of medical and technological progress to prolong life expectancy are clear. Currently, and in the next two to three decades, all efforts must be put in a closer interdisciplinary dialogue between biogerontologists and geriatricians to enable real-life measures of aging phenotypes to be used to uncover the physiological - and therefore translational - relevance of newly discovered aging clocks, biomarkers, and hallmarks.

Effectiveness of multi-professional educational interventions to train Comprehensive Geriatric Assessment (CGA) - a Systematic Review.

Introduction: As the world population ages, health and social care professionals are increasingly confronted with patients with chronic long-term conditions and multimorbidity, requiring an extensive assessment and integrated care management strategy. The aim of this paper was to systematically collect and assess evidence of interprofessional education and training strategies for Comprehensive Geriatric Assessment (CGA) to build a competent health workforce. Methods: A systematic review was conducted according to PRISMA guidelines and the databases Medline, CINAHL, Cochrane and Embase were searched for studies illustrating effectiveness of educational interventions for teaching and training CGA in an interprofessional context. Results: Based on 21 identified studies, a great variability and heterogeneity in duration, setting and design of the interventions was identified. Promising results were found in the domains analysed, ranging from knowledge and skills; practices and behaviour; patient health outcomes; attitudes and perceptions to collaboration and quality of care. Discussion: Education and training of transversal skills within a continuous learning approach is key to equip the health care workforce for successful CGA performance in an interprofessional environment. Conclusion: Further research in this field is recommended to strengthen the evidence-base towards development of a resilient and integrated health care workforce for an ageing population.

Effects of the Multicomponent Cognitive Training Program BrainProtect in Cognitively Healthy Adults: A Randomized Controlled Trial.

BACKGROUND: Cognitive integrity is a fundamental driver of health. The exact structure of strategies against cognitive impairment is still under debate. OBJECTIVE: To compare the short-term effects of a multicomponent cognitive training (BrainProtect) with those of general health counseling (GHC) on cognitive abilities and health-related quality of life (HRQoL) in healthy adults in Germany. METHODS: In this parallel randomized controlled trial (RCT), 132 eligible cognitively healthy adults (age ≥50 years, Beck Depression Inventory ≤9/63; Montreal Cognitive Assessment ≥26/30) were randomized to either GHC (N = 72) or to intervention with BrainProtect (intervention group, IG; N = 60). IG participants received 8 weekly sessions of 90 min of the group-based BrainProtect program focusing on executive functions, concentration, learning, perception, and imagination, plus nutritional and physical exercise units. Before and after intervention, all participants underwent neuropsychological testing and HRQoL evaluation, blinded for pretest. RESULTS: No significant training effect was observed for the primary endpoint of global cognition as assessed by CERAD-Plus-z Total Score (p = 0.113; ηp2 = 0.023). Improvements in several cognitive subtests were shown in the IG (N = 53) compared to the GHC (N = 62) without adverse events. Differences reached significance for verbal fluency (p = 0.021), visual memory (p = 0.013), visuo-constructive functions (p = 0.034), and HRQoL (p = 0.009). Significance was lost after adjustment, though several changes were clinically relevant. CONCLUSION: BrainProtect did not significantly impact global cognition in this RCT. Nevertheless, the results of some outcomes indicate clinically meaningful changes, so that a strengthening of the cognitive performance by BrainProtect cannot be excluded. Further studies with larger sample size are needed to confirm these findings.

On frailty and accelerated aging during SARS-Cov-2: senescence.

The COVID-19 pandemic is a burden for the worldwide healthcare systems. Whereas a clear age-dependent mortality can be observed, especially multimorbid and frail persons are at an increased risk. As bio-functional rather than calendrical age is in the meanwhile known to play a crucial role for COVID-19-related outcomes, aging-associated risk factors, overall prognosis and physiological age-related changes should be systematically considered for clinical decision-making. In this overview, we focus on cellular senescence as a major factor of biological aging, associated with organ dysfunction and increased inflammation (inflammaging).

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.

A Tailored Discharge Program Improves Frailty and Mood in Patients Undergoing Usual Rehabilitative Care: A Randomized Controlled Trial.

OBJECTIVE: To investigate whether a tailored intersectoral discharge program (TIDP) impacts on multidimensional frailty, rehospitalization days, and patient-related outcome measures in older in-patients undergoing acute care and usual rehabilitative care. DESIGN: Randomized controlled trial of TIDP vs usual rehabilitative care with a 6-month follow-up, 2019-2020, and historical control with a 6-month follow-up, 2016-2019. SETTING AND PARTICIPANTS: Geriatric co-managed internal medicine ward of a metropolitan university hospital. One hundred-twelve multimorbid patients older than age 60 years were consecutively assessed for eligibility and inclusion (age ≥60 years, multimorbidity, admitted for treatment of acute disease, at least 2 geriatric syndromes requiring usual rehabilitative care, and able to consent) and signed informed consent, with 110 recruited and randomized to either TIDP or usual rehabilitative care. At discharge, 104 patients were alive in the intention-to-treat group, the 6-month follow-up was completed for 91 patients. A historical control group of 468 patients was included for comparison. INTERVENTION: TIDP as intervention included contact with treating general practitioner to discuss the further treatment plan, a structured medical and lifestyle counseling to patients and caregivers at admission as well as a discharge program with internist, geriatrician, and general practitioner in shared decision making with patients. METHODS: Fifty-four patients underwent TIDP, 53 patients underwent usual rehabilitative care only. Rehospitalization days at follow-up as primary endpoint; multidimensional frailty and prognosis (Multidimensional Prognostic Index, Geriatric Depression Scale, Rosenberg Self-Esteem Scale, quality of life, falls, mortality, home care service need, and need of long-term care at 1-, 3- and 6-month follow-up as secondary endpoints. RESULTS: TIDP (median age 76.0 years, 56% female) showed significantly improved Multidimensional Prognostic Index scores at discharge compared with usual rehabilitative care (median age 78.5 years, 58% female) (0.43 vs 0.49, P = .011). Compared with usual rehabilitative care, TIDP improved self-confidence (Rosenberg Self-Esteem Scale 13.9 vs 12.4, P = .009) and mood (Geriatric Depression Scale 4 vs 5, P = .027) at follow-up. Compared with historical control (median age 77.0 years, 39 % female), usual rehabilitative care patients showed significantly lower rehospitalization rates (53% vs 70%, P = .002) and lower mortality rates (13% vs 32%, P < .001). CONCLUSIONS AND IMPLICATIONS: A feasible TIDP improves frailty and mood in advanced age. In older patients undergoing potentially disabling acute treatments, usual rehabilitative care significantly reduces rehospitalization rates. Therefore, implementing geriatric treatment in general is useful to improve outcomes in older in-patients and a tailored discharge program can further increase the benefit for this frail population.

Biomarkers of aging in real life: three questions on aging and the comprehensive geriatric assessment.

Measuring intrinsic, biological age is a central question in medicine, which scientists have been trying to answer for decades. Age manifests itself differently in different individuals, and chronological age often does not reflect such heterogeneity of health and function. We discuss here the value of measuring age and aging using the comprehensive geriatric assessment (CGA), cornerstone of geriatric medicine, and operationalized assessment tools for prognosis. Specifically, we review the benefits of employing the multidimensional prognostic index (MPI), which collects information about eight domains relevant for the global assessment of the older person (functional and cognitive status, nutrition, mobility and risk of pressure sores, multi-morbidity, polypharmacy, and co-habitation), in the evaluation of the functional status, and in the prediction of health outcomes for older adults. Further integration of biological markers of aging into multidimensional prognostic tools is warranted, as well as actions which could facilitate prognostic assessments for older persons in all healthcare settings.

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.

The prognostic fingerprint of quality of life in older inpatients : Relationship to geriatric syndromes' and resources' profile.

BACKGROUND: The Comprehensive Geriatric Assessment (CGA) provides essential information about older hospitalized patients but is either not systematically adopted or not adopted at all in clinical routine. As a consequence, critical factors influencing patients' trajectories, like personal resources (geriatric resources, GR), geriatric syndromes (GS), health-related quality of life (HRQoL) and multidimensional prognosis often escape routine diagnostics. OBJECTIVE: To investigate the association between HRQoL and GR/GS as well as its prognostic signature. MATERIAL AND METHODS: In this study 165 inpatients older than 65 years admitted to an internal medicine department of a German large metropolitan hospital were assessed by a CGA-based calculation of the multidimensional prognostic index (MPI). Ten different GR and 17 GS, as well as HRQoL were collected. After 3, 6 and 12 months the patients were followed-up by telephone. RESULTS: The HRQoL was associated with MPI (p < 0.001), number of GS (p < 0.001) and survival days after discharge (p = 0.008). Additionally, significant associations were found between HRQoL and number of GR (p < 0.001). GS displaying risk for physical dependence like instability (p < 0.001) and chronic pain (p = 0.007) and single GR/GS that influence patient's confidence like isolation (p < 0.001), depression (p < 0.001) and emotional resources (p = 0.002) were also associated with HRQoL. CONCLUSION: The HRQoL is significantly associated to specific risk and protective factor profiles of GR and GS. To improve quality of life, targeted, patient-centered diagnostics and treatment of GS as well as stabilization of GR should be encouraged in the management of older, multimorbid patients outside geriatric settings.

Atrial fibrillation: a geriatric perspective on the 2020 ESC guidelines.

BACKGROUND: The Task Force for the diagnosis and management of atrial fibrillation (AF) of the European Society of Cardiology (ESC) published in 2020 the updated Guidelines for the Diagnosis and Management of Atrial Fibrillation with the contribution of the European Heart Rhythm Association (EHRA) of the ESC and the European Association for Cardiothoracic Surgery (EACTS). METHODS AND RESULTS: In this narrative viewpoint, we approach AF from the perspective of aging medicine and try to provide the readers with information usually neglected in clinical routine, mainly due to the fact that while the large majority of AF patients in real life are older, frail and cognitively impaired, these are mostly excluded from clinical trials, and physicians' attitudes often prevail over standardized algorithms. CONCLUSIONS: On the basis of existing evidence, (1) opportunistic AF screening by pulse palpation or ECG rhythm strip is cost-effective, and (2) whereas advanced chronological age by itself is not a contraindication to AF treatment, a Comprehensive Geriatric Assessment (CGA) including frailty, cognitive impairment, falls and bleeding risk may assist in clinical decision making to provide the best individualized treatment.