Relationship Between Endothelial Function, Vital Parameters, and Cognitive Performance in Community Dwellers with Subjective Cognitive Decline: An Observational Study with Six Months Follow Up.

Background: With advancing age, cognitive decline is frequently associated with endothelial dysfunction, but data on vascular performance prior to the onset of mild cognitive impairment (MCI) is scarce. Objective: To investigate the relationship between endothelial function, vital parameters and cognitive performance in older adults with subjective cognitive decline (SCD). Methods: Forty-five volunteers aged 65 years and older with SCD underwent comprehensive geriatric assessment-based prognosis evaluation by means of the Multidimensional Prognostic Index (MPI), full neuropsychological examination and peripheral arterial tonometry measurement by means of EndoPAT™2000 to evaluate endothelial flexibility and vital parameters. Six months after initial evaluation, participants were contacted by phone and a telephone-administered version of the MPI (TELE-MPI) was conducted. Results: Fifteen study participants scored below the cutoff score of 26 on the Montreal Cognitive Assessment, suggesting MCI (26.56±2.23). Nominal significant correlations were found between heart rate (HR) and trail making test (TMT) A (ß= -0.49, p = 0.03), between heart rate variability (HRV) and TMT B (ß= 0.78, p = 0.041), between power of low-frequency band (LF) HRV and Mini Nutritional Assessment-Short Form (ß= 0.007, p = 0.037) as well as between augmentation index (AI) and CogState Detection Test (ß= 0.002, p = 0.034). Conclusions: HR, HRV, and AI, but not endothelial flexibility are associated with cognitive performance in SCD and suspected MCI patients and may serve as clinical biomarkers in the early diagnosis of neurodegenerative disorders with advancing age.

Geroscience in the continuum from healthy longevity to frailty.

The socioeconomic and technological developments of the past decades have enabled unique progress associated to increased life expectancy and better health for a large part of the world's population; however, multimorbidity, frailty and disability are also on the rise. Geroscience as the new biology of aging is based on the evidence that the main risk factor for noncommunicable chronic diseases (NCD) is the aging process; however, its technology is mostly used for the scientific study of longevity and its interaction with aging medicine and geriatrics is still limited. In this perspective, the need for a tighter exchange between geroscience and geriatrics for longer health span and intrinsic capacity is discussed in the context of existing evidence and knowledge gaps.

Long-Term Effects of the Multicomponent Program BrainProtect® on Cognitive Function: One-Year Follow-Up in Healthy Adults.

Background: Age-related neuronal changes impact cognitive integrity, which is a major contributor to health and quality of life. The best strategy to prevent cognitive decline and Alzheimer's disease is still debated. Objective: To investigate the long-term effects of the eight-week multicomponent training program BrainProtect® on cognitive abilities compared to general health counseling (GHC) in cognitively healthy adults in Germany. Methods: Healthy adults (age ≥50 years) previously randomized to either GHC (n = 72) or BrainProtect (intervention group, IG, n = 60) for eight-weeks (once weekly, 90 minutes, group-based) underwent a comprehensive neuropsychological test battery and health-related quality of life (HRQoL) evaluation 3- and 12-months after intervention end. Results: Dropout rates were n = 8 after 3 months and n = 19 after 12 months. No significant long-term effect of BrainProtect was observed for the primary endpoint Consortium to Establish a Registry for Alzheimer's Disease (CERAD-Plus) total score. Logical reasoning was significantly improved (p = 0.024) 12 months after completion of the training program in IG participants compared to the GHC group independent of sex, age, education, diet, and physical activity. In IG participants, thinking flexibility (p = 0.019) and confrontational naming (p = 0.010) were improved 3 months after completing the intervention compared to the GHC group, however, after conservative Bonferroni adjustment, significance was lost. Conclusions: BrainProtect® independently improved logical reasoning compared to GHC up to 12 months after cognitive training's end in healthy adults. To uncover the long-term clinical significance of multicomponent cognitive training in healthy adults, studies with larger sample size and frequent follow up visits are necessary.

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.

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.

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.

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.

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.