Prof. Dr. M. Cristina Polidori

During the demographic explosion, the baby-boomer generation is delivering the so-called “silver tsunami”, i.e. several millions old-old (75+) and most of all oldest-old (85+) persons which compose the large majority of healthcare users. Pathological processes have a major impact on the rate and character of organ changes with age that may not be easy to distinguish from “physiological aging”. Aging is not only a heterogeneous process in which age-related changes occur in a continuum from organ integrity to pathology; it is also a complex process mainly characterized by multifactoriality. A complex patient is defined as “one for whom clinical decision-making and required care processes are not routine or standard”. Any event or condition that negatively affects life trajectories of older persons, including medical, social and psychological wellbeing, contributes to enhancing complexity. From the demographic perspective, the world population is not only aged, but it is also increasingly suffering from multimorbidity and related disability.

With the dramatic increase of the older multimorbid population the organ-centered approach based upon the algorithm “one-cause-one-mechanism-one-therapy” is being strongly challenged. The recent advances of medicine have contributed to the development of Geroscience, a branch of biogerontology specifically addressing the fact that, if the main risk factor for age-related diseases is aging, the study of age-related changes will likely disclose important pathways of intervention on several diseases of advanced age. The increasing amount of evidence arising from Geroscience is going to be more and more decisive to guide healthcare advances for the rapidly growing older vulnerable population.    

Professor Polidori’s team works within the frame of the strong conceptual link between Geroscience and Geriatrics and focuses on the medicine of the aged person taking into account (1). multiple age-related biomolecular changes as well as (2). age-related changes in domains of the person beyond organs which highly impact on the success of recovery and intervention plans:

1. Age-related biomolecular changes predisposing to age-related diseases include energy imbalance, system homeostenosis, alterations of redox signaling and regulation, oxidative stress and mitochondrial dysfunction, DNA damage and repair mechanisms, telomere functioning, brain nutrient sensing, altered protein aggregation, inflammation, nitric oxide-mediated cascades, metabolic cascades. Aging science is rapidly improving through the  search for biomarkers of biological versus chronological age on the one hand and through  Geroscience, on the other hand. The best clinical decision algorithm for multimorbid older subjects might not be used adequately or properly recognized if information on ongoing biomolecular alterations such as senescence, hidden malnutrition, oxidative (eu)stress, or impaired adaptive response lack.
    
2. In order to perform value-based, goal-oriented, patient-centered medicine, a solid knowledge set of the multifactorial biomolecular basis of aging mediates the rationale for a multidimensional approach to the older frail and ill person. Insight to multifactoriality strongly supports understanding of challenges related to complexity and of necessity to therapy adaptation including no-treatment. In this sense, shared decision making based on prognosis and most adequate alternatives for best possible quality of life is key for contemporary medicine. The Comprehensive Geriatric Assessment (CGA) is a multidimensional, interdisciplinary diagnostic process focused on determining the medical, psychological and functional capabilities of older persons. The ultimate goal of the CGA is to develope a coordinated and integrated plan for treatment and long-term follow up. Due to its efficacy in addressing multiple domains of health, the CGA is the tool of choice to determine the clinical profile, pathological risk and skills / resources to shape a personalized therapeutic and care plan through shared decision making. CGA-based interventions have been clearly shown to improve clinical outcomes of older hospitalized patients. Nevertheless, the multidimensional, personalized approach to the older adults still lacks systematic implementation in the healthcare routine.

Our research: The Aging Clinical Research established in 2015 at the Dpt. II of Internal Medicine at the University Hospital of Cologne focuses on two main fields of research: 1) Early recognition of frailty, in particular cognitive frailty, and intrinsic capacity in older adults through the personalized multidimensional approach including biomolecular signatures; 2) Evaluation of multidimensional personal prognosis across healthcare settings to establish key performance indicators and shared decisional algorithms in age-related diseases.    

Field of Research #1, The personalized multidimensional approach with advancing age.

Professor Polidori’s group investigates the challenges of diagnosing and managing older adults with complex multidimensional  problems—medical, mental, and socioeconomic. On the other hand, not only older persons can be healthy and vital, constitute a resource for human wisdom and evolution, but they want  to stay healthy as long as possible independent of their chronologic age. One of the main priorities of the group is to explore the factors – biological, physical, and psychosocial – that maintain the so-called intrinsic capacity of the aging person. Finally, a third critical, challenging feature of a large part of the upcoming older population —not really vital, not really ill—is that they do not fall within the frame of a specific disease-associated algorithm; therefore, they are not easy to identify. This is also due to the lack of “age-attuned” medical thinking and language. The group explores ways to identify older persons with diminished organ reserve and increased susceptibility to system failure, which are defined frail and benefit extremely from age-attuned medical multidimensional interdisciplinary management. Frailty, as the field of action of geriatrics, is not only multifactorial, but is a dynamic process which is reversible if adequately managed. Therefore, its identification is mandatory in the population. To address these three components of the older population – multidimensional management, intrinsic capacity, frailty - persons are evaluated through the cornerstone of geriatric medicine, the Comprehensive Geriatric Assessment (CGA), and in particular with one tool which constitutes its development, i.e. the Multidimensional Prognostic Index (MPI).

Field of Research # 2, Age-related cognitive decline and its prevention through lifestyle: nutritional cognitive neuroscience and multidomain interventions.

Being cognitive decline in advanced age a multifactorial condition strikingly resembling the aging process itself, the group focuses on its systematic assessment by means of the CGA as well as on the effect of vascular risk control and lifestyle interventions including physical exercise, adherence to the Mediterranean Diet and cognitive training. Particular attention is given in this context to the role of circulating antioxidant micronutrients like tocopherols and carotenoids as mediators of protection and defense against age-related increased free radical production, a key pathophysiological mechanism of changes and dysfunctions occurring in advanced age.

Our successes: We dedicate much attention

(1). to providing MD students with the necessary gerontologic and geriatric competencies and skills to expect, recognize and adequately manage older prefrail and frail adults;
(2). to handing over residents in Geriatrics as well as health nonmedical professionals such as physiotherapists, occupational therapists, neuropsychologists and geriatric nurses an adequate training and knowledge to report relevant risks and occurrence of geriatric cascades and syndromes; (3). to offering the geriatric team but most of all the frail multimorbid person the best available clinical practice in all its value-based, goal-oriented, patient-centered features.

We were able to show that

1. a person-centered, goal-oriented care pursued by carrying out a CGA-based multidimensional personal prognosis discloses factors profoundly impacting patients‘ trajectories. The MPI allowed the identification of prognostic factors beyond organ medicine susceptible of modification through tailored interventions across several healthcare settings. Over 1200 older multimorbid patients were comprehensively assessed in internal medicine wards, geriatric hospitals, general practices, emergency department, intensive care units and nursing homes at the University Hospital of Cologne and in the Cologne region; the results of the observations were object of several peer-reviewed publications, presentations at national and international conferences, and research awards (including the 2018 Price for interdisciplinary Aging Research of the German Geriatrics Society and the 2020 Award of the Wilhelm Woort Foundation) and are the basis for ongoing international projects. The personalized approach to vulnerable patients and the attention dedicated during the past recent years to their quality of life obtained much attention and was one driver of the establishment of the recently grounded ward Universitäre Altersmedizin at the University Hospital of Cologne.
2. Specific blood micronutrient profiles are not only associated to successful aging and individual age-related diseases, but are also correlated to particular functional and performance motoric and cognitive tests in cognitive decline. These results are object of active research and led to several publications, presentations, research awards including the Catherine Pasquier Award of the Society for Free Radical Research Europe, the Schiffbauer Prize of the German Geriatrics Society and the Honorary Fellowship of the Royal College of Physicians.

Our goals: Future Directions of Research: Filling three Gaps

Geriatric medicine, among all existing medical disciplines, is the one most evidently struggling with the challenges of high-performance medicine in advanced age. Medical actions taking little or no account of aging physiology, decreased organ reserve, and increased vulnerability display a broad spectrum of iatrogenic implications – with iatrogenic complications being in fact one of the most prominent geriatric syndromes. In 2015, the official journal of the Royal College of Physicians of London, Clinical Science, dedicated its cover to the threat of „hospitals on the edge“ and called for actions and for setting higher standards. This threat is highly underlined by the forecast of a silver-tsunami-driven massive increase in hospitalizations inducing to ask policy makers for substantial investments in good alternatives. These alternatives, as mentioned above, are focus of geriatric medicine and research since several decades. The evidence-based efficient alternative to usual care leading to “hospitals on the edge” and poor quality of life of the older patient is the adequate, structured, systematic use of the CGA and related tools.

Goal #1. Filling the „know-do gap“, which represents the not yet filled distance between the evidence of the benefit of the multidimensional, CGA-based personalized approach to the older person and the CGA implementation in the clinical routine. Two additional related gaps in aging medicine are 1) that between steadily increasing life expectancy and slow-paced improvements in healthcare actions; this gap will be most likely filled by a “geriatric imperative” approach which has not been implemented adequately yet; and 2) the gap between aging science and geriatrics, for which each one of the two go in more and more distant directions (single-mechanism biomedical research on one side and healthcare research on the other side);

Goal #2. This latter gap will be most likely filled by increasing awareness of the fact that advanced age is the major risk factor for age-related diseases and therefore understanding the pathophysiology of aging is key for the management of older vulnerable adults. To achieve this goal, we are conducting and planning studies investigating the biomolecular profiles of age-related changes according to CGA-based multidimensional prognosis of older multimorbid patients.

Our methods/techniques: The MPI bases upon 8 scales exploring the psychosocial, physical, and functional domains of the patient. It represents a further evolution of the CGA, as the CGA scores are embedded in a mathematical algorithm delivering a continuous value from 0 to 1 where 0 indicates lowest and 1 highest chance to experience a negative outcome within one year after the evaluation. Our prospective studies are based upon the rigorous comprehensive evaluation of our older multimorbid patients admitted to different healthcare settings and their close monitoring during hospitalization. For the studies on nutritional cognitive neuroscience and lifestyle, we measure micronutrients and other biomarkers in blood of patients with cognitive impairment while carefully assessing several lifestyle variables including nutrition, physical exercise, cognitive activity among others.