Appetite decline in ageing and the link to worsening health

Appetite decline in ageing is well documented with increasing observational evidence linking poor appetite in older people to undernutrition, sarcopenia, frailty and disability^{(Reference Schilp, Wijnhoven and Deeg17–Reference Landi, Russo and Liperoti21)}. Thus, a focus on appetite may prove to be effective in the prevention and management of these conditions.

Appetite decline is common in later life, affecting 1 in 5 older community dwellers, with rates higher in long-term and acute care settings^{(Reference Malafarina, Uriz-Otano and Gil-Guerrero22)}. Secondary decline in appetite due to prevalent clinical causes in the older population is well recognised^{(Reference Cox, Morrison and Ibrahim23)}. These include chronic disease such as renal failure and heart failure, as well as high rates of malignancy. However, primary appetite decline related to the process of ageing itself, often termed the anorexia of ageing, has also been long acknowledged^{(Reference Morley and Silver24)}. Underlying drivers of primary appetite decline in ageing incorporate alterations in (1) physiological mechanisms of energy balance homeostasis, (2) reward-based eating behaviours and (3) wider socio-environmental cues related to eating (See^{(Reference Cox, Morrison and Ibrahim23,Reference Walker-Clarke, Walasek and Meyer25–Reference Chia, Yeager and Egan28)} for recent reviews on mechanisms of appetite decline in ageing), as well as an emerging role for age-related inflammation^{(Reference Sánchez-Sánchez, Guyonnet and Lucas29,Reference Pourhassan, Babel and Sieske30)} . These alterations act to produce reductions in hunger or desire to eat and increase feelings of satiety.

Observational studies have highlighted the predictive relationship between poor appetite and undernutrition^{(Reference Schilp, Wijnhoven and Deeg17)}. Proposed pathways of causality include an adverse shift in dietary choices and overall intake, following observations in older populations with poor appetite^{(Reference van der Meij, Wijnhoven and Lee31,Reference Scheufele, Rappl and Visser32)} . However, the emerging role of age-associated chronic inflammation in appetite decline^{(Reference Sánchez-Sánchez, Guyonnet and Lucas29,Reference Pourhassan, Babel and Sieske30)} , observed differences in the composition of the gut microbiome that are independent of diet in older adults with poor appetite^{(Reference Cox, Bowyer and Ni Lochlainn33)}, as well as the presence of healthy older adults reporting appetite decline^{(Reference Giezenaar, Chapman and Luscombe-Marsh34)}, indicate a more complex relationship between appetite decline and undernutrition.

Although an established pathway of causality between appetite decline in ageing and undernutrition is not yet fully elucidated, appetite remains a suitable focus. This is because appetite is a meaningful concept to older people and hence easily explored during clinical encounters. In addition, discussing appetite decline does not require conversations about weight or presence of weight loss, a topic that is challenging to address on the background of societal and potentially personal weight bias beliefs⁽³⁵⁾. Thus, alongside its predictive ability, appetite decline has real utility in being investigated to identify those at risk. It is also a key consideration when designing meaningful interventions for undernutrition, as they ultimately require the older person to meet their nutritional requirements often by increasing food intake. By acknowledging and mitigating appetite decline as part of the design of an intervention, it is then more likely to be relevant and acceptable to older people.

Limitations to the current evidence for managing appetite decline in ageing

Management approaches to alleviate appetite decline are key for both prevention and treatment of undernutrition in the older population. The current evidence for managing appetite decline with ageing has been summarised in recent systematic reviews^{(Reference Cox, Ibrahim and Sayer36–Reference Hubner, Boron and Koehler41)}. These reviews have identified that few trials have been conducted focussing on appetite decline in ageing (with the number of included studies ranging from 4 to 20); other trials have subsequently reported adding to this small evidence base^{(Reference Nielsen, Bornæs and Christensen42,Reference Fluitman, Wijdeveld and Davids43)} .

Amongst the few trials that have been conducted on older people, a highly diverse range of interventions for appetite decline have been studied. These comprise of nutritional supplementation in the form of food fortification or oral nutritional supplements (ONS), flavour enhancement of food through sauces, condiments and seasoning. Mealtime assistance by volunteers, nutritional educational counselling delivered by a clinical nutritionist and a dietary advice booklet have also been tested. In addition, orexigenic medications used in other populations have been assessed, including megestrol acetate (a synthetic progestogen used in cancer and acquired immunodeficiency syndrome (AIDS)-associated cachexia), dronabinol (a synthetic tetrahydrocannabinol) and other cannabinoids and anti-depressants (including mirtazapine, amitriptyline and duloxetine). Finally, exercise or physical activity (including strength and resistance training, mixed exercise, moderate physical activity, aerobic exercise and cycling) have also been examined in trials^{(Reference Cox, Ibrahim and Sayer36–Reference Hubner, Boron and Koehler41)}.

Alongside the wide range of interventions, sample sizes of trials for appetite decline in ageing are modest (ranging from n 12 to n 185 when reported) and encompass diverse populations of older adults (also defined as aged 60 or 65 years and older in the reviews), with own-home and long-term care community dwellers and acute care and rehabilitation inpatients all represented^{(Reference Cox, Ibrahim and Sayer36–Reference Hubner, Boron and Koehler41)}. Studies also defined the population of interest in different ways ranging from healthy older adults to older adults with diagnosed malnutrition^{(Reference Cox, Ibrahim and Sayer36)}. In addition, intervention effectiveness for appetite decline has been investigated through a range of primary outcome measures, adding to the heterogeneity. Outcome measures include subjective measures of appetite (predominantly through Likert or visual analogue scales (VAS)), gut hormone levels involved in appetite regulation, energy intake, weight change, BMI and nutritional risk scoring through different methods. Recent work by Courtney et al. ^{(Reference Courtney, Fitzpatrick and Volkert44)}, has scoped the different approaches to appetite assessment in community-dwelling older adults, identifying 30 different methods using Likert, VAS or questions. VAS were most robust for measuring appetite in controlled settings, with Likert methods such as the Simplified Nutritional Appetite Questionnaire (SNAQ) used with greatest frequency and predictive ability for health outcomes. They conclude that different appetite assessment methods are likely to be suitable depending on the study but further work is required to standardise methods and terminology to determine which of these approaches has greatest validity^{(Reference Courtney, Fitzpatrick and Volkert44)}.

The systematic reviews on interventions for appetite decline have consistently observed mixed effects on appetite and related outcomes but importantly with no reproducibility of results across studies^{(Reference Cox, Ibrahim and Sayer36–Reference Hubner, Boron and Koehler41)}. Therefore, no meaningful and clinically translatable conclusions can be drawn and overall, there are significant limitations within the current evidence base. These limitations comprise of the overall paucity of trials in this area as well as the heterogeneity of the outcome measure, intervention type and the older populations studied. Notably, appetite decline in ageing has largely been studied as a part of undernutrition rather than a distinct entity (albeit with overlapping elements), reflected by the measures used to define appetite but also to assess efficacy.

Appetite decline in ageing as a geriatric syndrome

True progress on management strategies for appetite decline in ageing have been hampered by a lack of distinction from undernutrition and heterogeneity in the intervention type, populations studied and outcome measures, but also perhaps by the approach to it as a concept. The diverse, individualised and complex mechanisms that underpin appetite decline in ageing make management challenging but indicate value in categorising it as a geriatric syndrome^{(Reference Morley45,Reference Cox and Lim46)} .

The recognition and management of geriatric syndromes are a key pillar of geriatric medicine. Well-described examples of geriatric syndromes include frailty, falls and gait instability, delirium and cognitive impairment and incontinence. The presence of a geriatric syndrome is predictive of poor outcomes including loss of independence and institutionalisation, hospitalisation and mortality^{(Reference Bell, Vasilevskis and Saraf47)}. The term syndrome refers to the ‘concurrence of several symptoms in a disease’⁽⁴⁸⁾, but it is important to note that geriatric syndromes are a distinct entity from other ‘traditional’ medical syndromes. The latter encompass symptomology that indicate disruption of a specific organ, physiological or psychological process. In comparison, a geriatric syndrome, while again displaying symptomology, is instead related to disruption of multiple physiological or psychological processes and various body systems^{(Reference Flacker49)}. These disruptions can accumulate over time until a point when the body’s ability to compensate is lost with a decline in function, which may be triggered by a new insult such as an infection. The symptomology of geriatric syndromes can also cluster into different phenotypes (observable characteristics), for example delirium can display as hypoactive, hyperactive and mixed phenotypes.

Perceived as a geriatric syndrome, the mechanisms of appetite decline could be described as an accumulation of deficits in the gastro-intestinal, neurological and endocrine systems relating to energy-balance homeostasis, an emerging role for disruption in immune response, deficits in sensation and psychological processing of food and eating-related behaviours, as well as wider deficits in the person’s social and environmental support structures. This aligns with descriptions by older people, who can recall a poor appetite that has developed over some time^{(Reference Cox, Morrison and Robinson50)}. In addition, experiences of appetite decline appear to differ, with descriptions of a disinterest in food and eating v. excessive feelings of satiety, which again fits with the clustering of geriatric syndromes into phenotypes^{(Reference Cox, Morrison and Robinson50)}.

Defining appetite decline in ageing as a geriatric syndrome may enable an improved understanding of the phenomenon and importantly, acknowledge its complexity, as well as creating a framework to progress research and management strategies to combat it. This framework would be holistic and underpinned by the gold standard clinical management of geriatric syndromes – Comprehensive Geriatric Assessment.

Comprehensive geriatric assessment

Comprehensive Geriatric Assessment (CGA) is a multidisciplinary assessment approach of an older person^{(Reference Pilotto, Cella and Pilotto51)}, which identifies issues of concern across physical, functional, psychological, social and environmental domains and synthesises these assessments to develop a person-centred management plan to optimise health and wellbeing in later life^{(Reference Pilotto, Cella and Pilotto51)}. The foundations of the CGA were first developed in the 1930s by Dr Marjory Warren, a pioneering geriatrician in the UK, who advocated for a whole-patient approach to older adults with an emphasis on social and environmental factors alongside medical management^{(Reference Matthews52)}. CGA has since become a cornerstone of geriatric medicine and has expanded its domains including assessment of nutritional status as a core part of the physical needs assessment of the CGA^{(Reference DiMaria-Ghalili53)}.

There is currently no standardised approach to assessing nutrition within the framework of a CGA. The British Geriatrics Society (BGS) recommends a multifocal approach when addressing undernutrition in frailty including considering appetite, fluid intake, polypharmacy, sensory loss, oral and gastrointestinal health, dysphagia, functional status and socioeconomic background⁽⁵⁴⁾. Additionally, the BGS recommends using resources to support nutritional assessment and intervention including British Dietetic Association guidance and the European Society for Clinical Nutrition and Metabolism (ESPEN) guideline on nutrition and hydration in geriatrics^{(54–Reference Volkert, Beck and Cederholm56)}.

Nutritional assessment within a CGA can vary in depth depending on the expertise of the assessors but can include use of validated assessment tools such as the Mini Nutritional Assessment, a full dietetic history, anthropometric assessment, body composition analysis, biochemical assessment and functional assessments^{(Reference Camina-Martín, de Mateo-Silleras and Malafarina57,Reference Loreck, Chimakurthi and Steinle58)} .

As CGA is by design a multidisciplinary assessment, it should be utilised by professionals across the breadth of the multidisciplinary team, including dietitians^{(Reference DiMaria-Ghalili53,Reference Ueshima, Maeda and Wakabayashi59)} . Whilst there is no specific UK guidance recommending when dietetic input should be considered within a CGA, there is evidence dietitian involvement in multidisciplinary assessment of older adults can improve outcomes including mortality and quality of life^{(Reference Rasmussen, Belqaid and Lugnet60)}.

The CGA can be deployed in all settings including patient homes, residential care facilities, hospital inpatient wards and outpatient clinics^{(Reference Pilotto, Cella and Pilotto51)}. CGA can be used both reactively, to address urgent care needs in response to an acute event, and proactively, as a preventative approach when an older person is not unwell^{(Reference Pilotto, Aprile and Veronese61)}.

CGA is recommended as the gold standard approach for the management of geriatric syndromes by key UK clinical and policy stakeholders involved in the health and care of older people, including the BGS, Age UK and the Royal College of General Practitioners^{(Reference Turner and Clegg62)}. The approach improves outcomes for older adults in both hospital and community settings^{(Reference Briggs, McDonough and Ellis63–Reference Veronese, Custodero and Demurtas65)}. Patients managed with CGA are more likely to remain alive and in their own homes for longer, less likely to experience deterioration following hospital admission, and more likely to experience improved cognition and physical function^{(Reference Ellis, Whitehead and Robinson66)}. It is important to note that the positive impact comes from the whole assessment approach, rather than optimisation of a single domain, emphasising the importance of holistic care for older people.

In relation to appetite decline, CGA enables a thorough assessment of the multiple contributory factors and the development of an individualised management plan which is person-centred. Working through the holistic domains of the GCA could identify physical factors such as diagnosis of chronic disease, swallow disorder or poor dentition, psychological factors including low mood, social factors such as isolation and loneliness or environmental factors such as a transition into long-term care, which can impact upon appetite^{(Reference Cox, Morrison and Ibrahim23)}. However, a barrier to the development of a multifaceted management plan in the current clinical setting is the paucity of robust evidence on optimal approaches to manage these known factors, alongside a full understanding of the underlying mechanisms that fundamentally drive appetite decline in ageing, how they may inter-relate and hence how we can optimally intervene.

Research implications of viewing appetite decline in ageing as a geriatric syndrome

Viewing appetite decline in ageing as a geriatric syndrome could provide an avenue to progress much-needed research in the area and allow acknowledgement of its complexity. However, this requires novel approaches to research.

The traditional linear model of research into disease has led to huge advances in medicine, providing greater understanding of genetic predisposition and disease progression through early and late stages. This approach works well in diseases of single organs or systems with intervention targets along the stages of disease progress. Alternatively, research models that emphasise the presence of multiple factors and mechanisms contributing to a disease have also enabled development of comprehensive multi-component interventions with subsequent treatment progress. However, these approaches are not optimal for geriatric syndromes^{(Reference Inouye, Studenski and Tinetti67)}. With the former, they may risk oversimplification by placing efforts on only one aspect of a complex phenomenon which is unlikely to yield effective intervention outcomes^{(Reference Inouye, Studenski and Tinetti67)}. Or they risk unfocussed understanding and then development of exhaustive multi-component treatments that are overly burdensome for older people if the latter approach is taken^{(Reference Inouye, Studenski and Tinetti67)}.

Inouye and colleagues^{(Reference Inouye, Studenski and Tinetti67)} have suggested a modification to the research approach of identifying and managing all the underlying mechanisms or risk factors associated with disease, while still acknowledging the complexity of geriatric syndromes. They have termed this approach the interactive concentric model. This model emphasises that the potentially overwhelming number of risk factors and mechanisms that contribute to deficits within geriatric syndromes may interact and work in a synergistic manner. They argue that by focussing on synergy within mechanistic research and intervention design, there is likely to be optimisation of management^{(Reference Inouye, Studenski and Tinetti67)}. This approach appears most likely to generate clinically translatable evidence for appetite decline as a geriatric syndrome, as it will identify synergistic targets that will yield greater efficacy and clinical use, as well as reducing burden to ensure interventions are acceptable to older people.

Future directions - research and management of appetite decline in ageing to optimise management of undernutrition

A focus on decline in appetite is key if we are to enhance both the prevention and optimal management of undernutrition, frailty and sarcopenia in the older population. Not only due to its role in the development of these conditions but also the way it impacts on treatment delivery and compliance. However, there is currently scarce translatable evidence for effective interventions to manage appetite decline in the older population.

To enable progress in the field, current efforts should be directed to different aspects of research on appetite decline in ageing. Firstly, consensus on the definition criteria of appetite decline and standardised methods to its assessment. Achieving this would firstly enable pooling of results and highlight potential areas of mechanistic synergy to focus efforts for targeted intervention. Secondly, it would enable unification of terminology in both research and clinical fields allowing enhanced communication and translation of findings into clinical practice. This would further benefit from framing appetite decline in ageing as a geriatric syndrome, with intervention design underpinned by the principles of CGA, as this terminology is relevant and meaningful to clinicians who work in the health and care of older people.

There is also a great need for progress in mechanistic research for appetite decline in ageing and how underlying drivers may work synergistically in pathways of causality. This sound evidence base is crucial to intervention development but also to identify characteristics which place certain individuals at greater risk of poor health outcomes, so interventions can be optimally applied to the correct people. This is particularly important given that declines in appetite are observed within healthy older adults^{(Reference Giezenaar, Chapman and Luscombe-Marsh34)}.

Moving forward, unifying the approach to appetite decline in ageing underpinned by the principles of geriatric syndromes and structured by CGA may prove an effective strategy to optimise early detection and treatment of the grand challenge of undernutrition in older people.