The paradox of aging, that is, improved mental well-being despite diminished physical and cognitive capacities, is particularly evident in those aging with mental illness (Jeste et al., Reference Jeste, Wolkowitz and Palmer2011). For many older adults, psychiatric symptoms are not the primary cause of impairment in function and quality of life, and efforts to address accelerated biological aging in mental illnesses are critical for geriatric psychiatry care. Frailty has recently been proposed for psychiatry as a clinical measure of biological age (Bersani et al., Reference Bersani2020). Frailty is a multidimensional construct that broadly refers to a state of increased vulnerability to stressors and can be described along a continuum of functional capacity, from robust at one end to experiencing disability in basic activities of daily living at the other (Dent et al., Reference Dent2019). The two most common constructs used to assess frailty are the physical phenotype, originally characterized by Fried et al. (Reference Fried2001), that includes assessing five items—unintentional weight loss, exhaustion, weakness, slow walking speed, and low levels of physical activity; and the deficit accumulation model or Frailty Index, originally proposed by Rockwood et al. (Reference Rockwood, Stadnyk, MacKnight, McDowell, Hébert and Hogan1999), that characterizes frailty on the basis of an accumulation of health conditions and deficits. Frailty is a leading contributor to functional decline and early mortality in the general aging population. However, at a prevalence of roughly 10-11% of adults over 65 years (Collard et al., Reference Collard, Boter, Schoevers and Oude Voshaar2012), frailty is not an obligatory consequence of aging and many individuals may continue to be robust into old age.
While frailty is an area of current focus in geriatric medicine, its etiology is still subject to debate, and it is less well recognized in geriatric psychiatry. In this issue of IPG, Aprahamian et al. (Reference Aprahamian2020) assessed physical frailty of geriatric psychiatry inpatients aged 65+ years using the FRAIL scale (an approximation of the physical phenotype) and the Frailty Index. They found that 55.3% of the sample was frail according to the physical phenotype and 83.6% according to the Frailty Index. These numbers are striking compared to the general aging population. There are several reasons why frailty may be disproportionally represented in older adults aging with mental illness. Long-term risk factors for frailty include overweight/obesity, physical inactivity, cardiovascular risk, poor self-rated health, and alcohol use (Dent et al., Reference Dent2019)—risk factors that are known to commonly occur in those with mental illness. Somatic comorbidities associated with these poor lifestyle behaviors are high in older adults with mental illnesses and are responsible for a large mortality gap compared to the general aging population. Though frailty and multimorbidity are mutually inclusive, they are considered separate constructs, with the proportion of community-dwelling older adults presenting both conditions around 6%, and approximately 42% of those with multimorbidity still considered “robust” (Vetrano et al., Reference Vetrano2019). Thus, it is unlikely that frailty is purely the result of the high multimorbidity in those aging with mental illness.
Frailty prevalence is also elevated in populations with less education, low socioeconomic position, and ethnic minority groups, which aligns with the well-known socioeconomic disparity associated with mental illnesses. Many of these factors relate to the living environment, which is now being recognized as a determinant of the Healthspan. Byrne et al. (Reference Byrne, Prvu Bettger, Brusilovskiy, Wong, Metraux and Salzer2013) found that the concentration of persons with serious mental illness within a neighborhood’s adult population was associated with higher levels of physical and structural inadequacy, crime, drug-related activity, social instability, and social isolation. Such factors may reduce the life space and limit community participation and social interactions. In addition, behavioral phenomena commonly associated with mental illnesses, such as physical anergia, avolition, and apathy, further impact the activities in which an individual chooses to participate. While these behavioral symptoms share overlap with some diagnostic criteria of the DSM-5, this does not necessarily invalidate them as risk factors for frailty. Apathy has been independently associated with the development of frailty in community-dwelling older adults (Ayers et al., Reference Ayers, Shapiro, Holtzer, Barzilai, Milman and Verghese2017), and exhaustion is often one of the initial manifestations of frailty criteria. It is plausible that lifestyles characterized by these environmental constraints and behavioral antecedents result in phenotypic rigidity versus adaptability of those with mental illnesses, which in turn predisposes these individuals to becoming frail.
Other groups in addition to Aprahamian et al. (Reference Aprahamian2020) have demonstrated the importance of assessing frailty in geriatric psychiatry inpatient settings. Stolz et al. (Reference Stolz, Rásky and Jagsch2020) found that geriatric psychiatry inpatients classified as frail had a 21% increased probability of in-hospital mortality and subsequently suggested implementation of a routine assessment of frailty based on a comprehensive geriatric assessment. Benraad et al. (Reference Benraad2020a) observed that frailty predicted unfavorable discharge destination following psychiatric hospital admission. In a separate publication, Benraad et al. (Reference Benraad2020b) further demonstrated that frailty independently predicted mortality in older adults within 5 years of psychiatric hospital admission. The presence of frailty is not restricted to psychiatric inpatients; Andrew and Rockwood (Reference Andrew and Rockwood2007) found that psychiatric illness was associated with a much higher odds of being physically frail in a large sample of community dwellers without dementia within the Canadian Study of Health and Aging. More recently, Tsai et al. (Reference Tsai, Lee, Chen and Wu2018) observed a 10.2% prevalence of frailty in adults with chronic schizophrenia and that frailty was further associated with an increased risk of falling. Of particular importance was that the mean age in this sample was only 53.8 years, suggesting that frailty may disproportionally affect younger adults with mental illness. This finding warrants further investigation, but if consistent, may support the concept of frailty as an indicator of accelerated biological age in mental illness.
Aprahamian et al. (Reference Aprahamian2020) in this issue observed that frailty was also significantly higher among in-patients with dementia compared to those without. There is a rising interest in comorbid frailty and cognitive decline, or cognitive frailty, as a prognostic indicator of incident dementia in the general aging population. Recent research from large sample sizes suggests that mental illness is associated with increased relative risk of developing dementia with age (Almeida et al., Reference Almeida, Ford, Hankey, Yeap, Golledge and Flicker2019). If frailty is indeed a risk factor for future cognitive impairment, it could represent an intervenable target to delay cognitive decline in mental illness.
Given the high prevalence of frailty in adults aging with mental illness, and the adverse outcomes associated with frailty status, recommendations to screen for frailty in geriatric psychiatry practice seem warranted. However, a recent survey of geriatric psychiatrists found a general consensus that frailty lacks a clear definition, or ways to address it, and is mostly used in geriatric medicine (Anantapong and Tinker, Reference Anantapong and Tinker2019). A better understanding of the pathways to frailty, including risk and preventative factors at the biological and behavioral levels, may better guide mental health practitioners in the identification and management of frailty in their patients. For example, polypharmacy is associated with higher odds of developing prefrailty in robust persons. Aprahamian et al. (Reference Aprahamian2020) in this issue found that the number of nonpsychotropic medications (but interestingly not psychotropic) was associated with frailty as assessed by both instruments. Addressing polypharmacy whenever possible is now a recommendation under the comprehensive care plan proposed by the task force of the International Conference of Frailty and Sarcopenia Research (ICFSR) (Dent et al., Reference Dent2019). Such recommendations should be emphasized in geriatric psychiatry care.
Besides the behavioral risk and preventative factors, shared biological pathways may underlie the co-occurrence of frailty and mental illness. Biological mechanisms potentially underlying frailty are a current topic of considerable interest and those at the forefront include chronic inflammation and mitochondrial dysfunction. Whether through primary or secondary pathways, there is also evidence of increased inflammation and oxidative stress in mental illness (Nguyen et al., Reference Nguyen, Eyler and Jeste2018). These mechanisms may be further intertwined with the microbiome, where early life stress may result in gut dysbiosis that contributes to a global inflammatory state and psychopathology of mental illnesses via the gut–brain axis (Nguyen et al., Reference Nguyen, Hathaway, Kosciolek, Knight and Jeste2019). In tandem, aging is associated with decreased species richness and biodiversity as well as reduced representation of beneficial taxa and their metabolic mediators; these alterations are further reduced in older adults who are physically frail (Claesson et al., Reference Claesson2012). Collectively, the associations of mental illness and frailty with biological pathways suggest the potential for therapeutic targets at the biological or physiological level in addition to behavioral modifications. The use of bioactive lipids to target immunity and inflammation in chronic diseases with similar pathophysiological mechanisms highlights the applicability of these mediators as a potential therapeutic strategy for counteracting frailty.
Frailty is not an inevitable consequence of aging nor should it be a consequence of aging with mental illness. However, in light of the large number of risk factors and potential biological predisposition of those with mental illness, frailty prevention must start early. In the general population, healthy behaviors related to nonsmoking, moderate alcohol intake, physical activity engagement, and healthy diet are associated with lower risk of frailty onset at older ages. Though interventions addressing healthy behaviors are not without challenges for those with mental illnesses, they are essential to promote healthy aging for these individuals. Our research group is currently investigating the effectiveness of a comprehensive lifestyle intervention, including health education, dietary intervention, increased physical activity, and smoking cessation or reduction, for persons with serious mental illnesses living in residential care facilities, to reduce the risk of diabetes and other cardiovascular diseases that contribute to accelerated biological aging. Early results suggest that such interventions are feasible, acceptable, and appropriate for individuals with serious mental illnesses and may have important implications for frailty. Clinical improvement from the frail state is also possible, and in addition to routine screening for frailty in geriatric psychiatry care, behavioral counseling regarding these healthy behaviors may be critical not only for reducing the multimorbidity common in mental disorders but also for establishing a better aging trajectory that mitigates early deterioration and functional decline.
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The paradox of aging, that is, improved mental well-being despite diminished physical and cognitive capacities, is particularly evident in those aging with mental illness (Jeste et al., Reference Jeste, Wolkowitz and Palmer2011). For many older adults, psychiatric symptoms are not the primary cause of impairment in function and quality of life, and efforts to address accelerated biological aging in mental illnesses are critical for geriatric psychiatry care. Frailty has recently been proposed for psychiatry as a clinical measure of biological age (Bersani et al., Reference Bersani2020). Frailty is a multidimensional construct that broadly refers to a state of increased vulnerability to stressors and can be described along a continuum of functional capacity, from robust at one end to experiencing disability in basic activities of daily living at the other (Dent et al., Reference Dent2019). The two most common constructs used to assess frailty are the physical phenotype, originally characterized by Fried et al. (Reference Fried2001), that includes assessing five items—unintentional weight loss, exhaustion, weakness, slow walking speed, and low levels of physical activity; and the deficit accumulation model or Frailty Index, originally proposed by Rockwood et al. (Reference Rockwood, Stadnyk, MacKnight, McDowell, Hébert and Hogan1999), that characterizes frailty on the basis of an accumulation of health conditions and deficits. Frailty is a leading contributor to functional decline and early mortality in the general aging population. However, at a prevalence of roughly 10-11% of adults over 65 years (Collard et al., Reference Collard, Boter, Schoevers and Oude Voshaar2012), frailty is not an obligatory consequence of aging and many individuals may continue to be robust into old age.
While frailty is an area of current focus in geriatric medicine, its etiology is still subject to debate, and it is less well recognized in geriatric psychiatry. In this issue of IPG, Aprahamian et al. (Reference Aprahamian2020) assessed physical frailty of geriatric psychiatry inpatients aged 65+ years using the FRAIL scale (an approximation of the physical phenotype) and the Frailty Index. They found that 55.3% of the sample was frail according to the physical phenotype and 83.6% according to the Frailty Index. These numbers are striking compared to the general aging population. There are several reasons why frailty may be disproportionally represented in older adults aging with mental illness. Long-term risk factors for frailty include overweight/obesity, physical inactivity, cardiovascular risk, poor self-rated health, and alcohol use (Dent et al., Reference Dent2019)—risk factors that are known to commonly occur in those with mental illness. Somatic comorbidities associated with these poor lifestyle behaviors are high in older adults with mental illnesses and are responsible for a large mortality gap compared to the general aging population. Though frailty and multimorbidity are mutually inclusive, they are considered separate constructs, with the proportion of community-dwelling older adults presenting both conditions around 6%, and approximately 42% of those with multimorbidity still considered “robust” (Vetrano et al., Reference Vetrano2019). Thus, it is unlikely that frailty is purely the result of the high multimorbidity in those aging with mental illness.
Frailty prevalence is also elevated in populations with less education, low socioeconomic position, and ethnic minority groups, which aligns with the well-known socioeconomic disparity associated with mental illnesses. Many of these factors relate to the living environment, which is now being recognized as a determinant of the Healthspan. Byrne et al. (Reference Byrne, Prvu Bettger, Brusilovskiy, Wong, Metraux and Salzer2013) found that the concentration of persons with serious mental illness within a neighborhood’s adult population was associated with higher levels of physical and structural inadequacy, crime, drug-related activity, social instability, and social isolation. Such factors may reduce the life space and limit community participation and social interactions. In addition, behavioral phenomena commonly associated with mental illnesses, such as physical anergia, avolition, and apathy, further impact the activities in which an individual chooses to participate. While these behavioral symptoms share overlap with some diagnostic criteria of the DSM-5, this does not necessarily invalidate them as risk factors for frailty. Apathy has been independently associated with the development of frailty in community-dwelling older adults (Ayers et al., Reference Ayers, Shapiro, Holtzer, Barzilai, Milman and Verghese2017), and exhaustion is often one of the initial manifestations of frailty criteria. It is plausible that lifestyles characterized by these environmental constraints and behavioral antecedents result in phenotypic rigidity versus adaptability of those with mental illnesses, which in turn predisposes these individuals to becoming frail.
Other groups in addition to Aprahamian et al. (Reference Aprahamian2020) have demonstrated the importance of assessing frailty in geriatric psychiatry inpatient settings. Stolz et al. (Reference Stolz, Rásky and Jagsch2020) found that geriatric psychiatry inpatients classified as frail had a 21% increased probability of in-hospital mortality and subsequently suggested implementation of a routine assessment of frailty based on a comprehensive geriatric assessment. Benraad et al. (Reference Benraad2020a) observed that frailty predicted unfavorable discharge destination following psychiatric hospital admission. In a separate publication, Benraad et al. (Reference Benraad2020b) further demonstrated that frailty independently predicted mortality in older adults within 5 years of psychiatric hospital admission. The presence of frailty is not restricted to psychiatric inpatients; Andrew and Rockwood (Reference Andrew and Rockwood2007) found that psychiatric illness was associated with a much higher odds of being physically frail in a large sample of community dwellers without dementia within the Canadian Study of Health and Aging. More recently, Tsai et al. (Reference Tsai, Lee, Chen and Wu2018) observed a 10.2% prevalence of frailty in adults with chronic schizophrenia and that frailty was further associated with an increased risk of falling. Of particular importance was that the mean age in this sample was only 53.8 years, suggesting that frailty may disproportionally affect younger adults with mental illness. This finding warrants further investigation, but if consistent, may support the concept of frailty as an indicator of accelerated biological age in mental illness.
Aprahamian et al. (Reference Aprahamian2020) in this issue observed that frailty was also significantly higher among in-patients with dementia compared to those without. There is a rising interest in comorbid frailty and cognitive decline, or cognitive frailty, as a prognostic indicator of incident dementia in the general aging population. Recent research from large sample sizes suggests that mental illness is associated with increased relative risk of developing dementia with age (Almeida et al., Reference Almeida, Ford, Hankey, Yeap, Golledge and Flicker2019). If frailty is indeed a risk factor for future cognitive impairment, it could represent an intervenable target to delay cognitive decline in mental illness.
Given the high prevalence of frailty in adults aging with mental illness, and the adverse outcomes associated with frailty status, recommendations to screen for frailty in geriatric psychiatry practice seem warranted. However, a recent survey of geriatric psychiatrists found a general consensus that frailty lacks a clear definition, or ways to address it, and is mostly used in geriatric medicine (Anantapong and Tinker, Reference Anantapong and Tinker2019). A better understanding of the pathways to frailty, including risk and preventative factors at the biological and behavioral levels, may better guide mental health practitioners in the identification and management of frailty in their patients. For example, polypharmacy is associated with higher odds of developing prefrailty in robust persons. Aprahamian et al. (Reference Aprahamian2020) in this issue found that the number of nonpsychotropic medications (but interestingly not psychotropic) was associated with frailty as assessed by both instruments. Addressing polypharmacy whenever possible is now a recommendation under the comprehensive care plan proposed by the task force of the International Conference of Frailty and Sarcopenia Research (ICFSR) (Dent et al., Reference Dent2019). Such recommendations should be emphasized in geriatric psychiatry care.
Besides the behavioral risk and preventative factors, shared biological pathways may underlie the co-occurrence of frailty and mental illness. Biological mechanisms potentially underlying frailty are a current topic of considerable interest and those at the forefront include chronic inflammation and mitochondrial dysfunction. Whether through primary or secondary pathways, there is also evidence of increased inflammation and oxidative stress in mental illness (Nguyen et al., Reference Nguyen, Eyler and Jeste2018). These mechanisms may be further intertwined with the microbiome, where early life stress may result in gut dysbiosis that contributes to a global inflammatory state and psychopathology of mental illnesses via the gut–brain axis (Nguyen et al., Reference Nguyen, Hathaway, Kosciolek, Knight and Jeste2019). In tandem, aging is associated with decreased species richness and biodiversity as well as reduced representation of beneficial taxa and their metabolic mediators; these alterations are further reduced in older adults who are physically frail (Claesson et al., Reference Claesson2012). Collectively, the associations of mental illness and frailty with biological pathways suggest the potential for therapeutic targets at the biological or physiological level in addition to behavioral modifications. The use of bioactive lipids to target immunity and inflammation in chronic diseases with similar pathophysiological mechanisms highlights the applicability of these mediators as a potential therapeutic strategy for counteracting frailty.
Frailty is not an inevitable consequence of aging nor should it be a consequence of aging with mental illness. However, in light of the large number of risk factors and potential biological predisposition of those with mental illness, frailty prevention must start early. In the general population, healthy behaviors related to nonsmoking, moderate alcohol intake, physical activity engagement, and healthy diet are associated with lower risk of frailty onset at older ages. Though interventions addressing healthy behaviors are not without challenges for those with mental illnesses, they are essential to promote healthy aging for these individuals. Our research group is currently investigating the effectiveness of a comprehensive lifestyle intervention, including health education, dietary intervention, increased physical activity, and smoking cessation or reduction, for persons with serious mental illnesses living in residential care facilities, to reduce the risk of diabetes and other cardiovascular diseases that contribute to accelerated biological aging. Early results suggest that such interventions are feasible, acceptable, and appropriate for individuals with serious mental illnesses and may have important implications for frailty. Clinical improvement from the frail state is also possible, and in addition to routine screening for frailty in geriatric psychiatry care, behavioral counseling regarding these healthy behaviors may be critical not only for reducing the multimorbidity common in mental disorders but also for establishing a better aging trajectory that mitigates early deterioration and functional decline.
Description of authors’ roles
S. Graham and T. Nguyen both wrote and edited the manuscript.