- Email: [email protected]
Frailty in older women
Maturitas 69 (2011) 203–207
Contents lists available at ScienceDirect
Maturitas journal homepage: www.elsevier.com/locate/maturitas
Review
Frailty in older women Ruth E. Hubbard a,∗ , Kenneth Rockwood b,c a
Department of Geriatric Medicine, School of Medicine, Cardiff University, 3rd Floor, Academic Centre, Llandough Hospital, Penarth, South Wales, CF64 2XX, United Kingdom Geriatric Medicine Research Unit, Dalhousie University and Queen Elizabeth Health Sciences Centre, Canada c Division of Geriatric Medicine, Department of Medicine, Dalhousie University, 5955 Veterans’ Memorial Lane, Halifax, B3H 2E1, Canada b
a r t i c l e
i n f o
Article history: Received 14 February 2011 Received in revised form 13 April 2011 Accepted 13 April 2011
Keywords: Frailty Frailty Index Women Aged Limit Physiological reserve Oestrogen Testosterone
a b s t r a c t It is a truth universally acknowledged that although men tend to have better health in old age, women live longer lives. Here, we briefly review the biological, social and behavioural factors that may contribute to women’s greater longevity. We consider in particular factors that might result in a greater frailty burden in women, focusing on frailty being measured by a Frailty Index. The Frailty Index represents the burden of health deficits, expressed for an individual as the proportion of deficits present – from 0 (no deficits) to 1.0 (the theoretical maximum, if all deficits were expressed). A greater frailty burden in women might first represent a male “fitness–frailty pleiotropy”, resulting in men having lower physiological reserves in old age so that health deficits are more lethal. In short, the price of more optimal physiological functioning during youth is a lower threshold for system failure in old age. Conversely, a female “fertility–frailty pleiotropy” might result in greater physiological reserves in women. Child birth and child rearing necessitate high levels of energetic and nutritional investment: women who have children live shorter lives. Women currently are limiting the number of children they bear and their life expectancies may be longer than predicted by evolutionary design. Third, though the Frailty Index captures physical, cognitive and psychological vulnerability, it may not include all factors that impact life expectancy in older people; these factors may be present more in men than in women. While these hypotheses seek to explain how frailty impacts men and women in different ways, there is clearly much to be done to understand frailty in older people. © 2011 Elsevier Ireland Ltd. All rights reserved.
Contents 1. 2.
3.
4.
5.
6.
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Why do women live longer than men? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1. Biological factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2. Social and behavioural factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Are women more frail than men? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1. Reporting bias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2. Contributors to frailty . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3. Pathophysiological factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Frailty in relation to the accumulation of deficits . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1. Why is frailty important? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2. What is the Frailty Index? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Why do women with health deficits live longer? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.1. Men may have lower physiological reserves . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.2. Women may have greater physiological reserves . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.3. More factors may contribute to frailty status . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
∗ Corresponding author. Tel.: +44 29 20 716986; fax: +44 29 20 711267. E-mail address: [email protected] (R.E. Hubbard). 0378-5122/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.maturitas.2011.04.006
204 204 204 204 205 205 205 205 205 205 205 206 206 206 206 207 207
204
R.E. Hubbard, K. Rockwood / Maturitas 69 (2011) 203–207
Competing interests . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Funding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Provenance and peer review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1. Introduction The world’s population is ageing. During the 19th and early 20th centuries, improvements in living conditions reduced infant mortality, resulting in greater numbers of people surviving to middle and old age; more recent medical advances have allowed older people themselves to live longer. Indeed, over the last 170 years average life expectancy has increased by three months per year in developed countries [1]. These increases have not been gained equally by men and women. In the UK, significant differences in life expectancy persist from birth (78.7 years for men and 83.6 years for women) throughout youth and middle age, becoming proportionally greatest for the oldest old (5.0 years and 6.4 years for 85 year old men and women, respectively) [2]. Although women live longer than men, they tend to have poorer health status. This well described phenomenon has been termed the male–female health-survival paradox [3]. In mid and old age, women have greater levels of disability, more psychological and physical co-morbidity and worse self-rated health. These deficits in multi-dimensional health domains can be measured by a “Frailty Index” [4]. A Frailty Index is a count of health deficits, expressed as a proportion. For example, if 50 health deficits were used to make up a Frailty Index, a person with no health deficits would have a Frailty Index of 0; someone with 20 deficits would have a Frailty Index of 0.4, and, in theory, were an individual to have all 50 health deficits – as we shall see, and intriguingly, this never happens – the maximum score of the Frailty Index would be 1.0. Frailty Indices can be calculated from most existing clinical and population health surveys, making them a feasible means of quantifying health status. Their validity is indicated by their high correlation with adverse outcomes, including institutionalisation, worsening disability and death [5]. Investigations of Frailty Indices in large population studies have consistently shown that at any given age older women have accumulated more deficits than do men, but have lower mortality [5,6]. This is of some interest. While in both men and women, increasing values of the Frailty Index, representing accumulation of a greater number of health deficits, are associated with worse mortality, it seems clear that the vulnerability to adverse outcomes cannot be mapped directly to the number of deficits. In other words, if we understand frailty as the variable vulnerability to adverse outcomes of people of the same chronological age, there must be some mediating factors between health deficits and susceptibility. Sex could be one such factor. Here, we briefly review the biological, social and behavioural factors that may explain women’s greater longevity. We consider the factors contributing to frailty status, evaluating why older women have a greater deficit burden. The measurement of frailty by a Frailty Index is consistent with the conceptualisation of ageing as the failure of a complex system: we explore how this may afford a mechanistic understanding of the male–female health-survival paradox. 2. Why do women live longer than men? In most countries throughout the developed and developing world, women tend to have longer life expectancy at birth and lower age-specific mortality rates [7]. There are a few exceptions: women in some South Asian countries have shorter life expectancy, thought to be secondary to preferential treatment of
207 207 207 207
male children and complications associated with pregnancy and childbirth [8]. Historical evidence suggests that longer lifespans of women are not a recent phenomenon. Although some believe that men lived longer than women in ancient and medieval times, historical documents from northern Italy in as early as the 14th century and from England and Wales in the 16th century report higher average ages at death for women. This finding is confirmed by more robust national Scandinavian data from the 18th century [9]. While there is no definitive explanation for women’s advantaged mortality profile, several biological, social and behavioural factors have been proposed. 2.1. Biological factors • Hormones may have a central role in women’s long life expectancy [3]. The tendency for cardiovascular disease to occur 10 years earlier in men than women has been attributed to the favourable impact of oestrogen on serum lipid profiles. Moreover, recent studies suggest that oestrogen may have a protective effect on cerebral areas known to be involved in age-related cognitive functions and Alzheimer’s disease [10]. Conversely, testosterone supplementation, even in men with evidence of late-onset hypogonadism, may be associated with a range of adverse effects [11]. • Women seem to have more robust immune systems and greater resistance to infections throughout their lives, in part because testosterone causes immunosuppression [12]. Men tend to experience more severe symptoms and be at increased risk of mortality from a variety of fungal, parasitic and bacterial diseases; this is exemplified by their response to respiratory infections [13]. • The presence of two X chromosomes with different potentials may provide a genetic longevity advantage. Loci on the X chromosome are protected in the germ line (they spend two-thirds of their time in oocytes rather than in sperm cells which may account for their slower mutation rate) yet vulnerable in the soma (because only one X chromosome is active in each human female cell, they lack a partner for repair by homologous recombination) [14]. Thus, the X chromosome is theoretically attractive as a site of crucial longevity genes, representing the trade-off between germ-line propagation and somatic maintenance [14]. 2.2. Social and behavioural factors • Gender-typical risk-avoidance behaviour may play a central role in the explanation of women’s longer life expectancy [15]. Women are less likely than men to take psychoactive substances, smoke cigarettes, drink excess alcohol and partake in risky sexual behaviour. Men, on the other hand, are more likely to be exposed to dangerous working environments, to take part in hazardous leisure pursuits (e.g. driving too fast) and to revert to openly aggressive problem-solving strategies such as war or suicide. Whether these behaviour differences are a social construct (determined by traditional role expectations) or biologically driven (women’s cautiousness secondary to their responsibility for child-rearing) remains controversial topic [15]. • Significant differences in health-care utilisation may contribute to women’s longevity. Even after adjusting for sex-specific conditions such as pregnancy, women have a significantly higher mean number of visits to primary care and diagnostic clinics [3]. Men
R.E. Hubbard, K. Rockwood / Maturitas 69 (2011) 203–207
tend to delay seeking medical help and are less compliant with both prescribed medication and medical advice [16]. • Men are generally less informed about the impact of nutrition on health [15]. Some of their nutritional choices are now known to be associated with adverse outcomes: they are less likely to have breakfast and more often eat a less varied diet with more meat and have a lower intake of vitamins and supplements. The crux of the gender health-survival paradox is that these biological, social and behavioural advantages do not seem to translate into advantages in health status for women. On the contrary, middle-aged and older women have greater levels of disability, more psychological and physical co-morbidity and worse self-rated health: they accumulate more deficits than do men. 3. Are women more frail than men? Just as it has been known for several centuries that women live longer lives than men, their poorer health status has also long been recognised. Physicians in 17th-century London, for example, reported that in addition to unique complications associated with pregnancy and childbirth, women generally suffered more than men from diseases [17]. The higher rates in lifetime prevalence of different diseases in women were previously attributed to the impact of their longer life expectancy on age-associated diseases and negative life events such as widowhood. However, epidemiological studies from several countries have now shown that at any given age, the burden of frailty is greater for women than for men, no matter how frailty is defined [5,6,18]. These differences in frailty status have been explained by reporting bias and differences in co-morbidity, mood and cognition. Pathophysiological factors may also provide a mechanistic understanding of these health-sex differences. 3.1. Reporting bias • Health and well-being are reported differentially by men and women. Men and women chose different aspects of life to describe their health status: men tend to define their well-being through performance and efficiency whereas women have a more holistic interpretation of health [15]. In some studies, men are more likely to under-report medical conditions, particularly anxiety and depression [3].
205
the poor psychological health of older women may represent a socialisation-based cohort effect [15]. A Swiss study of older men and women who had worked for decades in the maledominated environment of chemical industry showed no gender differences in psychological well-being [21]. These women may have developed certain instrumental attributes (task-focussed thinking, self-confidence, assertiveness) that were protective for their lifelong mental health [21]. • The incidence of Alzheimer’s disease is higher in women than in men. Pathogenic explanations have been proposed. Mitochondria seem to be protected against amyloid-beta toxicity in younger but not older females, possibly secondary to falling oestrogen levels [22]. More importantly, and relevant for any dementia illness, men’s higher levels of education and greater participation in physical activity may protect against cognitive decline [23]. 3.3. Pathophysiological factors • Inflammation may play a key role in frailty pathogenesis [24]. Older women accumulate more abdominal fat than older men and this may be an important contributor to their frailty status [25]. Abdominal adiposity is associated with low grade systemic inflammation, mediating its link with metabolic syndromes. Furthermore, those with increased waist circumference have higher markers of oxidative stress, independent of body mass index. Excessive and unopposed oxidative stress may be another core mechanism leading to age-associated frailty, with evidence supporting a direct causal role for reactive oxygen species in skeletal muscle damage and low grip strength [26]. • Child birth and child rearing necessitate high levels of physiological investment. The energetic and nutritional demands of pregnancy and breast-feeding render reproductive costs much greater in women than in men. Bearing sons may have particularly high physiological costs, due to their faster rate of intrauterine growth and heavier than average birth weights [27]. In Westendorp and Kirkwood’s pioneering analyses of historical datasets from the British aristocracy, female longevity was negatively correlated with number of progeny suggesting a “trade-off” between longevity and reproduction [28]. While no studies, to our knowledge, have investigated frailty status in relation to number of children, it is theoretically possible that women are more frail in older age because of their physiological investment in reproduction.
3.2. Contributors to frailty
4. Frailty in relation to the accumulation of deficits
• Some co-morbidities disproportionately affect women. The flip-side of testosterone-induced immunosuppression [12] (so advantageous to women’s response to infectious disease) is a higher prevalence of autoimmune disease. Men have a higher prevalence of diseases which are immediately fatal without a prior episode of impaired health [e.g. myocardial infarction and rapidly progressive cancer, such as pancreatic cancer]. Women seem more susceptible to conditions associated with chronic ill health [e.g. chronic obstructive pulmonary disease, stroke and diabetes]. This has a significant impact on levels of disability and functional impairment. • Women have higher rates of depression and anxiety. The lifetime probability of developing an episode of depression and/or anxiety is significantly higher in women than in men [19]. These results are important because in middle aged and older people depressive symptoms make a large and unique contribution to risks of disability and poor health perception [20]. It also impacts on the prescription of drugs such as benzodiazepines, known to increase risks of unintentional injuries and falls. Interestingly,
4.1. Why is frailty important? Frailty, as variable vulnerability to adverse outcomes, is an important concept for all those who plan and provide care for older people. It is closely linked to advanced age and disease-related processes, yet is a distinct construct. Frailty allows health status to be summarized in a parsimonious way, providing a more precise quantification of individual vulnerability than chronological age alone; those who are frail are at increased risk of death, institutionalisation and worsening disability [29]. Despite its significance in relation to adverse outcomes, there is there is no universally accepted definition of frailty and it continues to be operationalised in different ways. 4.2. What is the Frailty Index? The conceptualisation of frailty as a multidimensional risk state facilitates its measurement by the number rather than by the nature of health problems. The Frailty Index (FI) model employs a well-
206
R.E. Hubbard, K. Rockwood / Maturitas 69 (2011) 203–207
Table 1 A 60-point Frailty Index score, based on data routinely collected in a Comprehensive Geriatric Assessment. Health deficit
Scoring instructions
Cognition
Score 0 if within normal limits, 0.5 if “Cognitive Impairment, No Dementia”, 1 if “dementia 0 = absent, 0.33 = mild; 0.67 = moderate; 1 = severe 0 = absent, 1 = present 0 = normal; 0.5 = low mood; 1 = depression 0 = absent; 1 = present 0 = absent; 1 = present
Dementia stage Delirium Affect/mood Anxiety Behavioural and psychological symptoms of dementia Violence Health attitude Mobility Walking aid Balance Falls Transfers Bowels Bladder Hobbies Banking Medications Shopping Transportation Climbs stairs Bathing Dressing Toileting Grooming Feeding Weight Appetite Sleep Daytime drowsiness Smoking In Emergency Department in last 30 days In hospital in last 6 months Co-morbidities Medications
0 = absent; 1 = present 0 = excellent/good; 1 = fair/poor 0 = walks on own; 0.25 = slow 0.5 needs assistance; 1 = cannot walk 0 = absent 0.25 = cane; 0.75 = walker; 1 = wheelchair 0 = unimpaired; 1 = impaired 0 = none; 0.5 present, not in last month; 1 = within last month 0 = independent; 0.5 = standby; 1 = any hands-on assistance 0 = normal; 0.5 = constipation; 1 = incontinence 0 = normal; 0.5 = occasional incontinence; 1 = incontinence 0 = retained; 0.5 = reduced; 1 = abandoned 0 = independent; 0.5 = needs some assistance; 1 = dependent 0 = independent; 0.5 = needs some assistance; 1 = dependent 0 = independent; 0.5 = needs some assistance; 1 = dependent 0 = independent; 0.5 = needs some assistance; 1 = dependent 0 = independent; 0.5 = needs some assistance; 1 = dependent 0 = independent; 0.5 = needs some assistance; 1 = dependent 0 = independent; 0.5 = needs some assistance; 1 = dependent 0 = independent; 0.5 = needs some assistance; 1 = dependent 0 = independent; 0.5 = needs some assistance; 1 = dependent 0 = independent; 0.5 = needs some assistance; 1 = dependent 0 = independent; 0.5 = needs some assistance; 1 = dependent 0 = normal; 1 = reduced 0 = normal; 0.5 = sometimes disrupted; 1 = problem 0 = absent; 0.5 = occasional; 1 = present 0 = never; 0.25 none in last 25 years; 0.5 = past; 1 = present 0 = no; 1 point for each visit (maximum 3)
0 = 1; 1 point for each week in hospital (maximum = 6) Score 1 for each; maximum is 16 <5 = 0; 5–7 = 1.0; 8–11 = 2; 12–15 = 3; >15 = 4
Note on scoring: 1 point is added for each deficit; the total points are divided by 60 to achieve a Frailty Index score, where 0 = no deficits present, and 1.0 = all 60 deficits present. In practice, many fewer than 1% of people would have a Frailty Index score >0.67.
defined methodology to create an index as a proportion of health deficits [30]. An example of a 60-point Frailty Index score, based on data routinely collected in a Comprehensive Geriatric Assessment is given in Table 1. The robustness of this method is strikingly illustrated by the fact that Frailty Indices can be constructed from different numbers and types of variables, yet still yield very comparable results between datasets. For example, analysis of data for 36,424 older people in four developed countries found Frailty Index values to be closely comparable across countries. Even though the number of items used to make up a Frailty Index in the different dataset varied between 30 and 100, in each dataset the mean value increased with age at approximately 3% per year in communitydwellers and was highly correlated with mortality [5]. Further studies confirm that the risk of adverse outcomes is defined more precisely by deficit indices than by phenotypic definitions of frailty [31]. Frailty Indices also have informative mathematical properties; they are well represented by a gamma distribution and reach a submaximal limit (of approximately 0.67), i.e. there is an empir-
ical limit to frailty [4]. Furthermore, for institutionalised or very ill populations, frailty levels are high but no longer accumulate with age [5]. This suggests important parallels to the redundancy exhaustion hypothesis of the reliability theory of ageing [32]. The reliability theory conceptualises ageing as the accumulation of random damage to a complex system composed of redundant parts. As defects accumulate, an organism loses its redundancy until eventually it becomes comparable to a system with elements connected in series. Accordingly, the frailest older people are comparable to a system with no redundancy: they can no longer accumulate deficits (i.e. become more frail); the next insult will cause failure of the system (i.e. death). 5. Why do women with health deficits live longer? In this review, we have established that women have longer life expectancies and a greater frailty burden; the underlying reasons for these two disparate phenomena have been explored. We must now address the question of why women can tolerate this greater number of heath deficits. In one study, for example, women had an estimated 20% lesser chance of dying at a given time than did men of the same chronological age and degree of frailty [6]. The conceptualisation of ageing as the failure of a complex system and the measurement of frailty as an index of accumulated deficits may enable us to understand women’s tolerance of their health deficits. 5.1. Men may have lower physiological reserves During youth and middle age, men have greater muscle strength than women with higher levels of physical performance. Therefore, at any given level of the Frailty Index, men have changed more from their baseline status. The male system may be “calibrated” differently, with more “optimal” physiological functioning during youth but a lower threshold for system failure in old age. This male fitness–frailty pleiotropy is congruent with evolutionary design. It is advantageous to the species to ensure young men are highly physically able and that women have a longer post-reproductive lifespan in order to enhance the reproductive success of their offspring [33]. 5.2. Women may have greater physiological reserves The evolutionary driver for sex differences in system design may be the need for greater physiological reserves in women. Women who bear children live shorter lives [28] and birth rates have fallen significantly. In 1871, women in the UK had an average of 5.5 children but by 1921 this had fallen to 2.4 secondary to more delayed and non marriage and the use of traditional and (novel) barrier methods of birth control [34] each linked to higher female education levels [35]. The female “complex system” may be designed for maximum fecundity, with higher levels of frailty among older women but anticipation of equal life expectancies between the sexes. In this scenario, women bear a greater burden of frailty, greater still if they reached their reproductive potential: a female fertility–frailty pleiotropy. Since women are currently limiting the number of children they bear, their life expectancies are longer than predicted by evolutionary design. 5.3. More factors may contribute to frailty status Women’s greater tolerance of frailty may be related to more pragmatic reasons than ultimate causation. The Frailty Index may not include all factors that impact life expectancy in older people, factors that are present more in men than in women. The Frailty Index captures physical, cognitive and psychological vulnerability, but other characteristics and attributes impact health status.
R.E. Hubbard, K. Rockwood / Maturitas 69 (2011) 203–207
Both individual-level characteristics (such as poor social support) [36] and community-level economic factors (such as neighbourhood deprivation) [37] are increasingly recognised as predictive of mortality in older adults. Interestingly, women have higher levels of social vulnerability than men [36] and inclusion of these factors would increase rather minimise the frailty sex differential. However, the recent emergence of the importance of social vulnerability with respect to health status and life expectancy does illustrate that other crucial deterministic factors may as yet be unidentified. 6. Conclusions In old age, women tend to have more deficits than do men, and be frailer by current definitions, but live longer lives. While many explanations have been proposed to account for these phenomena separately, there is much that still needs to be done to understand frailty and why it impacts older men and women in different ways. Complex interventions, particularly education and exercise, may modify the rate of deficit accumulation and delay the onset of frailty. Whether such interventions will benefit men and women equally are questions that investigations of Frailty Indices can address. This is motivating further enquiries by our group. Contributors REH wrote the first draft which was revised by KR. Competing interests KR has applied for funding to commercialize a version of the Frailty Index. Funding KR receives career support from the Dalhousie Medical Research Foundation as Kathryn Allen Weldon Professor of Alzheimer Research. Much of the work done here was supported by the Canadian Institutes of Health Research through operating grant MOP005170. Provenance and peer review Commissioned and externally peer reviewed. References [1] Christensen K, Doblhammer G, Rau R, Vaupel JW. Ageing populations: the challenges ahead. Lancet 2009;374:1196–208. [2] Office for National Statistics. Health Expectancy. London; 2004. www.statistics.gov.uk. [3] Oksuzyan A, Juel K, Vaupel JW, Christensen K. Men: good health and high mortality. Sex differences in health and aging. Aging Clin Exp Res 2008;20:91–102. [4] Rockwood K, Mitnitski A. Frailty in relation to the accumulation of deficits. J Gerontol A: Biol Sci Med Sci 2007;62:722–7. [5] Mitnitski A, Song X, Skoog I, et al. Relative fitness and frailty of elderly men and women in developed countries and their relationship with mortality. J Am Geriatr Soc 2005;53:2184–9. [6] Goggins WB, Woo J, Sham A, Ho SC. Frailty index as a measure of biological age in a Chinese population. J Gerontol A: Biol Sci Med Sci 2005;60:1046–51. [7] Møller AP, Fincher CL, Thornhill R. Why men have shorter lives than women: effects of resource availability, infectious disease, and senescence. Am J Hum Biol 2009;21:357–64. [8] Fikree FF, Pasha O. Role of gender in health disparity: the South Asian context. BMJ 2004;328:823–6.
207
[9] Gage TB. Are modern environments really bad for us?: revisiting the demographic and epidemiologic transitions. Am J Phys Anthropol 2005;S41:96– 117. [10] Lord C, Engert V, Lupien SJ, Pruessner JC. Effect of sex and estrogen therapy on the aging brain: a voxel-based morphometry study. Menopause 2010;17:846–51. [11] Bassil N, Morley JE. Late-life onset hypogonadism: a review. Clin Geriatr Med 2010;26:197–222. [12] Owens IPF. Ecology and evolution: sex differences in mortality rate. Science 2002;297:2008–9. [13] Falagas ME, Vardakas KZ, Mourtzoukou EG. Sex differences in the incidence and severity of respiratory tract infections. Respir Med 2008;102:627. [14] Schachter F. Causes, effects, and constraints in the genetics of human longevity. Am J Hum Genet 1998;62:1008–14. [15] Perrig-Chiello P, Hutchison S. Health and well-being in old age: the pertinence of a gender mainstreaming approach in research. Gerontology 2010;56:208–13. [16] Galdas PM, Cheater F, Marshall P. Men and health help-seeking behaviour: literature review. J Adv Nurs 2005;49:616–23. [17] DeWitte SN. Sex differentials in frailty in medieval England. Am J Phys Anthropol 2010;143:285–97. [18] Syddall H, Roberts HC, Evandrou M, Cooper C, Bergman H, Aihie Sayer A. Prevalence and correlates of frailty among community-dwelling older men and women: findings from the Hertfordshire Cohort Study. Age Ageing 2010;39:197–203. [19] King M, Nazareth I, Levy G, et al. Prevalence of common mental disorders in general practice attendees across Europe. Br J Psych 2008;192:362–7. [20] Ormel J, Kempen GI, Deeg DJ, Brilman EI, van Sonderen E, Relyveld J. Functioning, well-being, and health perception in late middle-aged and older people: comparing the effects of depressive symptoms and chronic medical conditions. J Am Geriatr Soc 1998;46:39–48. [21] Perrig-Chiello P, Staehelin HB. Women and health in old age: objective and subjective health and health behaviour of retired female workers and employees. Z Gerontopsychol Psychiatr 1996;9:195–205. ˜ J, Lloret A. Why women have more Alzheimer’s disease than men: gen[22] Vina der and mitochondrial toxicity of amyloid-beta peptide. J Alzheimers Dis 2010;20(Suppl. 2):S527–33. [23] Middleton LE, Mitnitski A, Fallah N, Kirkland SA, Rockwood K. Changes in cognition and mortality in relation to exercise in late life: a population based study. PLoS One 2008;3(9):e3124. [24] Hubbard RE, Woodhouse KW. Frailty, inflammation and the elderly. Biogerontology 2010;11:635–41. [25] Hubbard RE, Lang IA, Llewellyn DJ, Rockwood K. Frailty, body mass index, and abdominal obesity in older people. J Gerontol A: Biol Sci Med Sci 2010;65: 377–81. [26] Howard C, Ferrucci L, Sun K, et al. Oxidative protein damage is associated with poor grip strength among older women living in the community. J Appl Physiol 2007;103:17–20. [27] Hurt LS, Ronsmans C, Quigley M. Does the number of sons born affect longterm mortality of parents? A cohort study in rural Bangladesh. Proc Biol Sci 2006;273:149–55. [28] Westendorp RG, Kirkwood TB. Human longevity at the cost of reproductive success. Nature 1998;396:743–6. [29] Rockwood K, Mitnitski A, Song X, Steen B, Skoog I. Long-term risks of death and institutionalization of elderly people in relation to deficit accumulation at age 70. J Am Geriatr Soc 2006;54:975–9. [30] Searle SD, Mitnitski A, Gahbauer EA, Gill TM, Rockwood K. A standard procedure for creating a frailty index. BMC Geriatr 2008;8:24. [31] Kulminski AM, Ukraintseva SV, Kulminskaya IV, Arbeev KG, Land K, Yashin AI. Cumulative deficits better characterize susceptibility to death in elderly people than phenotypic frailty: lessons from the Cardiovascular Health Study. J Am Geriatr Soc 2008;56:898–903. [32] Gavrilov LA, Gavrilova NS. Reliability theory of aging and longevity. In: Handbook of the biology of aging. 6th edition Academic Press; 2007. [33] Lahdenperä M, Lummaa V, Helle S, Tremblay M, Russell AF. Fitness benefits of prolonged post-reproductive lifespan in women. Nature 2004;428:178– 81. [34] Department of Health, UK. The UK population: past, present and future; 2005. http://www.statistics.gov.uk/downloads/theme compendia/fom2005/ 01 fopm population.pdf [Accessed February 2011]. [35] Lucas RE. Lectures on economic growth. Cambridge and London: Harvard University Press; 2004. [36] Andrew MK, Mitnitski AB, Rockwood K. Social vulnerability, frailty and mortality in elderly people. PLoS One 2008;3(5):e2232. [37] Major JM, Doubeni CA, Freedman ND, et al. Neighborhood socioeconomic deprivation and mortality: NIH-AARP diet and health study. PLoS One 2010;5(11):e15538.
Contents lists available at ScienceDirect
Maturitas journal homepage: www.elsevier.com/locate/maturitas
Review
Frailty in older women Ruth E. Hubbard a,∗ , Kenneth Rockwood b,c a
Department of Geriatric Medicine, School of Medicine, Cardiff University, 3rd Floor, Academic Centre, Llandough Hospital, Penarth, South Wales, CF64 2XX, United Kingdom Geriatric Medicine Research Unit, Dalhousie University and Queen Elizabeth Health Sciences Centre, Canada c Division of Geriatric Medicine, Department of Medicine, Dalhousie University, 5955 Veterans’ Memorial Lane, Halifax, B3H 2E1, Canada b
a r t i c l e
i n f o
Article history: Received 14 February 2011 Received in revised form 13 April 2011 Accepted 13 April 2011
Keywords: Frailty Frailty Index Women Aged Limit Physiological reserve Oestrogen Testosterone
a b s t r a c t It is a truth universally acknowledged that although men tend to have better health in old age, women live longer lives. Here, we briefly review the biological, social and behavioural factors that may contribute to women’s greater longevity. We consider in particular factors that might result in a greater frailty burden in women, focusing on frailty being measured by a Frailty Index. The Frailty Index represents the burden of health deficits, expressed for an individual as the proportion of deficits present – from 0 (no deficits) to 1.0 (the theoretical maximum, if all deficits were expressed). A greater frailty burden in women might first represent a male “fitness–frailty pleiotropy”, resulting in men having lower physiological reserves in old age so that health deficits are more lethal. In short, the price of more optimal physiological functioning during youth is a lower threshold for system failure in old age. Conversely, a female “fertility–frailty pleiotropy” might result in greater physiological reserves in women. Child birth and child rearing necessitate high levels of energetic and nutritional investment: women who have children live shorter lives. Women currently are limiting the number of children they bear and their life expectancies may be longer than predicted by evolutionary design. Third, though the Frailty Index captures physical, cognitive and psychological vulnerability, it may not include all factors that impact life expectancy in older people; these factors may be present more in men than in women. While these hypotheses seek to explain how frailty impacts men and women in different ways, there is clearly much to be done to understand frailty in older people. © 2011 Elsevier Ireland Ltd. All rights reserved.
Contents 1. 2.
3.
4.
5.
6.
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Why do women live longer than men? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1. Biological factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2. Social and behavioural factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Are women more frail than men? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1. Reporting bias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2. Contributors to frailty . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3. Pathophysiological factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Frailty in relation to the accumulation of deficits . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1. Why is frailty important? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2. What is the Frailty Index? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Why do women with health deficits live longer? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.1. Men may have lower physiological reserves . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.2. Women may have greater physiological reserves . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.3. More factors may contribute to frailty status . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
∗ Corresponding author. Tel.: +44 29 20 716986; fax: +44 29 20 711267. E-mail address: [email protected] (R.E. Hubbard). 0378-5122/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.maturitas.2011.04.006
204 204 204 204 205 205 205 205 205 205 205 206 206 206 206 207 207
204
R.E. Hubbard, K. Rockwood / Maturitas 69 (2011) 203–207
Competing interests . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Funding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Provenance and peer review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1. Introduction The world’s population is ageing. During the 19th and early 20th centuries, improvements in living conditions reduced infant mortality, resulting in greater numbers of people surviving to middle and old age; more recent medical advances have allowed older people themselves to live longer. Indeed, over the last 170 years average life expectancy has increased by three months per year in developed countries [1]. These increases have not been gained equally by men and women. In the UK, significant differences in life expectancy persist from birth (78.7 years for men and 83.6 years for women) throughout youth and middle age, becoming proportionally greatest for the oldest old (5.0 years and 6.4 years for 85 year old men and women, respectively) [2]. Although women live longer than men, they tend to have poorer health status. This well described phenomenon has been termed the male–female health-survival paradox [3]. In mid and old age, women have greater levels of disability, more psychological and physical co-morbidity and worse self-rated health. These deficits in multi-dimensional health domains can be measured by a “Frailty Index” [4]. A Frailty Index is a count of health deficits, expressed as a proportion. For example, if 50 health deficits were used to make up a Frailty Index, a person with no health deficits would have a Frailty Index of 0; someone with 20 deficits would have a Frailty Index of 0.4, and, in theory, were an individual to have all 50 health deficits – as we shall see, and intriguingly, this never happens – the maximum score of the Frailty Index would be 1.0. Frailty Indices can be calculated from most existing clinical and population health surveys, making them a feasible means of quantifying health status. Their validity is indicated by their high correlation with adverse outcomes, including institutionalisation, worsening disability and death [5]. Investigations of Frailty Indices in large population studies have consistently shown that at any given age older women have accumulated more deficits than do men, but have lower mortality [5,6]. This is of some interest. While in both men and women, increasing values of the Frailty Index, representing accumulation of a greater number of health deficits, are associated with worse mortality, it seems clear that the vulnerability to adverse outcomes cannot be mapped directly to the number of deficits. In other words, if we understand frailty as the variable vulnerability to adverse outcomes of people of the same chronological age, there must be some mediating factors between health deficits and susceptibility. Sex could be one such factor. Here, we briefly review the biological, social and behavioural factors that may explain women’s greater longevity. We consider the factors contributing to frailty status, evaluating why older women have a greater deficit burden. The measurement of frailty by a Frailty Index is consistent with the conceptualisation of ageing as the failure of a complex system: we explore how this may afford a mechanistic understanding of the male–female health-survival paradox. 2. Why do women live longer than men? In most countries throughout the developed and developing world, women tend to have longer life expectancy at birth and lower age-specific mortality rates [7]. There are a few exceptions: women in some South Asian countries have shorter life expectancy, thought to be secondary to preferential treatment of
207 207 207 207
male children and complications associated with pregnancy and childbirth [8]. Historical evidence suggests that longer lifespans of women are not a recent phenomenon. Although some believe that men lived longer than women in ancient and medieval times, historical documents from northern Italy in as early as the 14th century and from England and Wales in the 16th century report higher average ages at death for women. This finding is confirmed by more robust national Scandinavian data from the 18th century [9]. While there is no definitive explanation for women’s advantaged mortality profile, several biological, social and behavioural factors have been proposed. 2.1. Biological factors • Hormones may have a central role in women’s long life expectancy [3]. The tendency for cardiovascular disease to occur 10 years earlier in men than women has been attributed to the favourable impact of oestrogen on serum lipid profiles. Moreover, recent studies suggest that oestrogen may have a protective effect on cerebral areas known to be involved in age-related cognitive functions and Alzheimer’s disease [10]. Conversely, testosterone supplementation, even in men with evidence of late-onset hypogonadism, may be associated with a range of adverse effects [11]. • Women seem to have more robust immune systems and greater resistance to infections throughout their lives, in part because testosterone causes immunosuppression [12]. Men tend to experience more severe symptoms and be at increased risk of mortality from a variety of fungal, parasitic and bacterial diseases; this is exemplified by their response to respiratory infections [13]. • The presence of two X chromosomes with different potentials may provide a genetic longevity advantage. Loci on the X chromosome are protected in the germ line (they spend two-thirds of their time in oocytes rather than in sperm cells which may account for their slower mutation rate) yet vulnerable in the soma (because only one X chromosome is active in each human female cell, they lack a partner for repair by homologous recombination) [14]. Thus, the X chromosome is theoretically attractive as a site of crucial longevity genes, representing the trade-off between germ-line propagation and somatic maintenance [14]. 2.2. Social and behavioural factors • Gender-typical risk-avoidance behaviour may play a central role in the explanation of women’s longer life expectancy [15]. Women are less likely than men to take psychoactive substances, smoke cigarettes, drink excess alcohol and partake in risky sexual behaviour. Men, on the other hand, are more likely to be exposed to dangerous working environments, to take part in hazardous leisure pursuits (e.g. driving too fast) and to revert to openly aggressive problem-solving strategies such as war or suicide. Whether these behaviour differences are a social construct (determined by traditional role expectations) or biologically driven (women’s cautiousness secondary to their responsibility for child-rearing) remains controversial topic [15]. • Significant differences in health-care utilisation may contribute to women’s longevity. Even after adjusting for sex-specific conditions such as pregnancy, women have a significantly higher mean number of visits to primary care and diagnostic clinics [3]. Men
R.E. Hubbard, K. Rockwood / Maturitas 69 (2011) 203–207
tend to delay seeking medical help and are less compliant with both prescribed medication and medical advice [16]. • Men are generally less informed about the impact of nutrition on health [15]. Some of their nutritional choices are now known to be associated with adverse outcomes: they are less likely to have breakfast and more often eat a less varied diet with more meat and have a lower intake of vitamins and supplements. The crux of the gender health-survival paradox is that these biological, social and behavioural advantages do not seem to translate into advantages in health status for women. On the contrary, middle-aged and older women have greater levels of disability, more psychological and physical co-morbidity and worse self-rated health: they accumulate more deficits than do men. 3. Are women more frail than men? Just as it has been known for several centuries that women live longer lives than men, their poorer health status has also long been recognised. Physicians in 17th-century London, for example, reported that in addition to unique complications associated with pregnancy and childbirth, women generally suffered more than men from diseases [17]. The higher rates in lifetime prevalence of different diseases in women were previously attributed to the impact of their longer life expectancy on age-associated diseases and negative life events such as widowhood. However, epidemiological studies from several countries have now shown that at any given age, the burden of frailty is greater for women than for men, no matter how frailty is defined [5,6,18]. These differences in frailty status have been explained by reporting bias and differences in co-morbidity, mood and cognition. Pathophysiological factors may also provide a mechanistic understanding of these health-sex differences. 3.1. Reporting bias • Health and well-being are reported differentially by men and women. Men and women chose different aspects of life to describe their health status: men tend to define their well-being through performance and efficiency whereas women have a more holistic interpretation of health [15]. In some studies, men are more likely to under-report medical conditions, particularly anxiety and depression [3].
205
the poor psychological health of older women may represent a socialisation-based cohort effect [15]. A Swiss study of older men and women who had worked for decades in the maledominated environment of chemical industry showed no gender differences in psychological well-being [21]. These women may have developed certain instrumental attributes (task-focussed thinking, self-confidence, assertiveness) that were protective for their lifelong mental health [21]. • The incidence of Alzheimer’s disease is higher in women than in men. Pathogenic explanations have been proposed. Mitochondria seem to be protected against amyloid-beta toxicity in younger but not older females, possibly secondary to falling oestrogen levels [22]. More importantly, and relevant for any dementia illness, men’s higher levels of education and greater participation in physical activity may protect against cognitive decline [23]. 3.3. Pathophysiological factors • Inflammation may play a key role in frailty pathogenesis [24]. Older women accumulate more abdominal fat than older men and this may be an important contributor to their frailty status [25]. Abdominal adiposity is associated with low grade systemic inflammation, mediating its link with metabolic syndromes. Furthermore, those with increased waist circumference have higher markers of oxidative stress, independent of body mass index. Excessive and unopposed oxidative stress may be another core mechanism leading to age-associated frailty, with evidence supporting a direct causal role for reactive oxygen species in skeletal muscle damage and low grip strength [26]. • Child birth and child rearing necessitate high levels of physiological investment. The energetic and nutritional demands of pregnancy and breast-feeding render reproductive costs much greater in women than in men. Bearing sons may have particularly high physiological costs, due to their faster rate of intrauterine growth and heavier than average birth weights [27]. In Westendorp and Kirkwood’s pioneering analyses of historical datasets from the British aristocracy, female longevity was negatively correlated with number of progeny suggesting a “trade-off” between longevity and reproduction [28]. While no studies, to our knowledge, have investigated frailty status in relation to number of children, it is theoretically possible that women are more frail in older age because of their physiological investment in reproduction.
3.2. Contributors to frailty
4. Frailty in relation to the accumulation of deficits
• Some co-morbidities disproportionately affect women. The flip-side of testosterone-induced immunosuppression [12] (so advantageous to women’s response to infectious disease) is a higher prevalence of autoimmune disease. Men have a higher prevalence of diseases which are immediately fatal without a prior episode of impaired health [e.g. myocardial infarction and rapidly progressive cancer, such as pancreatic cancer]. Women seem more susceptible to conditions associated with chronic ill health [e.g. chronic obstructive pulmonary disease, stroke and diabetes]. This has a significant impact on levels of disability and functional impairment. • Women have higher rates of depression and anxiety. The lifetime probability of developing an episode of depression and/or anxiety is significantly higher in women than in men [19]. These results are important because in middle aged and older people depressive symptoms make a large and unique contribution to risks of disability and poor health perception [20]. It also impacts on the prescription of drugs such as benzodiazepines, known to increase risks of unintentional injuries and falls. Interestingly,
4.1. Why is frailty important? Frailty, as variable vulnerability to adverse outcomes, is an important concept for all those who plan and provide care for older people. It is closely linked to advanced age and disease-related processes, yet is a distinct construct. Frailty allows health status to be summarized in a parsimonious way, providing a more precise quantification of individual vulnerability than chronological age alone; those who are frail are at increased risk of death, institutionalisation and worsening disability [29]. Despite its significance in relation to adverse outcomes, there is there is no universally accepted definition of frailty and it continues to be operationalised in different ways. 4.2. What is the Frailty Index? The conceptualisation of frailty as a multidimensional risk state facilitates its measurement by the number rather than by the nature of health problems. The Frailty Index (FI) model employs a well-
206
R.E. Hubbard, K. Rockwood / Maturitas 69 (2011) 203–207
Table 1 A 60-point Frailty Index score, based on data routinely collected in a Comprehensive Geriatric Assessment. Health deficit
Scoring instructions
Cognition
Score 0 if within normal limits, 0.5 if “Cognitive Impairment, No Dementia”, 1 if “dementia 0 = absent, 0.33 = mild; 0.67 = moderate; 1 = severe 0 = absent, 1 = present 0 = normal; 0.5 = low mood; 1 = depression 0 = absent; 1 = present 0 = absent; 1 = present
Dementia stage Delirium Affect/mood Anxiety Behavioural and psychological symptoms of dementia Violence Health attitude Mobility Walking aid Balance Falls Transfers Bowels Bladder Hobbies Banking Medications Shopping Transportation Climbs stairs Bathing Dressing Toileting Grooming Feeding Weight Appetite Sleep Daytime drowsiness Smoking In Emergency Department in last 30 days In hospital in last 6 months Co-morbidities Medications
0 = absent; 1 = present 0 = excellent/good; 1 = fair/poor 0 = walks on own; 0.25 = slow 0.5 needs assistance; 1 = cannot walk 0 = absent 0.25 = cane; 0.75 = walker; 1 = wheelchair 0 = unimpaired; 1 = impaired 0 = none; 0.5 present, not in last month; 1 = within last month 0 = independent; 0.5 = standby; 1 = any hands-on assistance 0 = normal; 0.5 = constipation; 1 = incontinence 0 = normal; 0.5 = occasional incontinence; 1 = incontinence 0 = retained; 0.5 = reduced; 1 = abandoned 0 = independent; 0.5 = needs some assistance; 1 = dependent 0 = independent; 0.5 = needs some assistance; 1 = dependent 0 = independent; 0.5 = needs some assistance; 1 = dependent 0 = independent; 0.5 = needs some assistance; 1 = dependent 0 = independent; 0.5 = needs some assistance; 1 = dependent 0 = independent; 0.5 = needs some assistance; 1 = dependent 0 = independent; 0.5 = needs some assistance; 1 = dependent 0 = independent; 0.5 = needs some assistance; 1 = dependent 0 = independent; 0.5 = needs some assistance; 1 = dependent 0 = independent; 0.5 = needs some assistance; 1 = dependent 0 = independent; 0.5 = needs some assistance; 1 = dependent 0 = normal; 1 = reduced 0 = normal; 0.5 = sometimes disrupted; 1 = problem 0 = absent; 0.5 = occasional; 1 = present 0 = never; 0.25 none in last 25 years; 0.5 = past; 1 = present 0 = no; 1 point for each visit (maximum 3)
0 = 1; 1 point for each week in hospital (maximum = 6) Score 1 for each; maximum is 16 <5 = 0; 5–7 = 1.0; 8–11 = 2; 12–15 = 3; >15 = 4
Note on scoring: 1 point is added for each deficit; the total points are divided by 60 to achieve a Frailty Index score, where 0 = no deficits present, and 1.0 = all 60 deficits present. In practice, many fewer than 1% of people would have a Frailty Index score >0.67.
defined methodology to create an index as a proportion of health deficits [30]. An example of a 60-point Frailty Index score, based on data routinely collected in a Comprehensive Geriatric Assessment is given in Table 1. The robustness of this method is strikingly illustrated by the fact that Frailty Indices can be constructed from different numbers and types of variables, yet still yield very comparable results between datasets. For example, analysis of data for 36,424 older people in four developed countries found Frailty Index values to be closely comparable across countries. Even though the number of items used to make up a Frailty Index in the different dataset varied between 30 and 100, in each dataset the mean value increased with age at approximately 3% per year in communitydwellers and was highly correlated with mortality [5]. Further studies confirm that the risk of adverse outcomes is defined more precisely by deficit indices than by phenotypic definitions of frailty [31]. Frailty Indices also have informative mathematical properties; they are well represented by a gamma distribution and reach a submaximal limit (of approximately 0.67), i.e. there is an empir-
ical limit to frailty [4]. Furthermore, for institutionalised or very ill populations, frailty levels are high but no longer accumulate with age [5]. This suggests important parallels to the redundancy exhaustion hypothesis of the reliability theory of ageing [32]. The reliability theory conceptualises ageing as the accumulation of random damage to a complex system composed of redundant parts. As defects accumulate, an organism loses its redundancy until eventually it becomes comparable to a system with elements connected in series. Accordingly, the frailest older people are comparable to a system with no redundancy: they can no longer accumulate deficits (i.e. become more frail); the next insult will cause failure of the system (i.e. death). 5. Why do women with health deficits live longer? In this review, we have established that women have longer life expectancies and a greater frailty burden; the underlying reasons for these two disparate phenomena have been explored. We must now address the question of why women can tolerate this greater number of heath deficits. In one study, for example, women had an estimated 20% lesser chance of dying at a given time than did men of the same chronological age and degree of frailty [6]. The conceptualisation of ageing as the failure of a complex system and the measurement of frailty as an index of accumulated deficits may enable us to understand women’s tolerance of their health deficits. 5.1. Men may have lower physiological reserves During youth and middle age, men have greater muscle strength than women with higher levels of physical performance. Therefore, at any given level of the Frailty Index, men have changed more from their baseline status. The male system may be “calibrated” differently, with more “optimal” physiological functioning during youth but a lower threshold for system failure in old age. This male fitness–frailty pleiotropy is congruent with evolutionary design. It is advantageous to the species to ensure young men are highly physically able and that women have a longer post-reproductive lifespan in order to enhance the reproductive success of their offspring [33]. 5.2. Women may have greater physiological reserves The evolutionary driver for sex differences in system design may be the need for greater physiological reserves in women. Women who bear children live shorter lives [28] and birth rates have fallen significantly. In 1871, women in the UK had an average of 5.5 children but by 1921 this had fallen to 2.4 secondary to more delayed and non marriage and the use of traditional and (novel) barrier methods of birth control [34] each linked to higher female education levels [35]. The female “complex system” may be designed for maximum fecundity, with higher levels of frailty among older women but anticipation of equal life expectancies between the sexes. In this scenario, women bear a greater burden of frailty, greater still if they reached their reproductive potential: a female fertility–frailty pleiotropy. Since women are currently limiting the number of children they bear, their life expectancies are longer than predicted by evolutionary design. 5.3. More factors may contribute to frailty status Women’s greater tolerance of frailty may be related to more pragmatic reasons than ultimate causation. The Frailty Index may not include all factors that impact life expectancy in older people, factors that are present more in men than in women. The Frailty Index captures physical, cognitive and psychological vulnerability, but other characteristics and attributes impact health status.
R.E. Hubbard, K. Rockwood / Maturitas 69 (2011) 203–207
Both individual-level characteristics (such as poor social support) [36] and community-level economic factors (such as neighbourhood deprivation) [37] are increasingly recognised as predictive of mortality in older adults. Interestingly, women have higher levels of social vulnerability than men [36] and inclusion of these factors would increase rather minimise the frailty sex differential. However, the recent emergence of the importance of social vulnerability with respect to health status and life expectancy does illustrate that other crucial deterministic factors may as yet be unidentified. 6. Conclusions In old age, women tend to have more deficits than do men, and be frailer by current definitions, but live longer lives. While many explanations have been proposed to account for these phenomena separately, there is much that still needs to be done to understand frailty and why it impacts older men and women in different ways. Complex interventions, particularly education and exercise, may modify the rate of deficit accumulation and delay the onset of frailty. Whether such interventions will benefit men and women equally are questions that investigations of Frailty Indices can address. This is motivating further enquiries by our group. Contributors REH wrote the first draft which was revised by KR. Competing interests KR has applied for funding to commercialize a version of the Frailty Index. Funding KR receives career support from the Dalhousie Medical Research Foundation as Kathryn Allen Weldon Professor of Alzheimer Research. Much of the work done here was supported by the Canadian Institutes of Health Research through operating grant MOP005170. Provenance and peer review Commissioned and externally peer reviewed. References [1] Christensen K, Doblhammer G, Rau R, Vaupel JW. Ageing populations: the challenges ahead. Lancet 2009;374:1196–208. [2] Office for National Statistics. Health Expectancy. London; 2004. www.statistics.gov.uk. [3] Oksuzyan A, Juel K, Vaupel JW, Christensen K. Men: good health and high mortality. Sex differences in health and aging. Aging Clin Exp Res 2008;20:91–102. [4] Rockwood K, Mitnitski A. Frailty in relation to the accumulation of deficits. J Gerontol A: Biol Sci Med Sci 2007;62:722–7. [5] Mitnitski A, Song X, Skoog I, et al. Relative fitness and frailty of elderly men and women in developed countries and their relationship with mortality. J Am Geriatr Soc 2005;53:2184–9. [6] Goggins WB, Woo J, Sham A, Ho SC. Frailty index as a measure of biological age in a Chinese population. J Gerontol A: Biol Sci Med Sci 2005;60:1046–51. [7] Møller AP, Fincher CL, Thornhill R. Why men have shorter lives than women: effects of resource availability, infectious disease, and senescence. Am J Hum Biol 2009;21:357–64. [8] Fikree FF, Pasha O. Role of gender in health disparity: the South Asian context. BMJ 2004;328:823–6.
207
[9] Gage TB. Are modern environments really bad for us?: revisiting the demographic and epidemiologic transitions. Am J Phys Anthropol 2005;S41:96– 117. [10] Lord C, Engert V, Lupien SJ, Pruessner JC. Effect of sex and estrogen therapy on the aging brain: a voxel-based morphometry study. Menopause 2010;17:846–51. [11] Bassil N, Morley JE. Late-life onset hypogonadism: a review. Clin Geriatr Med 2010;26:197–222. [12] Owens IPF. Ecology and evolution: sex differences in mortality rate. Science 2002;297:2008–9. [13] Falagas ME, Vardakas KZ, Mourtzoukou EG. Sex differences in the incidence and severity of respiratory tract infections. Respir Med 2008;102:627. [14] Schachter F. Causes, effects, and constraints in the genetics of human longevity. Am J Hum Genet 1998;62:1008–14. [15] Perrig-Chiello P, Hutchison S. Health and well-being in old age: the pertinence of a gender mainstreaming approach in research. Gerontology 2010;56:208–13. [16] Galdas PM, Cheater F, Marshall P. Men and health help-seeking behaviour: literature review. J Adv Nurs 2005;49:616–23. [17] DeWitte SN. Sex differentials in frailty in medieval England. Am J Phys Anthropol 2010;143:285–97. [18] Syddall H, Roberts HC, Evandrou M, Cooper C, Bergman H, Aihie Sayer A. Prevalence and correlates of frailty among community-dwelling older men and women: findings from the Hertfordshire Cohort Study. Age Ageing 2010;39:197–203. [19] King M, Nazareth I, Levy G, et al. Prevalence of common mental disorders in general practice attendees across Europe. Br J Psych 2008;192:362–7. [20] Ormel J, Kempen GI, Deeg DJ, Brilman EI, van Sonderen E, Relyveld J. Functioning, well-being, and health perception in late middle-aged and older people: comparing the effects of depressive symptoms and chronic medical conditions. J Am Geriatr Soc 1998;46:39–48. [21] Perrig-Chiello P, Staehelin HB. Women and health in old age: objective and subjective health and health behaviour of retired female workers and employees. Z Gerontopsychol Psychiatr 1996;9:195–205. ˜ J, Lloret A. Why women have more Alzheimer’s disease than men: gen[22] Vina der and mitochondrial toxicity of amyloid-beta peptide. J Alzheimers Dis 2010;20(Suppl. 2):S527–33. [23] Middleton LE, Mitnitski A, Fallah N, Kirkland SA, Rockwood K. Changes in cognition and mortality in relation to exercise in late life: a population based study. PLoS One 2008;3(9):e3124. [24] Hubbard RE, Woodhouse KW. Frailty, inflammation and the elderly. Biogerontology 2010;11:635–41. [25] Hubbard RE, Lang IA, Llewellyn DJ, Rockwood K. Frailty, body mass index, and abdominal obesity in older people. J Gerontol A: Biol Sci Med Sci 2010;65: 377–81. [26] Howard C, Ferrucci L, Sun K, et al. Oxidative protein damage is associated with poor grip strength among older women living in the community. J Appl Physiol 2007;103:17–20. [27] Hurt LS, Ronsmans C, Quigley M. Does the number of sons born affect longterm mortality of parents? A cohort study in rural Bangladesh. Proc Biol Sci 2006;273:149–55. [28] Westendorp RG, Kirkwood TB. Human longevity at the cost of reproductive success. Nature 1998;396:743–6. [29] Rockwood K, Mitnitski A, Song X, Steen B, Skoog I. Long-term risks of death and institutionalization of elderly people in relation to deficit accumulation at age 70. J Am Geriatr Soc 2006;54:975–9. [30] Searle SD, Mitnitski A, Gahbauer EA, Gill TM, Rockwood K. A standard procedure for creating a frailty index. BMC Geriatr 2008;8:24. [31] Kulminski AM, Ukraintseva SV, Kulminskaya IV, Arbeev KG, Land K, Yashin AI. Cumulative deficits better characterize susceptibility to death in elderly people than phenotypic frailty: lessons from the Cardiovascular Health Study. J Am Geriatr Soc 2008;56:898–903. [32] Gavrilov LA, Gavrilova NS. Reliability theory of aging and longevity. In: Handbook of the biology of aging. 6th edition Academic Press; 2007. [33] Lahdenperä M, Lummaa V, Helle S, Tremblay M, Russell AF. Fitness benefits of prolonged post-reproductive lifespan in women. Nature 2004;428:178– 81. [34] Department of Health, UK. The UK population: past, present and future; 2005. http://www.statistics.gov.uk/downloads/theme compendia/fom2005/ 01 fopm population.pdf [Accessed February 2011]. [35] Lucas RE. Lectures on economic growth. Cambridge and London: Harvard University Press; 2004. [36] Andrew MK, Mitnitski AB, Rockwood K. Social vulnerability, frailty and mortality in elderly people. PLoS One 2008;3(5):e2232. [37] Major JM, Doubeni CA, Freedman ND, et al. Neighborhood socioeconomic deprivation and mortality: NIH-AARP diet and health study. PLoS One 2010;5(11):e15538.