2020 Volume 6 Pages 4-11
Increasing emphasis has been placed on extending healthy life expectancy. Patients with dementia, cerebrovascular disease, and frailty due to old age account for 24.8%, 18.4%, and 12.1%, respectively, of people aged 65 years or more requiring nursing care.
The causes of dementia are numerous, and the most common type is Alzheimer’s disease (AD), followed by vascular dementia (VaD), and dementia with Lewy bodies. Lifestyle-related diseases such as diabetes and hypertension are involved in the onset and progression of dementia.
The term “frailty” indicates an intermediate stage between a healthy state and one where an individual will require nursing care. Frailty involves physical, mental, and psychological decline, and possibly also social factors such as solitude and financial distress.
Sarcopenia, which causes muscle loss, and a decrease in muscular strength and physical function, is the key factor in physical decline.
Dementia, sarcopenia, and frailty are closely related. The frequency of frailty is higher in patients with AD than in healthy elderly people. Cerebrovascular disease (CVD), such as lacunes and white matter lesions, is common in elderly patients with AD. Frailty is more closely associated with AD + CVD than with AD alone; and it also shows a stronger association with VaD than with AD.
The close relationship between dementia and frailty/sarcopenia is believed to constitute a vicious cycle.
Healthy life expectancy refers to the period during which a person is able to live independently without needing care in their daily life. According to a survey conducted in 2016 by the Ministry of Health, Labor and Welfare of Japan, average life expectancy was 80.98 years for males and 87.14 years for females, while healthy life expectancy was 72.14 and 74.79 years, respectively.The difference between average life expectancy and healthy life expectancy was 12.35 years for women and 8.84 years for men. The results of the same survey also revealed the causes for the need for nursing care in people aged 65 years or over, with dementia, cerebrovascular disease (CVD), and frailty due to old age occupying 24.8%, 18.4%, and 12.1% of this particular population, respectively1).
Recently, increasing emphasis has been placed on extending healthy life expectancy, and achieving this goal will require new efforts to combat dementia, cerebrovascular disorders, and frailty. The causes of dementia are numerous, and the most common type is Alzheimer’s disease (AD), followed by vascular dementia (VaD), and dementia with Lewy bodies (DLB). Lifestyle-related diseases such as diabetes and hypertension are involved in the onset and progression of dementia.
Dementia, CVD, and frailty are closely related to each other. In this article, I would like to give an overview of the relationship between frailty and dementia, including findings made at our department related to this issue.
Frailty has been shown to be associated with increased physical limitations and disability, and results in generally poorer health in older people2).
The term “frailty” is used to denote the intermediate stage between a healthy state and one where the individual will require nursing care. This term was first proposed by the Japan Geriatrics Society in 2014. It is characterized by an increased susceptibility to stress due to the decrease that occurs in physiological reserves with advanced age, with likely outcomes including impaired function in daily activities, the need for nursing care, and death.
Before reaching a frail state, a healthy individual will also pass through another distinct stage termed “pre-frailty”. Both the pre-fail and frail states are not irreversible, however: appropriate intervention and support, including guidance on exercise and nutrition, can result in a return to a healthy state with improved function in daily activities. Therefore, early intervention is important3).
Frailty has three elements (Figure 2)
Frailty involves a decline not only in an individual’s physical condition, but also in their mental and psychological well-being. This may take the form of a decline in cognitive abilities or depression, for example. Social factors, such as solitude and financial distress, must also be taken into account in its development.
Sarcopenia is considered to be the key factor in physical decline with age, resulting in muscle loss, and a decrease in muscular strength and physical function.
Diagnostic criteria for frailty (Table 1)Evaluation method for frailty: Japanese-Cardiovascular Health Study (J-CHS) criteria
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Number of applicable items
0: healthy 1~2: pre-frailty 3 or more: frailty
Physical frailty was determined according to the revision of the screening test utilized in the Obu Study Health Promotion for the Elderly4). The criteria for physical frailty were based on the presence or absence of the following 5 measurable characteristics: weakness (low grip strength: men < 26 kg, women < 18 kg); slowness (walking speed of < 1.0 m/sec over 6m at usual pace); weight loss (2–3kg in 6months); low physical activity; and exhaustion. An individual meeting 3 or more, 2 or 1, and none of these 5 characteristics was deemed to be at the frail, pre-frail, and non-frail stage, respectively.
Comprehensive geriatric assessment (CGA), which is commonly used to assess physical impairment in the elderly, is also useful for assessing frailty.
One study investigated outcomes in individuals scoring frail in more than 8 out of 25 items included in a kihon checklist applied in a survey conducted by the Ministry of Health, Labor and Welfare of Japan in 2010. The results showed that at 1 year later, the number of these individuals requiring support/nursing care was 5 times greater than that in those who did not, while the number of deaths was 4 times greater5).
Diagnostic criteria for sarcopenia (Figure 3)
Sarcopenia is defined according to a set of criteria
developed by the Asian Working Group for Sarcopenia (AWGS)6). These criteria comprise the following 3 components: low handgrip strength (< 26 kg for men and < 18 kg for women); low gait speed (walking speed of < 0.8 m/sec at the usual space); and low muscle mass as assessed according to the skeletal muscle mass index (7.0 kg/m2 for men and 5.7 kg/m2 for women as measured by bioelectrical impedance: BIA ).
Relationship between AD and frailtyA meta-analysis of studies investigating the relationship between AD and frailty revealed that the prevalence of frailty in patients with mild-to-moderate AD was between 11.1% and 50.0% (prevalence, 31.9%; 95% confidence interval; 15.7% to 48.5%)7). Moreover, the prevalence of frailty in patients with AD (31.9%) was higher than that in the general elderly (10%)8).
One earlier study by our group investigating the prevalence of frailty in 140 outpatients with mild-to-moderate AD attending our memory clinic revealed that the ratio of frailty to pre-frailty in this group was 68% (frailty, 24%;pre-frailty, 44%)9).
Relationship between AD and sarcopenia (Figure 4)
Lower extremity muscle strength and walking speed already show decrease even in patients with early AD/MCI
A cohort study of community-dwelling elderly revealed an association between cognitive function and skeletal muscle mass or motor function10). Muscle strength has been shown to be associated with mild cognitive impairment and the development of Alzheimer’s dementia11). It has been reported that brain volume and lean mass are positively correlated in early AD patients12).
One study by our group investigating the relationship between the severity of AD and the frequency of sarcopenia demonstrated that the frequency of sarcopenia increased with the progression of dementia, with the results showing that it was 12% in the healthy elderly (MMSE, 27 points), 39% in patients with early AD or mild cognitive impairment (MCI) (MMSE, 25 points), 46% in patients with mild AD (MMSE, 22 points), and 56% in patients with moderate AD (MMSE, 17 points)13).
A decrease in lower extremity muscle strength and walking speed is already observed even in patients with early AD/MCI. One study showed that this decrease in strength was not only observed in the lower extremities, but also in the upper extremities in patients with moderate AD13), indicating the need for intervention to be commenced from an early stage in the development of AD.
Cerebrovascular disease, such as lacunes and white matter lesions, is common in elderly patients with AD.In one study, our group compared the prevalence of physical frailty in patients with AD alone with that in those with AD accompanied by CVD. A total of 82 outpatients with AD alone (AD group) and 25 with AD accompanied by CVD (AD + CVD group) aged 65 years and older attending our memory clinic were enrolled. The AD + CVD group showed a significantly higher frequency of frailty (40%) and pre-frailty (52%) than the AD group (frailty, 16%; pre-frailty, 38%).
The study also included an evaluation of sarcopenia in each group based on the above-mentioned criteria of the AWGS. The AD + CVD group showed a significantly higher frequency of sarcopenia (68%) than the AD group (30%)14).
Further work by our group based on MRI and SPECT imaging suggested an association between frailty and small vessel disease pathology, including periventricular hyper-intensity, deep white matter hyper-intensity, and decreased regional cerebral blood flow (rCBF) in the anterior cingulate in patients with AD15).
Frailty and sarcopenia show stronger association with VaD or DLB than with AD (Figure 6)
In one study, our group investigated frailty and sarcopenia in patients with AD (24 men and 53 women; mean age, 83.0 ± 5.1 years), VaD (10 men and 12 women; mean age, 80.4 ± 5.0 years), or DLB (28 men and 20 women; mean age, 81.2 ± 5.5 years) using a relatively simple screening test (Dr. SUPERMAN)16). Our results showed a correlation between Lewy body dementia or vascular dementia and an increase in dysfunction, such as a reduction in ADL, falls, and upper and lower limb dysfunction compared with in AD17).
A cross-sectional study of 654 local residents over the age of 75 years revealed that the risk of developing dementia from a state of frailty was 3.2 times the odds ratio (95% CI: 1.7 to 6.2) in patients with AD and 6.7 times the odds ratio (95% CI: 1.6 to 27.4) in those with vascular dementia18).
Another study monitoring 5,480 people in three French cities over a period of 7 years found that the risk of developing dementia from a status of frailty was 1.22 times the odds ratio in patients with AD (95% CI: 0.80 to 1.86) and 2.50 times the odds ratio in those with VaD (95% CI: 1.01 to 6.19). Frailty thus showed a stronger association with VaD than with AD19).
Common mechanisms for dementia, sarcopenia, and frailtyA systematic review investigating the relationship between frailty and cognitive impairment identified a number of common factors between them, including the presence of Alzheimer’s pathology, reduced testosterone, poor nutrition, chronic inflammation, the risk of cerebrovascular disease, and depression20).
Our group has shown that a greater degree of oxidative damage was found in AD with CVD than in AD alone21).
Much work remains to be done on the relationship between frailty/sarcopenia and cognitive impairment, however, and further research is needed.
There is a close correlation between dementia and frailty/sarcopenia, with the combination believed to constitute a vicious cycle. In patients with dementia, the amount of physical activity decreases due to decreased motivation, and ADL decreases due to the appearance of muscle weakness and fatigue. On the other hand, it has been reported that ADL is reduced and the risk of developing dementia is high in frail elderly people.
This close relationship among frailty, sarcopenia, and dementia in the elderly, indicates the importance of preventive measures, including guidance on nutrition and exercise, in the elderly, and more research needs to be done on this issue.
The authors would like to thank Professor Jeremy Williams of the Department of International Medical Communications at Tokyo Medical University for editing and reviewing the English of this manuscript.
The authors have no conflicts of interest.
