Nutritional management of older adults with cognitive decline and dementia
Age-related cognitive decline is a main predictor of disability among elderly people, and with the continued expansion of the aging population and the increase in life expectancy, the prevalence of mild cognitive impairment and dementia represented by Alzheimer's disease (AD), which is a multifactorial neurodegenerative disorder of older adults, have increased. Recent epidemiological and observational studies suggest a relationship exists between lifestyle factors, including nutrition and diet, and cognitive function in aging adults. It is also suggested that malnutrition and nutrient deficiencies are associated with cognitive decline in patients with dementia. There are a variety of nutritional factors, including nutritional status and dietary patterns, that might be associated with cognitive function, and specific micronutrients and dietary components have been suggested to have an association with cognitive function as well. Based on these findings and evidence, evaluation of nutritional state, as well as nutritional intervention, might be able to play a role in the management and prevention of dementia. Geriatr Gerontol Int 2014; 14 (Suppl. 2): 17–22.
Cognitive impairment and dementia are the major risk factors for disability among older adults, and optimizing mental health, as well as physical and social health, is important for maintaining independence and a good quality of life. With the increase in global life expectancy and the continual proportion of the aging population, the prevalence of mild cognitive decline and advanced forms of cognitive disorders represented by Alzheimer's disease (AD) has also increased. Several epidemiological and observational studies suggest that nutritional status, as well as health behaviors, frailty, disability, functionality status and chronic diseases (e.g. hypertension, cardiovascular disease, diabetes mellitus and metabolic syndrome), is associated with cognitive impairment and dementia.[1-6] Recent evidence has also shown that there is a relationship between lifestyle factors, including nutritional status, dietary patterns and cognitive function, in older adults.[2, 4, 7-10]
Advances in research into the mediators implicated in the pathogenic cascade of AD have suggested that specific nutrients and their combination might play a role in modulating the potential mediators involved in the pathology of AD. An association between nutritional status, including the intake of certain dietary nutrients, and the development of AD has been also shown by epidemiological studies. In practice, malnutrition and nutrient deficiencies, associated with cognitive decline, are often observed in patients with dementia, and recent epidemiological studies have suggested that an increased intake of certain nutrients might lower the risk of dementia. Despite these circumstances, supplementation of specific nutrients is not clinically established or routinely adopted in the cognitive management of AD. In the present review, recent findings on the relationship between nutritional state and dementia, together with the perspective of an efficient nutritional intervention for the management of dementia in clinical practice, will be described.
Nutritional status and cognitive function
Nutritional status is compromised among older adults in general, and the risk of malnutrition is prevalent in an aging population. A changes in nutritional status, specifically the presence of or the risk of malnutrition, has been associated with cognitive impairment among elderly patients in hospital and the community-dwelling elderly population.[6, 12-18] The cause of malnutrition is usually multifactorial and unintentional weight loss at any bodyweight as a result of loss of appetite, poor food intake, pain and acute gastrointestinal symptoms, which are well recognized as sensitive malnutrition indicators. These indicators are incorporated into various screening and assessment tools, such as subjective global assessment (SGA), the Mini-Nutritional Assessment (MNA)[21, 22] and the Malnutrition Universal Screening Tool (MUST), which were developed and validated to identify malnutrition or those at risk of malnutrition. Serum albumin and rapid turnover proteins, as well as white blood cells, are the useful indicators of nutrition status, especially in acute care settings (or hospitalized patients), whereas the markers need to be carefully evaluated along with other test values that might affect the assessment results.
It was shown that there was a positive relationship between nutritional status and cognitive function in a large sample of older adults living independently or in specialized housing, and that chronic malnutrition can lead to cognitive decline. In parallel, obesity is also suggested to be one of the major causes not only of insulin resistance and hyperinsulinemia, but also of cognitive impairment.[26-28] It was also reported that mild cognitive impairment (MCI) might be associated with nutritional risk in elderly patients. In that study, 38.3% of patients were diagnosed with MCI, and 51.6% were either in a state of malnutrition or at risk of malnutrition (n = 120). There was a significantly higher frequency of malnutrition or nutritional risk among older adults with MCI compared with those who had no cognitive impairment (P = 0.002), suggesting that older adults who were malnourished or at risk of malnutrition were more likely to suffer from MCI. Malnutrition often accompanies AD, ranging from 15 to 50%.[29-31] A longitudinal study in older adults aged more than 65 years showed that accelerated weight loss might precede diagnosis with AD. This result suggests that weight loss might be a preclinical indicator of AD, and that people with dementia tend to change their dietary habits.
It is important to assess the actual nutritional status of older adults using scales such as the MNA. Assessment with the MNA scale among patients with mild-to-moderate dementia (MMSE = 22 ± 6) showed that 9% belonged to the malnutrition group (MNA <17.5) and 34% were at in the risk of malnutrition group (MNA 17.5–23.5).[21, 33] Whereas the association between nutritional status and cognitive function in older adults is suggested, it is not still evident whether nutritional intervention or improvements in nutritional status positively affect cognitive function in the clinical setting. There is a study that found that the additional intake of protein and calories was associated with an improvement in the Mini-Mental State Examination (MMSE) scores in malnourished, community-dwelling older adults, suggesting that nutritional interventions to improve nutritional status could positively affect cognitive performance. Recent findings further support the clinical relevance of nutritional factors in AD, and that malnutrition in AD is related to increased mortality,[35, 36] aggravation of behavioral disorders and lower activities of daily living (ADL).
In terms of dietary patterns and cognitive function, observational studies have shown a positive association between dietary contents, nutritional factors and risk of cognitive decline leading to dementia.[2, 8, 9, 38-41] It was shown that daily consumption of vegetables and fruit was associated with a reduction in the risk of all-cause dementia (hazard ratio 0.72, 95% confidence interval 0.52–0.97) in non-demented older adults aged more than 65 years, suggesting that dietary patterns might be involved in the risk of subsequent progression of cognitive impairment. In addition to improving the dietary risk factor against the development of cognitive decline among older adults, it is recommended that other factors that might affect dietary habits, such as physical exercise, social interactions, mental stimulation and access to adequate healthcare, be modified.
Nutritional factors and dementia
Dietary intake and nutritional state are environmental lifestyle-related factors that might be related to cognitive decline and dementia in older adults. A large number of observational and epidemiological studies regarding the impact of nutrition on cognitive decline suggest that various dietary and nutritional factors have an association with cognitive decline and AD, including dietary patterns, nutritional status, and the type and distribution of fatty acid intake. A population-based prospective cohort study showed that a reduced risk of all-cause dementia in the general Japanese population is associated with a dietary pattern characterized by a high intake of soybeans and soybean products, vegetables, algae, and milk and dairy products, along with a low rice intake.
In addition, specific dietary and nutritional components might also have an association with cognitive performance. It has been suggested that Mediterranean-type diets, a multi-nutrient approach characterized by a high intake of fruits, vegetables, cereals, fish and monounsaturated fatty acids, are associated with a lower risk of dementia and mortality, protecting against age-related cognitive decline and MCI.[8, 40, 44-47] In contrast, an increased risk of MCI has been associated with a diet rich in saturated fatty acids, showing the potential association between lifestyle factors, including dietary patterns and cognitive decline, in older adults. In addition, specific dietary components and micronutrients, such as folate, vitamin B, vitamin C and vitamin E, have been suggested to have an association with cognitive decline and dementia. It was reported that dietary intake or supplementation of anti-oxidant vitamins, such as vitamin C and vitamin E[48-52] or omega-3 fatty acids,[41, 53] reduced the risk of the incidence of AD, whereas low serum concentrations of vitamin B, vitamin C and plasma accumulation of homocysteine were associated with an increased risk of AD.[54-62] Among the B vitamins, folate and vitamin B12 are mainly evaluated for their role in cognitive function, and vitamin B12 deficiency, characterized by peripheral neuropathy and depression,[63, 64] is also associated with cognitive decline.[10, 65-67] Insufficient intake of folate is known to contribute to neurological deficits including cognitive impairment, and low folate status has been shown to be associated with poor cognitive function. Preclinical studies have shown that administration of folic acid can inhibit amyloid toxicity.[70, 71] Although the evidence based on randomized clinical trials and epidemiological studies for the potential role of vitamin B12 and folate status in prevention of cognitive decline is intriguing and emerging, more research is required to evaluate the impact of vitamin B status on cognitive decline in older adults and to understand the effect of vitamin B supplementation on cognitive decline in this population.
It is widely recognized that the brain is also susceptible to oxidative stress and damage as a result of its high metabolic rate and relatively lower regenerative capacity, accounting for approximately 20% of total body oxygen consumption,[72-74] and oxidative stress and neural damage might be the fundamental basis for neurodegenerative diseases, such as AD.[10, 75] It was also shown by cell-culture studies in vitro that both vitamin C and vitamin E can inhibit Aβ deposition[76, 77] and neuronal cell death. There is some evidence to suggest that anti-oxidant nutrients represented by vitamin E might have an important role in cognitive function in older adults. Observational studies have shown a relationship between dietary intake of vitamin E and a change in cognitive performance among older adults.[10, 51, 79] It was reported that there was a 36% reduction in the rate of cognitive decline among the population whose intake of total vitamin E was in the highest quintile compared with those in the lowest quintile of its intake. In addition, a significant, positive effect of vitamin E supplementation on the rate of cognitive decline in women who had low dietary intake at baseline based on post-hoc analyses from the Women's Health Initiative was reported. These studies suggest that a higher dietary intake of anti-oxidant vitamins might be associated with age-related cognitive decline, whereas the relationship between the intake of these vitamins and management of AD are still conflicting.[81-83]
Epidemiological and animal studies have also suggested that dietary fish or fish oil rich in omega-3 fatty acids, represented by docosahexaenoic acid and eicosapentaenoic acid, might prevent AD.[84-87] Administration of omega-3 fatty acid in patients with mild to moderate AD patients did not delay the rate of cognitive decline according to the MMSE. Whereas evidence for the potential role of omega-3 fatty acids in cognitive performance is intriguing, more research is necessary to evaluate the impact of omega-3 fatty acids status on cognitive performance in older adults, and to gain a greater understanding of the effect of its supplementation on cognitive decline and dementia.
Nutritional approach toward the management of dementia
Nutrient deficiencies are suggested to be involved in age-related cognitive decline, as well as in the pathogenesis of AD, by epidemiological studies as described. At the same time, there is a still small number of randomized clinical trials regarding nutritional interventions and approaches for the prevention of AD, and further investigation based on well-designed randomized controlled clinical trials is important. There is also a possibility that the combinatorial intake of multiple nutrients might have more beneficial effects against cognitive impairment and dementia compared with single nutrient supplementation, which was suggested, in part, by studies using APP/PS1 transgenic mice where a multi-nutrient diet reduced AD-like neuropathology in these transgenic mice compared with their wild-type littermates. In this study, it was further suggested that the effectiveness of specific nutrients might depend on the dietary context in which they are provided.
The available evidence shows a relationship between lifestyle factors, including dietary patterns and nutritional status, and cognitive function in the elderly population,[2, 4, 7-10] and a variety of dietary components and nutritional factors might possess protective properties against cognitive decline and dementia. Also, potential targets for nutritional intervention will be provided based on research advances in the pathophysiology and mechanism of AD. In addition, specific dietary components and micronutrients have been identified as having an association with cognitive function, such as vitamin B12, folate, vitamin E, omega-3 fatty acids and a high ratio of polyunsaturated-to-saturated fats. These dietary components are relatively abundant in the Mediterranean diet, characterized by a high intake of fruits, vegetables, cereals, fish and monounsaturated fatty acids. The Mediterranean diet is suggested to have a potential to protect against age-related cognitive decline and cognitive impairment.
There are still few randomized clinical trials that have been designed to test for the role of nutrition in cognitive decline and dementia based on observations from epidemiological studies. More research is necessary to understand the multi-nutrient strategy for cognitive decline and dementia, as well as to unravel the specific role of each dietary component in cognitive function and the synergistic interaction between different nutrients. In the near future, the combinatorial effects of nutritional intervention and pharmacological therapy will be more effective for the treatment and prevention of dementia.
This study was supported by Health and Labor Sciences Research Grants (H23-Choju-002) from the Ministry of Health, Labor and Welfare of Japan, the Research Funding for Longevity Sciences (25-11) from National Center for Geriatrics and Gerontology (NCGG), Japan, and by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Culture and Sports of Japan (24590876). The authors declare no conflict of interest.
The author declares no conflict of interest.