Background

The World Alzheimer Report (2015) estimates that 46 million people worldwide are living with Alzheimer’s disease (AD) and other dementias, and that this prevalence will increase to 131.5 million in 2050. In developing countries, including Brazil, this calculated rate is three to four times larger than that in developed countries [1].

AD corresponds to 50–70% of all dementia syndromes, classified as a progressive neurodegenerative disease showing diffuse cortical atrophy with three stages of evolution: mild, moderate, and severe. Memory decline, attention, and language impairments may be seen during the disease course, followed by behavioral changes that end up spoiling the performance in basic activities of daily living and problem-solving abilities [2].

Despite the discovery of new treatments, there is no “cure” to stop or modify the disease course. For this reason, several non-pharmacological interventions are essential to improve the quality of life of these patients. Interdisciplinary assistance by nutritionists, psychologists, physical therapists, speech therapists, and other professionals who can provide appropriate guidance for the symptoms of these patients is, therefore, essential [3].

Regarding nutrition for patients with AD, weight loss and behavioral changes related to food are major objects of scientific study, as they trigger deterioration of the quality of life of patients and caregivers. The aim of this review is to show the current methods of nutritional treatments for patients with AD.

Review of the literature

Nutritional intervention strategies for mildly impaired patients with Alzheimer’s disease

Currently, in the early stage of AD, the nutritional approach has focused on two important points: (1) to correctly orient caregivers and patients regarding prevention of body weight reductions and (2) to decrease synaptic loss [4].

At this stage, the patient feeds alone and important nutritional modifications are not verified. Management of the nutritional state is suggested to evaluate any changes in body weight.

Regarding synaptic loss, the evolution of the knowledge on the pathophysiology of this disease has allowed the correlation of a protective factor for impaired neurons in AD. Countries that have dietary patterns characterized by high consumption of fish, fruits, and vegetables (foods that usually offer larger amounts of antioxidants and polyunsaturated fatty acids) have lower incidence of dementia [5].

A similar result was found in a prospective cohort study in New York where 2148 elderly without dementia followed for 1.5 years in order to verify the relationship between the intake of food groups (variation related four nutrients: saturated fatty acids, vitamin E, vitamin B12, and folic acid) and the risk of AD development found that when the action of these nutrients are evaluated in isolation to prevent AD there is no evidence of a protective effect, but when they are considered together, there is evidence that increased consumption of nuts, fish, tomatoes, poultry, cruciferous vegetables, fruits, vegetables, leafy dark green, lower intake of dairy lacteal products high in fat, and red meat may contribute to the decrease in AD development, demonstrated that the consumption of food sources of polyunsaturated fats, folic acid, and vitamin E should be encouraged at all stages of life [6].

There is evidence that encouraging consumption of specific nutrients, such as choline, docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and uridine monophosphate, can boost neurogenesis and also contribute to synaptic improvement in AD [7].

Choline is a micronutrient from the group of water-soluble B vitamins, synthesized by the human body. Usually, the exogenous intake of choline is performed in the chemical form of phosphatidylcholine that apparently has the ability to cross the blood–brain barrier [8].

When used as a drug, it is in the bioavailable form of citicoline in which its main functions treat cerebrovascular disease origin, among them dementias. Important systematic literature review conducted to verify the effects of citicoline in attention and memory of elderly with cognitive disabilities found that in the short and medium time of use, beneficial effects are found, but it is emphasized that there is a need to develop further studies of longer duration of follow-up for real evaluation of the choline about memory and attention [9].

However, another systematic literature review conducted in order to verify the effects of this nutrient at different stages of life that addressed from pregnancy to adult phase, demonstrated that choline may have positive effects on cognition in any of these ;life steps since it is supplemented in high amounts. Due to lack of studies on this subject, there is still no consensus of the exact amount of choline to be supplemented in cases of dementia [10].

DHA is an important fatty acid with key roles in cellular homeostasis and in the formation of cell membranes. Another function regards participation in neurogenesis and neural integrity. Since its consumption is recommended for patients with dementia, its main food sources are fish, algae, and krill (crustacean). It is known that nutrient intake imbalances of DHA can result in cellular dysfunction [11–13].

Jicha and Markesbery (2010) [14] reported that the DHA concentration in patients with mild cognitive impairment (MCI) and AD is decreased in the hippocampus and in the cerebral cortex, highlighting the importance of this nutrient.

Randomized, double-blind, placebo-controlled trials designed to investigate the potential effect of DHA were conducted in the USA, following 485 individuals with 55 years presenting Mini Mental State Examination scores over 26 and logic memory (Weschler Memory Scale III) baseline score 1. Participants were randomly assigned to 900 mg of DHA for 24 weeks and found that supplementation with DHA is associated with better scores of immediate and late verbal recognition. This study also found that serum levels of DHA in the plasma of supplemented individuals doubled, demonstrating its importance for the improvement of memory and health as a whole [15].

To establish what test or exams are to be used to verify the efficiency of consumption of the nutrients may have a protective action on cortical morphology, Pistollato et al. (2015) [16]. By review of the literature, it was indicated that neuroimaging can be a useful instrument, in this regard, because it detects changes in the cerebral cortex. But, the authors related that in addition to the images, there is a need to apply neuropsychological batteries and examine biochemical blood of specific parameters of these nutrients because all these measures when used together can express more accurate results.

Available in the Brazilian and European markets, a nutritional compound was registered as Fortasyn Connect®, containing EPA/DHA, uridine, choline, phospholipids, vitamins E, C, B complex, and selenium. This product is marketed as dietary supplement Souvenaid® and was developed specifically to work in the formation of more phospholipid structures in the brain; it appears to influence the increase of dendritic spines and synaptic proteins in the growth of neurites, which are important for the formation of synapses [17, 18].

A 12-week study was performed to analyze memory improvements by the action of this nutritional compound, finding that after daily supplementation patients showed improvements in delayed memory [18].

Scheltens et al. (2012) [19] also studied the efficacy of this dietary supplement in 259 patients with mild AD, without use of any cholinesterase inhibitors for 24 weeks; 130 patients received supplementation and 129 were only monitored for neuropsychological test results. The group of supplemented patients had improved memory performance by the neuropsychological test battery (NTB), concluding that the adoption of this supplement as part of treatment can improve memory in mildly impaired patients with Alzheimer’s disease. Extended results for another 24 weeks concluded that patients with AD can safely tolerate this product for 48 weeks [20].

Souvenaid® was initially developed with the purpose of maintaining or restoring synaptic function in the early stage of AD but, due to the nature of its compounds, its use has already been extended to study rats with induced spinal cord injury. It was found that supplementation led to protection of the spinal cord tissue with increased neuronal and oligodendrocyte survival and preservation of axonal integrity [21].

So far, these are the most studied points of the nutritional approach for mildly impaired patients. The consensus is that most studies in nutrition are developed to contribute to treatment and quality of life of patients.

Nutritional Intervention strategies for moderately impaired patients with Alzheimer’s disease

For moderately impaired patients, significant behavioral changes are seen that affect feeding and often result in an insufficient supply of nutrients for maintenance of nutritional status. Distraction, passivity, refusal of food, difficulty chewing or swallowing food, and increased mealtime are some of the symptoms [22].

For these reasons, feeding time can result in conflicts for the caregiver because supervision or task orientation is needed, which is more burdensome than only preparing food and leaving the patient alone. This care during the meals along with the supervision of all activities of daily living of patients brings fatigue and often exhaustion to caregivers [23].

Orientation to the caregiver at this stage is essential to encourage the adoption of specific strategies for the experience which is significant for both the social engagement and the nutritional acceptance of the elderly [24].

A Swedish study was undertaken to properly train caregivers in relation to food; among its results, the better the interaction of the patient with the caregiver, the greater the food intake [25].

In patients with apraxia, the movement to fill the cutlery and drive them to the mouth is difficult. The use of hands in this case is considered as a means to allow greater independence in feeding time. Finger foods are also oriented in order to achieve a greater caloric intake [26].

Making verbal or gestural guidance, indicating the meal time and how the patient should proceed is essential, since it helps in visual agnosia, which is manifested in dementia, preventing the recognition of food and cutlery combined with forgetfulness of not knowing how use them. Touching the patient or making hand-in-hand aids are effective at the beginning of the meal [27].

All these measures are orientated to caregivers in order to prevent weight loss, commonly found in all stages of dementia. There are several explanations for weight loss. One is the presence of cognitive and behavioral disorders that patients have, such as exacerbated agitation, for example [28].

It is important to note that the use of multiple medications, adopted for the treatment of AD and also their behavioral symptoms, increase the risk of adverse effects on the gastrointestinal tract (nausea, vomiting, diarrhea, loss of taste, smell, and appetite) that can harm food intake and also contribute to weight loss of these patients [29].

There is also evidence that weight loss may be directly related to the morphological impairment of the brain, which is caused by the disease. A significant association of low body weight with atrophy of the mesial temporal cortex was observed in patients with AD, particularly in the region involved in control of feeding behavior [30, 31].

Another possible explanation for weight loss is based on the dysfunction caused by low energy consumption and the sharp state of hypercatabolism of these patients. It has been suggested that malnutrition can be a factor in the etiology of dementia and other psychiatric and cognitive disorders, although nothing has been proven [32, 33]. This process is worrisome because it generates decrease in mass and muscle strength resulting in reduced functional capacity [34].

To recover weight and maintain a good nutritional status, proper nutritional guidelines regarding adoption of the correct amount of protein and calories needed to recover the patient’s weight are required. The recommendation of the protein intake of the elderly changed; 1.0 g/kg weight per day used to be enough for proper maintenance of muscle mass, but now, several studies have shown that 1.5 g/kg weight per day are required to maintain a positive nitrogen balance and generate muscle mass [35].

In most cases, protein and caloric recommendations are achieved only with the use of dietary supplements, defined as concentrated sources of nutrients and calories that should be prescribed to increase the intake of specific nutrients normally used in addition to the usual diet of the patient. The use of dietary supplements optimizes the nutritional status and contributes to improvement of the immune response [26].

A recent review, conducted in order to evaluate the impact of the use of oral nutritional supplements (ONS), found that the independently supplemented patient has an average readmission time of 2 to 3 days while patients that are not supplemented often return to service, staying 8 to 10 days. This study proves the hypothesis that, once supplemented, patients tend to have better recovery and shorter stays while decreasing healthcare system costs [36].

Still in relation to protein-energy supplementation studies, in Toronto, 34 institutionalized patients with AD were assessed to check their effectiveness on the body composition; it was found that after 21 days of supplementation the body mass index (BMI) had considerably improved [37].

Trelis and Lopez (2004) [38] showed that, despite the benefits of food supplements, only 11% of outpatients use them. There are no studies in Brazil that indicate how much outpatients resort to some sort of supplementation in the diet, but it is known to provide the elderly with low volume, high concentration of calories and protein, stimulate consumption, and adherence to the treatment [39].

Stratton and Elia (2007) [40], in a review of the clinical practice of adopting the use of oral nutritional supplements, came to the conclusion that patients with dementia, both in mild and moderate stages, should make use of ONS to ensure adequate supplies of energy and provide essential nutrients to prevent malnutrition and reduce the formation of pressure ulcers.

A meta-analysis by Alen et al. (2013) [41] stated that malnutrition is the most prevalent nutritional status in people diagnosed with dementia and therefore the use of ONS is indicated by having a positive effect on weight gain.

Pivi et al. (2011) [42] demonstrated that oral nutritional supplement used for 6 months increased all anthropometric measurements (weight, arm, and muscle circumference), with a positive impact on the body mass index and improvement of the immune status of these patients.

The European Society for Clinical Nutrition and Metabolism (ESPEN) in 2015 developed a guideline of nutritional strategies to be taken for patients with dementias and established that the use of ONS has high level of evidence; it significantly contributes to the improvement of the nutritional status [43]. Despite the use of ONS being well established, unfortunately in Brazil, there is no distribution of oral nutritional supplements for the population. The elderly statute, established by law, guarantees only the right to food when the elderly or their relatives do not have economic conditions to provide their maintenance. The statute also mentions the right to treatment of full health for the elderly but does not specify the distribution of dietary supplements [44]. Nutritional intervention in these cases should be guided individually and depending on the nutritional status according to multiple comorbidities, as well as the biological and psychological changes associated with aging, functional capacity, and nutritional needs of the individual in order to provide all the necessary nutrients and adequate amounts to maintain a good nutritional state [45].

Nutritional intervention strategies for severely impaired patients with Alzheimer’s disease

At this stage of the disease, the patient presents severe anatomical and physiological changes, such as weakness of oral and/or lingual muscles, making it difficult to chew; reduction of smell and taste, often caused by the use of drugs that alter the viscosity and volume of saliva produced thereby reducing oral sensitivity and ultimately culminating in dysphagia [4].

Dysphagia is any type of difficulty in the effective progress of food from the mouth to the stomach through the interrelated phases, controlled by a complex neurological mechanism [46].

Proper knowledge of the physiology of swallowing is essential for the satisfactory progress of food in each instance [47]. Its detection is multidisciplinary as it involves doctors, speech therapists, nutritionists, and nurses who contribute with their expertise interdependently to the improvement of the patient in order to identify clinical signs such as coughing and choking during feeding as well as functionality and also the pulmonary complications [48].

Studies by Sato et al. (2014) [49] in patients with AD found that mortality from aspiration pneumonia is high in this group, accounting for 70% of causes of death, indicating that they need daily measures to diagnose and treat dysphagia.

Major consequences of dysphagia include malnutrition and dehydration caused by inadequate diets due to the modification of food consistency. In an attempt to adapt to symptoms, the caregiver often changes the feeding consistency, adding more water and reducing the caloric density of the meal [50].

It is up to the speech therapist to determine the safest food consistency to be adopted, after thorough evaluation by the nutritionist to correct caloric and protein intake for the indicated consistency. A feature often used in these cases is the use of thickeners, such as gums and mucilage that suit the consistency of meals and the continued use of dietary supplements, which also contribute to increase the caloric value of the diet also provide significant amounts of protein.

A study in Germany with 160 patients with various forms of dementia and 30 control patients was conducted to evaluate the impact of the recommended changes regarding food texture for patients with dysphagia. It was found that patients with dementia show signs of aspiration more frequently with water (35.6%) than with a slice of an apple (15.1%) or applesauce (6.3%). It was concluded that patients in severe stages of dementia benefit from changes in the texture of foods that need to be constantly monitored [50].

With the development of dysphagia, the risk of pulmonary aspiration increases and in those cases oral nutrition is interrupted by the use of alternative energy sources, either by nasoenteric tubes (NGT) or percutaneous endoscopic gastrostomy (PEG) [51].

The use of enteral nutritional therapy (ENT) is controversial, since there seems to be no real clinical benefit in terms of survival for patients with dementia [52]. Nevertheless, the number of patients older than 65 years who underwent PEG in the USA increased exponentially (15,000 in 1989 to 123,000 in 1995), whereas most of these patients (60%) have AD or multiple cerebrovascular lesions [53].

An important study was conducted by Rabenek (1996) [54] to investigate the mortality of terminal patients in use of PEG, finding that the average survival after gastrostomy placement was 7.5 months.

In Brazil, there are no specific rules under the bioethical and legal points of view regarding the use or non-use of artificial nutrition therapy in the terminal stages of the disease; it is up to the professional to indicate ENT and explain the benefits and adverse effects that its use can cause. In this case, patient autonomy must be respected, considering that the legal representative will decide whether this form of nutrition must be used.

The present literature review included the main nutritional complications and their approaches. The flowchart in Fig. 1 summarizes the text.

Fig. 1
figure 1

Flow chart of the main nutritional complications and their approaches

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Conclusions

This review presented the general aspects of nutritional guidelines adopted in each stage of AD. These guidelines are employed at the Behavioral Neurology Section, Nutrition Area of the Federal University of São Paulo, and were developed after a broad review of the literature; so far, we have had good results with this protocol, but more studies in this field are required.