Adequacy of food consumption in elderly Alzheimer’s disease in a community of Southern Brazil: a Cross-sectional study [version 1; referees: awaiting peer review]

Alzheimer's disease (AD) is the most common cause of Background: dementia, with a multifactorial etiology, in which the person has great difficulty identifying feelings of hunger, satiety, and feeding, which may affect their nutritional status. Pathologically, it is associated with neurodegeneration of synapses followed by neuronal loss, accompanied by glial proliferation surrounded by neurofibrillary tangles, beta-amyloid peptide (Aβ) deposition, inflammation and cerebrovascular injury hindering the ability to perform activities of daily living. This study aimed to analyze quantitatively the differences between an elderly group with AD and a control group, in terms of macro and micronutrient consumption evaluation. the study involved 69 participants who were assessed via collection Methods: of anthropometric measurements (weight, height and body mass index) with nutritional status being assessed by 24-hour food recall and three-day food record. Cognitive assessments were performed using the Mini-Mental State Examination (MMSE) and Clinical Dementia Ranting (CDR). The intake of lipids in patients with severe dementia, was lower (p Results: <0.05). The consumption of proteins showed a decrease with demential advance. For vitamins, there was a significant difference (p <0.05) in the amount of thiamine, niacin, vitamin D, E and K and calcium, chromium and iodine minerals, which were significantly reduced in AD patients (p <0.05). Decreases in macronutrient and micronutrient consumption may Conclusions: Decreases in macronutrient and micronutrient consumption may Conclusions: result in a consequent impairment of nutritional status, dementia progression, and decreased quality and life expectancy of elderly patients with AD.


Decreases in macronutrient and micronutrient consumption may
Conclusions: result in a consequent impairment of nutritional status, dementia progression, and decreased quality and life expectancy of elderly patients with AD.

Introduction
Alzheimer's disease (AD) is the most common type of dementia, characterized by cognitive and neuropsychiatric manifestations that result in progressive disability 1,2 . Several factors contribute to the neurodegenerative process of AD. Lack of availability of certain nutrients, abnormal protein processing and neuronal membrane degeneration accelerate dysfunction and synaptic loss from the onset of disease 3 .
The medial temporal lobe is an area of the brain that is involved in the regulation of food intake 4 , and a site where neurodegeneration is typically present 5 . The behavioral modification of the AD patient interferes directly with the reduction of food consumption and the absorption of essential nutrients for the normal functioning of the body 6 .
The synthesis of synaptic membranes is dependent on various nutrients, such as folate, vitamin B12, vitamin B6, vitamin E, vitamin C and selenium. Inadequate ingestion and metabolism of these nutrients is related to increased phospholipid degradation and degeneration of neuronal membranes responsible for synapse loss 3 .
The nutritional status and food intake in the elderly differ by their cognitive, physical and biological capabilities. Taste reduction, difficulty in swallowing and xerostomia may be the result of neuropathological disorders, senility, or even induced by polypharmacy due to a higher incidence of chronic diseases resulting in them being more likely to be taking a combination of pharmaceuticals 7,8 .
Since the nutritional status directly affects the patient's physiological condition, causing the elderly to be more susceptible to decreased biological function, making them more susceptible to falls, fractures, protein-energy malnutrition, and associated nutritional deficiencies 6 , this study had the intention of analyze the food intake in patients with AD, comparing it with the control group, identifying micro and macronutrient deficits that lead to worsening dementia and decreased quality of life.

Ethics and approval
This study was approved by the Ethics Committee of the State University of Midwest (UNICENTRO) under number 026/2011. Patients and their caregivers received information on the purpose, methods, risks and benefits of research and gave written informed consent to participate in the study. Patients with any nutritional changes were referred to the Nutrition School Clinic of UNICENTRO for follow-up.

Sample
A cross-sectional study with a control group was performed, with 37 elderly controls and 32 AD patients.
The elderly were attended and diagnosed clinically with AD in the health centers through the Unified Health System (SUS) and were passed through a confirmed diagnosis issued by a geriatric doctor or neurologist, and assisted by the Association of Studies, Research and Assistance to People with Alzheimer's (AEPAPA) in Guarapuava, Paraná.
The control group, in turn, was formed by healthy elderly participants of exercise groups and cultural activities for seniors, provided by the Social Welfare Department of the city of Guarapuava. A Mini-Mental State Examination (MMSE) was performed and evaluated by a trained healthy professional, applied to the health elderly as exclusion criteria for the control group. Also, they agreed in participate of the study and gave written informed consent in participate in the study.
Patients and elderly without AD not found in their homes on three attempted visits on different days of the week, those who died, the residents of the countryside, and those who had moved to other cities, in addition to those unwilling or who rejected the survey after the first visit, along with those who did not agree with the terms of the Free and Informed Consent Term (TCLE) were excluded from the study.

Data collection
The study occurred between August 2013 to June 2014, with an initial sample of 55 AD patients attending SUS in Guarapuava, and after applying the exclusion criteria, the sample consisted of 32 patients. The sample of healthy elderly was initially 50 participants, of which 13 declined to continue due to the amount of data that needed to collected and the time it would take to collect this data, consisting of 37 patients. All remaining individuals after applying exclusion criteria completed the study.

Assessment of nutritional status and food intake
To evaluate the nutritional status, anthropometric measurements were collected: weight (kg), height (m), body mass index -BMI (kg/m 2 ). Weight and height were collected according to the methods recommended by the Food and Nutrition Surveillance System -SISVAN 9 . When weighing and stature measurement was not possible due to the patient's health conditions, weight and height were estimated using theoretical formulas, using arm circumference (AC) and calf circumference (CC) measures, knee height and subscapular cutaneous fold. The formulae used to estimate weight were: All values obtained from the average of four days of each nutrient were compared with the recommendations of the Dietary Reference Intakes (DRIs), according to the gender and age of the patient. As yet there are no specific recommendations for AD patients.
Evaluated consumption in grams (g), milligrams (mg) and micrograms (mcg) of nutrients, and calculated the percentage of adequacy by the following formula: adjustment percentage = amount of ingested nutrient (g/mg/mcg)/DRI recommendation (g/mg/mcg) × 100.

Cognitive evaluation
The elderly were evaluated through the Mini Mental State Examination (MMSE) and Clinical Dementia Rating (CDR) between August 2013 to June 2014. Each category is classified based on scores -none/questionable dementia, mild dementia, moderate or severe 11 . The CDR and MMSE was applied and evaluated by a trained health professional.

Statistical analysis
Data were analyzed using the SPSS 20.0 statistical software for Windows, presented as median and interquartile range, relative and absolute frequency. Prior to the analysis, the following assumptions were tested on the numerical variables: homogeneity of the variances using the Levene test, and distribution of the data using the Shapiro-Wilk test. If the assumptions were incorrect data was analyzed using the Kruskal-Wallis test. When necessary, we used the multiple comparisons analysis with the Bonferroni level of significance correction. The Chi-square test, Fisher's Continuity Correction and Exact Correction were used to identify associations between the diagnosis of AD and clinical and sociodemographic variables. A significance level of p <0.05 was adopted.

Results
In total, 69 participants took part in the study: 37 from the control group and 32 from the AD group. Table 1 shows anthropometric characteristics of the sample, these data are characterizing this population according to CDR, age, current weight, height and BMI. Data are presented as median (P25-P75).
The age of the elderly ranged from 57 to 94 years, with a median of 74 years, with a median height of 1.58m of the total sample. Regarding body weight, the control group had the highest average, and the weight in AD patients decreased with increased severity of disease.
Regarding the sociodemographic characteristics (Table 2), 45 (65.2%) were female; 20 were married in the control group (29.0%) and in the AD group there were 7 (10.1%); 3 from the control group were unmarried (4.3%) and in the AD group there were 7 (10.0%). There were 13 widowers in the control group (18.8%), and 17 (24.5%) in the AD group.
The average family income reported by the participants in the control group was R$ (Brazilian real -BRL) 904.00 ± 8.99 (US$ 275.76) and the participants with the disease presented income around R$ 1.031.13 ± 67.29 (US$ 314.54). Table 3 shows the comparison of carbohydrate intake. The consumption was lower in the control group but there was no difference between the groups of patients with dementia (p> 0.05). In contrast, with respect to the consumption of proteins, as disease progressed this concomitantly decreases. The only macronutrient that gave a significant difference (p <0.05) was the lipid values, in relation to the control group (113.64% adequacy), which presented a greater consumption than CDR-1, mild dementia (86.95% adequacy) and CDR-3, severe dementia (7751% adequacy).   Among the minerals shown in Table 5, only calcium, chromium and iodine showed differences between the groups (p <0.05). Data are presented as median (P25-P75). CDR: clinical dementia rating (cases); n; sample number; Kruskall-Waliss (Bonferroni for multiple comparisons). ** There was a statistical difference between elderly control subjects and elderly with moderate dementia (p<0.05). *** There was a statistical difference between elderly control subjects and elderly with mild and advanced dementia (p<0.05). † There was a statistical difference between elderly control subjects and elderly with mild, moderate and advanced dementia (p<0.05). ‡ There was no difference between groups (p>0.05).

Discussion
Diet and nutritional factors are known modifiable factors for dementia and cognitive decline later in life, with significant associations between an inadequate nutritional status and behavioral disorders with greater impact on activities of daily living 12 .
The sample was made up mostly of patients with advanced dementia (50% of AD patients), and is similar to the study of Goes et al. 7 where 40% of the sample were in the advanced stages of the disease. Advanced disease is characterized by severe memory loss, with no capacity to make decisions, and requires a caregiver or person who can assist in the practice of activities of daily living, and most of them can result in food imbalances and consequent malnutrition.
A high BMI in middle age is associated with an increased risk for the development of dementia 7 . The elderly studied in the control group, and in the CDR1 and CDR2 groups, were overweight and as the staging of the disease increases, BMI decreases. This overweight condition is likely related to the food preferences found for this group, carbohydrates and lipids. These preferences and dietary deficiencies could be caused by the low family income found in the study, and also due to the decrease in  Data are presented as median (P25-P75). CDR: clinical dementia rating (cases); n; sample number; Kruskall-Waliss (Bonferroni for multiple comparisons). ** There was a statistical difference between elderly control subjects and elderly with moderate dementia (p<0.05). *** There was a statistical difference between elderly control subjects and elderly with mild and advanced dementia (p<0.05). † There was a statistical difference between elderly control subjects and elderly with mild, moderate and advanced dementia (p<0.05). ‡ There was no difference between groups (p>0.05).
executive functionality and dysphagia 3 , changing the consumption of proteins for carbohydrates 13 .
Tieland et al. 12 , in the Netherlands, analyzed three groups of elderly people, 707 individuals living independently in the community, of which 194 were fragile and 276 were institutionalized. The results showed that 35% of the institutionalized elderly had inadequate protein intake, below 0.7g/kg/day. As protein intake is impaired, there is an accelerated loss of muscle mass, sarcopenia 13 , low hemoglobin levels, and a consequent increase in the mortality rate 14 .
According to IBGE research 15 held in Brazil, the average consumption of lipids for men and women 60 years or more, is approximately 49 grams. In the present study, the control group had a higher intake, at 42.89 grams, in comparison to CDR 3, 32.24 grams. Diets high in fat contribute significantly in β-amyloid accumulation, tau hyperphosphorylation and an inflammatory state in the peripheral organs and brain 16 .
Analyzing the thiamine intake (vitamin B1), differences in consumption between groups can be seen. The control group had the lowest intake, likely related to the vitamin supplementation initiated after diagnosis of dementia. Relating IBGE data 15 , the micronutrient ingestion for elderly is approximately 1.05 mg, while the amount for the AD group was far below.
In the study by Morris et al. 17 , the total of 3,718 participants aged 65 years and over had dietary data taken, with at least two evaluations and analyzes of cognitive changes over a median of 5.5 years. In this prospective study, nutritional deficiencies of niacin (vitamin B3) were associated with AD and cognitive decline. Since the higher intake of vitamin B3 was associated with a slow rate of cognitive decline and its retardation. The nutritional recommendation for the elderly aged 60 years or more is the intake of approximately 22.7 mg/day 7 .
There are studies in which the importance of vitamin D is postulated in cases of dementia 18,19 as it promotes the regulation of calcium homeostasis, β-amyloid peptide clearance, slows down and/or improves cognitive decline, and has an important antioxidant and anti-inflammatory effect 20 . In the cohort study conducted by Karakis et al. 18 , in the USA, the final sample being composed of 1663 patients, vitamin D was associated with lower hippocampal volumes, helping to prevent brain lesions and cognitive decline. The ingestion of calciferol in the related study was impaired in all dementia phases. This may be due to their eating habits. The recommendation according to IBGE 15 for individuals over 60 years or more is on average 3.05 mcg/day.
Vitamin E eliminates free radicals, with some chemical forms have a potent anti-inflammatory effect, and the α-tocotrienol congener protects the cortical and hippocampal neurons from apoptosis. Vitamin E deficiency in human manifests primarily as peripheral sensory neuropathy, which demonstrates its essential role in the formation and maintenance of CNS function, supporting its potential use in the prevention and treatment of neurodegenerative diseases 21 . According to the recommendations of the National Institutes of Health of the United States, the recommended daily dose of vitamin E for an adult is 15mg 22 . For the IBGE 15 , 3.8 mg/day is recommended for elderly individuals.
A study in the Netherlands 23 involved a sample of 5395 participants over 55 years of age who did not present with dementia.
These individuals completed checklists about their eating habits over the past year. The indicated food would have been consumed at least twice a month. Participants were followed for 9.6 years. Of these, 465 developed dementias, of which 365 were diagnosed as having AD. Individuals with vitamin E consumption had a 25% lower risk of developing dementia. It is interesting to analyze the control group of the present study, because it was observed that when comparing the group without AD, all the dementia groups had a lower consumption of this important vitamin.
However, with regard to vitamin K, studies demonstrate the importance of activities related to the brain 24,25 . It is related to the transport of the apolipoprotein E (ApoE), a major of marker 26,27 .
In the study of Carrié et al. 28 , conducted with mice to analyze the cognitive ability of a diet low in vitamin K, a vitamin K depleted diet resulted in higher cognitive deficits. In the study by Presse et al. 24 , a paired control case study of 31 control subjects and with AD, respectively, as in the present study, the healthy group consumed more food containing this vitamin.
The number of works that present calcium as an important underlying factor in the process functional changes of aging, especially in AD has increased 29,30 . Its dysregulation causes loss of function and mutations in the protein presenilin 1 (PS1), which is a risk factor for the onset of the disease. Other effects include alterations in the autophagic and lysosomal pathways 31,32 , increased oxidative stress and consequent inflammation in neuronal cells 33,34 . Patients without neurodegeneration, however, consumed less calcium in their diet compared to those who had moderate dementia, CDR-2 and advanced dementia, CDR-3. The increased intake of dairy products in the diet of survey participants with dementia due to preference from soft textures of the food at this stage of life and stage of disease is the likely cause of this finding.
Among the micronutrients observed in Table 5, we highlight the chromium, which was less consumed by AD patients in CDR-3, as recommended by IBGE 17 . In the study by Krikorian et al. 34 , a double-blind study was conducted in Cincinnati, USA, to evaluate whether chromium supplementation helps in memory and neuronal function in the elderly with cognitive decline. The results were that chromium picolinate supplementation may significantly improve cognitive inhibitory control and brain function in individuals who have neurodegeneration.
A cross-sectional study was conducted in Brazil in a group of 135 elderly women with mean age of 68 years, in which 42% of the women analyzed had iodine deficiency 35 . Iodine deficiency causes thyroid dysfunction, as well as hypertension, dyslipidemia, muscle wasting, frailty and neuromuscular dysfunction, reducing quality and life expectancy 36 . There is still no daily recommendation for iodine intake specifically for the elderly population.
The sample size and the fact that the values presented being an estimative from the nutritional consumption were the limitations of the study. Therefore, these results are in agreement with similar researches that consider nutritional consumption 7 .

Conclusion
The nutritional status of an individual is associated with cognitive health and disease progression. According to the results, it is concluded that the progression of dementia is associated with lower levels of dietary intake of some macro and micronutrients. Among the macros, reduced intake of lipids in mild and severe dementia can be observed. Regarding the micronutrients vitamin D intake showed a reduction in mild dementia stage. The vitamins B5, E, and K, and minerals calcium and chromium, had reduced consumption in severe dementia cases. Specific nutritional interventions can alter the development of the disease with low risk of side effects and with satisfactory results particularly in the early stages of the disease.