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Role of Nutrition in the Prevention of Cognitive Decline


Dupont Frechette J, Marraccini ME. Role of nutrition in the prevention of cognitive decline. Annals of Long-Term Care: Clinical Care and Aging. 2014;22(2):41-48.


Jennifer Dupont Frechette;


Jennifer Dupont Frechette, MA1; Marisa Ellen Marraccini, MASeries Editor: Liz Friedrich, PhD, RD, LDN 2


The author reports no relevant financial relationships. The series editor has received speaker honoraria from Abbott Nutrition and has served as a consultant or paid advisory member for Abbott Nutrition.


1PhD student, School of Psychology, University of Rhode Island, Kingston; 2Friedrich Nutrition Counseling, Salisbury, NC


Approximately 36 million people globally are living with dementia, and the average likelihood of dementia being diagnosed in a patient doubles every 5 years after the age of 65 years. Due to the ever-growing prevalence of neurodegenerative diseases and their social and economic repercussions, environmental and behavioral interventions and prevention strategies that may delay the onset of these disorders are imperative. This article discusses the role of specific nutrients in the prevention and progression of dementia through the examination of current published scientific literature. The findings of this review contribute further evidence for the role of nutrition in the clinical management of dementia and related symptoms.

Key words: Alzheimer’s disease, dementia, neurocognitive disorder, nutrition, vitamins.

Affiliations: 1PhD student, School of Psychology, University of Rhode Island, Kingston; 2Friedrich Nutrition Counseling, Salisbury, NC

Abstract: Approximately 36 million people globally are living with dementia, and the average likelihood of dementia being diagnosed in a patient doubles every 5 years after the age of 65 years. Due to the ever-growing prevalence of neurodegenerative diseases and their social and economic repercussions, environmental and behavioral interventions and prevention strategies that may delay the onset of these disorders are imperative. This article discusses the role of specific nutrients in the prevention and progression of dementia through the examination of current published scientific literature. The findings of this review contribute further evidence for the role of nutrition in the clinical management of dementia and related symptoms.

Key words: Alzheimer’s disease, dementia, neurocognitive disorder, nutrition, vitamins.

Dementia has been used as an umbrella term to refer to a variety of degenerative diseases that lead to a loss of brain function due to neurons dying or malfunctioning, impacting memory, thinking, language, decision-making capabilities, and behavior.1 In 2010, approximately 35.6 million people globally were living with dementia, which is now referred to as major neurocognitive disorder in the latest edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5).2 This number is expected to more than triple by 2050, impacting an estimated 115.4 million people worldwide.3 According to the Alzheimer’s Association, in the United States, the direct costs associated with a diagnosis of Alzheimer’s disease—the most common form of dementia—was $200 billion in 2011, which included physician services, hospitalizations, and nursing home care.1 This number is expected to increase to $1.1 trillion by the year 2050.1 These estimates do not include indirect costs, such as loss of work productivity, absenteeism, and unpaid care by nonprofessional caregivers.4,5 The combined social, physical, psychological, and economic costs associated with dementia and cognitive decline are alarming.
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According to the DSM-5, neurocognitive disorders (NCDs) include delirium; major NCD, which includes dementia and amnestic disorder; and mild NCD, which describes a level of cognitive decline that requires an individual to make use of compensatory strategies and accommodations to help maintain independence and perform activities of daily living.2 The DSM-5 notes that the prevalence of NCD cannot be accurately presented in broad age categories because of the sharp increase in prevalence that occurs with age. For example, prevalence rates vary from approximately 2% for individuals around the age of 65 years to 30% for those aged 85 years and older.2 Prevalence rates, therefore, are presented separately in narrow band age categories. In 2007, Plassman and colleagues7 conducted a nationally representative study and reported that the prevalence of dementia increased with age, from 5% for individuals between age 71 and 79 years to 37.4% for individuals aged 90 years and older. Other research has reported that Alzheimer’s disease is prevalent in approximately 4% to 6% of individuals aged 65 years and younger, which increases to one in eight people aged 65 years and older.1 This number dramatically increases after the age of 85 years, with approximately 45% of these individuals having an Alzheimer’s diagnosis.1 The average American’s likelihood of receiving a dementia diagnosis doubles every 5 years after the age of 65 years.3 The increasing incidence of dementia as the population ages may be due in part to longer life expectancies and a growing elderly population. Research has also pointed to a number of other factors that may be associated with dementia, such as depression, stress, lack of physical exercise, and malnutrition.5,8 Further, technological advances have uncovered some of the basic neurologic mechanisms and etiologies associated with various forms of dementia and preclinical subtypes (eg, mild NCD).9

Although targeted pharmaceuticals that may provide a temporary abatement of symptomatology in some patients are available, no long-term solutions toward a cure have been established.10 Both the growing prevalence of neurodegenerative diseases and their socioeconomic repercussions necessitate environmental and behavioral interventions, as well as prevention strategies that may delay their onset. Epidemiologic, neurologic, and neuroimaging research have offered promising evidence for environmental protective factors in preventing or delaying neurodegeneration and associated diseases.8,10-12 Identified strategies include engagement in social activities, physical and mental exercises, reduction of alcohol consumption, and improved nutrition.13

Specific nutrients in foods are easily accessible and may work synergistically to serve as a therapeutic function for individuals with NCD by affecting the synthesis and integrity of brain membranes.10 Research exploring the benefits of particular nutrients, such as carotenoids, folic acid, polyunsaturated fatty acids, and curcuminoids, and research examining lifestyle changes, including calorie restriction and adherence to specific diets (eg, Mediterranean diet), have reported mixed results.14,15 Sano and colleagues,16 for example, found that vitamin E may help slow the progression of Alzheimer’s disease, while Lloret and associates17 reported that vitamin E had no effects and may actually be detrimental in terms of cognition. These inconsistencies may be due to methodological limitations (eg, self-report measures), methodological variability (eg, diagnosis of mild cognitive impairment [MCI] vs Alzheimer’s disease), and an overreliance on nonexperimental studies, which cannot control for the transactional effects of other nutrients and outside influences. To shed light on these equivocal findings, this review article provides an overview of the current research on the role of antioxidants and calorie restriction on cognitive decline and neurodegenerative disease associated with dementia.


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Effects of Antioxidants on Cognitive Decline

Many studies, particularly those using animal models, have demonstrated the positive effect of vitamins, nutritional substances, and diet on the aging brain and processes associated with cognitive decline.18 Micronutrients and antioxidant vitamins may aid in the reduction of oxidative stress and increase proteolytic systems in glial cells that may play a role in the reduction of extraneuronal accumulation of protein plaques within these neurofibrillary tangles.19,20 Further, brain-accessible antioxidants may potentially play a role in delaying the onset of Alzheimer’s disease and other cognitive impairment by reducing oxidative stress and slowing the neuronal damage associated with amyloid-beta (Abeta) peptides.21 Nutritional interventions, dietary changes, and the use of supplements in clinical trials have provided evidence supporting the use of specific nutrients in the reduction of cognitive decline before the onset of dementia.22,23 When activated, these brain-accessible antioxidants may serve as neuroprotective agents in the reduction of oxidative stress.21 The Table provides an overview of the antioxidants vitamin C, vitamin E, vitamin B, carotenoids, and polyphenols, and the common foods in which they are found.24-30

table 1


Vitamins C and E

Vitamin E is a lipid-soluble vitamin that has been effective in modulating free radicals and reductions in cell apoptosis associated with Abeta proteins in conjunction with vitamin C.24,25 For their 2008 study, Fotuhi and colleagues24 analyzed data from 3376 elderly residents of a large county in Utah who were administered the Modified Mini-Mental State Examination, a common screening test for dementia used in individuals demonstrating cognitive impairment. Researchers determined which individuals took nonsteroidal anti-inflammatory drugs (NSAIDs), alpha-tocopherol (vitamin E), or ascorbic acid (vitamin C) at least four times per week for a minimum of 1 month or the comparable amount from a multivitamin (vitamin E 400 international unit [IU] or vitamin C 500 mg) through interviews with the patients and visual examinations of medical containers at baseline. These individuals were categorized into the following five groups: nonusers of vitamin E, vitamin C, and NSAIDs; users of NSAIDs alone; users of vitamins E and C alone; users of vitamin E or vitamin C; and combined users of vitamin E, vitamin C, and NSAIDs. All individuals were assessed over 8 years, and both t-tests and random effects models were used to assess the effects of each group. Analyses revealed that participants carrying the apolipoprotein E (APOE) e4 allele who used vitamins C and E in combination with NSAIDs had a slower rate of decline than nonusers 8 years after baseline measurements, after controlling for age, sex, education, history of diabetes, and stroke.24

Findings of a randomized, double-blind, placebo-controlled study by Sano and colleagues16 suggest that vitamin E may delay the onset of death, institutionalization, or the inability to complete basic activities of daily living (eg, self-feeding, using the toilet independently) in individuals with Alzheimer’s disease. Individuals included in the study were considered to have probable Alzheimer’s disease of moderate severity, as determined by a Clinical Dementia Rating score of 3, and were recruited from 23 different sites. Patients were excluded from the study if they were taking any psychoactive medications or had any other central nervous system disease(s) at the time of enrollment. Four stratified participant groups were established: those who received selegiline (5 mg twice daily); those who received vitamin E (1000 IU twice daily); those who received selegiline and vitamin E (5 mg and 1000 IU twice daily, respectively); and those who received placebo. Based on Cox proportional hazards models, researchers found that vitamin E increased median survival rates in individuals who received an Alzheimer’s diagnosis by 230 days compared with the placebo group. Furthermore, pairwise post-hoc comparisons revealed that participants taking vitamin E alone (P=.021) and vitamin E in combination with an NSAID (P=.014) required significantly less supervision. Groups who were given vitamin E and an NSAID also showed a reduction in behavioral symptoms (P=.020).16 Although these results offer positive implications for the role of vitamin E in the delay of cognitive decline, the amount of vitamin E given to the patients in this study was nearly 100 times the medically recommended dosage. Specifically, the Food and Nutrition Board at the Institute of Medicine of the National Academies recommend 22.4 IUs of vitamin E per day, and the present study used 2000 IUs per day.31 Future randomized clinical trials should differentiate between the positive effects of vitamin E in respect to specific dosages and possible side effects.

While double-blind, clinical trials help to provide insight into possible causative factors, longitudinal data may provide insight into the trajectory of neurodegeneration associated with cognitive decline. A recent longitudinal study conducted by Devore and colleagues32 examined the effects of antioxidant intake in relation to cognitive decline within a sample of female patients aged 70 years and older. Nutritional data were collected every 4 years beginning in 1980, and four cognitive assessments were conducted approximately 2 years apart between 1995 and 2001. Analyses revealed that intake of vitamin E, vitamin C, and carotenoids from food or supplement sources was not related to cognitive decline; however, a positive relationship was found between greater consumption of carotenoids from food sources and higher levels of cognition. Specifically, results suggest a possible relationship between higher levels of very long-term carotenoid intake and better overall cognitive status at older ages. Further, lycopene intake was shown to be associated with slower cognitive decline. Individuals with higher intake of lycopene from food sources had a mean decline of verbal cognition of 0.08 standard units less over time, which was equivalent to approximately 1 to 2 years over a 6-year span of time.32 Although encouraging, the results of this study may not be generalizable due to methodological limitations and its observational design. In addition, the study participants were comprised exclusively of women and relied on a self-report measure of food consumption (potentially lacking reliability). Encouragingly, however, the researchers were able to account for many potential confounding variables, including socioeconomic status and dietary variables, increasing the validity of the observational study. Further randomized, controlled clinical trials should be conducted to determine whether specific food sources and phytonutrients mediate cognitive decline and potential biochemical properties that alter oxidative stress levels associated with neurodegeneration.

B-Complex Vitamins

Higher levels of serum homocysteine and lower levels of folate have been associated with an increased risk for dementia.33,34 More specifically, increased levels of homocysteine, a sulfur-containing amino acid, have demonstrated a positive correlation with vascular disease, brain atrophy, cognitive impairment, and Alzheimer’s disease.33,34 Folate (one of the eight B vitamins) is commonly understood to be an important factor in fetal brain development and also has implications for cognitive health later in life.35 Folate is essential for maintaining the integrity of DNA and mitochondrial DNA.36,37 Folate deficiency is associated with oxidative stress, synaptic and neuronal impairment, poor calcium regulation, neuronal apoptosis, and Alzheimer’s disease.35,36 The benefits of folate are well known considering that several countries, including the United States, use fortified flour and grain to increase serum folate levels within their populations.35 Further, folic acid, which is an artificial chemical analog of naturally occurring folate, is commonly used in supplements.38

Kado and associates33 conducted a cross-sectional and longitudinal analysis of high-functioning individuals aged 70 to 79 years residing in three different communities to determine whether homocysteine and vitamin B plasma concentrations were related to cognitive functioning and cognitive decline. Participants were only included in the analysis if they scored in the top third for physical and cognitive functions within their community; further inclusion criteria was assessed by the seven-item Katz Activities of Daily Living scale, self-report of physical functioning, semi-tandem balancing demonstration, speed in moving from a seated position to a standing position, delayed recall, and the nine-item Short Portable Mental Status Questionnaire. Individuals who demonstrated poor baseline cognitive functioning on five of the aforementioned cognitive assessments had higher levels of homocysteine and lower levels of folate and vitamin B6. Seven years following baseline assessment, individuals with higher levels of homocysteine showed a downward trend associated with cognitive decline; however, these results were not significant. The effects of decreased cognitive functioning were primarily accounted for by low plasma concentrations of folate.33 Goebels and Soyka39 described the use of vitamin B12 for the treatment of dementia, and previous research has found an association between vitamin B6 and improved cognitive function.40 Both clinical trials and longitudinal studies are therefore warranted to help shed light on the impact of vitamin B on cognitive functioning.

While the study by Kado and colleagues33 demonstrates possible neuroprotective mechanisms associated with folate in the reduction of homocysteine in high-functioning individuals, research conducted with individuals demonstrating preclinical subtypes of dementia offer implications for at-risk populations. Blasko and associates34 examined the influence of folic acid and vitamin B12 longitudinally with a sample of 81 individuals with a diagnosis of MCI. Participant serum levels were tested for homocysteine, folate, and vitamin B12 at fasting, and supplemental information regarding folate and vitamin B12 was assessed by clinical interview. At baseline, participants with dementia versus those who were considered unimpaired were grouped as nonusers (65.3% vs 59.4%, respectively), combination users (4.1% vs 25%, respectively), and inconsistent users (30.6% vs 15.6%, respectively). The nonparametric Mann-Whitney U test (accounting for skewed distribution) was used to assess comparisons between users and nonusers, and nonparametric correlation analyses using Spearman’s rank correlation coefficients were used to assess further associations. Additionally, delta changes were estimated for time-course changes (a measurement at 5-year follow-up minus baseline).34 After a 5-year period, 60% of individuals were found to have dementia, 25% were found to have stable MCI, and 15% had demonstrated improved cognitive health. Individuals who self-reported use of folic acid and vitamin B12 for more than 1 year (corroborated by medical records, caregivers, and serum samples) were less likely to receive a dementia diagnosis after 5 years. Higher levels of folate were associated with a lower conversion rate to dementia, independent of the presence of the APOE e4 allele. Additionally, magnetic resonance imaging at baseline showed less medial temporal lobe atrophy associated with higher levels of folate and higher grades of white matter lesions in individuals who did not report folate or vitamin B12 use.34 Collectively, these studies33,34 demonstrate possible protective factors associated with vitamin B intake for cognitive decline in both normative and clinical populations.


Carotenoids are a group of fat-soluble organic plant pigments and antioxidants that are found primarily in fruits and vegetables.26,27,41 The most commonly studied and prevalent types of carotenoids in Western diets include alpha-carotene, beta-carotene, lycopene, lutein, zeaxanthin, and beta-cryptoxanthin. Carotenoids have been associated with increased antioxidant levels, enhanced immune function, inhibition of mutagenesis, treatment of specific skin diseases, inhibition of premalignant lesions, and decreased risk of certain cancers.41,42 Heber and Lu43 posit that fruits and vegetables containing carotenoids may have unique phytochemicals that provide a preventive benefit indirectly through antioxidant processes by regulating mechanisms involved in the absorption of carcinogens and cellular apoptosis. Furthermore, Obulesu and associates44 conducted a review on the therapeutic role of carotenoids in Alzheimer’s disease in animal models, and concluded that adequate consumption of carotenoids in combination with vitamins, fruits, and vegetables may lead to reduced levels of oxidative stress.

Retinoic acid is a metabolite of vitamin A, and it has been shown to reduce Abeta proteins within the hippocampus.44,45 Ding and associates45 studied the effect of all-trans retinoic acid (ATRA) on an Alzheimer’s disease mouse model and a control wild mouse model. The results of their 8-week study demonstrated a reduction of Abeta deposits and tau hyperphosphorylation, as well as improved spatial learning memory with the mouse models treated with ATRA. Western blot analysis revealed a significant decrease in the production of amyloid precursor protein carboxy terminal fragments (APP-CTFs) in ATRA-treated APP/presenilin 1 (PS1) mice, with a 70% reduction in the frontal cortex and 50% reduction in the hippocampus. APP-CTFs are considered potential early biomarkers for Alzheimer’s disease. Additionally, there was a reduction of tau phosphorylation. Western blot bands of the phosphorylated tau at Ser519 indicated a 50% decrease in the tau phosphorylation in the frontal cortex and a 75% decrease in the hippocampus in the ATRA-treated APP/PS1 mice relative to untreated APP/PS1 mice.45 While these results are promising, the majority of related retinoid research has been conducted using mouse models, and the exact mechanisms are not well understood.

Lycopene, a member of the carotenoid family, has high antioxidant properties. It can cross the blood-brain barrier, is taken up by the central nervous system, inhibits cancer cell migration, and reduces oxidative stress in the brain.46-48 Qu and associates47 studied the neuroprotective effects of lycopene against Abeta25-35 in cultured rat neurons and found reduced numbers of apoptotic cells and increased intracellular reactive oxygen species (antioxidant ability). Protective effects of lycopene were demonstrated with an optimal dose of 2M (P<.01) against Abeta–induced neurotoxicity in cultured rat cortical neurons after 24 hours of exposure to lycopene compared with an increase in amyloid (P<.01) in untreated rat cortical neurons.47 These results show promise for the role of lycopene in the reduction of neurotoxicity; however, considering that the bulk of this research was conducted with animals, the generalizability of these findings are questionable, and further research examining lycopene’s role in human neurodegenerative diseases is needed.


Polyphenols are one of the most abundant antioxidants in the human diet, along with vitamin E, vitamin C, and carotenoids, and thus may have a large impact on oxidative stress biomarkers in relation to neurodegerative diseases.49 Evidence from in vitro and in vivo studies of polyphenols have demonstrated that they are comprised of diverse biological components that provide anti-inflammatory, antitumorigenic, antimicrobial, and antioxidant effects; therefore, they may play an integral role in preventing and treating diseases associated with neurodegeneration due to oxidative stress.49-52 Curcumin, a powerful polyphenol found in many Indian dishes, has been shown to intercept and neutralize free radicals, protect cortical neurons against cell death induced by Abeta peptides, and stimulate the transcription factor nuclear factor E2-related factor 2 (Nrf2) and the expression of heme oxygenase 1 (HO-1) genes.21 Nrf2 may aid in the protection against neurotoxicity associated with Abeta deposits and may activate HO-1, a gene that may potentially protect neurons against cell apoptosis.21 Specific polyphenol compounds, however, may differ in their bioavailability and the mechanisms in which they alter oxidative stress and modulate Abeta peptides.51

The polyphenols in red wine may be of therapeutic value for patients with Alzheimer’s disease when consumed in moderation.51,53 Researchers found that consuming approximately 4 mL of red wine significantly reduced cognitive degeneration and accumulation of Abeta neuropathology in a transgenic Alzheimer’s disease mouse model.51 This equates to approximately 5 oz of wine for humans and is consistent with moderate wine consumption.54 The type of grape used may modulate Abeta peptides differently, however. Cabernet Sauvignon wine, for example, promotes nonamyloidogenic alpha-secretase activity, while the polyphenols from muscadine wines interfere with the accumulation of Abeta peptides into high-molecular-weight oligometric Abeta species in the brain. Both show positive effects on the reduction of Abeta peptides associated with neurodegeneration in Alzheimer’s disease.51 Considering the risks associated with moderate drinking, including stroke, interactions with other medications, and increased risk of certain cancers, practitioners should advocate for the responsible use of alcohol, and recommendations should account for individual risk factors.55

The limitations of these findings reflect those of previous research in that most of the studies on polyphenols have been conducted with animal models and may not be easily generalized to humans. Further, the complexity associated with dose-specific and concentration accumulation, along with understanding the bioactivity and metabolisms associated with polyphenols and their effect on neurodegeneration, are not well understood.52 Previous research has demonstrated low concentrations of polyphenols in animal brain models after oral administration, which in turn may negate potential neuroprotective mechanisms.56 Finally, most foods are not eaten in isolation, making it difficult—if not impossible—to unpack the effects specifically related to polyphenols. Future research should seek to understand how diets rich in polyphenols work in combination with lifestyle factors to provide neuroprotective properties.


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Effects of Calorie Restriction on Cognitive Decline

Current research suggests that excessive caloric intake together with a sedentary lifestyle is associated with a higher risk of developing cognitive impairment in later life and receiving an Alzheimer’s diagnosis.22,57 Diets that are high in calories and fat may reduce brain-derived neurotropic factor by impairing hippocampal activity.58 Alternatively, diets that include caloric restriction or intermittent fasting may increase cellular stress mechanisms, resulting in a reduction of oxidative stress.59 The ketogenic diet, a type of calorie-restricted diet that specifies a 2:1 to 5:1 fat:carbohydrate ratio plus protein, has been prescribed for patients with epilepsy to suppress seizures.59 Studies have also implicated ketone feeding as a potential mechanism for preventing dementia.60,61 Considering the negative side effects associated with ketogenic diets, such as increased lipid levels and renal stones,59 research examining the effects of calorie restriction without the presence of ketones is important to consider.

Halagappa and associates62 compared the effects of a calorie-restricted, intermittent fasting, and control diet on nontransgenic mice (C57BL/6) versus a mutant mouse model (3xTgAD) that expressed a familial Alzheimer’s disease and exhibited age-dependent Abeta and tau pathology in the hippocampus and cerebral cortex. Mice on the calorie-restricted diet received 40% fewer calories than the control mice, whereas mice on the intermittent fasting diet were deprived of food for 24 hours every other day. The mice following the calorie-restricted and intermittent fasting diets exhibited increased memory and learning performance compared with the control group, as determined by behavioral testing after 7 months and 14 months on the diet (P<.05). However, the findings support a calorie-restriction model that led to decreased levels of Abeta in the hippocampus in the transgenic mice compared with the control and intermittent fasting groups (group effect, F(2,32)=3.161; P<.05), and possible decreased levels of cognitive deficits associated with Abeta. Additionally, levels of phosphorylated tau were significantly lower in the mice following the calorie-restricted diet compared with the other groups as measured by immunoblot analysis using HT7 and AT8 antibodies (P<.05). These findings are consistent with other animal models that have demonstrated the effect of caloric restriction on restoring cognitive abilities.58

Many studies involving calorie restriction have been conducted using animal models, and there is now increasing evidence that the same positive effects found in these animal models can be seen in humans.63 Witte and associates64 conducted a study using 49 participants who were divided into the following three groups: calorie-restriction group (treatment group); high unsaturated fatty acid group; and control group. Individuals in the calorie-restriction group sought to reduce their caloric intake by 30% over a 3-month period while consuming a minimum of 1200 kcal per day to avoid effects associated with malnutrition. Individuals in the high unsaturated fatty acid group were asked to increase their intake of unsaturated fatty acids by 20% over the same period of time. Baseline information was collected for all participants who met the inclusion criteria (eg, aged 50-80 years; body mass index [BMI] >21 kg/m2) and did not have a history of drug/alcohol dependence, did not have severe disease, were not taking psychiatric medication, and had Mini-Mental State Examination scores of less than 26. Results of the study support previous findings in animal models, as individuals in the calorie-restricted treatment group had a significant improvement in memory performance (t(18)=-4.73; P=.0002) that was correlated with decreases in fasting insulin (r=-0.45; P=.06) and high-sensitivity C-reactive protein (r=0.41; P=.083) compared with the high unsaturated fatty acid group (P>.31) and the control group (P>.62).58,64 Memory was assessed using the Rey Auditory Verbal Learning Test, and participants did not differ on tests assessing their attention or working memory before or after the intervention. Additionally, individuals who reported greater compliance to the calorie-restricted diet were more likely to have better memory performance on outcome measures. There were no differences, however, between groups for serum levels for neurotrophic factors associated with neuronal growth, including brain-derived neurotrophic factor, insulin-like growth factor 1, interleukin-1 beta, and memory scores.64 Future research on the impact of diet on neurotrophic factors is needed.

The authors hypothesized that reduced fasting insulin levels are associated with lower insulin resistance, higher insulin sensitivity, and improved insulin signaling, and may result in increased synaptogenesis.64 Calorie restriction led to a significant decrease in weight and BMI (P<.01), and studies examining a less-restrictive diet may be necessary to ascertain whether results would be similar for individuals who do not drastically reduce their caloric intake. Due to the small sample size, use of self-report measures, and lack of participants exhibiting signs associated with cognitive decline, future research examining clinical populations is needed to determine whether caloric restriction is a preventive mechanism in cognitive decline. Additionally, ethical standards, including those related to malnutrition and minimum caloric intake standards, must be well understood before further research with human participants is conducted.


It is clear that nutritional interventions, including the use of various vitamins, carotenoids, and polyphenols, have demonstrated positive results in the reduction of cognitive neurodegenerative disease pathophysiology associated with dementia and Alzheimer’s disease. Unfortunately, existing systematic reviews of the literature have suggested that there is insufficient evidence for the benefits of specific vitamins and supplements that mitigate normative cognitive decline or dementia in humans.10,15,23 Although some studies have demonstrated that vitamins E and C are promising in the slowing of cognitive decline24 and some of its associated negative outcomes,16 other studies have reported no effects from these vitamins on cognitive decline.32 The effects of vitamin B, however, are even more encouraging, as both of the previously mentioned studies demonstrated an association between B vitamins and cognitive functioning.33,34 Research examining carotenoids in animal
models suggests positive effects on cognitive functioning,45,47 but may need to be considered in combination with other nutrients.44 Additionally, the exact role of oxidative stress in the progression of Alzheimer’s disease is not well understood, and research examining carotenoid intake by individuals with neurodegenerative diseases is needed.44 Similarly, polyphenols may help reduce cognitive degeneration,51 but it is unclear how polyphenols transact with the intake of other substances. Finally, research related to caloric restriction and cognitive effects has demonstrated a restoration of cognitive abilities in animal models and an improvement in memory.58,62

The dependency on animal models and the limited number of large clinical trials conducted with human participants demonstrating normative cognitive decline, mild NCD (previously known as MCI), and clinical subtypes of dementia leave many questions unanswered. Future research should examine the impact of nutrients and phytochemicals within healthy and clinical populations. Malnutrition may advance the progression of cognitive dysfunction, and considerations of historical nutrient intake may play a role in the etiology of neurodegenerative diseases and nutritional interventions. Vitamins and food items are rarely consumed in isolation; therefore, future research should explore the combinations and transactions of nutrients to more fully understand their relationships and possible benefits on cognition. Additionally, lifestyle factors, such as exercise, stress levels, and sleep patterns, should be investigated in combination with nutrient intake to yield more comprehensive prevention and intervention strategies.


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Disclosures: The author reports no relevant financial relationships. The series editor has received speaker honoraria from Abbott Nutrition and has served as a consultant or paid advisory member for Abbott Nutrition.

Address correspondence to: Jennifer Dupont Frechette;

Article series summary: This is the fifth article in a continuing series on nutrition issues in long-term care (LTC). The first article in the series was published in the May 2013 issue and discussed evidence-based organizational strategies to prevent weight loss in frail elders. The second article was published in the August 2013 issue and discussed management of obesity in LTC. The third article in the series was published in the October 2013 issue and discussed end-of-life nutrition. The fourth article was published in the November 2013 issue and discussed putting nutrition-focused physical assessment into practice in the LTC setting.

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