Diet and Aging

The purpose of this 2020 review was to present the recently reported evidence of diet’s effects in preventing and reducing age-related cognitive decline and neurodegenerative diseases. Angeloni et al. (2020) tells us that nutraceuticals and whole diet approaches have recently been reported to protect against cognitive impairment due to aging, and neurodegeneration. This review discusses the whole diet (Mediterranean Diet, Nordic Ketogenic for examples) versus single nutrient approach (polyphenols, B vitamins etc.) and the potential mechanisms of action underlying these beneficial effects. The authors believed that large-scale preventative measures should be implemented based on dietary patterns identified as having a positive impact on brain health and should be regarded as a research and public health priority.

This 2020 narrative review aimed to present the existing research on the efficacy of the Mediterranean diet (MedDi) and Ketogenic Diet (KD) against Alzheimer’s Disease (AD)-related cognitive decline and explore the proposed mechanism of action of this protective effect. Vinciguerra et al. (2020) state that there is not a single dietary pattern that has unequivocally been proven to prevent AD although there are several dietary habits that, especially if accompanied with a good lifestyle, could potentially delay the problematic signs of AD. Although the current knowledge on this topic did not allow exhaustive conclusions to be drawn, the review studied the MedDi and KD, both of which have demonstrated a considerable amount of promise in reducing or delaying cognitive decline, and could provide assistance in the mission to better characterize the possible role of MedDi and KD as non-pharmacological therapies in the treatment of AD, and of neurodegenerative disorders.

Klimova, Novotny & Valis (2020) aimed to review the evidence for proper nutrition having a positive impact on prevention/decline of depressive symptoms among elderly people. The six eligible articles indicated that: proper nutrition is associated with improvements in mental health (reduction in depressive symptoms) among the elderly population; there is a considerable correlation between intakes of vitamin B with reduced incidence of depression; and sufficient dietary consumption of tryptophan is important in terms of nutrition and serotonin levels in the body. From these findings, the authors deduce that the use of preventative measures may be the rational way of promoting greater mental health in seniors, and exploring associations between depression with dietary intake rather than focusing on nutrients is important. Klimova and the other authors (2020) call for more studies including interdisciplinary collaboration, which might involve diagnosis by a psychiatrist, analysis of individual nutrient metabolism by biochemists, and the construction of a nutritional plan by a nutritional therapist.

This 2019 review takes a look at nutrients and its role specifically in reducing risk of noncommunicable diseases (NCDs) such as musculoskeletal disorders, dementia, loss of vision and cardiometabolic diseases during aging. Surveys have revealed nutrient intake levels of the aging population were lacking in optimally supporting healthy aging, and these deficiencies have been linked to increased risk of NCDs like fatigue, cardiovascular disease, plus cognitive and neuromuscular function impairments. Bruins et al. (2019) found current knowledge on the protective effects of improving individual nutrient intakes in chronic disease was still emerging with varying effect sizes and degrees of proof. Most pronounced benefits of nutrients were found in participants who had low nutrient intake or status at baseline or who had increased genetic and metabolic needs for that nutrient. The writers felt that authorities should implement ways to optimize essential nutrient intake as an integral part of their strategies to address NCDs.

between diet and Alzeimer’s disease (AD), with the aim of summarising all the evidence considering diet as a protective or risk factor for AD, of identifying methodological challenges and limitations, and of providing future research directions. Sixty four studies were included, all of which were published between 1997 and 2015, accumulating a total of 132,491 participants, and generating 141 dietary patterns or “models”. Twelve of the studies examined the relationship between the Mediterranean diet (MeDi) and AD development, with 10 reporting a significant association. However, the findings were inconsistent in terms of sample size, AD diagnosis, and food measures. Yusufov et al. (2017) mention 81.3% of the studies included samples with mean baseline ages that were at risk of AD based on age (>65 years), ranging from 52 to 85.4 years. Since AD has a long prodromal phase prior to the manifestation of symptoms and decline, the mean ages of these sample populations were considered limitations in determining the influence of diet on AD. Despite these imperfections, the finding that 50 of the 64 reviewed studies revealed an association between diet and AD incidence offers promising implications for diet as a modifiable risk factor for AD.

Anastasiou et al. (2017) evaluated the association between adherence to an a priori (pre-existing conditions) defined Mediterranean dietary pattern and its components with dementia and certain aspects of cognitive function among a Greek population taken from the Hellenic Longitudinal Investigation of Ageing and Diet (HELIAD) - an on-going population-based study exploring potential associations between diet and cognitive performance. In HELIAD, dementia was diagnosed after full clinical and neuropsychological evaluation, while cognitive performance was assessed according to memory, language, attention-speed, executive functioning, and visuospatial perception (the five cognitive domains) and a composite cognitive score. The adherence to MeDi was evaluated by an a priori score (range 0-55), derived from a detailed food frequency questionnaire. Among the 1,865 individuals (mean age 73±6 years, 41% male), 90 were diagnosed with dementia and 223 with mild cognitive impairment. The analysis indicated a 10% decrease in dementia risk associated with each unit increase in Mediterranean diet score (MedDietScore). Adherence to MeDi was linked to improvements in memory, language, visuospatial perception and the composite cognitive score, with the association most prominent with memory. The researchers also found other associations such as higher consumption of non-refined cereal with enhanced cognitive performance, as well as fish intake’s negative correlation with dementia. Following the results suggesting an association between increased adherence to the MeDi with better cognitive performance and lower dementia rates in Greek elders, it was concluded that the MeDi in its a priori constructed prototype form may improve cognitive function in traditional Mediterranean populations.

Mirabelli et al. (2020) remark that in obesity, the unbalanced production of pro- and anti-inflammatory adipocytokines (inflammatory cytokines) can lead to the development of insulin resistance (IR), which is a fundamental defect in type 2 diabetes (T2D) potentially reversible through weight-loss programs. When considering diet interventions, the Mediterranean Diet (MedDiet) - consisting of extra-virgin olive oils (EVOO), nuts, red wine, vegetables and other polyphenol-rich elements - has proven its association with greater improvement of IR in obese people. Moreover, numerous nutritional supplements derived from MedDiet food sources are insulin-sensitizing and have shown promise in modulating certain traits of IR-related conditions, including polyunsaturated fatty acids from olive oil and seeds, anthocyanins from purple vegetables and fruits, resveratrol from grapes, and the EVOO-derived, oleacein. The molecular mechanism(s) underlying the metabolic benefits appear to be compound-specific. Mirabelli et al. (2020) state that the pharmacological properties and clinical uses of these functional nutrients are still under investigation.

Davison et al. (2019) used the cohort data from the baseline Canadian Longitudinal Study on Aging (n = 27,162) of adults aged 45-85, to examine depression and socio-economic, health, immigration, and nutrition-related factors in older adults. Depression was assessed using the Center for Epidemiologic Studies Short Depression (CESD-10) rating scale while the sample were also categorized for immigration status as: native-born, recent and mid-term (< 20 years), and long-term immigrants (≥20 years). It was discovered the majority of the respondents were Canadian-born (82.6%), women (50.6%), 56-65 years (58.9%), earning between C$50,000-99,999 (33.2%), and in a relationship (69.4%). Also when compared to Canadian-born residents, recent, mid-term (< 20 years), and longer-term (≥ 20 years) immigrant women were more likely to report depression and this relationship was robust to adjustments for 32 covariates. In women, depression was associated with not completing secondary school (OR = 1.23, p < 0.05), stage 1 hypertension (OR = 1.31, p < 0.001), chronic pain (OR = 1.79, p < 0.001), low fruit/vegetable intakes (OR = 1.33, p < 0.05), and fruit juice (OR = 1.80, p < 0.001), chocolate (ORs = 1.15-1.66, p's < 0.05), or salty snack (OR = 1.19, p < 0.05) consumption. Whereas for men, chronic conditions (ORs = 1.36-3.65, p's < 0.001), chronic pain (OR = 1.86, p < 0.001), smoking (OR = 1.17, p < 0.001), or chocolate consumption (ORs = 1.14-1.72, p's < 0.05) predicted a higher likelihood of depression. Men were less likely to be depressed if they were: in a relationship (OR = 0.62, p < 0.001), completing post-secondary education (OR = 0.82, p < 0.05), consuming higher fat (ORs = 0.67-83, p's < 0.05) and greater amounts of omega-3 egg (OR = 0.86, p < 0.05) as well as eating moderate levels of fruits/vegetables and calcium/high vitamin D sources (ORs = 0.71-0.743, p's < 0.05). For all participants, depression was connected to lower grip strength (OR = 1.25, p < 0.001) and high nutritional risk (OR = 2.24, p < 0.001). The researchers concluded that immigrant women were associated with the highest risk of depression, although depression was linked with socioeconomic, physical, and nutritional factors among middle-aged and older adults, and the relationships varied by sex.

symptomatic benefits and do not provide a cure, Szczechowiak et al. (2019) address the proposed inflammation hypothesis that the modulatory role of dietary factors on inflammation may contribute to the prevention, delay of onset, and slowing the progression of AD. The paper summarizes the available evidence of pro- and anti-inflammatory activity of some dietary components including fatty acids, vitamins, flavonoids, polyphenols, probiotics and d-AGE, and their potential for AD prevention and treatment. But current evidence also shows that synergistic action of combined supplementation and complex dietary patterns provides stronger benefits than any single component considered separately. It was also revealed that the importance of novel factors such as dietary advanced glycation end products (d-AGE), gut microbiota, butyrate and vitamin D3 on the inflammatory processes in AD were gaining attention recently.

This 2019 review examined plant-based dietary patterns and polyphenol-rich plant foods and their role in preventing age-related cognitive decline (ARCD) and improving cognitive function. Rajaram et al. (2019) came across emerging evidence for brain-health-promoting effects of several plant foods rich in polyphenols, anti-inflammatory dietary patterns, and plant-based dietary patterns such as the Mediterranean diet that include a variety of fruits, vegetables, legumes, nuts, and whole grains. These dietary habits consist of antioxidant vitamins, polyphenols, other phytochemicals, and unsaturated fatty acids, which in animal models, have been shown to enhance neurogenesis, synaptic plasticity, and neuronal survival by reducing oxidative stress and neuroinflammation. Furthermore, this review presents evidence from randomized clinical trials, some of which support the role of plant foods such as citrus fruits, grapes, berries, cocoa, nuts, green tea, and coffee in improving specific domains of cognition, most notably frontal executive function. Gaps in the current knowledge are exposed, while the writers also offer recommendations for future studies aimed at finding the cognitive beneficial effects of plant-exclusive diets compared with plant-centered diets with fish and/or small amounts of animal foods for example.

Mintzer et al. (2019) aimed to provide an overview of evidence from current literature and expert opinion on the key elements associated with preserving brain health as people age, and focused on areas such as mental well-being, exercise, cognitively stimulating activities, sleep, nutrition, and social connectedness. By using the recommendations of the AARP's Global Council on Brain Health (GCBH) largely as a basis, this review concluded the aforementioned areas of focus offered opportunities for aging individuals to make lifestyle adjustments to positively affect brain health.

McGrattan et al. (2019) examined research studies on healthy dietary patterns and age-related cognition, and in this review discussed the potential neuroinflammatory actions of diet on cognitive function. Recent findings indicated neuroinflammation associated with Alzheimer’s disease (AD) could be inhibited by components consumed in the anti-inflammatory diets, Mediterranean diet (MD) and dietary approaches to stop hypertension (DASH) such as omega-3 fatty acids, antioxidants and polyphenols, and suggest these diets have neuroprotective effects. It was thought these anti-inflammatory diets may also block neuroinflammation through indirect immune pathways from the gut microbiome and systemic circulation. It was also implied that diet may influence cognitive aging via multiple inflammatory pathways, although the mechanism underlying this link is not known and data from human studies are lacking. McGrattan et al. (2019) believe further diet intervention studies focusing on the diet-associated neurological change from the earliest to latest stages of cognitive decline are required, while using neuroimaging measures in these intervention studies would also help with the progress in understanding the mechanisms behind the neuroinflammatory effects of dietary modification in the aging brain.

This 2018 review evaluated the evidence for the neuroprotective effects of some dietary components, supplements and patterns and discussed their potential in delaying cognitive decline and onset of dementia. Some studies that examined the function of dietary habits on late-life cognition have gathered evidence that combining foods and nutrients may act synergistically and would provide greater benefits than those conferred by individual dietary components. Moreover, while higher adherence to the Mediterranean dietary pattern has been associated with reduced cognitive decline and incidence of Alzheimer’s disease, the Dietary Approach to Stop Hypertension (DASH) also exhibits neuroprotective qualities. The combination of these 2 dietary patterns has also been linked to slowing the rate of cognitive impairment and significantly lowering risk of developing AD.

Wu & Sun (2017) performed a systematic review and meta-analysis to evaluate the potential association between the Mediterranean diet with incidence of cognitive disorders, and to study the dose-response pattern, since recent articles had presented inconsistent findings. A total of 9 cohort studies were included, allowing data analysis of 34,168 participants. The pooled analysis revealed the highest Mediterrranean diet score was inversely associated with the occurrence of cognitive disorders, with pooled relative risk (RR) of 0.79 compared with the lowest category. It was also observed that the Mediterranean diet score of the median category was not significantly associated with cognitive disorders, also that there was a near-linear relationship of the Mediterranean diet score with the incident risk of cognitive disorders identified. The authors expressed their desire to see more randomized controlled trials to confirm this association in different populations.

Gardener & Rainey-Smith (2018) evaluated the role of nutrition in cognitive function and brain aging, focusing on the Mediterranean diet (MeDi), Dietary Approaches to Stop Hypertension (DASH), and Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diets and examining the literature from the last 5 years. Results showed the MIND diet substantially slowed cognitive impairment, over and above the MeDi and DASH diets. High adherence to healthy dietary patterns does appear to be associated with preservation of brain structure and function too. Despite these associations, Gardener & Rainey-Smith (2018) feel additional work is required to develop dietary guidelines with the greatest potential benefit for public health, as the world’s population ages and demand for research into this topic increases further.

The aim of this 2019 study was to explore the relationship between diet quality and vegetable variety with cognition among a population of older adults in Taipei, Taiwan. A food frequency questionnaire completed at baseline was used to attain the Alternative Healthy Eating Index (mAHEI) and consequently the diet quality in the 436 community-dwelling elders (aged 65 and over) who participated. The vegetable variety indicated the number of different vegetable groups, adjusted for vegetable quantity. High diet quality (highest tertile of mAHEI) was linked to lower risk of both global cognitive decline [adjusted odds ratio (AOR) = 0.54] and decline of attention domain (AOR = 0.56) compared with low diet quality. This trend was observed for the elders with high vegetable variety also, with an adjusted odds ratio of 0.49 for those consuming diets high in quality also, relative to those with low quality diets. Chou et al. (2019) concluded that high diet quality along with diverse vegetable intake was associated with a lower risk of cognitive decline in older adults.

Fart et al. (2019) investigated the relationship between gut health, well-being and nutrient intake among a sample of older adults over the age of 65, with the objective of identifying areas through which health can be promoted since it was considered likely that they will be relying on increased healthcare in the future. The cross-sectional observational study enrolled 229 older adults, and used validated questionnaires to assess gut health, nutrient intake and general health. The results displayed the majority (65%) of participants experienced gastrointestinal issues, which were found to correlate to anxiety, stress and lower quality of life. Also, the protein, fat and fibre intakes of the subjects represented levels lower than the nutritional recommendations, while their consumption of alcohol and saturated fats were above the recommended levels. It was deduced that gut health, diet and well-being all represent important areas for future intervention studies.

Although a number of dietary patterns have been attempted in order to reduce the pathology of Alzheimer’s disease (AD) and to slow cognitive decline, this 2019 review focused on the roles of the Mediterranean diet (MedDi) and Mediterranean-DASH diet Intervention for Neurological Delay (MIND) diet in the battle against Alzheimer’s disease and cognitive impairment. Both diets have been associated with decreasing incidence of AD and slowing cognitive decline, with significant reduction in AD rate observed for the MIND diet. Omar (2019) mentions olives, one of the components of both MedDi and MIND diets, may have potential to improve health due to the presence of its bioactive constituents such as oleic acids and phenolic compounds (biophenols). The author also reported a few trials using medical food showed an optimal result in presymptomatic or early stages of AD. This review reveals the gaps in this research topic and presents future directions for studies.

Van den Brink et al. (2019) presented a review of the existing evidence examining the associations of the Mediterranean, Dietary Approaches to Stop Hypertension (DASH), and Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diets and their dietary components with cognitive decline, dementia, and Alzheimer's disease (AD). Among the 56 studies included in this review, greater adherence to the Mediterranean diet was related to higher cognitive scores in 9 of 12 cross-sectional studies, 17 of 25 longitudinal studies, and 1 of 3 trials, while higher DASH diet adherence was associated with better cognitive function in 1 cross-sectional study, 2 of 5 longitudinal studies, and 1 trial. Improved cognitive scores were seen in those who adhered well to the MIND diet in 1 cross-sectional study and 2 of 3 longitudinal studies. Evidence connecting these dietary patterns with dementia were limited, however higher adherence to the Mediterranean diet was associated with a lower risk of AD in 1 case-control study and 6 of 8 longitudinal studies, with the same observed for either DASH or MIND diets in 1 longitudinal study. With respect to the components of these dietary patterns, olive oil may be associated with less cognitive decline. In summary, the findings of this review suggest that higher adherence to the Mediterranean, DASH, or MIND diets is associated with less cognitive decline and a lower risk of AD, with the strongest associations observed with the MIND diet.

Hosking et al. (2019) investigated the associations between the Mediterranean-DASH diet Intervention for Neurological Delay (MIND) diet with the incidence of cognitive impairment and incidence of Alzheimer's disease/Vascular dementia (over 12 years) using the Personality and Total Health (PATH) Through Life cohort (n = 1220) set in Canberra, Australia since this relationship had not been evaluated outside the United States. MIND diet and two alternate Mediterranean diet scores were calculated from the baseline food frequency questionnaire responses, with higher dietary scores consequently translating to greater adherence. The results from the adjusted logistic regression models revealed that the MIND diet (OR = 0.47, 95% CI 0.24, 0.91), but not Mediterranean diet, was associated with reduced odds of 12-year cognitive impairment. This study reported preliminary evidence suggesting that the protective effects of the MIND diet are geographically generalizable, while also it exposed the need for more prospective studies with diverse samples that examine the relative effects of the MIND and the Mediterranean diets against cognitive decline.

The purpose of this 2018 meta-analysis was to test the strength of the association that exists between increased fruit and vegetable consumption with reduced risk of cognitive impairment and dementia. Nine studies were included in this meta-analysis, five of which were cohort studies and four were cross-sectional studies, adding up to a total of 31,104 participants and 4,583 incident cases of cognitive impairment and dementia. Jiang et al. (2017) found a significant reduction in risk of cognitive decline and dementia (20% drop in probability) was related to increased consumption of fruits and vegetables, with dose-response meta-analysis revealing approximately 13% of risk reduction linked to an increment of 100g increase of fruit and vegetables per day. Although subgroup analysis indicated this inverse association only applied to participants with average ages of over 65 years and combined sexes. Nevertheless, it was concluded that increased consumption of fruit and vegetables was associated with a lower risk of experiencing cognitive impairment and dementia.

Kim & Yun (2018) undertook this study investigating the relationship between dietary consumption with cognitive function among an adult population aged over 50 years of age, because the correlation between diet and cognition was uncommon and debated. Of the 324 adults from Gwangju Sun-Han hospital who participated in this study, 276 were examined using the mini-mental state examination (MMSE), while a semi-quantitative food frequency questionnaire (SQ-FFQ) was also utilised for collecting dietary information. The results showed the following food groups either significantly reduced the odds ratio for the risk of mild cognitive impairment (MCI): cooked white rice (< 2 times/day compared with ≥ 3 times/day) (P < 0.05), properly cooked rice with other grains and legumes (P < 0.001), fruits (P < 0.05), milk (low fat and normal) (P = 0.044), liquid-type yogurt (P = 0.019), and curd-type yogurt (P = 0.015). To summarize, a moderate intake of cooked white rice and an adequate intake of whole grains, fruits, milk, and dairy products were associated with reduced risks of MCI among adults aged over 50 years.

The aim of this 2019 narrative article was to provide practical guidance for healthcare professionals working with older adults experiencing mood disorders, and to raise awareness of some existing health issues. Harbottle (2019) found it imperative that the rise in occurrence of physical illness and of mood disorders among older adults are addressed. She believes the increased nutritional vulnerability that accompanies late adulthood is connected to the physiological impact of ageing as well as social and economic challenges. Specific nutrients and overall diet quality may influence mood, while depression and anxiety can affect interest in and ability to eat, which may further exacerbate problems/symptoms. The author raised these concerns for nurses either working with older adults living at home or in the care setting, since Harbottle (2019) regards it crucial that they are able to identify the signs, refer and support those who need the assistance.

The purpose of this 2019 review was to present the current knowledge of the preventative roles that protein and amino acids play in Alzheimer’s disease and related dementias (ADRD), while also providing future recommendations for this body of research. Glenn et al. (2019) explain that scientists and clinicians have primarily focused on dietary intake to combat the rise in ADRD that has followed the rapid growth in aging populations, and protein/amino acid intake is relevant since its consumption is connected to a number of disease-related risk factors as such low-muscle mass, sleep, stress, depression, and anxiety. It was admitted that the research was still speculative and certain mechanisms need to be proven. In this review, Glenn et al. (2019) discussed the current recommendations for protein consumption and dosing for adults who desire to manage long-term risk for cognitive decline.

Simonetto et al. (2019) describes the link between atherosclerosis, vascular cognitive impairment and dementia (VCID) and inflammation, and explains why omega-3 polyunsaturated fatty acid (PUFA) supplementation may be useful to prevent and treat inflammatory-related diseases. Simonetto and her team (2019) state that the relationship between atherosclerosis and VCID has already been established, with risk of VCID increased by induction of cerebral infarction, or through systemic or local inflammatory factors that underlie both atherosclerosis and cognition. It was also highlighted that omega-3 PUFAs exert anti-inflammatory properties and decrease production of pro-inflammatory eicosanoids, which explains why supplementation of these fatty acids resulted in lower risks of different phenotypes of atherosclerosis and cardiovascular disease in experimental studies and clinical trials.

This 2019 article outlines the objectives of the REACH (Researching Eating, Activity and Cognitive Health) study, which is to investigate associations between dietary patterns, cognitive function and metabolic syndrome, while accounting for a range of covariates since Mumme et al. (2019) believed that previous research had not considered some relevant covariates such as physical activity and the Apolipoprotein E genotype. The REACH study will include covariates and interaction factors such as age, education, socio-economic status, physical activity, Apolipoprotein E ε4 genotype, family history of dementia or cognitive impairment, and lifestyle factors. Older adults (65-74 years old) will be recruited from Auckland, New Zealand, while dietary data will be collected via a 109-item food frequency questionnaire, cognitive function will be examined using the Montreal Cognitive Assessment (paper based) and the Computerised Mental Performance Assessment System (COMPASS). Additionally, biochemical markers including fasting glucose, HbA1c, lipids profile of the participants will be measured, as well as anthropometric measurements (weight, height, waist and hip circumference, body composition using dual X-ray absorptiometry), blood pressure, physical activity, health and demographics. Mumme and her group (2019) believe this study will provide new knowledge on the relationships between dietary patterns and cognitive function and metabolic health in older adults living in New Zealand. This would prove useful for developing nutrition related recommendations to help older adults maintain cognitive function.

The purpose of this 2019 trial was to assess the efficacy of CoQ10 (a novel treatment with potential to enhance brain function in healthy elderly populations and known to possess beneficial impacts on oxidative stress, and mitochondrial and vascular function) in ameliorating cognitive decline among a healthy, non-demented sample (aged 60 and over). CoQ10 at a dose of 200mg will be tested against placebo for 90 days in this randomised controlled trial, while cardiovascular function, oxidative stress, liver function and mood will be monitored across 30-, 60- and 90- day time points. Several cognitive determinants were to be used including CogTrack composite measures of cognition (the primary outcome). Stough et al. (2019) regard this trial to be the first of its kind, to provide key clinical and mechanistic data regarding the efficacy of Ubiquinol as a treatment for age-related cognitive impairment in a healthy and elderly population. The trial will provide important implications for productivity and quality of life within this age group.

Since there were a few suggestions that a healthy diet is related to lower risk of frailty, Ward and colleagues (2020) set out to measure the diet qualities of male physicians from the U.S. and assess its relationship with frailty. The data was collected from the Physicians’ Health Study, with a total of 9861 participants aged 60 years or older. A cumulative deficit frailty index (FI) was calculated using 33 variables encompassing domains of comorbidity, functional status, mood, general health, social isolation, and change in weight, while the 3 measures of diet quality were the Alternative Healthy Eating Index (aHEI), Mediterranean Diet Score (MDS), and Dietary Approaches to Stop Hypertension (DASH). The FI revealed that 38% of the physicians were non-frail, 44% were pre-frail, while 18% were identified as being frail. In variable-adjusted models, the subjects in the highest quintiles for aHEI possessed significantly lower risk of frailty and pre-frailty when compared with those in the lowest quintiles. Furthermore, similar relationships were found for DASH and MDS quintiles with frailty and pre-frailty, and also restricted cubic splines showed an inverse dose-response relationship of diet quality scores with odds of frailty and pre-frailty. While Ward and her colleagues (2020) have described their findings from cross-sectional data, longitudinal studies are also required in order to investigate whether healthier diet is a modifiable risk factor for frailty.

Phillips (2017) mentions there is evidence that modifiable lifestyle factors such as physical activity, cognitive engagement, and diet can provide key strategies for maintaining healthy brains during the aging process, and thus aims to identify mechanisms in which brain health can be improved while aging and to highlight future directions for scientists and clinicians. There have also been a multitude of studies that have demonstrated correlations between lifestyle factors, brain structure and function, and cognitive function in aging adults: physical activity and diet modulate common neuroplasticity substrates (neurotrophic signaling, neurogenesis, inflammation, stress response, and antioxidant defense) in the brain; while cognitive engagement has been shown to enhance brain and cognitive reserve. This is why this review evaluated the relationship between modifiable lifestyle factors, neuroplasticity, and optimal brain health during aging, with the motive of further advancing the world’s understanding and clinical treatment interventions for maintaining brain health.

The aim of this mini review published in 2019 was to provide an updated overview of intracellular oxidative stress and mitochondrial abnormalities in the brain of an individual with insulin resistance (IR). Maciejczyk et al. (2019) reports that indications from the latest studies strongly link systemic IR with higher incidence of neurodegeneration, dementia, and mild cognitive impairment, possibly owing to the hyperglycaemia, hyperinsulinemia, dyslipidaemia, and/or prolonged whole-body inflammation. However, the main role was attributed to the neuronal redox imbalance and oxidative damage. This mini review highlighted important correlations discovered between brain oxidative stress, ceramide generation, β-amyloid accumulation, as well as neuronal apoptosis in the IR conditions.

With emerging evidence that suggest diet can prevent or reverse cognitive decline, a sign also observed in neurological disorders such as Alzheimer’s disease and multiple sclerosis, Francis & Stevenson (2018) decided to examine the whole diets prominent in the scientific literature (ketogenic, caloric restriction, high polyphenol, and Mediterranean diets) and to discuss the possible underlying neurophysiological mechanisms.

This 2019 systematic review examined the effects of multiple dietary patterns on cognitive health among older adults, by compiling evidence submitted from randomized controlled trials and cohort studies and following PRISMA guidelines. Chen and the team (2019) assembled all the data on the Mediterranean diet, Dietary Approach to Stop Hypertension (DASH) diet, the Mediterranean-DASH diet Intervention for Neurodegenerative Delay (MIND) diet, Anti-inflammatory diet, Healthy diet recommended by guidelines via dietary index, or Prudent healthy diets generated via statistical approaches, and the cognitive impacts they had. Of the 38 studies included in this review, the Mediterranean diet was the most investigated with evidence supporting protection against cognitive decline among older adults. Other dietary habits such as the MIND, DASH, Anti-inflammatory, and Prudent healthy diets produced positive results especially for those at risk of cardiovascular diseases, however the evidence was more limited. Chen et al. (2019) expressed there was a need for better understanding of the underlying mechanisms in general in order to develop comprehensive and practical dietary recommendations for those fighting against age-related cognitive decline.

Pagliai et al. (2018) investigated dietary habits, including adherence to the Mediterranean diet (MD) and their relationship with the risk of depression, using data from the Mugello study, an epidemiological study that analysed a total of 388 subjects aged 90-99 living in the homes and nursing homes in Florence, Italy. The Mugello study examined various health issues including those related to nutritional status, which enabled the extraction of dietary data, while a shorter version of the Geriatric Depression Scale (GDS) was used to detect the possible presence of depressive symptoms, and cognitive and functional status were assessed using the Mini-Mental State Examination, the Clock Drawing Test, as well as the Basic and Instrumental Activities of Daily Living test. Pagliai et al. (2018) found that depressed subjects were more likely to be older, female, or widows, than those not depressed. The depressed participants were also less adherent to the MD (no statistical significance) than non-depressed subjects (NDS). A lower risk of depression was related to greater consumption of olive oil and fruit, with odds ratios of 0.35 and 0.46 respectively (after adjustment for many possible confounders). As for sex, similar results were observed for women, while no statistically significant differences emerged for men. To conclude, this study’s results implicated diets enriched in olive oil and fruit to protect against the development of depressive symptoms in older age.

The purpose of this 2018 study was to evaluate the longitudinal associations between haemoglobin (HbA1c) levels, diabetes status and subsequent cognitive decline over a 10 year follow-up period, using data from the English Longitudinal Study of Ageing (ELSA). In total, this study was composed of information on 5189 participants (55.1% women, mean age 65.6 ± 9.4 years). Cognitive function was assessed at baseline and also every 2 years. After adjustment for a multitude of factors, a 1 mmol/mol increment in HbA1c (indicating increase in glucose levels in previous 3 months) was significantly associated with an enhancement in rate of decline in global cognitive z scores, memory z scores, and executive function z scores. Moreover, when those with prediabetes and diabetes were compared to those with normal sugar levels (normoglycemia), the multivariable-adjusted rate of global cognitive decline was increased by -0.012 SD/year and -0.031 SD/year, respectively (p for trend <0.001). In addition, results of memory, executive function and orientation z scores demonstrated a rise in rate of cognitive decline with diabetes. Although future studies are warranted to determine the impacts of maintaining optimal glucose control on rate of cognitive impairment in people with diabetes, Zheng et al. (2018) have exposed significant longitudinal associations between HbA1c levels, diabetes status and long-term cognitive decline.

This 2018 review explored the aging brain and examined the emerging evidence linking diet and nutrients with cognitive function and depression in aging, which could potentially aid the development of strategies to improve the quality of life in the growing aging population. Moore et al. (2018) point out the estimations that there will be two billion people aged 60 years or over by 2050, with 131 million predicted to suffer from dementia, while depression was also projected to be the second leading cause of disability by 2020. Several dietary patterns, especially the Mediterranean diet, have shown signs of reducing risk of dementia and depression, while the strongest support with regards to dietary-related total evidence was for folate and the metabolically related B-vitamins (vitamin B12, vitamin B6 and riboflavin) in slowing the progression of cognitive impairment and possibly reducing the risk of depression in aging. While the authors found promise also in new technologies such as MRI and magnetoencephalography in identifying effective nutrition interventions that could reduce occurrences of cognitive and mental disorders.

This 2020 article summaries the molecular mechanisms involved in the pathology of Alzheimer’s Disease (AD), an incurable neurodegenerative disease), and also discusses the possible positive impacts lifestyle and nutritional interventions (diet, exercise, calorie restriction, bioactive compounds) can have on cognitive decline and dementia. Bhatti et al. (2020) explain that due to the lack of methods of early diagnosis and limited knowledge on the exact pathophysiology of AD, discovering effective therapeutic strategies has been challenging, and the roles of lifestyle interventions and nutraceuticals in the prevention of many metabolic and neurodegenerative diseases have given hope to the scientific community. This article provides insights into the function of non-pharmacological interventions in the modulation of AD pathology, hopefully showing evidence of reduced cognitive decline, incidence of AD, and better quality of life.

Moradi et al. (2020) conducted a systematic review and meta-analysis, using frailty risk data from 5 studies (13,908 older adults) and frailty-related parameters results from 2 studies (sample of 7539), to examine the association between Dietary Inflammatory Index (DII®) score with frailty risk. Positive associations were discovered between DII score with frailty risk (OR = 1.24, 95%CI: 1.6-1.33, P < 0.001, I2 = 0.0%), and between DII score with weakness risk (OR = 1.12, 95%CI: 1.05-1.19, P = 0.014, I2 = 0.0%). Apart from weakness risk, other frailty-related parameters (exhaustion, low BMI, low physical activity) did not show correlations with DII score. Also prospective cohort studies with longer follow-up periods are required to support this potential association between DII score and frailty risk, the findings of this meta-analysis suggest that older adults who score highly on DII are at a greater risk of frailty.

Hardman et al. (2020) designed this study to investigate the effect of a 6-month intervention program involving the Mediterranean diet (MedDiet), exercise, and a combination of both on cognition, mood, and general health among an older population (aged 60-90) living independently in care communities. This study, named the Lifestyle Intervention in Independent Living Aged Care (LIILAC) Study, recruited 102 older adults and randomly assigned the individuals to 1 of 4 intervention groups. While overall memory performance was the primary outcome of the study, the researchers also investigated changes in cognitive task performance, mood, wellness, cardiovascular function and measured blood biomarkers. Although there was nom significant change in overall memory performance, the subjects in the combined exercise and diet group displayed significant improvements in spatial working memory performance, compared to the control group. Improved emotional state - indicated by the Depression Anxiety Stress scale - was also seen in this combined diet+exercise group and in the exercise-only group. Hartman et al. (2020) provided evidence that diet and exercise programs have potential in improving aspects of cognition and mood in an aging population, while larger randomised controlled trials investigating the diet and exercise programs in a larger sample size of older people would reinforce the validity of this study’s findings.

O’brien et al. (2014) retrieved data from the Nurses’ Health Study, including 15,467 women aged 70 or older without a history of stroke, in order to examine the effects of long-term consumption of nuts on cognition among older women. Nut intake was collected from the results of food-frequency questionnaires completed in 1980 and every 4 years thereafter, while the Telephone Interview for Cognitive Status (TICS), immediate and delayed verbal recall, category fluency, and attention were all assessed to determine cognitive function. The study found that higher long-term total nut intake was associated with better average cognitive status for all cognitive outcomes. A global score averaging the results of all tests revealed women who consumed at least 5 servings of nuts per week scored higher than those who didn’t eat as many portions, with a mean difference of 0.08 standard units (which is equivalent to the mean difference between women 2 years apart in age for example). Long term intake of nuts could not be associated with rates of cognitive decline, but it was concluded that greater nut consumption may be related to enhanced overall cognition at late adulthood, and could be a conveniently modifiable public health intervention.

Shishtar et al. (2020) examined the prospective relation between dietary flavonoid intake with risk of Alzheimer disease and related dementias (ADRD) and Alzheimer’s disease (AD) using the data from the Framingham Heart Study Offspring Cohort exams 5-9, while also discussing the limitations of the existing prospective observational studies on the flavonoid-ADRD risk association. Flavonoid consumption was updated at each exam using a food frequency questionnaire (FFQ), and was expressed as percentile categories of intake (≤15th, >15th to 30th, >30th to 60th, >60th) to manage their non-linear relation with ADRD and AD. Over an average follow-up of 19.7 years in 2801 participants (mean baseline age = 59.1; 52% females), there were 193 ADRD events, 158 of which were AD. Compared to the subjects with the lowest consumption (≤15th percentile) of flavonols, anthocyanins, and flavonoid polymers, those with the highest intakes (>60th percentile) were less likely to develop ADRDs: hazard ratios (HRs) for flavonols were 0.54; 0.24 for anthocyanins; and 0.58 for flavonoid polymers. Identical trends in associations were found for AD with flavonoids and anthocyanins but not with flavonoid polymers. To summarize the findings, it can be implied that greater long-term intakes of flavonoids are associated with lower risks of both ADRD and AD in adults in the U.S.

Given the fact that eating habits are inseparably linked with human physical health, this 2018 systematic review aimed to identify effective diet interventions for those older adults, while providing marked evidence and direction for future research. The 16 studies included in the review, found through literature searches on PubMed, Scopus and Web of Science Core Collection, were primarily conducted in European countries and ranged in duration from 3 weeks to 7 years. Zhou et al. (2018) admitted that 7 of the studies were considered to be of moderate quality while the remaining were less than moderate level. The findings included improvements in dietary variety, nutrition status, and various other health-related eating behaviours among the older participants in studies involving dietary educational interventions (3) and all meal service- related interventions. Zhou et al. (2018) realized multicomponent dietary interventions mainly contributed to the reduction of risk of chronic disease. Although many more high-quality studies may be needed to promote healthy eating among older individuals, the results of this systematic review supported the concept that better diet quality can be achieved through making diet-related alterations by receiving either dietary education or healthier meal services.

This 2020 article outlines in detail possible mechanisms in which nutritional ketosis may be capable of mitigating changes observed in several neurodegenerative and neuroprogressive disorders. Detrimental effects of oxidative stress, mitochondrial dysfunction and neuroinflammation on neuronal function have been observed in disorders such as cognitive impairment, Parkinson’s disease, schizophrenia, bipolar disorder, autistic spectrum disorder, and all of which can be potentially ameliorated by the use of oral ketogenic compounds, fractionated coconut oil, very low carbohydrate intake, or ketone monoester supplementation. The detailed mechanisms led Morris et. al (2020) to hypothesize that nutritional ketosis may have therapeutic applications in the aforementioned disorders.

The MedLey study (2015) aims to be the first randomized controlled trial to validate the efficacy of a Mediterranean diet (MedDiet) approach in safely reducing the onset of age-related cognitive decline and promoting optimal cognitive performance among a sample of healthy older adults (≥65 years and above). The 166 participants recruited were aged 65 and over, from Adelaide in South Australia, and were randomly allocated to either the control diet (maintenance of regular lifestyle and diet) for six months, or the experimental group, which involved an intervention dietary pattern based from the traditional Cretan MedDiet, involving vegetables, fruits, olive oil, legumes, fish, whole grain cereals, nuts and seeds and low consumption of processed foods, dairy products, red meat and vegetable oils, for six months. The primary outcomes of the study were the differences in age-related cognitive performance in quantitative forms (speed of processing, memory, attention, executive functions, visual spatial and visuomotor ability), while the secondary outcomes included changes in biomarkers of inflammation, oxidative stress, lipid metabolism, glucose, insulin, blood flow velocity, as well as measures of psychological well-being such as stress, sleep, anxiety, depression. The assessments were to be done at baseline, and repeated every 3 months. Knight et al. (2015) believed this would be one of the first randomized clinical trials to prove the cause-effect relationship between the MedDiet and age-related cognitive function in a healthy older adult population.

In 2019 Cherian and several researchers investigated the Mediterranean-Dash Intervention for Neurodegenerative Delay (MIND) diet and aimed to determine its efficacy in preventing cognitive decline after stroke among 106 people. The participants who had a history of stroke, completed a food frequency questionnaire (FFQ), which was later used to determine the MIND diet score. The components of the MIND diet included whole grains, leafy greens and other vegetables, berries, beans, nuts, lean meats, fish, poultry, and olive oil and reduced consumption of cheese, butter, fried foods, and sweets (the diet is described as a hybrid of the Mediterranean and Dash diets). The results showed a slower rate of global cognitive decline over an average of 5.9 years of follow-up when comparing the top with the bottom tertiles of MIND diet scores after multiple variable adjustments. The study concluded that high adherence to the MIND diet was related to slowing the speed of cognitive decline following stroke.

Agarwal et al. (2018) tested whether there was a correlation between the Mediterranean-DASH Diet Intervention for Neurodegenerative Delay (MIND) diet with incidence and progression of parkinsonism among older adults, by assessing individuals annually for the presence of four parkinsonian signs using a 26-item modified version of the United Parkinson’s Disease Rating Scale. This study involved 706 Memory and Aging Project participants aged 59 −97 years and without parkinsonism at baseline, and defined incident parkinsonism as the first appearance of 2 or more parkinsonism signs over 4.6 years of follow-up while a change in global parkinsonian score signified the progression. Moreover, Mediterranean, and DASH diet pattern scores were computed based on a validated food frequency questionnaire including 144 food items. In adjusted models, greater MIND diet scores correlated to less incidence of parkinsonism (hazard risk = 0.89) as well as slower progression of the disorder [(β= −0.008; SE=0.0037; p=0.04)]. Also, the Mediterranean diet was marginally associated with reduced parkinsonism progression, while the DASH diet was not associated with either outcome. This study found the MIND diet to be associated with a decreased risk and slower progression of parkinsonism among older adults.

The objective of this 2019 study was to examine whether adherence to the Mediterranean-DASH diet intervention for neurodegenerative delay (MIND) was associated with subjective memory complaints (SMC)(as measured by the cognitive difficulties scale) in the NutriNet-Santé cohort. The 6011 study participants were aged 60 and over at baseline and did not have SMCs (defined as a CDS score ≥ 43). The MIND diet score, which is a hybrid of the Mediterranean Diet and the Dietary Approaches to Stop Hypertension (DASH) scores), was not significantly associated with SMC in the sample population as a whole nor among those aged 60-69, whereas a significant inverse association was identified between SMC and adherence to MIND diet among the participants aged 70 and over. This relationship was also strengthened after participants with depressive symptoms were excluded from the equation. Over a mean follow-up of 6 years, the subjects aged ≥ 70 years reported 30% of the SMC cases, while the younger participants between 60-69 only reported 15%. To summarize the findings, the MIND diet could help prevent or delay subjective memory complaints among older adults with depressive symptoms.

This 2017 randomized crossover study examined the effect of consuming a berry beverage every day for a period of 5 weeks on cognitive function and on cardiometabolic risk markers, among 40 healthy older adults (50-70 years old). The subjects were given either a cocktail of berries including exact quantities of blueberries, blackcurrants, elderberries, ligonberries, strawberries and tomatoes, or a water-based control beverage (with the same concentration of monosaccharides, pH, and volume). To determine cognitive performance the samples were investigated on working memory capacity, selective attention, and psychomotor reaction time, while the cardiometabolic markers included blood pressure, fasting blood concentrations of glucose, insulin, blood lipids, inflammatory markers, and markers of oxidative stress. Reductions in total and LDL cholesterol were observed after completion of the berry intervention compared to both the baseline readings and to those individuals who were assigned to consume the control drink. The berry intervention group performed better in the working memory test compared to the control beverage group, while no significant effects in the other variables were observed. Among the subjects in the control group, glucose concentrations were greater and insulin levels appeared to be higher compared to baseline, while also the rise in insulin exceeded that of the berry group. The results suggested berries may have the potential to prevent type 2 diabetes, cardiovascular disease, and associated cognitive decline. Since the berry beverage contained dietary fiber (DF) and polyphenol and the control beverage lacked these components, Nilsson et al. (2017) hypothesized that the beneficial effects observed could be linked to DF and polyphenols.

Bigford & Del Rossi (2014) reviewed experimental and clinical data on supplemental substances such as curcuminoids, rosmarinic acid, resveratrol, acetyl-L-carnitine, and ω-3 (n-3) polyunsaturated fatty acids that have demonstrated encouraging therapeutic effects on chronic diseases. The many mechanistic parallels discovered between various neurodegenerative diseases suggest that a single therapeutic approach may be used to treat multiple disease conditions. The writers explain that natural compounds and supplemental substances have gained a considerable amount of support in their possible roles in treating neurodegenerative disorders and diseases (NDDs) due to their potential adjunctive therapeutic effects on various neurodegenerative diseases.

The aim of this 2019 study was to assess the relationship between adherence to the Mediterranean diet and cognitive function in a sample outside of the Mediterranean basin. Wade et al. also planned to compare the difference in this association between middle-aged and older individuals. Using the data from the Maine-Syracuse Longitudinal Study (MSLS), a literature-based Mediterranean diet score was applied to determine adherence to the Mediterranean diet. A battery of tests was conducted to determine the cognitive function of the participants. The analyses did not produce any correlations between Mediterranean diet adherence and cognitive function. However, over a period of 5 years, higher adherence to a Mediterranean diet was linked with improved Global Cognitive Function, Visual-Spatial Organization and Memory and scanning and tracking in the 70+ age group. There were no other marked associations found considering the subjects under the age of 70. Therefore, the data suggest that higher adherence to a Mediterranean diet is related to enhanced cognitive performance in older but not middle-aged individuals.

The aim of this 2017 study was to find associations between dietary patterns and inflammation, and to examine whether these diets are linked to cognitive decline. Ozawa et al. utilized the data on 5083 individuals (28.7% female) from the Whitehall II cohort study. In this study, diet and the inflammatory marker, interleukin-6 (IL-6), were measured twice (in 1991-1993 and 1997-1999). While cognitive tests were conducted in 1997-1999 and again later in 2002-2004 and 2007-2009. The researchers identified an inflammatory dietary pattern (characterized by higher intakes of red meat, processed meat, peas and legumes, and fried food, and lower intakes of whole grains) was associated with elevated interleukin-6 levels in both 1991-1993 and 1997-1999. This dietary habit was also linked with faster cognitive decline after multivariable adjustment. These trends were stronger in those individuals younger than 55 years, which suggests that reverse causation is unlikely. The participants who had diets more adherent to the inflammatory dietary pattern (highest tertile) were seen to experience worse drops in reasoning ability, compared with those who don’t eat as much inflammatory foods (lowest tertile). To summarize, a dietary pattern characterized as higher consumption of red and processed meat, peas, legumes and fried food, and lower consumption of whole grains were related with higher levels of inflammatory markers and accelerated cognitive decline at older ages.

While the evidence shows that adherence to the Mediterranean diet is linked with lower prevalences of Alzheimer’s Disease, Hill et al. (2019) conducts the first systematic review and meta-analysis to inspect the relationship between Mediterranean-style diet adherence and the hallmark AD biomarkers that appear many years before clinical symptomatology. Several databases were systematically searched for articles that investigated diet and AD biomarkers in the past 2 decades. Of the 15 studies that met the inclusion criteria, 13 found a significant relationship: 4 studies discovered a correlation between high glycaemic load with elevated AD biomarker levels; while six studies indicated that adherence to a Mediterranean or "AD-protective" dietary pattern resulted in a lower AD biomarker burden. The meta-analysis revealed that diet had a small but significant effect on AD biomarkers. While there is a lack of efficacious pharmacological options for Alzheimer’s disease, this review suggests that diet and nutrition have potential use cases in the prevention of AD in a non-pharmacological way.

This 2012 trial tested the impact of taking multivitamin supplementation (Swisse Women's 50+ Ultivite ®) for 16 weeks on cognition in elderly women. The 56 participants were community dwelling, elderly women, with subjective complaints of memory loss. Each subject was randomly selected to either consume the multivitamins or a placebo, while neither them nor the experimenters knew which was received. Cognition was then assessed using a battery of memory, while specific biochemical measures (selected nutrients, homocysteine, markers of inflammation, oxidative stress, and blood safety parameters) were also taken at baseline and 16 weeks post-treatment. The multivitamin supplement was found to improve speed of response on a measure of spatial working memory. No other benefits to cognition were detected. The vitamin consumption elevated the levels of vitamin B(6) and B(12), while decreasing plasma concentrations of homocysteine. The safety of taking these vitamins daily was confirmed, as no hepatotoxic effects were reported. In conclusion, 16 weeks of supplementation with a combined multivitamin, mineral and herbal formula may positively influence working memory in elderly women at risk of cognitive impairment.

Although age is the strongest predictor of cognitive decline, Dominguez & Barbagallo (2018) focus on another contributing factor in cognitive impairment that is nutrition. The authors believe that nutritional approaches for the prevention or slowing of cognitive decline could greatly influence public health. Prevention strategies are particularly important since there is a lack of effective pharmaceutical treatments for age-related cognitive dysfunction. Many studies have examined the association between dietary components and supplements with the development of cognitive decline, while some studies have inspected the role of dietary patterns on late-life cognition. The evidence suggests that combinations of foods and nutrients may have synergistically positive effects, compared with individual dietary components. Higher adherence to the Mediterranean diet specifically has been shown to correlate with decreased cognitive impairment and incidence of Alzheimer’s Disease. Another dietary pattern with neuroprotective actions, the Dietary Approach to Stop Hypertension (DASH), in combination with the Mediterranean diet, has been linked with slowing rates of cognitive decline and significantly reducing AD incidence. This review evaluated the literature on the impacts of some dietary components, supplements, and dietary patterns on cognitive decline and the onset of dementia.