Dietary patterns for healthier cognitive ageing

With ageing of our population and the accompanying increase in the number of people living with dementia, it is important to find modifiable risk factors to postpone the onset of cognitive decline. Diet has been proposed such a modifiable risk factor. To date, numerous studies have been conducted demonstrating a possible role of specific nutrients and foods in cognitive functioning. However, as people do not consume single nutrients, the research field has shifted towards studying dietary patterns in which synergistic effects of single nutrients and/or foods can be studied. The main aim of this thesis was to study the association of healthful dietary patterns with cognitive functioning. In addition, nutrient intake inadequacies were assessed and the potential to change dietary intake in older adults aged 65 years and older was studied. Chapter 2 describes nutrient intake of 245 Dutch adults aged 65-80 years. We identified the contribution of nutrient dense foods, fortified foods and dietary supplements to the total intake of micronutrients. Nutrient density of foods was evaluated using the Nutrient Rich Food score 9.3. Nutrient intake inadequacies were observed for vitamin D, vitamin B6 and selenium. Conventional foods were the main source of vitamin D, vitamin B6 and selenium intake. Foods with the highest nutrient density contributed most to total vitamin B6 intake. In order to optimize nutrient intakes of elderly, combinations of natural food sources, fortified foods and dietary supplements should be considered. Chapter 3 provides a systematic review of the literature on human studies up to May 2014 that examined the role of dietary patterns in relation to cognitive decline or dementia. The results demonstrate that better adherence to a Mediterranean diet was associated with less cognitive decline, dementia or Alzheimer’s Disease (AD) in four out of six cross-sectional studies, six out of 12 longitudinal studies, one trial and three meta-analyses. Other healthy dietary patterns, among which the Healthy Diet Indicator, have shown to be associated with reduced cognitive decline and/or a reduced risk of dementia in all six cross-sectional studies and six out of eight longitudinal studies. The conclusion of this literature review was that more conclusive evidence is needed to come to more targeted and detailed dietary guidelines to prevent or postpone cognitive decline. In chapter 4 the association between the Healthy Diet Indicator (HDI) and cognitive functioning in older adults from three different cohort studies was investigated. The cohorts included in total 21,837 subjects from Europe (SENECA and the Rotterdam Study [RS]) and the Unites States (Nurses’ Health Study [NHS]). Cognitive functioning was measured using the Mini-Mental State Examination (MMSE) in SENECA and RS, and the Telephone Interview for Cognitive Status (TICS) in NHS. In all three cohorts, the HDI was not significantly associated with cognitive decline, nor with cognitive function. In chapter 5 the association of long-term adherence to the Dietary Approaches to Stop Hypertension (DASH) diet with cognitive function and decline in older American women was examined. A total of 16,144 women from the Nurses’ Health Study, aged ≥70 years, who underwent cognitive testing a total of 4 times by telephone from 1995-2001 (baseline), with multiple dietary assessments between 1984 and the first cognitive exam were studied. Greater adherence to long-term DASH score was significantly associated with better average global cognition, verbal memory and TICS score at older ages, but not with cognitive decline. In chapter 6, the same cohort as in chapter 5 was studied to examine the association between long-term adherence to a recently developed Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet with cognitive function and decline. Higher MIND diet scores were associated with better verbal memory at older ages, but not with cognitive decline over 6 years in global cognition, verbal memory or TICS. Chapter 7 provides an overview of the NU-AGE (NUtrients and AGEing) dietary intervention study. The NU-AGE study is a randomized one-year intervention in 1,250 apparently healthy, independently living European subjects aged 65 to 80 years. Subjects were randomised into either the intervention group or the control group. Participants in the intervention group received dietary advice aimed at meeting the dietary recommendations of the ageing population. At the start of this thesis, the NU-AGE study was the first dietary intervention investigating the effect of a whole diet and providing targeted dietary recommendations for optimal health and quality of life in apparently healthy European elderly. In chapter 8, we evaluated if the NU-AGE intervention could be effective to shift the dietary intake of apparently healthy older adults aged 65-80 years living in Italy, the UK, the Netherlands, Poland, and France towards a more healthful diet. The NU-AGE index was created to assess adherence to the NU-AGE diet. At baseline and after one-year follow-up dietary intake was assessed by means of 7-day food records. In total, 1,296 participants were randomized and 1,145 participants completed the intervention (571 in intervention group, 570 in control group). After one-year follow-up, the intervention group improved mean intake of 13 out of 16 dietary recommendations of the NU-AGE diet (p Chapter 9 shows the results of the NU-AGE parallel randomized dietary intervention study on cognitive functioning in the Dutch NU-AGE subpopulation, including 252 older adults aged 65-80 years (123 intervention, 129 control). The primary outcome was one-year change in global cognition and in four cognitive domains as measured through a comprehensive neuropsychological test battery. Comparing the intervention with the control group, there was no effect of the intervention on cognitive functioning. In chapter 10 the main findings of this thesis were summarized and a reflection on methodological aspects was given. When grading the reported associations in previous studies and studies in this thesis, it was concluded that there is probable evidence for a role of the Mediterranean diet on cognitive functioning. For the DASH and MIND diet there is a possible link with cognitive functioning; for the HDI and the NU-AGE diet there is no sufficient evidence yet to conclude that there is a relation with cognitive functioning. Not only is there a need for well-designed intervention and prospective studies, we also call for communication strategies to the general public about the consumption of healthier diets to not only impact cardiovascular but also potentially impact brain health as many individuals will face progressive cognitive decline in the near future.</p

Dietary fibre may mitigate sarcopenia risk:Findings from the NU-AGE cohort of older european adults

Sarcopenia is characterised by a progressive loss of skeletal muscle mass and physical function as well as related metabolic disturbances. While fibre-rich diets can influence metabolic health outcomes, the impact on skeletal muscle mass and function is yet to be determined, and the moderating effects by physical activity (PA) need to be considered. The aim of the present study was to examine links between fibre intake, skeletal muscle mass and physical function in a cohort of older adults from the NU-AGE study. In 981 older adults (71 ± 4 years, 58% female), physical function was assessed using the short-physical performance battery test and handgrip strength. Skeletal muscle mass index (SMI) was derived using dual-energy X-ray absorptiometry (DXA). Dietary fibre intake (FI) was assessed by 7-day food record and PA was objectively determined by accelerometery. General linear models accounting for covariates including PA level, protein intake and metabolic syndrome (MetS) were used. Women above the median FI had significantly higher SMI compared to those below, which remained in fully adjusted models (24.7 ± 0.2% vs. 24.2 ± 0.1%, p = 0.011, η2p = 0.012). In men, the same association was only evident in those without MetS (above median FI: 32.4 ± 0.3% vs. below median FI: 31.3 ± 0.3%, p = 0.005, η2p = 0.035). There was no significant impact of FI on physical function outcomes. The findings from this study suggest a beneficial impact of FI on skeletal muscle mass in older adults. Importantly, this impact is independent of adherence to guidelines for protein intake and PA, which further strengthens the potential role of dietary fibre in preventing sarcopenia. Further experimental work is warranted in order to elucidate the mechanisms underpinning the action of dietary fibre on the regulation of muscle mass

The Glycaemic Index-Food-Frequency Questionnaire: Development and validation of a food frequency questionnaire designed to estimate the dietary intake of glycaemic index and glycaemic load:An effort by the PREVIEW Consortium

Dietary glycaemic index (GI) and glycaemic load (GL) are indices used to quantify the effect of carbohydrate quality and quantity on postprandial glycaemia. GI/GL-health associations are widely studied but data on the validity of integrated GI/GL measurements are scarce. We evaluated the performance of a food-frequency questionnaire (FFQ) specifically developed to assess GI/GL. In total, 263 Dutch men and 212 women (aged 55 ± 11 years) completed a 58-item GI-FFQ, an 183-item general-FFQ and a 2-day 24 h-recall and donated blood for glycated haemoglobin (HbA1c) determination. The level of agreement between these methods was evaluated by (1) cross-classification, (2) correlations and (3) Bland and Altman plots. The three dietary assessment methods provided comparable mean intake estimates for total carbohydrates (range: 214–237 g/day), mono/disaccharides (100–107 g/day), polysaccharides (114–132 g/day), as well as bread, breakfast cereals, potatoes, pasta, rice, fruit, dairy, cakes/cookies and sweets. Mean (±SD) GI estimates were also comparable between the GI-FFQ (54 ± 3), general-FFQ (53 ± 4) and 24 h-recalls (53 ± 5). Mean (±SD) GI-FFQ GL (117 ± 37) was slightly lower than the general-FFQ GL (126 ± 38) and 24 h-recalls GL (127 ± 37). Classification of GI in quartiles was identical for the GI-FFQ and general-FFQ for 43% of the population (r = 0.58) and with 24 h-recalls for 35% of the population (de-attenuated r = 0.64). For GL, this was 48% (r = 0.65) and 44% (de-attenuated r = 0.74). Correlations between GI and HbA1c were low (r = −0.09 for GI-FFQ, r = −0.04 for general-FFQ and r = 0.07 for 24 h-recalls). In conclusion, compared to a general-FFQ and 24 h-recalls, the GI-FFQ showed a moderate to good relative validity for carbohydrates, carbohydrate-rich foods and GI/GL. No metric predicted HbA1c

Associations between Pro- and Anti-Inflammatory Gastro-Intestinal Microbiota, Diet, and Cognitive Functioning in Dutch Healthy Older Adults : The NU-AGE Study

Dietary modulation of the gastro-intestinal microbiota is a potential target in improving healthy ageing and age-related functional outcomes, including cognitive decline. We explored the association between diet, gastro-intestinal microbiota and cognition in Dutch healthy older adults of the 'New dietary strategies addressing the specific needs of the elderly population for healthy aging in Europe' (NU-AGE) study. The microbiota profile of 452 fecal samples from 226 subjects was determined using a 16S ribosomal RNA gene-targeted microarray. Dietary intake was assessed by 7-day food records. Cognitive functioning was measured with an extensive cognitive test battery. We observed a dietary and microbial pro- to anti-inflammatory gradient associated with diets richer in animal- or plant-based foods. Fresh fruits, nuts, seeds and peanuts, red and processed meat and grain products were most strongly associated to microbiota composition. Plant-rich diets containing fresh fruits, nuts, seeds and peanuts were positively correlated with alpha-diversity, various taxa from the Bacteroidetes phylum and anti-inflammatory species, including those related to Faecalibacterium prausnitzii and Eubacterium rectale and E. biforme. Animal product-rich diets associated with pro-inflammatory species, including those related to Ruminococcus gnavus and Collinsella spp.. Cognition was neither associated with microbiota composition nor alpha-diversity. In conclusion, diets richer in animal- and plant-based foods were related to a pro- and anti-inflammatory microbial profile, while cognition was associated with neither.Peer reviewe

Mediterranean-style diet improves systolic blood pressure and arterial stiffness in older adults: Results of a 1-year European multi-center trial

We aimed to determine the effect of a Mediterranean-style diet, tailored to meet dietary recommendations for older adults, on blood pressure and arterial stiffness. In 12 months, randomized controlled trial (NU-AGE [New Dietary Strategies Addressing the Specific Needs of Elderly Population for Healthy Aging in Europe]), blood pressure was measured in 1294 healthy participants, aged 65 to 79 years, recruited from 5 European centers, and arterial stiffness in a subset of 225 participants. The intervention group received individually tailored standardized dietary advice and commercially available foods to increase adherence to a Mediterranean diet. The control group continued on their habitual diet and was provided with current national dietary guidance. In the 1142 participants who completed the trial (88.2%), after 1 year the intervention resulted in a significant reduction in systolic blood pressure (−5.5 mm Hg; 95% CI, −10.7 to −0.4; P=0.03), which was evident in males (−9.2 mm Hg, P=0.02) but not females (−3.1 mm Hg, P=0.37). The −1.7 mm Hg (95% CI, −4.3 to 0.9) decrease in diastolic pressure after intervention did not reach statistical significance. In a subset (n=225), augmentation index, a measure of arterial stiffness, was improved following intervention (−12.4; 95% CI, −24.4 to −0.5; P=0.04) with no change in pulse wave velocity. The intervention also resulted in an increase in 24-hour urinary potassium (8.8 mmol/L; 95% CI, 0.7–16.9; P=0.03) and in male participants (52%) a reduction in pulse pressure (−6.1 mm Hg; 95% CI, −12.0 to −0.2; P=0.04) and 24-hour urinary sodium (−27.1 mmol/L; 95% CI, −53.3 to −1.0; P=0.04). In conclusion, a Mediterranean-style diet is effective in improving cardiovascular health with clinically relevant reductions in blood pressure and arterial stiffness

Changes in Dietary Intake and Adherence to the NU-AGE Diet Following a One-Year Dietary Intervention among European Older Adults—Results of the NU-AGE Randomized Trial

Background: The Mediterranean Diet has been proposed as an effective strategy to reduce inflammaging, a chronic low grade inflammatory status, and thus, to slow down the aging process. We evaluated whether a Mediterranean-like dietary pattern specifically targeting dietary recommendations of people aged over 65 years (NU-AGE diet) could be effective to shift dietary intake of older adults towards a healthful diet. Methods: Adults aged 65–80 years across five EU-centers were randomly assigned to a NU-AGE diet group or control group. The diet group followed one year of NU-AGE dietary intervention specifying consumption of 15 food groups plus the use of a vitamin D supplement. Participants in the diet group received counselling and individually tailored dietary advice, food products and a vitamin D supplement. Dietary intake was assessed by means of seven-day food records at baseline and one-year follow-up. A continuous NU-AGE index (0–160 points) was developed to assess NU-AGE diet adherence. Results: In total 1296 participants were randomized and 1141 participants completed the intervention (571 intervention, 570 control). After one year, the diet group improved mean intake of 13 out of 16 NU-AGE dietary components (p < 0.05), with a significant increase in total NU-AGE index (difference in mean change = 21.3 ± 15.9 points, p < 0.01). Conclusions: The NU-AGE dietary intervention, based on dietary recommendations for older adults, consisting of individual dietary counselling, free healthy foods and a vitamin D supplement, may be a feasible strategy to improve dietary intake in an aging European population

Short Telomere Length Is Related to Limitations in Physical Function in Elderly European Adults

The present study aims to explore the potential influence of leucocyte telomere length (LTL) on both a single indicator and a composite construct of physical functioning in a large European population of elderly men and women across diverse geographical locations. A total of 1,221 adults (65–79 years) were recruited from five European countries within the framework of NU-AGE study. The physical functioning construct was based on the 36-item Short Form Health Survey. Handgrip strength was used as a single indicator of muscle function and LTL was assessed using quantitative real-time PCR. Women had significantly longer (p < 0.05) LTL than men. Participants in Poland had significantly shorter LTL than in the other study centers, whereas participants in the Netherlands had significantly longer LTL than most of the other centers (p < 0.01). An analysis of LTL as a continuous outcome against physical functioning by using linear models revealed inconsistent findings. In contrast, based on an analysis of contrasting telomere lengths (first vs. fifth quintile of LTL), a significant odds ratio (OR) of 1.7 (95% CI: 1.1 – 2.6; p < 0.05) of having functional limitation was observed in those belonging to the first LTL quintile compared to the fifth. Interestingly, having the shortest LTL was still related to a higher likelihood of having physical limitation when compared to all remaining quintiles (OR: 1.5, 95% CI: 1.1 – 2.1; p < 0.05), even after adjustment by study center, age, sex, and overweight status. Collectively, our findings suggest that short LTL is an independent risk factor that accounts for functional decline in elderly European populations. The influence of LTL on functional limitation seems driven by the detrimental effect of having short telomeres rather than reflecting a linear dose-response relationship

Changing from a Western to a Mediterranean-style diet does not affect iron or selenium status:Results of the New Dietary Strategies Addressing the Specific Needs of the Elderly Population for Healthy Aging in Europe (NU-AGE) 1-year randomized clinical trial in elderly Europeans

Background: Mediterranean diets limit red meat consumption and increase intakes of high-phytate foods, a combination that could reduce iron status. Conversely, higher intakes of fish, a good source of selenium, could increase selenium status. Objectives: A 1-y randomized controlled trial [New Dietary Strategies Addressing the Specific Needs of the Elderly Population for Healthy Aging in Europe (NU-AGE)] was carried out in older Europeans to investigate the effects of consuming a Mediterraneanstyle diet on indices of inflammation and changes in nutritional status. Methods: Selenium and iron intakes and status biomarkers were measured at baseline and after 1 y in 1294 people aged 65–79 y from 5 European countries (France, Italy, the Netherlands, Poland, and the United Kingdom) who had been randomly allocated either to a Mediterranean-style diet or to remain on their habitual, Western diet. Results: Estimated selenium intakes increased significantly with the intervention group (P < 0.01), but were not accompanied by changes in serum selenium concentrations. Iron intakes also increased (P < 0.001), but there was no change in iron status. However, when stratified by study center, there were positive effects of the intervention on iron status for serum ferritin for participants in Italy (P = 0.04) and France (P = 0.04) and on soluble transferrin receptor (sTfR) for participants in Poland (P < 0.01). Meat intake decreased and fish intake increased to a greater degree in the intervention group, relative to the controls (P < 0.01 for both), but the overall effects of the intervention on meat and fish intakes were mainly driven by data from Poland and France. Changes in serum selenium in the intervention group were associated with greater changes in serum ferritin (P = 0.01) and body iron (P = 0.01), but not sTfR (P = 0.73); there were no study center × selenium status interactions for the iron biomarkers. Conclusions: Consuming a Mediterranean-style diet for 1 y had no overall effect on iron or selenium status, although there were positive effects on biomarkers of iron status in some countries. The NU-AGE trial was registered at clinicaltrials.gov as NCT01754012. Am J Clin Nutr 2019;00:1–12

A Mediterranean-like dietary pattern with vitamin D3 (10 µg/d) supplements reduced the rate of bone loss in older Europeans with osteoporosis at baseline: results of a 1-y randomized controlled trial

Background: The Mediterranean diet (MD) is widely recommended for the prevention of chronic disease, but evidence for a beneficial effect on bone health is lacking.  Objective: The aim of this study was to examine the effect of a Mediterranean-like dietary pattern [NU-AGE (New Dietary Strategies Addressing the Specific Needs of the Elderly Population for Healthy Aging in Europe)] on indexes of inflammation with a number of secondary endpoints, including bone mineral density (BMD) and biomarkers of bone and collagen degradation in a 1-y multicenter randomized controlled trial (RCT; NU-AGE) in elderly Europeans.  Design: An RCT was undertaken across 5 European centers. Subjects in the intervention group consumed the NU-AGE diet for 1 y by receiving individually tailored dietary advice, coupled with supplies of foods including whole-grain pasta, olive oil, and a vitamin D3 supplement (10 µg/d). Participants in the control group were provided with leaflets on healthy eating available in their country.  Results: A total of 1294 participants (mean ± SD age: 70.9 ±4.0 y; 44% male) were recruited to the study and 1142 completed the 1-y trial. The Mediterranean-like dietary pattern had no effect on BMD (site-specific or whole-body); the inclusion of compliance to the intervention in the statistical model did not change the findings. There was also no effect of the intervention on the urinary biomarkers free pyridinoline or free deoxypyridinoline. Serum 25-hydroxyvitamin D significantly increased and parathyroid hormone decreased (P < 0.001) in the MD compared with the control group. Subgroup analysis of individuals with osteoporosis at baseline (site-specific BMD T-score ≤ −2.5 SDs) showed that the MD attenuated the expected decline in femoral neck BMD (n = 24 and 30 in MD and control groups, respectively; P = 0.04) but had no effect on lumbar spine or whole-body BMD.  Conclusions: A 1-y intervention of the Mediterranean-like diet together with vitamin D3 supplements (10 µg/d) had no effect on BMD in the normal age-related range, but it significantly reduced the rate of loss of bone at the femoral neck in individuals with osteoporosis. The NU-AGE trial is registered at clinicaltrials.gov as NCT01754012

Cross-sectional analysis of the correlation between daily nutrient intake assessed by 7-day food records and biomarkers of dietary intake among participants of the NU-AGE study

Methods for measuring diet composition and quantifying nutrient intake with sufficient validity are essential to study the association between nutrition and health outcomes and risk of diseases. 7-day food records provides a quantification of food actually and currently consumed and is interesting for its use in intervention studies to monitor diet in a short-term period and to guide participants toward changing their intakes. The objective of this study is to analyze the correlation/association between the daily intake of selected nutrients (collected by a 7-day food records plus a mineral/vitamin supplementation questionnaire) and estimates of energy expenditure as well as blood and urine biomarkers of dietary intakes in 1,140 healthy elderly subjects (65–79 years) at baseline of the NU-AGE intervention study (NCT01754012, clinicaltrials.gov). The results show that: the daily intake of energy correlated significantly with predicted total energy expenditure (pTEE) (ρ = 0.459, p < 0.001, and q < 0.001); protein intake correlated significantly with the ratio of 24 h urinary urea to creatinine excretion (ρ = 0.143 for total protein intake, ρ = 0.296 for animal protein intake, and ρ = 0.359 for protein intake/body weight, p < 0.001 and q < 0.001 for each correlation); vitamin B12 and folate intakes correlated significantly with their serum concentrations (ρ = 0.151 and ρ = 0.363, respectively; p < 0.001 and q < 0.001 for each correlation); sodium and potassium intakes correlated significantly with their 24 h urinary excretion (ρ = 0.298 and ρ = 0.123, respectively; p < 0.001 and q < 0.001 for each correlation); vitamin B12 and folate intakes were negatively associated with plasma homocysteine measure (p = 0.001 and p = 0.004, respectively); stratifying subjects by gender, the correlations between energy intake and pTEE and between potassium intake and its 24 h urinary excretion lost their significance in women. Even if the plasma and urinary levels of these nutrients depend on several factors, the significant correlations between daily reported intake of nutrients (protein, vitamin B12, folate, and sodium) and their blood/urinary markers confirmed that the 7-day food records (plus a supplementation questionnaire) provides reliable data to evaluate short-term current dietary intake in European elderly subjects and it can be exploited to guide and monitor NU-AGE participants through the shift of their diet according NU-AGE recommendations