Pregnancy as a window of opportunity for dementia prevention: a narrative review.

Dementia is a debilitating condition with a disproportionate impact on women. While sex differences in longevity contribute to the disparity, the role of the female sex as a biological variable in disease progression is not yet fully elucidated. Metabolic dysfunctions are drivers of dementia etiology, and cardiometabolic diseases are among the most influential modifiable risk factors. Pregnancy is a time of enhanced vulnerability for metabolic disorders. Many dementia risk factors, such as hypertension or blood glucose dysregulation, often emerge for the first time in pregnancy. While such cardiometabolic complications in pregnancy pose a risk to the health trajectory of a woman, increasing her odds of developing type 2 diabetes or chronic hypertension, it is not fully understood how this relates to her risk for dementia. Furthermore, structural and functional changes in the maternal brain have been reported during pregnancy suggesting it is a time of neuroplasticity for the mother. Therefore, pregnancy may be a window of opportunity to optimize metabolic health and support the maternal brain. Healthy dietary patterns are known to reduce the risk of cardiometabolic diseases and have been linked to dementia prevention, yet interventions targeting cognitive function in late life have largely been unsuccessful. Earlier interventions are needed to address the underlying metabolic dysfunctions and potentially reduce the risk of dementia, and pregnancy offers an ideal opportunity to intervene. This review discusses current evidence regarding maternal brain health and the potential window of opportunity in pregnancy to use diet to address neurological health disparities for women.

The Role of Fresh Beef Intake and Mediterranean Diet Adherence during Pregnancy in Maternal and Infant Health Outcomes.

Beef is an excellent source of nutrients important for maternal health and fetal development. It is also true that the Mediterranean diet is beneficial for the health of both the mother and offspring; however, the relative value of fresh beef intake within Mediterranean diet patterns during pregnancy is unknown. The objective of this project was two-fold: (1) assess the relationship between beef intake and nutrient intake in a pregnant population; (2) assess the relationship between maternal beef consumption among varying degrees of Mediterranean diet adherence with maternal risk of anemia and infant health outcomes. This is a secondary analysis of an existing cohort of pregnant women (n = 1076) who participated in one of two completed clinical trials examining the effect of a docosahexaenoic acid supplementation on birth and offspring outcomes. Women were enrolled between 12 and 20 weeks of gestation and were followed throughout their pregnancies to collect maternal and infant characteristics, food frequency questionnaires [providing beef intake and Mediterranean diet (MedD) adherence], and supplement intake. Women with the highest fresh beef intake had the highest intake of many micronutrients that are commonly deficient among pregnant women. Fresh beef intake alone was not related to any maternal or infant outcomes. There was a reduced risk of anemia among women with medium to high MedD quality and higher fresh beef intake. Women in the medium MedD group had 31% lower odds of anemia, and women in the high MedD group had 38% lower odds of anemia with every one-ounce increase in fresh beef intake, suggesting that diet quality indices may be misrepresenting the role of fresh beef within a healthy diet. These findings show that beef intake increases micronutrient intake and may be protective against maternal anemia when consumed within a healthy Mediterranean diet pattern.

Association of diabetes mellitus with dementia- and non-dementia-related mortality amongst women: a secondary competing risks analysis of the California Teachers Study.

BACKGROUND AND PURPOSE: The prevalence of dementia is rapidly increasing. Attempts to further understand modifiable risk factors such as diabetes mellitus (DM) are urgently needed to inform public health policies for prevention. Thus, the objective of the current study was to assess the relationship between DM and risk of dementia and non-dementia mortality amongst women in the California Teachers Study prospective cohort. METHODS: Women (n = 124,509) aged 22-104 years at baseline were included. DM was ascertained from self-reported questionnaires and hospital-linked records. Dementia-related deaths were ascertained from state and national records. Competing risk regression models were used to estimate cause-specific hazard ratios and 95% confidence intervals for the association of DM with dementia- and non-dementia-related mortality. RESULTS: There were 10,511 total DM cases and 3625 deaths due to dementia over a mean of 21.3 years of follow-up. Fully adjusted cause-specific hazard ratios of the association with DM were 2.26 (2.01, 2.55) for dementia-related and 1.97 (1.89, 2.05) for the competing risk of non-dementia-related mortality. This association was strongest amongst participants with incident DM, younger age at baseline and higher alcohol consumption or who were overweight. CONCLUSIONS: In the California Teachers Study, women with DM had increased risk of mortality due to both dementia and non-dementia causes; however, the risk of mortality due to dementia was elevated compared to non-dementia causes only amongst participants with incident DM.

Protocol for a single-arm, pilot trial of creatine monohydrate supplementation in patients with Alzheimer's disease.

BACKGROUND: Impaired brain bioenergetics is a pathological hallmark of Alzheimer's disease (AD) and is a compelling target for AD treatment. Patients with AD exhibit dysfunction in the brain creatine (Cr) system, which is integral in maintaining bioenergetic flux. Recent studies in AD mouse models suggest Cr supplementation improves brain mitochondrial function and may be protective of AD peptide pathology and cognition. AIMS: The Creatine to Augment Bioenergetics in Alzheimer's disease (CABA) study is designed to primarily assess the feasibility of supplementation with 20 g/day of creatine monohydrate (CrM) in patients with cognitive impairment due to AD. Secondary aims are designed to generate preliminary data investigating changes in brain Cr levels, cognition, peripheral and brain mitochondrial function, and muscle strength and size. METHODS: CABA is an 8-week, single-arm pilot study that will recruit 20 patients with cognitive impairment due to AD. Participants attend five in-person study visits: two visits at baseline to conduct screening and baseline assessments, a 4-week visit, and two 8-week visits. Outcomes assessment includes recruitment, retention, and compliance, cognitive testing, magnetic resonance spectroscopy of brain metabolites, platelet and lymphocyte mitochondrial function, and muscle strength and morphology at baseline and 8 weeks. DISCUSSION: CABA is the first study to investigate CrM as a potential treatment in patients with AD. The pilot data generated by this study are pertinent to inform the design of future large-scale efficacy trials. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05383833 , registered on 20 May 2022.

Creatine as a Therapeutic Target in Alzheimer's Disease.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease, affecting approximately 6.5 million older adults in the United States. Development of AD treatment has primarily centered on developing pharmaceuticals that target amyloid-ß (Aß) plaques in the brain, a hallmark pathological biomarker that precedes symptomatic AD. Though recent clinical trials of novel drugs that target Aß have demonstrated promising preliminary data, these pharmaceuticals have a poor history of developing into AD treatments, leading to hypotheses that other therapeutic targets may be more suitable for AD prevention and treatment. Impaired brain energy metabolism is another pathological hallmark that precedes the onset of AD that may provide a target for intervention. The brain creatine (Cr) system plays a crucial role in maintaining bioenergetic flux and is disrupted in AD. Recent studies using AD mouse models have shown that supplementing with Cr improves brain bioenergetics, as well as AD biomarkers and cognition. Despite these promising findings, no human trials have investigated the potential benefits of Cr supplementation in AD. This narrative review discusses the link between Cr and AD and the potential for Cr supplementation as a treatment for AD.

Higher Diet Quality in Latina Women during Pregnancy May Be Associated with Sociodemographic Factors.

Acculturation contributes to low diet quality and can foster health inequities for Latina women during pregnancy. Conversely, nutrition literacy (NL) increases diet quality and could promote health equity. This study assessed the associations between the diet quality, acculturation, and NL of Latina women (n = 99) participating in the Assessment of Docosahexaenoic Acid On Reducing Early Preterm Birth (ADORE) study. Acculturation and nutrition literacy factored together tended to modify diet quality, but this was not statistically significant. Diet quality was associated with acculturation, age, and nativity. Most (76.8%) demonstrated low nutrition literacy. Women who were bicultural and were born in Latin American countries other than Mexico had lower diet quality scores than women who had lower acculturation and were born in Mexico. Women who were 35 years or older had better diet quality than those who were younger. Future studies are needed to explore diet quality differences for pregnant Latina women with high nutrition literacy and high acculturation, as well as for women from the Caribbean, Central and South American countries living in the US, to promote nutrition and maternal health for Latina women.

Milk intake enhances cerebral antioxidant (glutathione) concentration in older adults: A randomized controlled intervention study.

Background: A major antioxidant, glutathione (GSH), is a key factor in the antioxidant defense mechanism against oxidative stress and aging-related functional declines. Our previous observational study showed positive correlations between brain GSH concentrations and dairy food consumption, particularly milk (p < 0.001), in older adults. Objective: To investigate whether a recommended amount of milk intake (3 cups/day) in low dairy consumers enhances brain GSH concentrations through an intervention trial. Methods: Seventy-three older adults (60-89 years) with a low dairy intake (≤1.5 servings/day) were randomized (5:2 ratio) in this 3-month randomized clinical trial. The intervention group was provided 1% milk weekly and instructed to consume 3 cups of milk/day for 3 months while the control group continued their habitual intake of total dairy ≤ 1.5 servings/day (<1 cup of milk/day). Brain GSH concentrations were measured in the fronto-parietal region using our unique 3 T magnetic resonance chemical shift imaging technique at baseline and 3 months. Results: Among 73 randomized participants, 66 participants (49 intervention; 17 controls) completed the study. Milk intake in the intervention group increased from 0.2 ± 0.3 cups/day to 3.0 ± 0.6 cups/day (p < 0.001) between baseline and the end of the study, while milk intake in the control group did not differ throughout the study duration (0.4 ± 0.4 cups/day). The intervention group showed increases in brain GSH concentrations by 7.4 ± 11.7% (p < 0.001) in parietal and 4.7 ± 9.8% (p = 0.003) in fronto-parietal regions, and 4.6 ± 8.7% (p < 0.001) in overall brain concentration after the intervention compared with baseline, while the control group showed no changes. Conclusion: This study provides evidence that milk serves as a good dietary source to increase and/or restore brain GSH concentrations in older adults. Identifying dietary sources that effectively enhance antioxidant defenses and neuroprotection could lead to the development of new strategies to promote brain health in the aging population. Clinical trial registration: [https://ClinicalTrials.gov], identifier [NCT02957422].

Potential for Ketotherapies as Amyloid-Regulating Treatment in Individuals at Risk for Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive neurodegenerative condition characterized by clinical decline in memory and other cognitive functions. A classic AD neuropathological hallmark includes the accumulation of amyloid-ß (Aß) plaques, which may precede onset of clinical symptoms by over a decade. Efforts to prevent or treat AD frequently emphasize decreasing Aß through various mechanisms, but such approaches have yet to establish compelling interventions. It is still not understood exactly why Aß accumulates in AD, but it is hypothesized that Aß and other downstream pathological events are a result of impaired bioenergetics, which can also manifest prior to cognitive decline. Evidence suggests that individuals with AD and at high risk for AD have functional brain ketone metabolism and ketotherapies (KTs), dietary approaches that produce ketone bodies for energy metabolism, may affect AD pathology by targeting impaired brain bioenergetics. Cognitively normal individuals with elevated brain Aß, deemed "preclinical AD," and older adults with peripheral metabolic impairments are ideal candidates to test whether KTs modulate AD biology as they have impaired mitochondrial function, perturbed brain glucose metabolism, and elevated risk for rapid Aß accumulation and symptomatic AD. Here, we discuss the link between brain bioenergetics and Aß, as well as the potential for KTs to influence AD risk and progression.

Relationship of fasting glucose and longitudinal Alzheimer's disease imaging markers.

INTRODUCTION: Fasting glucose increases with age and is linked to modifiable Alzheimer's disease risk factors such as cardiovascular disease and Type 2 diabetes (T2D). METHODS: We leveraged available biospecimens and neuroimaging measures collected during the Alzheimer's Prevention Through Exercise (APEx) trial (n = 105) to examine the longitudinal relationship between change in blood glucose metabolism and change in regional cerebral amyloid deposition and gray and white matter (WM) neurodegeneration in older adults over 1 year of follow-up. RESULTS: Individuals with improving fasting glucose (n = 61) exhibited less atrophy and regional amyloid accumulation compared to those whose fasting glucose worsened over 1 year (n = 44). Specifically, while individuals with increasing fasting glucose did not yet show cognitive decline, they did have regional atrophy in the hippocampus and inferior parietal cortex, and increased amyloid accumulation in the precuneus cortex. Signs of early dementia pathology occurred in the absence of significant group differences in insulin or body composition, and was not modified by apolipoprotein E ε4 carrier status. DISCUSSION: Dysregulation of glucose in late life may signal preclinical brain change prior to clinically relevant cognitive decline. Additional work is needed to determine whether treatments specifically targeting fasting glucose levels may impact change in brain structure or cerebral amyloid in older adults.

Correlation of Skin Carotenoid Content with 3-Day Dietary Intake in Community Dwelling Older Adults.

Pressure-mediated reflection spectroscopy (RS) measures skin carotenoid content (SCC). Continued validation of this method is pertinent to validate its use as an objective measure of fruit and vegetable intake. This study aimed to assess relationships between SCC scores and self-reported dietary carotenoid intake from 3-day food records in community dwelling older adults. This was a cross-sectional analysis of baseline data among cognitively normal older adults (n=95) participating in the Nutrition Interventions for Cognitive Enhancement (NICE) study. Food-derived vitamin A (R=0.24, p<0.05) and food plus supplemental vitamin A (R=0.29, p<0.01) were correlated with SCC. All food-derived carotenoids (R: 0.20-0.39, p<0.05) except beta-cryptoxanthin and lycopene were correlated with SCC. Lutein + zeaxanthin from food more strongly correlated with SCC (R=0.38, p<0.001) than combined food plus supplemental intake (R=0.31, p=0.002). Correlations for total fruit and SCC (R=0.23, p=0.02), total vegetable and SCC (R= 0.31, p=0.002), and combined total fruit and vegetable and SCC (R=0.35, p<0.001) were significant; no sub-categories of fruit or vegetables except dark green vegetables (Rho=0.4, p<0.001) had significant correlations with SCC. The current study demonstrates RS-derived SCC scores correlate with 3-day self-reported intakes of F/V and certain carotenoids in community dwelling older adults.

US Older Adults That Consume Avocado or Guacamole Have Better Cognition Than Non-consumers: National Health and Nutrition Examination Survey 2011-2014.

Purpose: The goal of this study is to examine how avocado relates to cognitive function among older adults. Methods: A total of 2,886 National Health and Nutrition Examination Survey 2011-2014 participants aged 60 or older met the eligibility criteria and were included of our cross-sectional study. Participants were binarily classified as avocado consumers (i.e., reported consuming any avocado/guacamole in either 24-h dietary recalls) or non-consumers. Cognitive performance was evaluated with: Consortium to Establish a Registry for Alzheimer's disease (CERAD)-immediate and delayed recall (IWR/DWR), the Animal Fluency test, and the Digit Symbol Substitution Test. We calculated the education-dependent z-scores for each subject because education level can impact cognitive function. Global cognitive score, an average of the z-scores for each cognitive test, was calculated in participants who had completed all four tests. To account for relevant covariates, we tested for mean differences in cognition between consumers and non-consumers using independent sample t-tests and ANCOVA, special cases of ordinary least squares regression. Results: Avocado consumers had significantly better cognitive scores across all cognitive tests and the global cognition score (p < 0.05) in the unadjusted model. Some mean differences attenuated after adjusting for potential confounders, but others remained significant. Compared to non-consumers, avocado consumers had significantly higher z-scores of 0.15, 0.15, and 0.11 for CERAD IWR and DWR, and global cognition score, respectively (all p < 0.05 in adjusted models). Conclusion: Avocado consumption was associated with significantly better IWR, DWR, and the overall global cognition score, which remained significant when controlling for all relevant confounders.

High Glycemic Diet Is Related to Brain Amyloid Accumulation Over One Year in Preclinical Alzheimer's Disease.

Objective: To test the hypothesis that high glycemic diet is related to 1-year change in brain amyloid based on our prior cross-sectional evidence that high glycemic diet is associated with brain amyloid. Methods: This longitudinal, observational study assessed the relationship between reported habitual consumption of a high glycemic diet (HGDiet) pattern and 1-year brain amyloid change measured by Florbetapir F18 PET scans in 102 cognitively normal older adults with elevated or sub-threshold amyloid status that participated in a 1-year randomized, controlled exercise trial at the University of Kansas Medical Center in Kansas City. Results: Among all participants (n = 102), higher daily intake of the HGDiet pattern (ß = 0.06, p = 0.04), sugar (ß = 0.07, p = 0.01), and total carbohydrate (ß = 0.06, p = 0.04) were related to more precuneal amyloid accumulation. These relationships in the precuneus were accentuated in participants with elevated amyloid at enrollment (n = 70) where higher intake of the HGDiet pattern, sugar, and carbohydrate were related to more precuneal amyloid accumulation (ß = 0.11, p = 0.01 for all measures). In individuals with elevated amyloid, higher intake of the HGDiet pattern was also related to more amyloid accumulation in the lateral temporal lobe (ß = 0.09, p < 0.05) and posterior cingulate gyrus (ß = 0.09, p < 0.05) and higher sugar and carbohydrate intake were also related to more amyloid accumulation in the posterior cingulate gyrus (ß = 0.10, p < 0.05 for both measures). Conclusion: This longitudinal observational analysis suggests that a high glycemic diet relates to higher brain amyloid accumulation over 1 year in regions of the temporoparietal cortex in cognitively normal adults, particularly in those with elevated amyloid status. Further studies are required to assess whether there is causal link between a high glycemic diet and brain amyloid. Clinical Trial Registration: ClinicalTrials.gov, Identifier (NCT02000583).

The Ketogenic Diet in the Treatment of Post-concussion Syndrome-A Feasibility Study.

Concussion is the most common form of mild traumatic brain injury (mTBI). Although most patients' symptoms resolve within a month, patients with post-concussion syndrome (PCS) may continue to experience symptoms for years and have limited treatment options. This pilot study assessed the feasibility and symptom-related effects of a ketogenic diet (KD) in patients with PCS symptoms. The Ketogenic Diet in Post-Concussion Syndrome (KD-PCS) was a single-arm trial of a 2-month KD high in non-starchy vegetables and supplemented with medium-chain triglyceride (MCT) oil. Macronutrient targets were ≥70% fat, ≤10% carbohydrate, and the remainder as protein as energy. We assessed feasibility by daily self-reported measure of urine acetoacetate and collection of 3-day food records and serum beta-hydroxybutyrate at multiple timepoints. We assessed symptoms by administering the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) and Modified Balance Error Scoring System (M-BESS) at baseline and month 2 and the Post-Concussion Symptom Scale (PCSS) at baseline, month 1, and month 2. Fourteen participants enrolled in the KD-PCS. Twelve participants completed the study and 11 implemented the KD (73% fat, 9% carbohydrate, and 18% protein) and achieved ketosis. One participant complained of MCT-related diarrhea that resolved and another reported nausea and fatigue that resulted in withdrawal from the study. Among compliant participants, the visual memory domain of the ImPACT improved by 12 points (p = 0.02) and PCSS scores improved by 9 points, although not statistically significant. This pilot trial suggests that the KD is a feasible experimental treatment for PCS and justifies further study of its efficacy.

NHANES 2011-2014 Reveals Cognition of US Older Adults may Benefit from Better Adaptation to the Mediterranean Diet.

Although the Mediterranean diet (MedD) has gained interest for potential Alzheimer's disease (AD) prevention, it is unknown how well US older adults follow a MedD. We used two National Health and Nutrition Examination Survey (NHANES) cycles (2011-2014) to conduct our primary aim of reporting population estimates of MedD adherence among older adults (60+ years) in the US (n = 3068). The mean MedD adherence score for US older adults was 5.3 ± 2.1 (maximum possible = 18), indicating that older adults in the US do not adhere to a MedD. There were various differences in MedD scores across demographic characteristics. We also assessed the cross-sectional relationship between MedD adherence and cognitive performance using survey-weighted ordinary least squares regression and binary logistic regression models adjusted for 11 covariates. Compared to the lowest MedD adherence tertile, the highest tertile had a lower odds ratio of low cognitive performance on three of five cognitive measures (p < 0.05 for each). Sensitivity analyses within participants without subjective memory complaints over the past year revealed similar results on the same three cognitive measures. We conclude that MedD interventions are a departure from usual dietary intake of older adults in the US and are a reasonable approach for AD prevention trials.

Dietary Neuroketotherapeutics for Alzheimer's Disease: An Evidence Update and the Potential Role for Diet Quality.

Alzheimer's disease (AD) is a devastating neurodegenerative disease with growing prevalence as the global population ages. Currently available treatments for AD have minimal efficacy and there are no proven treatments for its prodrome, mild cognitive impairment (MCI). AD etiology is not well understood and various hypotheses of disease pathogenesis are currently under investigation. A consistent hallmark in patients with AD is reduced brain glucose utilization; however, evidence suggests that brain ketone metabolism remains unimpaired, thus, there is a great deal of increased interest in the potential value of ketone-inducing therapies for the treatment of AD (neuroketotherapeutics; NKT). The goal of this review was to discuss dietary NKT approaches and mechanisms by which they exert a possible therapeutic benefit, update the evidence available on NKTs in AD and consider a potential role of diet quality in the clinical use of dietary NKTs. Whether NKTs affect AD symptoms through the restoration of bioenergetics, the direct and indirect modulation of antioxidant and inflammation pathways, or both, preliminary positive evidence suggests that further study of dietary NKTs as a disease-modifying treatment in AD is warranted.

Nutrition literacy predicts adherence to healthy/unhealthy diet patterns in adults with a nutrition-related chronic condition.

OBJECTIVE: To describe the relationship between adherence to distinct dietary patterns and nutrition literacy. DESIGN: We identified distinct dietary patterns using principal covariates regression (PCovR) and principal components analysis (PCA) from the Diet History Questionnaire II. Nutrition literacy was assessed using the Nutrition Literacy Assessment Instrument (NLit). Cross-sectional relationships between dietary pattern adherence and global and domain-specific NLit scores were tested by multiple linear regression. Mean differences in diet pattern adherence among three predefined nutrition literacy performance categories were tested by ANOVA. SETTING: Metropolitan Kansas City, USA. PARTICIPANTS: Adults (n 386) with at least one of four diet-related diseases. RESULTS: Three diet patterns of interest were derived: a PCovR prudent pattern and PCA-derived Western and Mediterranean patterns. After controlling for age, sex, BMI, race, household income, education level and diabetes status, PCovR prudent pattern adherence positively related to global NLit score (P < 0·001, ß = 0·36), indicating more intake of prudent diet foods with improved nutrition literacy. Validating the PCovR findings, PCA Western pattern adherence inversely related to global NLit (P = 0·003, ß = -0·13) while PCA Mediterranean pattern positively related to global NLit (P = 0·02, ß = 0·12). Using predefined cut points, those with poor nutrition literacy consumed more foods associated with the Western diet (fried foods, sugar-sweetened beverages, red meat, processed foods) while those with good nutrition literacy consumed more foods associated with prudent and Mediterranean diets (vegetables, olive oil, nuts). CONCLUSIONS: Nutrition literacy predicted adherence to healthy/unhealthy diet patterns. These findings warrant future research to determine if improving nutrition literacy effectively improves eating patterns.

An Experimental Ketogenic Diet for Alzheimer Disease Was Nutritionally Dense and Rich in Vegetables and Avocado.

BACKGROUND: The ketogenic diet (KD) has gained interest as a potential therapy for numerous conditions; however, studies rarely report the food and micronutrient profile of the diet. OBJECTIVE: The aim of this study was to report changes in food selection and nutritional quality from the baseline diet (BD) to a KD therapy in participants with Alzheimer disease (AD). METHODS: Fifteen AD patients participated in a single-arm clinical trial to assess the feasibility of a 3-mo KD intervention. A registered dietitian instructed participant study partners to assist participants with a self-selected, nutritionally dense KD. We collected food and nutrient intake via monthly 3-d food records. Serum ß-hydroxybutyrate was measured within 48 h of each 3-d food record to assess ketosis status. Food records before KD initiation characterized the BD. Food records during the intervention coincident with the most robust ketosis characterized the KD. Principal components analysis identified foods affiliated with the BD and KD. Mean food and nutrient intake change was tested by the Kruskal-Wallis test for variance with significance set at P ≤ 0.025. RESULTS: Ten participants adhered to the KD. Study partners provided complete food records for 6 KD-adherent individuals. The KD was characterized by increased medium-chain triglyceride (MCT) oil, nonstarchy vegetables, butter, eggs, olive oil, avocados, and nuts and seeds with practical elimination of potatoes, grains, red meat, sugar-sweetened beverages, and desserts. Fruit intake, including avocado, was similar between diets. Nonstarchy vegetable intake increased from 1.2 servings/d to 4.3 servings/d (P < 0.01) on the KD. Micronutrient intake was similar between diets, meeting Dietary Reference Intakes for most nutrients. Between diets, the KD was associated with increased intake of choline and vitamin K and decreased intake of manganese and fiber. CONCLUSION: As a potential therapy in AD, the KD can be nutritionally dense with high intake of vegetables and substantial variety. This trial was registered at clinicaltrials.gov as NCT03690193.

Feasibility and efficacy data from a ketogenic diet intervention in Alzheimer's disease.

INTRODUCTION: We assessed the feasibility and cognitive effects of a ketogenic diet (KD) in participants with Alzheimer's disease. METHODS: The Ketogenic Diet Retention and Feasibility Trial featured a 3-month, medium-chain triglyceride-supplemented KD followed by a 1-month washout in clinical dementia rating (CDR) 0.5, 1, and 2 participants. We obtained urine acetoacetate, serum ß-hydroxybutyrate, food record, and safety data. We administered the Alzheimer's Disease Assessment Scale-cognitive subscale and Mini-Mental State Examination before the KD, and following the intervention and washout. RESULTS: We enrolled seven CDR 0.5, four CDR 1, and four CDR 2 participants. One CDR 0.5 and all CDR 2 participants withdrew citing caregiver burden. The 10 completers achieved ketosis. Most adverse events were medium-chain triglyceride-related. Among the completers, the mean of the Alzheimer's Disease Assessment Scale-cognitive subscale score improved by 4.1 points during the diet (P = .02) and reverted to baseline after the washout. DISCUSSION: This pilot trial justifies KD studies in mild Alzheimer's disease.

A high-glycemic diet is associated with cerebral amyloid burden in cognitively normal older adults.

Background: Little is known about the relation between dietary intake and cerebral amyloid accumulation in aging.Objective: We assessed the association of dietary glycemic measures with cerebral amyloid burden and cognitive performance in cognitively normal older adults.Design: We performed cross-sectional analyses relating dietary glycemic measures [adherence to a high-glycemic-load diet (HGLDiet) pattern, intakes of sugar and carbohydrates, and glycemic load] with cerebral amyloid burden (measured by florbetapir F-18 positron emission tomography) and cognitive performance in 128 cognitively normal older adults who provided eligibility screening data for the University of Kansas's Alzheimer's Prevention through Exercise (APEX) Study. The study began in November 2013 and is currently ongoing.Results: Amyloid was elevated in 26% (n = 33) of participants. HGLDiet pattern adherence (P = 0.01), sugar intake (P = 0.03), and carbohydrate intake (P = 0.05) were significantly higher in participants with elevated amyloid burden. The HGLDiet pattern was positively associated with amyloid burden both globally and in all regions of interest independently of age, sex, and education (all P ≤ 0.001). Individual dietary glycemic measures (sugar intake, carbohydrate intake, and glycemic load) were also positively associated with global amyloid load and nearly all regions of interest independently of age, sex, and educational level (P ≤ 0.05). Cognitive performance was associated only with daily sugar intake, with higher sugar consumption associated with poorer global cognitive performance (global composite measure and Mini-Mental State Examination) and performance on subtests of Digit Symbol, Trail Making Test B, and Block Design, controlling for age, sex, and education.Conclusion: A high-glycemic diet was associated with greater cerebral amyloid burden, which suggests diet as a potential modifiable behavior for cerebral amyloid accumulation and subsequent Alzheimer disease risk. This trial was registered at clinicaltrials.gov as NCT02000583.