Background Nutrition risk is common in Alzheimer's disease and is associated with symptoms of dementia, cognitive decline, institutionalization, and mortality. Family caregivers who increasingly manage nutrition needs of persons with dementia (PWD) experience high caregiver burden, low health literacy, and nutrition risk. Few interventions for informal caregivers have included nutrition. Objective To inform design of a future caregiver nutrition intervention. Methods This cross-sectional study used a convergent mixed methods approach to 1) assess nutrition status among PWD and caregiver dyads (measures in common included Mini Nutrition Assessment, skin carotenoid, and handgrip strength), and 2) interview caregivers to identify needs and barriers for nutrition intervention. We hypothesized caregiver nutrition literacy is associated with PWD nutrition risk. Data collected in nutrition assessment and interviews were analyzed separately then side-by-side for comparison. Results Of 50 dyads, 48% had at least one individual exhibiting nutrition risk, and nutrition status categories (χ 2 = 6.25, p = 0.012) between caregivers and PWD were related. Caregiver nutrition literacy was associated with 1) PWD factors including nutrition risk (rho = 0.244), body mass index (BMI) (rho = 0.421), handgrip strength (rho = 0.283), and skin carotenoid (rho = 0.351), and 2) Caregiver factors including nutrition risk (rho = 0.304), diet quality (rho = 0.304), and BMI (rho = 0.333). Interviews with 18 caregivers found caregivers prioritize PWD nutrition, provide more PWD nutrition care since diagnosis, experience social isolation, and would attend nutrition interventions if PWD are included. Conclusions Nutrition risk was more common among caregivers when PWD demonstrated nutrition risk. Factors present in individuals within the dyad were associated with partner nutrition risk. Future research should identify effective approaches for intervening on dyadic nutrition risk.

Diminished muscle function and strength are linked to an increased risk and accelerated progression of Alzheimer’s disease (AD). Although these are direct consequences of the disease, recent preclinical evidence suggests decreased muscle function and strength may directly influence AD risk and progression via the muscle-brain axis. Therefore, interventions to improve muscle strength may prevent functional decline related to AD. However, such specific interventions in AD are lacking. In this context, creatine monohydrate (CrM), a dietary supplement that boosts muscle strength, presents a promising intervention. This single-armed pilot study explores the potential effects of an 8-week creatine monohydrate supplementation on handgrip strength in AD. Data from 16 participants with AD who completed a one-arm, 8-week trial examining the feasibility and preliminary efficacy of 20 g/day of CrM in AD were analyzed. Handgrip strength, a reliable measure of muscle strength, was assessed on the dominant hand at baseline and at the end of the study on a calibrated hand dynamometer, measured in kilograms (kg) of force. At baseline and 8 weeks, 3 measurements were taken; the highest value was selected. We conducted a paired t-test to test for an 8-week change in mean handgrip strength. Statistical analyses were performed using R (v. 4.3.2; R Foundation, Vienna, Austria). Statistical significance was set at p < 0.05. Participants were 56% male with a mean age of 72.1 ± 6.4 years at baseline. The mean hand grip strength and body mass index (BMI) at baseline were 33.6 ± 11.6 kg and 25.4 ± 3.6 kg/m 2 , respectively. After 8 weeks of CrM supplementation, mean handgrip strength improved by 2.6 kg (36.1 ± 12.1 kg, p < 0.001). BMI did not change. In this study, 20 g/day of CrM supplementation for 8 weeks was associated with improved handgrip strength in individuals with AD. Our pilot data suggests that CrM may be valuable for maintaining or preventing AD-related functional decline by improving muscle strength.

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.

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.

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.

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.

Objectives: The objectives of this study were to 1) determine whether whole egg intake influences brain choline levels in cognitively normal older adults and 2) assess the relationship between whole egg consumption and cognitive performance. Methods: This cross-sectional study recruited 60 cognitively unimpaired community dwelling individuals aged 60 or over with diverse weekly egg consumption in the Midwestern region of the US. All participants completed 7-day food records. Nutritional analysis was conducted using the Nutrition Data System for Research to confirm intakes of whole egg and dietary choline. Brain choline concentrations were measured by 1H magnetic resonance scans using a 20-channel head/neck coil at a 3 T clinical MR system. Cognitive performance was assessed using the NIH Toolbox® fully corrected T-scores, which has been adjusted for age, sex, race/ethnicity, and educational attainment. Ordinary least squares regression models were performed to analyze relations between whole egg consumption and brain choline concentrations as well as the relationship between whole egg consumption and cognitive performance. Age and sex were included as covariates to assess the relationship between whole egg consumption and brain choline concentrations. Results: A total of 57 participants were included in the analyses. Approximately 65% participants were female, and overall participants ranged in age from 60 to 85 years (age, 69.5 ± 5.7 years). Whole egg intake was positively associated with brain choline concentrations in the parietal (β = 0.29, p = 0.03) and occipital regions (β = 0.38, p < 0.01) without adjusting for age and sex. Age was inversely associated with whole egg consumption (β = -0.29, p = 0.03). After adjusting for age and sex, higher whole egg intake was significantly associated with higher brain choline concentrations in the occipital region (β = 0.27, p = 0.04). No associations were observed between whole egg intake and cognitive performance scores. Conclusions: Greater whole egg consumption was associated with higher brain choline concentration in older adults. Ensuring adequate consumption of dietary choline (i.e., by the incorporation of whole eggs) may be significant to maintain adequate brain choline concentrations, in particular, for the aging population. Funding Sources: This study was supported by American Egg Board's Egg Nutrition Center.

Alzheimer’s Disease (AD) is a systemic metabolic disease with a variable number and type of clinical symptoms mostly impacting the brain. Skin carotenoid content (SCC) is an objective measure of carotenoid-containing fruit and vegetable intake that has been validated in diverse populations. Our previous findings suggest SCC scores are impacted by various metabolic disease states. Therefore, our objective was to analyze SCC scores and dietary intake across matched pairs including unimpaired adults and those with AD. Baseline data from two dietary interventions (NCT03860792, NCT03841539) were analyzed. Pairs are exact matches for sex, race/ethnicity, and education and are matched within two years of age and 4 kg/m 2 body mass index. Each pair (n = 12 pairs) includes one cognitively normal (MMSE > 25), community dwelling older adult (‘CN’) and one community dwelling older adult with AD (‘AD’). Baseline self-reported dietary intake data (3-day food records) were collected, reviewed, and entered into the Nutrition Data System for Research (NDSR 2019) database by a Registered Dietitian. SCC scores were collected through pressure-mediated reflection spectroscopy via VeggieMeter® (Longevity Link Corporation, Holladay, UT). Two-sample independent t-tests assuming unequal variances were used to compare differences in SCC scores and dietary intake. Significance was set at p = 0.05. There was a significant difference in SCC scores between matched pairs (SCC scores: CN 284.25, AD 207.67, p = 0.008). There was no difference between pairs for total daily energy (kcal/day; p = 0.60), fat (g/day; p = 0.91), carbohydrate (g/day; p = 0.85), or protein (g/day; p = 0.26) intake. Both groups had similar food group intake (p-value range 0.09-0.79), including all fruit and vegetable groups except CN had higher intake of non-citrus fruit (p = 0.046). Total fruit (p = 0.09) and fruit plus vegetable (p = 0.24) were not different between pairs. Dietary intake by individual carotenoid was not significantly different (total vitamin A, p = 0.48; beta-carotene, p = 0.49; alpha-carotene, p = 0.57; beta-cryptoxanthin, p = 0.60; lutein plus zeaxanthin, p = 0.07; lycopene, p = 0.37). Individuals with AD have lower carotenoid skin content compared to matched cognitively unimpaired individuals. These differences are not explained by differences in diet suggesting that AD may be associated with disease-associated biochemical features that are metabolism-related and not limited to the brain.

Lower body mass is related to the progression of Alzheimer’s disease (AD). Carriers of the APOE e4 (APOE4) allele have an increased risk of developing AD, and APOE4 status has been shown to be associated with decreased body mass and fat mass in AD. However, this relationship in cognitively normal older adults is unclear. We investigated whether body mass index (BMI) and body composition are related with APOE4 status in cognitively normal older adults. Baseline data from 211 cognitively normal older adults in an ongoing nutrition intervention RCT (Nutrition Intervention for Cognitive Enhancement; NICE study) were analyzed. Whole blood was attained, and genetic analyses were used to determine APOE genotype. Participants with ≥ 1 APOE4 allele were classified as APOE4 carriers. BMI was calculated from weight and height. Fat mass percentage was measured using dual energy x-ray absorptiometry. We compared means between APOE4 carriers and non-carriers for BMI and fat mass percentage using covariate-adjusted ordinary least squares (OLS) regression models (i.e., ANCOVA), adjusting for age and sex. Statistical analyses were performed using R (v. 4.2.2; R Foundation, Vienna, Austria). Statistical significance was set at p < 0.05. Participants were 75% female with a mean age of 71.4 ± 4.9 years. 34% of participants were APOE4 carriers. Mean BMI and percent fat mass were 28.4 ± 4.6 kg/m 2 and 40% ± 4.6, respectively. ApoE4 carriers had significantly lower BMI (27.5 kg/m 2 ± 3.9 vs. 28.9 kg/m 2 ± 4.8, p = 0.02) and lower body fat percentage (38% ± 8.0 vs. 42% ± 6.7, p < 0.01) compared to non-carriers, respectively. In this study, cognitively normal older adult APOE4 carriers had lower BMI and lower body fat percentage compared to non-carriers. These findings suggest that APOE4 status may influence body weight and body composition, which may represent a way APOE4 increases the risk of symptomatic AD. Future studies are needed to explore the mechanisms underpinning the relationship of APOE4 with decreased body mass and differential body compositions and to determine if these results are consistent in different life stages.

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-β (Aβ) plaques in the brain, a hallmark pathological biomarker that precedes symptomatic AD. Though recent clinical trials of novel drugs that target Aβ 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.

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.

Abstract 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.

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-β (Aβ) plaques, which may precede onset of clinical symptoms by over a decade. Efforts to prevent or treat AD frequently emphasize decreasing Aβ through various mechanisms, but such approaches have yet to establish compelling interventions. It is still not understood exactly why Aβ accumulates in AD, but it is hypothesized that Aβ 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 Aβ, 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 Aβ accumulation and symptomatic AD. Here, we discuss the link between brain bioenergetics and Aβ, as well as the potential for KTs to influence AD risk and progression.

Amyloid-β is a classical hallmark and risk factor for development of Alzheimer’s disease (AD). Observational data suggest that having higher body mass index (BMI) is associated with lower cerebral amyloid burden in cognitively normal adults. However, the influence of body composition on cerebral amyloid deposition has not been investigated. We investigated whether baseline body composition influences 1-year change in cerebral amyloid in a sample enriched with older adults with elevated amyloid. Data from 103 cognitively normal adults with high normal or elevated cerebral amyloid that participated in a 1-year exercise RCT were analyzed. Cerebral amyloid burden was quantified in 6 cortical regions of interest by Florbetapir F18 PET. Global amyloid burden was calculated by averaging the 6 regions. Total lean body mass and fat mass percentages were measured using DXA. We constructed ordinary least squares regression models to investigate the relationship between our baseline measures of body composition and 1-year change in regional and global amyloid. All models included age, APOE4 carrier status, study arm, sex, and baseline regional amyloid standard uptake value ratios as covariates. Participants were 67% female with a mean age of 72.4 ± 5.0 years. Mean BMI was 28.0 ± 5.4, lean body mass percentage was 61% ± 7.5%, and fat mass percentage was 38% ± 7.1%. Higher BMI was related to less 1-year amyloid accumulation in 5 regions (anterior cingulate gyrus, precuneus, inferior medial frontal gyrus, lateral temporal lobe, and superior parietal lobe) and globally (β range = -0.003 to -0.004, p<0.03 for all). Higher fat mass percentage was related to less amyloid accumulation in all 6 brain regions and the global average (β range = -0.25 to -0.34, p<0.03 for all). Higher lean body mass percentage was related to less amyloid accumulation in the lateral temporal lobe (β = -0.003, p = 0.01). In this study, having larger body stature and higher fat mass percentage were related to less amyloid accumulation in individuals with elevated risk for AD. Further studies are necessary to explore these relationships in greater detail and to ascertain if these findings are modulated by other biological variables.

BackgroundA 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.ObjectiveTo investigate whether a recommended amount of milk intake (3 cups/day) in low dairy consumers enhances brain GSH concentrations through an intervention trial.MethodsSeventy-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.ResultsAmong 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.ConclusionThis 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].

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.

Research on risk factors for dementia and in preclinical populations has shown that glucose regulation may be involved in amyloid synthesis, cognitive processing, and neurodegeneration; however, the extent to its involvement is unclear. Fasting glucose is a straightforward measure that could be a window into metabolic changes either associated with or preceding dementia. We sought to test whether a change in fasting glucose over one year was related to multi-modal brain imaging measures of neuropathological changes in the brain associated with dementia. We leveraged longitudinal biospecimens and neuroimaging measures collected during the Alzheimer’s Prevention through Exercise (APEX) trial (n=109) to examine the longitudinal relationship between change in fasting glucose and change in neurodegeneration and cerebral amyloid over 1 year of follow-up. The group of individuals with stable or improving fasting glucose (n=65) exhibited less atrophy and regional amyloid accumulation compared to the group 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, reduced diffusion in limbic white matter, 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 APOE4 carrier status. Increasing fasting glucose may reflect changes in cellular bioenergetics associated with Alzheimer’s disease neuropathophysiology. Dysregulation of glucose in late life may signal preclinical brain change prior to clinically relevant cognitive decline. Additional work is needed to determine if treatments specifically targeting fasting glucose levels may impact change in brain structure or cerebral amyloid in older adults.

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 (β = 0.06, p = 0.04), sugar (β = 0.07, p = 0.01), and total carbohydrate (β = 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 (β = 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 (β = 0.09, p < 0.05) and posterior cingulate gyrus (β = 0.09, p < 0.05) and higher sugar and carbohydrate intake were also related to more amyloid accumulation in the posterior cingulate gyrus (β = 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).

Understand how avocado and guacamole relates to cognitive function among older adults.