Changes in Alzheimer's disease blood biomarkers in kidney failure before and after kidney transplant.

INTRODUCTION: Alzheimer's disease (AD) blood biomarkers show promise for clinical diagnosis but their reliability in chronic kidney disease (CKD) is debated. This study investigates the impact of kidney transplant (KT) on AD biomarkers in CKD. METHODS: We assessed AD biomarkers in 46 CKD patients pre-KT, at 12 weeks and 12 months post-KT, with baseline measures from 13 non-CKD controls. Using linear mixed models, we examined associations with participant groups, estimated glomerular filtration rate (eGFR) and cognition. RESULTS: CKD patients showed elevated levels of neurofilament light (117 ± 72 vs. 11 ± 5 pg/mL), phosphorylated tau 181 (75 ± 42 vs. 13 ± 8 pg/mL), glial fibrillary acidic protein (193 ± 127 vs. 94 ± 39 pg/mL), amyloid ß 42 (17 ± 5 vs. 5 ± 1 pg/mL), and amyloid ß 40 (259 ± 96 vs. 72 ± 17 pg/mL) compared to controls. Post-KT, biomarker levels approached normal with improved eGFR, paralleled by enhanced cognitive function. DISCUSSION: AD blood biomarker elevations in CKD are reversible with improved kidney function through KT. Highlights: AD biomarker levels are extremely high in severe CKD.AD biomarker levels are higher in patients with kidney failure on dialysis when compared to CKD patients not on dialysis.These elevations in AD biomarker levels in kidney failure are reversable and decrease dramatically after kidney transplantation.The change in biomarker levels after transplantation align with changes in kidney function.The change in biomarker levels after transplantation align with changes in cognitive function.

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.

Universal screening in kindergarten: Validity and classification accuracy of Istation's Indicators of Progress-Early Reading.

Universal screening in reading is a common, and often required, practice in early elementary school. Computer-adaptive screening tools, such as Istation's Indicators of Progress-Early Reading (ISIP-ER), are often chosen for this purpose in schools. In our present study, we examine the validity evidence between the ISIP-ER in kindergarten and third grade State of Texas Assessments of Academic Readiness (STAAR) reading scores, the classification accuracy of ISIP-ER to predict which students will meet STAAR reading expectations, and a cut score to maximize classification accuracy for the local context. The sample included 962 students (Mage = 6.19 years; SDage = 0.37) from 15 elementary schools in one suburban school district in Texas. As for validity, the correlation between ISIP-ER in kindergarten and the third grade STAAR was moderate (r = 0.48). Classification accuracy analyses using the vendor-recommended cut score found sensitivity (0.63) and specificity (0.70) were all below recommended levels. Using a locally determined cut score, sensitivity (0.92) was improved, but specificity (0.33) was substantially decreased. The findings suggest ISIP-ER has some limitations in the accurate identification of students at risk for poor outcomes on a state-mandated reading test and will likely need to be combined with other assessments or progress monitoring data. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Biomarker Responses to Acute Exercise and Relationship with Brain Blood Flow.

BACKGROUND: There is evidence that aerobic exercise is beneficial for brain health, but these effects are variable between individuals and the underlying mechanisms that modulate these benefits remain unclear. OBJECTIVE: We sought to characterize the acute physiological response of bioenergetic and neurotrophic blood biomarkers to exercise in cognitively healthy older adults, as well as relationships with brain blood flow. METHODS: We measured exercise-induced changes in lactate, which has been linked to brain blood flow, as well brain-derived neurotrophic factor (BDNF), a neurotrophin related to brain health. We further quantified changes in brain blood flow using arterial spin labeling. RESULTS: As expected, lactate and BDNF both changed with time post exercise. Intriguingly, there was a negative relationship between lactate response (area under the curve) and brain blood flow measured acutely following exercise. Finally, the BDNF response tracked strongly with change in platelet activation, providing evidence that platelet activation is an important mechanism for trophic-related exercise responses. CONCLUSIONS: Lactate and BDNF respond acutely to exercise, and the lactate response tracks with changes in brain blood flow. Further investigation into how these factors relate to brain health-related outcomes in exercise trials is warranted.

Blood Biomarkers Discriminate Cerebral Amyloid Status and Cognitive Diagnosis when Collected with ACD-A Anticoagulant.

BACKGROUND: The development of biomarkers that are easy to collect, process, and store is a major goal of research on current Alzheimer's Disease (AD) and underlies the growing interest in plasma biomarkers. Biomarkers with these qualities will improve diagnosis and allow for better monitoring of therapeutic interventions. However, blood collection strategies have historically differed between studies. We examined the ability of various ultrasensitive plasma biomarkers to predict cerebral amyloid status in cognitively unimpaired individuals when collected using acid citrate dextrose (ACD). We then examined the ability of these biomarkers to predict cognitive impairment independent of amyloid status. METHODS: Using a cross-sectional study design, we measured amyloid beta 42/40 ratio, pTau-181, neurofilament-light, and glial fibrillary acidic protein using the Quanterix Simoa® HD-X platform. To evaluate the discriminative accuracy of these biomarkers in determining cerebral amyloid status, we used both banked plasma and 18F-AV45 PET cerebral amyloid neuroimaging data from 140 cognitively unimpaired participants. We further examined their ability to discriminate cognitive status by leveraging data from 42 cognitively impaired older adults. This study is the first, as per our knowledge, to examine these specific tests using plasma collected using acid citrate dextrose (ACD), as well as the relationship with amyloid PET status. RESULTS: Plasma AB42/40 had the highest AUC (0.833, 95% C.I. 0.767-0.899) at a cut-point of 0.0706 for discriminating between the two cerebral amyloid groups (sensitivity 76%, specificity 78.5%). Plasma NFL at a cut-point of 20.58pg/mL had the highest AUC (0.908, 95% CI 0.851- 0.966) for discriminating cognitive impairment (sensitivity 84.8%, specificity 89.9%). The addition of age and apolipoprotein e4 status did not improve the discriminative accuracy of these biomarkers. CONCLUSION: Our results suggest that the Aß42/40 ratio is useful in discriminating clinician-rated elevated cerebral amyloid status and that NFL is useful for discriminating cognitive impairment status. These findings reinforce the growing body of evidence regarding the general utility of these biomarkers and extend their utility to plasma collected in a non-traditional anticoagulant.

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.

Alzheimer's disease cortical morphological phenotypes are associated with TOMM40'523-APOE haplotypes.

Both the APOE ε4 and TOMM40 rs10524523 ("523") genes have been associated with risk for Alzheimer's disease (AD) and neuroimaging biomarkers of AD. No studies have investigated the relationship of TOMM40'523-APOE ε4 on the structural complexity of the brain in AD individuals. We quantified brain morphology and multiple cortical attributes in individuals with mild cognitive impairment (MCI) and AD, then tested whether APOE ε4 or TOMM40 poly-T genotypes were related to AD morphological biomarkers in cognitively unimpaired (CU) and MCI/AD individuals. We identified several AD-specific phenotypes in brain morphology and found that TOMM40 poly-T short alleles are associated with early, AD-specific brain morphological differences in healthy aging. We observed decreased cortical thickness, sulcal depth, and fractal dimension in CU individuals with the poly-T short alleles. Moreover, in MCI/AD participants, the APOE ε4 (TOMM40 L) individuals had a higher rate of gene-related morphological markers indicative of AD. Our data suggest that TOMM40'523 is associated with early brain structure variations in the precuneus, temporal, and limbic cortices.

When is the best time to screen and evaluate for treatable genetic disorders?: A lifespan perspective.

This paper focuses on the question of, "When is the best time to identify an individual at risk for a treatable genetic condition?" In this review, we describe a framework for considering the optimal timing for pursuing genetic and genomic screening for treatable genetic conditions incorporating a lifespan approach. Utilizing the concept of a carousel that represents the four broad time periods when critical decisions might be made around genetic diagnoses during a person's lifetime, we describe genetic testing during the prenatal period, the newborn period, childhood, and adulthood. For each of these periods, we describe the objectives of genetic testing, the current status of screening or testing, the near-term vision for the future of genomic testing, the advantages and disadvantages of each approach, and the feasibility and ethical considerations of testing and treating. The notion of a "Genomics Passbook" is one where an early genomic screening evaluation could be performed on each individual through a public health program, with that data ultimately serving as a "living document" that could be queried and/or reanalyzed at prescribed times during the lifetime of that person, or in response to concerns about symptoms of a genetic disorder in that individual.

Moving away from one disease at a time: Screening, trial design, and regulatory implications of novel platform technologies.

Most rare diseases are caused by single-gene mutations, and as such, lend themselves to a host of new gene-targeted therapies and technologies including antisense oligonucleotides, phosphomorpholinos, small interfering RNAs, and a variety of gene delivery and gene editing systems. Early successes are encouraging, however, given the substantial number of distinct rare diseases, the ability to scale these successes will be unsustainable without new development efficiencies. Herein, we discuss the need for genomic newborn screening to match pace with the growing development of targeted therapeutics and ability to rapidly develop individualized therapies for rare variants. We offer approaches to move beyond conventional "one disease at a time" preclinical and clinical drug development and discuss planned regulatory innovations that are necessary to speed therapy delivery to individuals in need. These proposals leverage the shared properties of platform classes of therapeutics and innovative trial designs including master and platform protocols to better serve patients and accelerate drug development. Ultimately, there are risks to these novel approaches; however, we believe that close partnership and transparency between health authorities, patients, researchers, and drug developers present the path forward to overcome these challenges and deliver on the promise of gene-targeted therapies for rare diseases.

Relationship of Muscle Apolipoprotein E Expression with Markers of Cellular Stress, Metabolism, and Blood Biomarkers in Cognitively Healthy and Impaired Older Adults.

BACKGROUND: Individuals with mild cognitive impairment (MCI) have reduced lipid-stimulated mitochondrial respiration in skeletal muscle. A major risk factor for Alzheimer's disease (AD), the apolipoprotein E4 (APOE4) allele, is implicated in lipid metabolism and is associated with metabolic and oxidative stress that can result from dysfunctional mitochondria. Heat shock protein 72 (Hsp72) is protective against these stressors and is elevated in the AD brain. OBJECTIVE: Our goal was to characterize skeletal muscle ApoE and Hsp72 protein expression in APOE4 carriers in relationship to cognitive status, muscle mitochondrial respiration and AD biomarkers. METHODS: We analyzed previously collected skeletal muscle tissue from 24 APOE4 carriers (60y+) who were cognitively healthy (CH, n = 9) or MCI (n = 15). We measured ApoE and Hsp72 protein levels in muscle and phosphorylated tau181 (pTau181) levels in plasma, and leveraged previously collected data on APOE genotype, mitochondrial respiration during lipid oxidation, and VO2 max. RESULTS: Muscle ApoE (p = 0.013) and plasma pTau181 levels (p < 0.001) were higher in MCI APOE4 carriers. Muscle ApoE positively correlated with plasma pTau181 in all APOE4 carriers (R2 = 0.338, p = 0.003). Hsp72 expression negatively correlated with ADP (R2 = 0.775, p = <0.001) and succinate-stimulated respiration (R2 = 0.405, p = 0.003) in skeletal muscle of MCI APOE4 carriers. Plasma pTau181 negatively tracked with VO2 max in all APOE4 carriers (R2 = 0.389, p = 0.003). Analyses were controlled for age. CONCLUSION: This work supports a relationship between cellular stress in skeletal muscle and cognitive status in APOE4 carriers.

Outcomes of the 2019 hydrocephalus association workshop, "Driving common pathways: extending insights from posthemorrhagic hydrocephalus".

The Hydrocephalus Association (HA) workshop, Driving Common Pathways: Extending Insights from Posthemorrhagic Hydrocephalus, was held on November 4 and 5, 2019 at Washington University in St. Louis. The workshop brought together a diverse group of basic, translational, and clinical scientists conducting research on multiple hydrocephalus etiologies with select outside researchers. The main goals of the workshop were to explore areas of potential overlap between hydrocephalus etiologies and identify drug targets that could positively impact various forms of hydrocephalus. This report details the major themes of the workshop and the research presented on three cell types that are targets for new hydrocephalus interventions: choroid plexus epithelial cells, ventricular ependymal cells, and immune cells (macrophages and microglia).

Are we prepared to deliver gene-targeted therapies for rare diseases?

The cost and time needed to conduct whole-genome sequencing (WGS) have decreased significantly in the last 20 years. At the same time, the number of conditions with a known molecular basis has steadily increased, as has the number of investigational new drug applications for novel gene-based therapeutics. The prospect of precision gene-targeted therapy for all seems in reach… or is it? Here we consider practical and strategic considerations that need to be addressed to establish a foundation for the early, effective, and equitable delivery of these treatments.

Increased Functional Connectivity of the Precuneus in Individuals with a Family History of Alzheimer's Disease.

BACKGROUND: First-degree relatives of individuals with late-onset Alzheimer's disease (AD) have increased risk for AD, with children of affected parents at an especially high risk. OBJECTIVE: We aimed to investigate default mode network connectivity, medial temporal cortex volume, and cognition in cognitively healthy (CH) individuals with (FH+) and without (FH-) a family history of AD, alongside amnestic mild cognitive impairment (aMCI) and AD individuals, to determine the context and directionality of dysfunction in at-risk individuals. Our primary hypothesis was that there would be a linear decline (CH FH- > CH FH+ > aMCI > AD) within the risk groups on all measures of AD risk. METHODS: We used MRI and fMRI to study cognitively healthy individuals (n = 28) with and without AD family history (FH+ and FH-, respectively), those with aMCI (n = 31) and early-stage AD (n = 25). We tested connectivity within the default mode network, as well as measures of volume and thickness within the medial temporal cortex and selected seed regions. RESULTS: As expected, we identified decreased medial temporal cortex volumes in the aMCI and AD groups compared to cognitively healthy groups. We also observed patterns of connectivity across risk groups that suggest a nonlinear relationship of change, such that the FH+ group showed increased connectivity compared to the FH- and AD groups (CH FH+ > CH FH- > aMCI > AD). This pattern emerged primarily in connectivity between the precuneus and frontal regions. CONCLUSION: These results add to a growing literature that suggests compensatory brain function in otherwise cognitively healthy individuals with a family history of AD.

Hippocampal blood flow rapidly and preferentially increases after a bout of moderate-intensity exercise in older adults with poor cerebrovascular health.

Over the course of aging, there is an early degradation of cerebrovascular health, which may be attenuated with aerobic exercise training. Yet, the acute cerebrovascular response to a single bout of exercise remains elusive, particularly within key brain regions most affected by age-related disease processes. We investigated the acute global and region-specific cerebral blood flow (CBF) response to 15 minutes of moderate-intensity aerobic exercise in older adults (≥65 years; n = 60) using arterial spin labeling magnetic resonance imaging. Within 0-6 min post-exercise, CBF decreased across all regions, an effect that was attenuated in the hippocampus. The exercise-induced CBF drop was followed by a rebound effect over the 24-minute postexercise assessment period, an effect that was most robust in the hippocampus. Individuals with low baseline perfusion demonstrated the greatest hippocampal-specific CBF effect post-exercise, showing no immediate drop and a rapid increase in CBF that exceeded baseline levels within 6-12 minutes postexercise. Gains in domain-specific cognitive performance postexercise were not associated with changes in regional CBF, suggesting dissociable effects of exercise on acute neural and vascular plasticity. Together, the present findings support a precision-medicine framework for the use of exercise to target brain health that carefully considers age-related changes in the cerebrovascular system.

Current Perspectives: Obesity and Neurodegeneration - Links and Risks.

Obesity is increasing in prevalence across all age groups. Long-term obesity can lead to the development of metabolic and cardiovascular diseases through its effects on adipose, skeletal muscle, and liver tissue. Pathological mechanisms associated with obesity include immune response and inflammation as well as oxidative stress and consequent endothelial and mitochondrial dysfunction. Recent evidence links obesity to diminished brain health and neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). Both AD and PD are associated with insulin resistance, an underlying syndrome of obesity. Despite these links, causative mechanism(s) resulting in neurodegenerative disease remain unclear. This review discusses relationships between obesity, AD, and PD, including clinical and preclinical findings. The review then briefly explores nonpharmacological directions for intervention.

Assessing Cognitive Behavioral Therapy for Insomnia to Improve Sleep Outcomes in Individuals With a Concussion: Protocol for a Delayed Randomized Controlled Trial.

BACKGROUND: Sleep disturbances post concussion have been associated with more frequent and severe concussion symptoms and may contribute to poorer recovery. Cognitive behavioral therapy for insomnia (CBT-I) is an effective treatment for insomnia; however, it remains unclear if this treatment method is effective in improving sleep outcomes and reducing concomitant postconcussion symptoms. OBJECTIVE: The hypotheses for this study are that (1) CBT-I will improve sleep outcomes and (2) CBT-I will improve concomitant postconcussion symptoms. METHODS: In total, 40 individuals who are within ≥4 weeks of postconcussion injury and have insomnia symptoms will be enrolled in this randomized controlled trial. Participants will be randomized into either a group that starts a 6-week CBT-I program immediately after baseline or a waitlist control group that starts CBT-I following a 6-week waiting period. All participants will be reassessed 6, 12, and 18 weeks after baseline. Standardized assessments measuring sleep outcomes, postconcussion symptoms, and mood will be used. Linear regression and t tests will be used for statistical analyses. RESULTS: Enrollment of 40 participants was completed July 2022, data collection will be completed in November 2022, and publication of main findings is anticipated in May 2023. It is anticipated that participants experience reduced insomnia symptoms and postconcussion symptoms following CBT-I and these improvements will be retained for at least 12 weeks. Additionally, we expect to observe a positive correlation between sleep and postconcussion symptom improvement. CONCLUSIONS: Successful completion of this pilot study will allow for a better understanding of the treatment of insomnia and postconcussion symptoms in individuals following a concussion. TRIAL REGISTRATION: ClinicalTrials.gov NCT04885205; https://clinicaltrials.gov/ct2/show/NCT04885205. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/38608.

Dementia risk and dynamic response to exercise: A non-randomized clinical trial.

BACKGROUND: Physical exercise may support brain health and cognition over the course of typical aging. The goal of this nonrandomized clinical trial was to examine the effect of an acute bout of aerobic exercise on brain blood flow and blood neurotrophic factors associated with exercise response and brain function in older adults with and without possession of the Apolipoprotein epsilon 4 (APOE4) allele, a genetic risk factor for developing Alzheimer's. We hypothesized that older adult APOE4 carriers would have lower cerebral blood flow regulation and would demonstrate blunted neurotrophic response to exercise compared to noncarriers. METHODS: Sixty-two older adults (73±5 years old, 41 female [67%]) consented to this prospectively enrolling clinical trial, utilizing a single arm, single visit, experimental design, with post-hoc assessment of difference in outcomes based on APOE4 carriership. All participants completed a single 15-minute bout of moderate-intensity aerobic exercise. The primary outcome measure was change in cortical gray matter cerebral blood flow in cortical gray matter measured by magnetic resonance imaging (MRI) arterial spin labeling (ASL), defined as the total perfusion (area under the curve, AUC) following exercise. Secondary outcomes were changes in blood neurotrophin concentrations of insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), and brain derived neurotrophic factor (BDNF). RESULTS: Genotyping failed in one individual (n = 23 APOE4 carriers and n = 38 APOE4 non-carriers) and two participants could not complete primary outcome testing. Cerebral blood flow AUC increased immediately following exercise, regardless of APOE4 carrier status. In an exploratory regional analyses, we found that cerebral blood flow increased in hippocampal brain regions, while showing no change in cerebellum across both groups. Among high inter-individual variability, there were no significant changes in any of the 3 neurotrophic factors for either group immediately following exercise. CONCLUSIONS: Our findings show that both APOE4 carriers and non-carriers show similar effects of exercise-induced increases in cerebral blood flow and neurotrophic response to acute aerobic exercise. Our results provide further evidence that acute exercise-induced increases in cerebral blood flow may be regional specific, and that exercise-induced neurotrophin release may show a differential effect in the aging cardiovascular system. Results from this study provide an initial characterization of the acute brain blood flow and neurotrophin responses to a bout of exercise in older adults with and without this known risk allele for cardiovascular disease and Alzheimer's disease. TRIAL REGISTRATION: Dementia Risk and Dynamic Response to Exercise (DYNAMIC); Identifier: NCT04009629.

COMbined Exercise Trial (COMET) to improve cognition in older adults: Rationale and methods.

Substantial evidence suggests physical exercise may sustain cognitive function and perhaps prevent Alzheimer's Disease (1, 2). Current public health recommendations call for older adults to do at least 150 min a week of aerobic exercise (e.g. walking) and twice a week resistance exercise (e.g. weight lifting) for physical health. Yet, much remains unknown about how these exercise modalities support brain health independently or in combination. The COMbined Exercise Trial (COMET) is designed to test the combined and independent effects of aerobic and resistance training specifically focusing on exercise-related changes in 1) cognitive performance, 2) regional brain volume, 3) physical function, and 4) blood-based factors. To explore these questions, we will enroll 280 cognitively normal older adults, age 65-80 years, into a 52-week community-based exercise program. Participants will be randomized into one of four arms: 1) flexibility/toning- control 2) 150 min of aerobic exercise only, 3) progressive resistance training only, or 4) combined aerobic and progressive resistance training. Outcomes assessed include a comprehensive cognitive battery, blood biomarkers, brain magnetic resonance imaging, physiological biomarkers, cardiorespiratory fitness, physical function, and battery of psychosocial questionnaires is assessed at baseline, 6 and 12-months. COMET will provide rigorous randomized controlled trial data to understand the effects of the most common exercise modalities, and their combination (i.e., the standard public health recommendation), on brain health.

Exploring nutrition education for migrants to Canada in Alberta's health and community sectors: Promising practices and gaps as informed by community workers and healthcare providers.

This qualitative study explored how migrant-serving agencies and healthcare providers in Alberta can support migrants to maintain healthy eating patterns. Through semi-structured interviews, respondents provided insight on their experiences working with migrant populations in the community. Observations about dietary acculturation (including food access, unfamiliar food environments, and perceptions of common foods in Canada) point to nutrition information that may be relevant for migrants. Respondents provided recommendations, noting the importance of culturally appropriate services, visual education materials, and collaboration between healthcare providers and community workers. The collective knowledge presented here could be applied by those developing programming supports for migrant communities.

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.