Addressing Pain Using a Mediterranean Ketogenic Nutrition Program in Older Adults with Mild Cognitive Impairment.

Chronic pain has negative physical and cognitive consequences in older adults and may lead to a poorer quality of life. Mediterranean ketogenic nutrition (MKN) is a promising nonpharmacological intervention for pain management, but long-term adherence is challenging due to the carbohydrate restrictive diet regimen. The main objective of this study was to evaluate the effects of the pilot MKN Adherence (MKNA) Program on pain in older adults with mild cognitive impairment and to assess whether improvements in self-reported pain were associated with adherence to MKN. Older adults (N = 58) aged 60-85 with possible mild cognitive impairment were randomized to a 6-week MKNA arm or an MKN Education (MKNE) program arm. Both arms received the same nutrition education and group format; however, the MKNA arm received additional motivational interviewing and cognitive behavioral skills to enhance adherence. Changes in self-reported pain (Brief Pain Inventory, Roland Morris, Patient's Global Impression of Change) and adherence to MKN (ketone levels, self-reported adherence) were assessed at baseline, 6-weeks, and 3-months post intervention. Both arms showed clinically significant reductions in pain. Greater adherence to MKN across the 6-week intervention was associated with higher ratings of pain-related changes on the Patient's Global Impression of Change scale. Based on these findings, adherence to MKN may promote improvements in self-reported pain in older adults with mild cognitive impairment and findings support the need for future full-scale randomized clinical trials evaluating MKN programs on pain. Trial Registration: Clinicaltrials.gov ID: NCT04817176.

Sleep Quality as a Critical Pathway Between Adverse Childhood Experiences and Multimorbidity and the Impact of Lifestyle.

OBJECTIVES: This study aims to establish the effects of ACEs on multimorbidity through sleep quality and investigate whether lifestyle factors (e.g., eating habits and exercise) may influence this relationship among middle-aged and older adults. METHODS: Participants were drawn from a cross-sectional sample of community dwelling older adults (N = 276, 55+) and three waves of data from the Midlife in the United States study (MIDUS, N = 843). We examined the direct and indirect effects of ACEs, sleep quality, and health conditions, as well as the conditional effects of physical activity and eating habits. RESULTS: Across both samples, sleep quality mediated the relationship between ACEs and chronic health conditions. Moderating effects of unhealthy eating and physical activity differed between samples. DISCUSSION: Sleep quality is an important pathway connecting ACEs and adult multimorbidity, and health behaviors may provide targets for intervention particularly in older adults.

A modified Mediterranean-style diet enhances brain function via specific gut-microbiome-brain mechanisms.

Alzheimer's disease (AD) is a debilitating brain disorder with rapidly mounting prevalence worldwide, yet no proven AD cure has been discovered. Using a multi-omics approach in a transgenic AD mouse model, the current study demonstrated the efficacy of a modified Mediterranean-ketogenic diet (MkD) on AD-related neurocognitive pathophysiology and underlying mechanisms related to the gut-microbiome-brain axis. The findings revealed that MkD induces profound shifts in the gut microbiome community and microbial metabolites. Most notably, MkD promoted growth of the Lactobacillus population, resulting in increased bacteria-derived lactate production. We discovered elevated levels of microbiome- and diet-derived metabolites in the serum as well, signaling their influence on the brain. Importantly, these changes in serum metabolites upregulated specific receptors that have neuroprotective effects and induced alternations in neuroinflammatory-associated pathway profiles in hippocampus. Additionally, these metabolites displayed strong favorable co-regulation relationship with gut-brain integrity and inflammatory markers, as well as neurobehavioral outcomes. The findings underscore the ameliorative effects of MkD on AD-related neurological function and the underlying gut-brain communication via modulation of the gut microbiome-metabolome arrays.

Dietary Patterns and Alzheimer's Disease: An Updated Review Linking Nutrition to Neuroscience.

Alzheimer's disease (AD) is a growing concern for the aging population worldwide. With no current cure or reliable treatments available for AD, prevention is an important and growing area of research. A range of lifestyle and dietary patterns have been studied to identify the most effective preventive lifestyle changes against AD and related dementia (ADRD) pathology. Of these, the most studied dietary patterns are the Mediterranean, DASH, MIND, ketogenic, and modified Mediterranean-ketogenic diets. However, there are discrepancies in the reported benefits among studies examining these dietary patterns. We herein compile a narrative/literature review of existing clinical evidence on the association of these patterns with ADRD symptomology and contemplate their preventive/ameliorative effects on ADRD neuropathology in various clinical milieus. By and large, plant-based dietary patterns have been found to be relatively consistently and positively correlated with preventing and reducing the odds of ADRD. These impacts stem not only from the direct impact of specific dietary components within these patterns on the brain but also from indirect effects through decreasing the deleterious effects of ADRD risk factors, such as diabetes, obesity, and cardiovascular diseases. Importantly, other psychosocial factors influence dietary intake, such as the social connection, which may directly influence diet and lifestyle, thereby also impacting ADRD risk. To this end, prospective research on ADRD should include a holistic approach, including psychosocial considerations.

Characteristics of international primary care practices and physicians related to advance care planning: a cross-sectional survey study.

BACKGROUND: Primary care providers (PCPs) are well-situated to delivery primary palliative care such as advance care planning (ACP). The aim of this work is to identify practice characteristics, including features found in advanced primary care models (APCMs), that predict PCP engagement of patients in ACP. METHODS: We analyzed characteristics of physician respondents and their practices associated with ACP conversations in older and sicker patients using data from 11 countries who participated in the 2015 Commonwealth Fund International Survey of Primary Care Physicians in 10 Nations. The primary outcome was how routinely these ACP conversations are reported. We used a validated measure to describe practice-level characteristics of advanced primary care models. We conducted bivariate and multivariable analyses to determine PCP and practice characteristics associated with routinely engaging patients in ACP and with documenting patient preferences in medical records. RESULTS: Respondents (N = 12,049) predominantly were older than 45 and did not view their jobs as high stress. PCPs reported routinely engaging patients in ACP work in practices with more APCM features. They are more likely to view their jobs as high stress, to work more hours, to practice in rural areas, and to work in smaller practices. Multivariable analyses showed that older PCP age, higher perceived stress of the job, practice location in rural areas, and increased number of APCM features were associated with more ACP conversations. Increased number of APCM features was also associated with higher odds of routinely recording patient preferences in their medical records. CONCLUSIONS: In this international survey, physician and practice characteristics, including having features associated with APCMs, were associated with whether physicians routinely discuss ACP with patients who are older and sicker. Many features of APCMs may facilitate ACP discussions between PCPs and patients.

Improving Adherence to a Mediterranean Ketogenic Nutrition Program for High-Risk Older Adults: A Pilot Randomized Trial.

(1) Background: Mediterranean ketogenic nutrition (MKN) may directly target multiple neurobiological mechanisms associated with dementia risk in older adults. Despite its promise, this type of nutrition can be challenging to learn and adhere to in a healthy manner. Our team used the National Institutes of Health Obesity Related Behavioral Intervention Trials (NIH ORBIT) model to develop and pilot a program to help older adults with memory concerns use MKN. (2) Methods: Using a two-arm, randomized design, we evaluated an MKN Adherence (MKNA) program compared to an MKN education (MKNE) program (N = 58). The primary difference between study arms involved the use of motivational interviewing (MI) strategies and behavior change techniques (BCT) only in the MKNA arm. Participants were included if they evidenced subjective memory concerns or objective memory impairment on the Montreal Cognitive Assessment (Score 19 ≤ 26). Primary outcomes examined included feasibility, acceptability, adherence, and clinical outcomes associated with the program. (3) Results: Overall, there was relatively high program completion in both groups, with 79% of participants completing the 6-week program. The recruitment protocol required adjustment but was successful in reaching the target sample size. Retention (82%) and session attendance (91%) were higher in the MKNA arm compared to the MKNE (retention = 72%; attendance = 77%). Overall, most participants in both groups rated the program as "excellent" using the client satisfaction questionnaire. Participants in the MKNA arm evidenced higher objective and self-reported adherence to MKN during the 6-week program. Further, there was some evidence of clinical benefits of the program, although these effects diminished as adherence decreased in the 3 months follow-up. (4) Discussion: This pilot trial demonstrated that the MKN program incorporating MI and BCT strategies may better engage and retain participants than a nutrition education program alone, although participants in both groups reported high satisfaction.

Global rural health disparities in Alzheimer's disease and related dementias: State of the science.

INTRODUCTION: Individuals living in rural communities are at heightened risk for Alzheimer's disease and related dementias (ADRD), which parallels other persistent place-based health disparities. Identifying multiple potentially modifiable risk factors specific to rural areas that contribute to ADRD is an essential first step in understanding the complex interplay between various barriers and facilitators. METHODS: An interdisciplinary, international group of ADRD researchers convened to address the overarching question of: "What can be done to begin minimizing the rural health disparities that contribute uniquely to ADRD?" In this state of the science appraisal, we explore what is known about the biological, behavioral, sociocultural, and environmental influences on ADRD disparities in rural settings. RESULTS: A range of individual, interpersonal, and community factors were identified, including strengths of rural residents in facilitating healthy aging lifestyle interventions. DISCUSSION: A location dynamics model and ADRD-focused future directions are offered for guiding rural practitioners, researchers, and policymakers in mitigating rural disparities. HIGHLIGHTS: Rural residents face heightened Alzheimer's disease and related dementia (ADRD) risks and burdens due to health disparities. Defining the unique rural barriers and facilitators to cognitive health yields insight. The strengths and resilience of rural residents can mitigate ADRD-related challenges. A novel "location dynamics" model guides assessment of rural-specific ADRD issues.

A longitudinal examination of the protective effect of resilience against anxiety among older adults with high COVID-related worry.

This longitudinal study of community dwelling older adults (N = 453) examined consequences of COVID-related worries on changes in anxiety symptoms before relative to during the pandemic. We further evaluated if pre-COVID psychological resilience (PR) buffered the impact of COVID-related worry. Pre-COVID data were collected in September 2018. COVID-related worry and COVID anxiety symptoms were collected in October 2020 (Wave 2). Controlling for pre-COVID anxiety symptoms, we examined if COVID-related worries (e.g. I'm worried that I might die from COVID-19) were associated with increased anxiety symptoms, and whether pre-COVID PR moderated the association between COVID-related worries and prospective increases in anxiety symptoms. COVID-related worries were associated with increased anxiety symptoms (ß = 0.005, p < .01), whereas pre-COVID PR was associated with a decrease in anxiety symptoms (ß = -0.029, p < .05). PR moderated the association; COVID-related worries were associated with greater increases in anxiety symptoms among those with low pre-COVID PR (Model η2 = 0.35). Thus, the extent to which COVID-related worries influenced psychological health was dependent on pre-COVID levels of PR. We conclude the combined vulnerabilities of low pre-COVID PR and high COVID-related worries significantly increased the psychological consequences of COVID-19 for our sample of older adults.

Feasibility, Acceptability, and Efficacy of Home-Based Transcranial Direct Current Stimulation on Pain in Older Adults with Alzheimer's Disease and Related Dementias: A Randomized Sham-Controlled Pilot Clinical Trial.

Although transcranial direct current stimulation (tDCS) is emerging as a convenient pain relief modality for several chronic pain conditions, its feasibility, acceptability, and preliminary efficacy on pain in patients with Alzheimer's disease and related dementias (ADRD) have not been investigated. The purpose of this pilot study was to assess the feasibility, acceptability, and preliminary efficacy of 5, 20-min home-based tDCS sessions on chronic pain in older adults with ADRD. We randomly assigned 40 participants to active (n = 20) or sham (n = 20) tDCS. Clinical pain intensity was assessed using a numeric rating scale (NRS) with patients and a proxy measure (MOBID-2) with caregivers. We observed significant reductions of pain intensity for patients in the active tDCS group as reflected by both pain measures (NRS: Cohen's d = 0.69, p-value = 0.02); MOBID-2: Cohen's d = 1.12, p-value = 0.001). Moreover, we found home-based tDCS was feasible and acceptable intervention approach for pain in ADRD. These findings suggest the need for large-scale randomized controlled studies with larger samples and extended versions of tDCS to relieve chronic pain on the long-term for individuals with ADRD.

Adverse Childhood Experiences and Poor Sleep Quality in Older Adults: The Influence of Emotion Regulation.

BACKGROUND: Adverse childhood experiences (ACEs) are associated with sleep impairment across the life span, but little is known about modifiable factors that may ameliorate this relationship, such as adaptive emotion regulation (ER) skills. METHODS: Data were obtained from an online questionnaire completed by a community sample of older adults (N = 278). The questionnaire included the Pittsburgh Sleep Quality Index, an Adverse Childhood Experiences questionnaire, the Cognitive Emotion Regulation Questionnaire (CERQ), and measures of health conditions, and other sample demographics. Moderation analyses were used to examine the interaction between ACEs and 5 adaptive ER skills of CERQ on sleep quality in older adults, while accounting for the effects of age, sex, income, body mass index, and health. RESULTS: ACEs were significantly associated with worse sleep quality in older adults, and this effect was moderated by positive reappraisal and refocusing on planning (all ps < .05). For individuals reporting greater use of these ER skills, ACEs had no effect on sleep quality, whereas for individuals reporting less frequent use of these ER skills, ACEs were associated with substantially worse sleep quality. This relationship remained significant after accounting for age, sex, income, body mass index, and health conditions in the model. CONCLUSIONS: The effects of ACEs on sleep quality persist into older age; however, greater use of ER skills that focus on positively reframing negative events and identifying strategies for coping protect against sleep impairment in individuals with higher ACEs.

The Role of Physical Activity on the Relationships Between Pain, Anxiety, and Sleep Quality in Older Age.

BACKGROUND: Sleep quality is associated with a range of negative outcomes in older adults, including a higher risk for cognitive decline, greater disability, and poorer quality of life. Pain and anxiety are both important factors associated with poor sleep quality. Physical activity (PA) is frequently recommended to enhance sleep quality and may have additional benefits for pain and anxiety symptoms. However, current models have not examined the interplay among these factors in relation to sleep quality in older adults. METHODS: We examined survey data from a community sample of 281 older adults (aged 55-98 years). Bootstrapped mediation and moderated mediation models using the PROCESS macro in SPSS were used to analyze indirect pathways from pain and anxiety to sleep quality and the conditional effects of exercise. RESULTS: Higher levels of pain and anxiety were significantly and independently associated with poorer sleep quality in older adults. The effect of pain on sleep quality was partially mediated by anxiety symptoms. PA significantly moderated the effects of anxiety on sleep quality, while it did not significantly impact the relationship between pain and sleep quality. The overall indirect effect was not moderated by PA. CONCLUSION: Pain and anxiety are both significant predictors of sleep quality in older adults, and pain influences sleep quality in older adults partially through its influence on anxiety symptoms. PA may be beneficial for sleep quality for individuals with high anxiety, but patients may see fewer benefits from PA if sleep problems are primarily related to pain.

Daytime sleepiness, addictive-like eating, and obesity sequelae in Black and African American youth with obesity.

OBJECTIVES: The purpose of the current study was to examine the association between poor sleep health (ie, excessive daytime sleepiness), obesity sequelae (ie, percent overweight and serum leptin levels), and addictive-like eating behaviors, an obesity phenotype, in a sample of Black/African American (B/AA) adolescents. DESIGN: The current study analyzed archival baseline data from a sample of B/AA adolescents with obesity enrolled in a sequential randomized clinical trial. SETTING: Data were collected in the participants' homes by trained research assistants unaware of treatment condition. PARTICIPANTS: A sample of 181 B/AA adolescents with obesity between the ages of 12 and 16 years (M = 14.26, SD = 1.46) and having a body mass index (BMI) above the 95th percentile for age and gender were sampled. MEASUREMENTS: Self-report measures included the Cleveland Adolescent Sleepiness Questionnaire and the Yale Food Addiction Scale-Children (YFAS-C). Anthropomorphic data and blood samples were used to determine BMI and serum leptin levels, respectively. RESULTS: Excessive daytime sleepiness was positively correlated with YFAS-C symptom count, r = 0.295, P < .001. Serum leptin levels and percent overweight were both positively correlated with each other, r = 0.445, P < .001 and with YFAS-C symptom count, r = 0.215, P = .006. After controlling for age and gender, results supported an indirect effect from daytime sleepiness to both serum leptin levels (estimate = 2.210, SE = 0.932, P = .018) and percent overweight (estimate = 2.817, SE = 1.415, P = .046) through YFAS-C symptom count. CONCLUSIONS: Culturally informed interventions on eating behaviors (ie, addictive-like eating) when excessive daytime sleepiness is reported are needed. Early intervention may help prevent the onset or worsening of obesity among adolescents.

Brief, interoceptive exposure focused treatment for anxiety in mild cognitive impairment.

Anxiety is common in older adults with mild cognitive impairment (MCI), and Alzheimer's disease and related dementias (ADRD). Anxiety has also been identified as a risk factor for cognitive decline. Brief interventions targeting risk mechanisms of anxiety, such as anxiety sensitivity (AS), have been effective in reducing overall anxiety in a variety of populations. This case series investigated the feasibility and efficacy of a brief AS intervention in anxious older adults with MCI (n = 9). Paired samples t-test results indicate that this intervention is capable of significantly reducing AS as measured by the Anxiety Sensitivity Index-3 (Δ = 5.11, Hedges g = 0.82, P < 0.05). Given these large AS reductions and high acceptability, further investigation of this intervention is warranted in older adults with MCI.

Assessing the use of prescription drugs and dietary supplements in obese respondents in the National Health and Nutrition Examination Survey.

INTRODUCTION: Obesity is a common disease and a known risk factor for many other conditions such as hypertension, type 2 diabetes, and cancer. Treatment options for obesity include lifestyle changes, pharmacotherapy, and surgical interventions such as bariatric surgery. In this study, we examine the use of prescription drugs and dietary supplements by the individuals with obesity. METHODS: We conducted a cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES) data 2003-2018. We used multivariate logistic regression to analyze the correlations of demographics and obesity status with the use of prescription drugs and dietary supplement use. We also built machine learning models to classify prescription drug and dietary supplement use using demographic data and obesity status. RESULTS: Individuals with obesity are more likely to take cardiovascular agents (OR = 2.095, 95% CI 1.989-2.207) and metabolic agents (OR = 1.658, 95% CI 1.573-1.748) than individuals without obesity. Gender, age, race, poverty income ratio, and insurance status are significantly correlated with dietary supplement use. The best performing model for classifying prescription drug use had the accuracy of 74.3% and the AUROC of 0.82. The best performing model for classifying dietary supplement use had the accuracy of 65.3% and the AUROC of 0.71. CONCLUSIONS: This study can inform clinical practice and patient education of the use of prescription drugs and dietary supplements and their correlation with obesity.

Tailored Motivational Interviewing in Adolescent HIV Clinics: Primary Outcome Analysis of a Stepped Wedge Implementation Trial.

BACKGROUND: Youth continue to have the poorest outcomes along the HIV prevention and care continua. Motivational Interviewing (MI) may promote behavior change and reduce perceived stigma, but providers often demonstrate inadequate MI competence. This study tested Tailored Motivational Interviewing (TMI), a set of implementation strategies designed to improve MI competence in youth HIV providers. SETTING: Ten HIV clinics in the Adolescent Trials Network for HIV/AIDS Interventions. METHODS: In a stepped wedge design, 10 clinics (N = 151 providers) were randomized in 5 clusters every 3 months to receive TMI for a 12-month implementation period. Sites were rerandomized within each cluster to receive communities of practice guidance with or without internal facilitator support in the sustainment period. Standard patient assessments were coded every 3 months for 36 months. RESULTS: Nesting was addressed using mixed-effects regression models, with random effects for providers and sites. TMI resulted in significantly improved MI competence over baseline. Despite small reductions in competence in the sustainment window, competence was still significantly improved over baseline, with no difference between the 2 sustainment conditions. CONCLUSIONS: TMI may be an important tool to capacitate the HIV HealthForce to end the HIV epidemic in young people.

The P300, loneliness, and depression in older adults.

Depression is associated with high levels of cognitive impairment and increased loneliness among older adults. The current study examines associations between a reliable and robust neural marker of cognitive impairment (i.e., the P300 event-related brain potential [ERP]), loneliness, and depression and assesses the role of loneliness in the P300─depression relationship. In a community sample of 70 older adults between 61 and 75 years, we evaluated cross-sectional associations between depressive symptoms (Geriatric Depression Scale), loneliness (NIH Toolbox), and P300 amplitude measured from the electroencephalogram during a go/no-go task. Results indicated that reduced go and no-go P300 amplitudes were associated with increased depressive symptom severity, with the most unique variance accounted for by a reduced no-go P300 amplitude. Notably, loneliness significantly moderated the no-go P300-depressive symptom severity relationship, such that there was no relationship between the no-go P300 and depressive symptom severity among older adults reporting low levels of loneliness. This finding provides insight into the possibility that social support may offer protection against the depressogenic effects of poor inhibitory control in older adults. Taken together, this study provides a novel examination of the relationships between depression, loneliness, and the P300 ERP in older adults, with important implications for understanding the role of neural inhibition and loneliness in relation to depressive symptomatology.

Emotion regulation and the late positive potential (LPP) in older adults.

Emotion regulation (ER) processes in older adults may be important for successful aging. Neural correlates of ER processes have been examined using event-related brain potentials (ERPs), such as the late-positive potential (LPP) during cognitive reappraisal paradigms. The current study sought to extend this research by examining the LPP from an ER task in a sample of 47 community-dwelling older adults between the ages of 60 and 84 years, scoring either high on emotional well-being (as measured by habitual ER use and resiliency; high WB group, n = 20) or low on emotional well-being (as measured by habitual ER use, resiliency, and depression; low WB group, n = 27). Participants viewed unpleasant and neutral images and were instructed to simply react to the images or reappraise their emotional response. Both pre- and post-instruction LPP amplitudes were scored, in addition to self-reported ratings of negative emotion collected during the task. We found greater LPP amplitude to emotionally salient compared to neutral stimuli, reduced LPP amplitude following instructions to reappraise emotional response to stimuli across groups, and a blunted LPP overall for individuals with higher depressive symptoms. Additionally, we demonstrated that older adults with low emotional well-being were less successful at reappraisal according to self-reported ratings of negative emotion, although this was not reflected in the LPP. Collectively, these data suggest that laboratory-based ER tasks might be used to understand abnormal ER use-though the LPP may be more sensitive to depression than individual differences in ER ability.

The Mediating Role of Cardiometabolic Dysregulation on the Relation Between Adverse Childhood Experiences and Adult Cognition.

OBJECTIVE: Adverse childhood experiences (ACEs) are uncontrollable stressful events during early life that predispose adults to adverse health outcomes, such as impaired cognitive functioning. However, little is known about the factors indirectly impacting this relation. Biological dysregulation may be one pathway that can help explain the relations between ACEs and later cognition. The current study examined the mediating role of cardiometabolic dysregulation on the relation between ACEs and cognition. METHODS: Our study gathered data from 1053 participants using three waves of the Midlife in the United States longitudinal study. Linear regression analyses and bootstrapped mediation analyses were performed to analyze the direct and indirect associations of cardiometabolic dysregulation on ACEs and cognition. RESULTS: Our results showed a significant linear relationship between ACEs and cardiometabolic dysregulation ( b = 0.152, standard error [SE] = 0.056, p = .007), and a significant indirect association, such that cardiometabolic dysregulation mediated the relation between ACEs and cognitive status at wave II ( b = -0.007, SE = 0.004, p = .044) and cognitive status at wave III ( b = -0.006, SE = 0.003, p .042). There was no significant direct or indirect relation when cognitive change was the outcome variable. CONCLUSIONS: The present study identifies a combined biological pathway that connects ACEs to cognition in late life. These findings supports the need to empirically determine biological mechanism that can be used to develop targeted clinical interventions to prevent the progression of chronic cognitive impairment.

Feasibility of an MI-CBT ketogenic adherence program for older adults with mild cognitive impairment.

BACKGROUND: The National Institutes of Health Obesity-Related Behavioral Intervention Trials model for intervention development was used to establish the feasibility and proof of concept of a motivational ketogenic nutrition adherence program for older adults with mild cognitive impairment. METHODS: This was a single-arm, single-center feasibility trial. A comprehensive assessment protocol, including a clinical interview, neuropsychological testing, and genetic sequencing was used as an initial screening. Nine participants (aged 64-75) with possible amnestic mild cognitive impairment were consented for the intervention. Participants completed pre- and post-intervention neuropsychological assessments using the updated Repeatable Battery for Assessment of Neuropsychological Status. Participants tracked their macronutrient consumption using food diaries and ketone levels using urinalysis test strips daily. Mood and other psychosocial variables were collected through surveys, and qualitative exit interviews were completed. RESULTS: 100% of participants who began the trial completed the 6-week ketogenic nutrition adherence program, including completion of the pre- and post-assessments. Eight participants achieved measurable levels of ketones during the program. The average self-rated adherence across the program was 8.7 out of 10. A Wilcoxon Signed-Rank test demonstrated significant improvement in cognitive performance from baseline (median = 88) to follow up (median = 96, Z = - 2.26, p = .024). The average difference in cognitive performance from baseline to follow-up was - 7.33 (95% CI - 12.85, - 1.82). CONCLUSIONS: Results supported the feasibility for moving to the next phase and demonstrated proof of concept for the intervention. The next step is a randomized pilot trial to test clinical signals of effect compared to a control condition. TRIAL REGISTRATION: This trial was retrospectively registered with clinicaltrials.gov on July 13, 2021. The trial number is NCT04968041.

Multi-sample assessment of stress reactivity as a mediator between childhood adversity and mid- to late-life outcomes.

OBJECTIVES: We examined whether adult stress reactivity accounts for the relationship between early life adversity (ELA) and psychological, physical, and cognitive outcomes. METHODS: We examined the relationship between ELA, stress reactivity, psychological well-being, physical health, and cognitive function in two separate datasets - a cross-sectional community sample of older adults (N = 510) aged 60 and older, and waves I-III of the Midlife in the United States (MIDUS) dataset. Age, sex, and income served as covariates in all analyses. Bootstrapped mediation models were used to assess recent stress as a mediator between ELA and mid- to late-life outcomes. RESULTS: ELA was significantly associated with adult stress, anxiety, depression, health conditions, and object cognitive assessments. Adult stress partially accounted for the relationships between ELA and depression, anxiety, health conditions, and memory problems. CONCLUSION: Our findings demonstrate that ELA may influence increased stress in older age, which confers additional risks for developing depression, anxiety, health problems, and cognitive decline. It is possible that intervening on adult stress may reduce risk for both psychological and physical pathology across the lifespan. Further research is needed to develop targeted interventions for mid and late-life stress to improve overall health as individuals age.