'With or without you': associations between noteworthy events and cognitive complaints across 100 days.

OBJECTIVES: Daily noteworthy events have implications for physical and mental health, but less is known about the role daily events have for self-reported cognition and whether the involvement of close social partners differentiates these associations. The current study examined how daily positive and negative noteworthy events relate to subjective memory and attentional difficulties and whether close social partners moderated associations. METHOD: We used data from a 100-day microlongitudinal web-based study of 104 older adults (Nobservations=7,051; Mage=63.13 years, SDage=7.81, 88.46% Female). Participants reported on exposure to and valence of noteworthy events, involvement of close social partners, and subjective cognitive complaints at the end of each day. RESULTS: Logistic multilevel models revealed that days with a negative event were associated with increased odds of forgetting something and trouble concentrating whereas days with positive events were associated with decreased odds of trouble concentrating. Close social partner involvement did not moderate within-person associations. CONCLUSION: Our results suggest that day-to-day events are correlates of cognitive complaints regardless of close social partner involvement in the events. Research should clarify the role of daily positive and negative events in personalized interventions and determine whether this person-centered approach to self-reported cognitive health helps inform diagnostic practices.

D-Loop Mutations as Prognostic Markers in Glioblastoma-A Pilot Study.

Glioblastoma, a highly aggressive brain tumor, poses significant treatment challenges. A deeper investigation into its molecular complexity is essential for the identification of novel prognostic biomarkers and therapeutic strategies, potentially improving patient outcomes in terms of survival and quality of life. While nuclear DNA mutations have been extensively studied, the role of mitochondrial DNA (mtDNA) mutations, specifically in the D-loop region, remains poorly understood. This prospective case-control study aimed to assess the prognostic significance of the mtDNA D-loop m.16126T>C variant in glioblastoma patients. Immunohistochemistry and droplet digital PCR (ddPCR) were employed for mutation analysis, complemented by statistical analyses and a literature review. The study cohort comprised 22 glioblastoma patients (mean age 59.36 ± 14.17, 12 (54.55%) females), and 25 controls (59.48 ± 13.22, 12 (80%) females). The D-loop m.16126T>C variant was observed in four (18%) of the glioblastoma samples and was associated with shorter median survival (9.5 vs. 18 months; p = 0.016, log-rank test). This study underscores the importance of investigating mtDNA, especially D-loop variants, in glioblastoma, suggesting its potential as a prognostic biomarker and, therefore, its possible therapeutic targets, warranting further exploration.

Accelerating Progress Towards the 2030 Neglected Tropical Diseases Targets: How Can Quantitative Modeling Support Programmatic Decisions?

Over the past decade, considerable progress has been made in the control, elimination, and eradication of neglected tropical diseases (NTDs). Despite these advances, most NTD programs have recently experienced important setbacks; for example, NTD interventions were some of the most frequently and severely impacted by service disruptions due to the coronavirus disease 2019 (COVID-19) pandemic. Mathematical modeling can help inform selection of interventions to meet the targets set out in the NTD road map 2021-2030, and such studies should prioritize questions that are relevant for decision-makers, especially those designing, implementing, and evaluating national and subnational programs. In September 2022, the World Health Organization hosted a stakeholder meeting to identify such priority modeling questions across a range of NTDs and to consider how modeling could inform local decision making. Here, we summarize the outputs of the meeting, highlight common themes in the questions being asked, and discuss how quantitative modeling can support programmatic decisions that may accelerate progress towards the 2030 targets.

Individual differences in frequency and impact of daily memory lapses: results from a national lifespan sample.

BACKGROUND: Everyday memory problems are believed to increase with age, leading many researchers to focus on older ages when examining reports of memory lapses. However, real world memory lapses are ubiquitous across the adult lifespan, though less is known about the types of problems and their impacts at younger ages. The current study examined occurrence and impacts of memory lapses using daily diaries in a broad age range and whether characteristics of lapses varied across age, gender, or education level. METHODS: Using an 8-day daily diary protocol, 2,018 individuals (ages 25-91) provided reports of their experiences of two types of daily memory lapses (retrospective and prospective) as well as the impact those lapses had on their emotional and functional well-being that day. Using multilevel modeling, we examined the likelihood of reporting memory lapses and their impacts on daily life and whether these depended on age, gender, or education level. RESULTS: Participants reported lapses on approximately 40% of days; retrospective memory lapses were significantly more likely than prospective lapses. Older ages and higher education level were related to greater likelihood of reporting retrospective lapses. Women (compared to men) were more likely to report prospective memory lapses. Women also tended to report greater impacts of their memory lapses. Lower education levels were related to greater impacts of memory lapses compared to higher education levels. Interestingly, age was not related to impacts of lapses. DISCUSSION: Our results indicate that memory lapses are common across the lifespan and that those individuals more likely to report lapses are not necessarily those that experience the greatest impacts of those lapses on daily life. Additional work is needed to understand the daily experience of memory lapses and how they differentially affect individuals regardless of age, gender, and education. CONCLUSIONS: Memory lapses are an important aspect of daily life across the lifespan and require measurement in an individual's real-world environments. Better measurement of these experiences will allow the development of more sensitive measures of changes in cognitive functioning that may impact an individual's ability to live independently.

Daily Caregiving Appraisals, Future Self-Views, and Physical Activity Goals Among Adult-Daughter Dementia Caregivers.

OBJECTIVES: Caregiving dynamics may shape caregivers' views on their own aging in ways that affect their (de)motivation to improve their current and future health and well-being. In this study, we investigated within-person associations of daily positive and negative caregiving appraisals, future self-views (physical functioning, cognitive, and overall health domains), and physical activity goal pursuit among adult-daughter dementia caregivers. METHODS: Data came from 33 middle-aged caregivers (M = 55.03) who participated in a 30-day microlongitudinal study of caregiving (N of occasions = 855). We used multilevel modeling to analyze within-person associations. RESULTS: Daily positive caregiving appraisals were not associated with daily future self-views. However, on days when caregivers reported higher negative caregiving appraisals, they thought more negatively about their future older selves in all domains. In turn, on days when caregivers thought more negatively about their future older selves in all domains, they reported lower physical activity goal pursuit. Future self-views in all domains mediated the association between negative caregiving appraisals and physical activity goal pursuit. Future self-views did not mediate the association between positive caregiving appraisals and physical activity goal pursuit. However, cognitive future self-views moderated the association between positive caregiving appraisals and physical activity goal pursuit. DISCUSSION: Results suggest that one pathway through which subjective caregiving experiences, especially negative caregiving appraisals, affect caregivers' physical activity goal pursuit is through future self-views. Thus, this study offers a deeper theoretical understanding of caregivers' self-regulatory health behavior and new empirical information on how caregiving might affect life-span developmental motivation.

Effect of Exercise Repetitions on Arylesterase Activity of PON1 in Plasma of Average-Trained Men-The Dissociation between Activity and Concentration.

Exercise may increase the antioxidant capacity of plasma by stimulating antioxidant enzymes. The study aimed to measure the effect of three repetitions of acute exercise on arylesterase (ARE) activity of the paraoxonase 1 (PON1) enzyme. Eleven average-trained men (age 34.0 ± 5.2 years) completed three treadmill runs. ARE activity in plasma was evaluated spectrophotometrically and compared with PON1 concentration (PON1c), paraoxonase (PON) activity, and high-density lipoprotein cholesterol (HDL-C) at rest and after exercise. In all repetitions of the exercise, ARE activity remained stable, and ARE activity standardized for PON1c (ARE/PON1c) was lower post- than pre-exercise. The ARE/PON1c ratio changes returned to baseline levels during rest after each exercise session. Pre-exercise ARE activity correlated negatively with post-exercise C-reactive protein (CRP) (ρ = -0.35, p = 0.049), white blood cell count (WBC) (ρ = -0.35, p = 0.048), polymorphonuclear leukocytes (PMN) (ρ = -0.37, p = 0.037), and creatine kinase (CK) (ρ = -0.37, p = 0.036). ARE activity may be depleted under conditions of oxidative stress, as increases in PON1c during acute exercise did not result in parallel increases in ARE activity. No adaptation of the response of ARE activity to exercise was detected in subsequent exercise sessions. Individuals with lower pre-exercise ARE activity may develop a higher inflammatory response to strenuous exercise.

Affective Reactions to daily interpersonal stressors: Moderation by family involvement and gender.

The goal of this study was to examine whether family involvement and gender moderated daily changes in affect associated with interpersonal stressors. Adults (N = 2022; M age = 56.25, Median = 56, SD = 12.20, Range = 33-84) from the second wave of the National Study of Daily Experiences participated in eight consecutive daily diaries. Each day they reported whether a daily interpersonal stressor occurred, whether family was involved, and their positive and negative affect. Results from multilevel models indicated that family involvement did not significantly moderate daily interpersonal stressor-affect associations; however, gender was a significant moderator in some instances. Women showed greater increases in negative affective reactivity to arguments and avoided arguments compared to men. Further, compared to men, women reported larger decreases in positive affective reactivity, but only for avoided arguments. Neither family involvement, gender, nor the interaction between family involvement and gender predicted affective residue. Gender differences in daily interpersonal stressors and affective reactivity may be attributable to overarching gender norms and roles that are still salient in the U.S. Our results suggest that daily interpersonal stressors may be detrimental to affective well-being, regardless of family involvement. Future work should explore associations between daily interpersonal stressors and family involvement by specific relationship roles, such as mother or spouse, for a more comprehensive understanding of what stressor characteristics impact daily affective well-being.

How Do Marital Transitions Affect Self-Perceptions of Aging?

OBJECTIVES: We analyzed whether marital status and experiences of marital loss or gain were associated with self-perceptions of aging (SPA), a major psychosocial mechanism of healthy aging. METHOD: We used data from 7028 participants of the Health and Retirement Study. Participants reported their marital status and their positive and negative SPA on two occasions 4 years apart. We ran general linear models to analyze differences in SPA between men and women who remained married, became divorced or widowed, or remarried following divorce or widowhood. RESULTS: Participants who experienced marital loss had lower positive SPA than participants who remained marred. Participants who experienced marital gain had lower negative SPA than participants who remained married. None of the associations differed between men and women. DISCUSSION: Results suggest that it may not be marital status itself, but rather the transition into or out of marriage, that impacts how people appraise their own aging.

Daily Stress Processes as Potential Intervention Targets to Reduce Gender Differences and Improve Mental Health Outcomes in Mid- and Later Life.

The current study examines daily stress processes as risk factors for comprised mental health in midlife and later life, specifically for gender differences in depression risk. Using data from the Midlife in the United States (MIDUS) study and the National Study of Daily Experiences (NSDE), we examine (1) gender differences in depression; (2) the prospective effects of differential exposure and affective responses on 10-year depression status; (3) gender differences in daily stress-depression links. Furthermore, we explore whether the protective factor of help-seeking behavior moderates the effects of daily stress on depression. Participants included 1289 (mage = 55; SD = 12; range = 34-83; 56% female) individuals who completed the second waves of MIDUS and the 8-day NSDE daily diary protocol and participated in the third wave of MIDUS approximately 10 years later. Respondents completed assessments of depression and their seeking assistance from a psychiatrist, mental health professional, counselor, or religious leader. Covariate-adjusted logistic regression analyses revealed increased odds of depression among women compared to men, but no significant gender difference after taking daily stress into account. Higher levels of stressor exposure, negative affect, and affective reactivity were associated with increased odds of depression for both men and women. Compared to those who did not engage in help-seeking behavior, those who did had significantly greater odds of depression, and there were asymmetric patterns of daily stress effects across groups. These findings highlight differential exposure, negative affect, and affective responses to daily stress as potentially accessible intervention targets for reducing stress in daily life and mitigating longer-term depression risk during mid- and later life.

Computing Components of Everyday Stress Responses: Exploring Conceptual Challenges and New Opportunities.

Repeated assessments in everyday life enables collecting ecologically valid data on dynamic, within-persons processes. These methods have widespread utility and application and have been extensively used for the study of stressors and stress responses. Enhanced conceptual sophistication of characterizing intraindividual stress responses in everyday life would help advance the field. This article provides a pragmatic overview of approaches, opportunities, and challenges when intensive ambulatory methods are applied to study everyday stress responses in "real time." We distinguish between three stress-response components (i.e., reactivity, recovery, and pileup) and focus on several fundamental questions: (a) What is the appropriate stress-free resting state (or "baseline") for an individual in everyday life? (b) How does one index the magnitude of the initial response to a stressor (reactivity)? (c) Following a stressor, how can recovery be identified (e.g., when the stress response has completed)? and (d) Because stressors may not occur in isolation, how can one capture the temporal clustering of stressors and/or stress responses (pileup)? We also present initial ideas on applying this approach to intervention research. Although we focus on stress responses, these issues may inform many other dynamic intraindividual constructs and behaviors (e.g., physical activity, physiological processes, other subjective states) captured in ambulatory assessment.

Interleukin-4 during post-exercise recovery negatively correlates with the production of phagocyte-generated oxidants.

Exhaustive run induced a biphasic oxidative response of circulating phagocytes in 16 amateur sportsmen. The first phase involved an increment just after exercise of enhanced whole blood chemiluminescence normalized per phagocyte count, whereas in the second phase a decrement from 1 h post-exercise and ongoing till 24 h. We tested whether plasma Interleukin IL-4, IL-8, IL-10 and Tumor Necrosis Factor α concentrations change in response to exhaustive run and whether there are associations between their levels and delta resting. Moreover, IL-8 and IL-10 significantly increased immediately post-exercise and after 1 h, but later normalized. Tumor necrosis factor α rose by 1.1-times only just after exercise. However, none of these cytokines showed any correlation with the investigated chemiluminescence. Exercise did not alter plasma concentrations of IL-4. However, pre-exercise IL-4 negatively correlated with measured luminescence just after exercise (ρ = -0.54, p < 0.05), and also tended to be negatively associated with decrements of the second phase at 1 h post-exercise ρ = -0.45, p = 0.08. It is suggested that plasma IL-4, by a negative association with blood phagocytes oxidants production, could be involved in the maintenance of proper balance between oxidants and anti-oxidants during strenuous exercise and post-exercise recovery.

Cell-Free DNA: Potential Application in COVID-19 Diagnostics and Management.

WHO has declared COVID-19 as a worldwide, public health emergency. The elderly, pregnant women, and people with associated co-morbidities, including pulmonary disease, heart failure, diabetes, and cancer are the most predisposed population groups to infection. Cell-free DNA is a very commonly applied marker, which is elevated in various pathological conditions. However, it has a much higher sensitivity than standard biochemical markers. cfDNA appears to be an effective marker of COVID-19 complications, and also serves as a marker of certain underlying health conditions and risk factors of severe illness during COVID-19 infection. We aimed to present the possible mechanisms and sources of cfDNA released during moderate and severe infections. Moreover, we attempt to verify how efficiently cfDNA increase could be applied in COVID-19 risk assessment and how it corresponds with epidemiological data.

Exhaustive Exercise Increases Spontaneous but Not fMLP-Induced Production of Reactive Oxygen Species by Circulating Phagocytes in Amateur Sportsmen.

Strenuous exercise alters the oxidative response of blood phagocytes to various agonists. However, little is known about spontaneous post exercise oxidant production by these cells. In this cross-over trial, we tested whether an exhaustive treadmill run at a speed corresponding to 70% of VO2max affects spontaneous and fMLP-provoked oxidant production by phagocytes in 18 amateur sportsmen. Blood was collected before, just after, and 1, 3, 5 and 24 h post exercise for determination of absolute and normalized per phagocyte count spontaneous (a-rLBCL, rLBCL) and fMLP-induced luminol-enhanced whole blood chemiluminescence (a-fMLP-LBCL, fMLP-LBCL). a-rLBCL and rLBCL increased by 2.5- and 1.5-times just after exercise (p < 0.05) and then returned to baseline or decreased by about 2-times at the remaining time-points, respectively. a-fMLP-LBCL increased 1.7- and 1.6-times just after and at 3 h post-exercise (p < 0.05), respectively, while fMLP-LBCL was suppressed by 1.5- to 2.3-times at 1, 3, 5 and 24 h post-exercise. No correlations were found between elevated post-exercise a-rLBCL, a-fMLP-LBCL and run distance to exhaustion. No changes of oxidants production were observed in the control arm (1 h resting instead of exercise). Exhaustive exercise decreased the blood phagocyte-specific oxidative response to fMLP while increasing transiently spontaneous oxidant generation, which could be a factor inducing secondary rise in antioxidant enzymes activity.

Age differences in allostatic load among veterans: The importance of combat exposure.

The current study examinedage differences in allostatic load among nonveterans, noncombat veterans, and combat veterans. Participants included 280 individuals from the Midlife Development in the United States (MIDUS) survey, including 164 veterans (n = 48 combat veterans; n = 116 noncombat veterans) and 116 nonveterans. Age differences in allostatic load were similar among nonveterans and noncombat veterans, B = 0.002, SE = .011, p = .878, with older adults showing higher levels of allostatic load than their comparatively younger counterparts. Among combat veterans, however, a different pattern emerged. In this group, levels of allostatic load were similar across age, seemingly due to higher levels of allostatic load among younger combat veterans, B = -0.029, SE = .014, p = .031, ƞp 2  =  .022. Results reveal the importance of considering combat exposure when examining health outcomes of military veterans, particularly in the context of age.

Linking widowhood and later-life depressive symptoms: Do childhood socioeconomic circumstances matter?

Objectives: Widowhood and adverse childhood socioeconomic circumstances (CSC) have both been linked to increased levels of depressive symptoms in old age. Beyond their independent impact on depressive symptoms, experiencing adverse CSC may also trigger a cascade of cumulative adversity and secondary stressors across the life course that shapes how individuals weather stressful life events later on.Method: We examine whether exposure to adverse CSC moderates the relationship between later-life widowhood and depressive symptoms using data from the Survey of Health, Ageing and Retirement in Europe (2004-2017).Results: Mixed-effects models revealed that both widowhood and adverse CSC were associated with increased levels of depressive symptoms among men and women. Associations between widowhood and depressive symptoms, however, were not moderated by CSC for both genders.Conclusion: Persisting differences in the levels of mental health in response to later-life widowhood did not further widen in the presence of disparities experienced early in the life course. This may reflect the life-altering impact of this age-normative, yet stressful life event across the social strata.

Repetitions of Strenuous Exercise Consistently Increase Paraoxonase 1 Concentration and Activity in Plasma of Average-Trained Men.

OBJECTIVES: Oxidative stress, induced by physical activity, may stimulate the expression, release, and activity of certain antioxidant enzymes. We investigated the effect of three repeated bouts of strenuous exercise on paraoxonase 1 concentration (PON1c) and paraoxonase activity (PON). METHODS: Eleven average-trained healthy men (age 34.0 ± 5.2 years) performed three strenuous exercise tests on a treadmill separated by 72 hours periods of resting. PON1c, PON, ferric-reducing activity of plasma (FRAP), lipid profile, C-reactive protein concentration (CRP), and lactate concentration were determined in plasma. RESULTS: Each exercise bout resulted in similar PON1c, PON, FRAP, and high-density lipoprotein concentration (HDL-C) increments, while PON/HDL-C ratio remained stable in all repetitions. Percentage increments at the bout of each exercise were higher for PON1c (by 64.82% at the first, by 92.9% at the second, and by 77.02% at the third exercise) than for PON (by 6.49% at the first, 10.06% at the second, and by 12.32% at the third exercise). Association was found between preexercise PON and PON1c (r = 0.56, p = 0.029), pre- (r = 0.87, p = 0.00003) and postexercise HDL-C (r = 0.6, p = 0.0002), preexercise PON and cardiovascular fitness level of participants measured as VO2max (r = 0.39, p = 0.026), and postexercise PON and lactate concentration (r = 0.44, p = 0.01). CONCLUSIONS: PON1c and PON increase during strenuous exercise, yet the effect of exercise on PON1 concentration is more pronounced. PON1 does not show tolerance to physical activity. The enzyme may provide short-term protection from oxidative stress in each exercise bout. PON may depend on exercise load. Cardiovascular fitness levels may be associated with PON1 activity.

Creation and validation of a polysocial score for mortality among community-dwelling older adults in the USA: the health and retirement study.

BACKGROUND: the interrelatedness between social determinants of health impedes researchers to identify important social factors for health investment. A new approach is needed to quantify the aggregate effect of social factors and develop person- centred social interventions. METHODS: participants ([n = 7,383], 54.5% female) were aged 65 years or above who complete an additional psychosocial questionnaire in the health and retirement study in 2006 or 2008. Social determinants of health encompassed five social domains: economic stability, neighbourhood and physical environment, education, community and social context, and healthcare system. We used the forward stepwise logistic regression to derive a polysocial score model for 5-year mortality. Indices of goodness-of-fit, discrimination and reclassification were used to assess model performance. We used logistic regression to identify the association between polysocial score and mortality. Subgroup analyses were conducted to examine sex- and race-specific association. RESULTS: polysocial score was created using 14 social determinants of health. In the training cohort, the C-statistic was 0.71 for the reference model (only age, sex and race/ethnicity) and increased to 0.75 for the continuous and categorical polysocial score. Compared with the reference model, the integrated discrimination index for adding the continuous or categorical polysocial score was both 0.03 (P values < 0.001). Participants with an intermediate (odds ratio [OR] = 0.69; 95% confidence interval [CI], 0.51-0.82) or high (OR = 0.48; 95% CI, 0.38-0.60) polysocial score had lower odds of death than those in the low category in the fully adjusted model, respectively. CONCLUSIONS: the polysocial approach may offer possible solutions to monitor social environments and suggestions for older people to improve their social status for specific health outcomes.

Current Trends in Cell-Free DNA Applications. Scoping Review of Clinical Trials.

We aimed to summarize the current knowledge about the trends in cfDNA application based on the analysis of clinical trials registered until April 2021. International Clinical Trials Registry Platform (ICTRP) and Clinicaltrials.gov were searched with the keywords: "cf-DNA"; "Circulating DNA"; "Deoxyribonucleic Acid"; and "Cell-Free Deoxyribonucleic Acid". Of 605 clinical trials, we excluded 237 trials, and 368 remaining ones were subject to further analysis. The subject, number of participants, and study design were analyzed. Our scoping review revealed three main trends: oncology (n = 255), non-invasive prenatal diagnostic (n = 48), and organ transplantation (n = 41), and many (n = 22) less common such as sepsis, sport, or autoimmune diseases in 368 clinical trials. Clinical trials are translating theory into clinical care. However, the diagnostic value of cfDNA remains controversial, and diagnostic accuracy still needs to be evaluated. Thus, further studies are necessary until cfDNA turns into a standard in clinical practice.

Increased Circulating H3 Histone in Response to Repeated Bouts of Exercise Does Not Associate with Parallel Alterations of Cell-Free DNA.

Numerous studies have shown that cf nDNA significantly rises in stress caused by exercise. However, during nuclear decondensation, released DNA is followed by histones. Histones are also a common disease marker. After PAD4 mediated hypercitrullination extracellular H3Cit exhibits high toxicity contributing to tissue damage which, in cases of systemic inflammation, may lead to multiorgan failure and finally to death. We tested whether circulating histones rise in response to strenuous exercise. Eleven average-trained men performed three treadmill exercise tests to exhaustion at speed corresponding to 70% VO2max separated by 72 h of resting. Blood was collected before and just after each bout of exercise and plasma proteins were measured using enzyme-linked immunosorbent assay, whereas platelet activity was estimated with Light Transmission Aggregometry. Both, circulating histones and PAD4 raised in response to exercise. Plasma citrullinated histones increased from 3.1 ng/mL to 5.96 ng/mL (p = 0.0059), from 3.65 ng/mL to 6.37 ng/mL (p = 0.02), and from 3.86 ng/mL to 4.75 ng/mL (p = 0.033) after the first, second, and third treadmill run, respectively. However despite the parallel increase, no significant correlation between citrullinated histone and aggregation or cell-free nDNA was found. Furthermore, positive correlations of cf nDNA with aggregation and PAD4, lactate with aggregation, and lactate with citrullinated histone have been observed.

Aging-Related Changes in the Association between Negative Affect and Response Time Inconsistency in Older Adulthood.

Negative affect (NA) and positive affect (PA) are established modifiable psychosocial correlates of cognitive health and have demonstrated capacity for meaningful within-person fluctuations based on person-environment interactions, age, and measurement approach. Previous research has shown NA is associated with increased response time inconsistency (RTI), an early performance-based indicator of cognitive health and aging. It is unclear, however, whether PA is associated with RTI, and whether affect-RTI associations exist within persons over time or change as individuals get older. We utilized data from a measurement burst study (Cognition, Health and Aging Project) to explore within- and between-person associations between affect and RTI in community-dwelling older adults (N=111, M=80.04 years, SD=6.30). Affect and RTI were assessed on six days over a two-week period, every six months for two years. Results revealed a significant association between NA-low arousal and RTI within persons over time. RTI was higher on sessions when NA-low arousal was higher than usual (b=0.21, 95%CI=0.08 to 0.35, p<.01). This association decreased in magnitude over time (b=-0.09, 95%CI=-0.14 to - 0.03, p<.001), ultimately resulting in increased NA-low arousal being associated with decreased RTI two years later (b=-.14, 95%CI=-0.27 to -0.01, p<.05). No PA-RTI associations emerged. The results suggest efforts focused on maximizing resource allocation and personalizing cognitive health efforts should consider for whom and when mitigating NA may be maximally beneficial to daily cognition, whereas additional work is needed to determine influences from PA.