Subsequent Cognitive Performance Research Articles

Lipophilic statins in cognitively normal subjects: Associations with conversion to mild cognitive impairment in a long‐term longitudinal multi‐center study

AbstractBackgroundStudies of the relationship between the use of statins (HMG‐CoA reductase inhibitors) and subsequent cognitive performance have been variously reported to demonstrate beneficial, harmful, or no significant effects. We aimed to help clarify the relationship between statin use and long‐term trajectory in subjects cognitively normal at baseline, comparing users of statins with known moderate (atorvastatin) or high (simvastatin) lipophilicity and blood‐brain barrier penetrance (LS), to non‐users (nonS), or users of other statins (OS).MethodFrom a consecutive series of 2305 subjects enrolled in the Alzheimer’s Disease Neuroimaging Initiative, 69 were excluded for taking combination statin drugs. Excluding statin users with less than 66 months of usage resulted in 340 CN subjects ( 189 nonS, 121 LS, and 30 OS) who were further studied. Subjects were stratified into groups with low (<175mg/dl), medium (175‐207mg/dl), or high ( ≥207mg/dl) baseline cholesterol levels. The significance of differential conversion rates was assessed by Chi‐Squared tests for homogeneity. Survival trajectories were created using the Kaplan‐Meier method, where an event was defined as conversion to mild cognitive impairment (MCI), and the significance of difference was assessed by the log‐rank test.ResultWhile serum cholesterol levels at baseline ranged widely (112‐174 mg/dl), among 112 subjects with low baseline cholesterol, levels did not significantly differ between those who did convert to MCI within 72 months (157 mg/dl) vs. those who did not (155 mg/dl), but their rates of conversion to MCI significantly differed according to LS use: 39.5% among LS vs. 14.8% among nonS+OS converted (p=0.025). The 6‐year event‐free survival of the nonS+OS group (88.7%; 95% CI 0.785‐1) and the LS group (64.0%; 95% CI 0.519‐0.789) also differed significantly (p=0.019). LS usage was associated with an increased absolute (+24.7%) and relative (+167%) risk.ConclusionLipophilic statin use was associated with more than double the risk of declining to MCI over 72 months of follow‐up in cognitively normal patients with low baseline cholesterol. In separate analyses, no such risk was observed among other statin users, nor among subjects with medium or high baseline cholesterol levels.

The effects of positive and negative experiences on subsequent behavior and cognitive performance in capuchin monkeys (Sapajus [Cebus] apella).

Our understanding of animals' affective processing is notably limited compared to the wealth of research on humans, largely due to difficulties in measurement. Moreover, despite a recent increase in the understanding of the interaction between affect and cognition in animals, most research has focused on negative affect, with the result that we continue to know little about the effects of positive affect. In this study, we tested 15 adult capuchin monkeys (Sapajus [Cebus] apella) using a novel methodology that took advantage of capuchins' species-typical behavior to engineer both a positive and negative experience, using the same apparatus to minimize extraneous impacts. Following a positive or negative experience (that presumably induced positive and negative affect, respectively), or a control with no manipulation, we assessed subjects' performance on a cognitive task, a computerized delayed match-to-sample. As predicted, behavior following the negative condition suggested a negative affective state, with increased rates of scratching (commonly used as an indicator of stress in nonhuman primates) compared to both the positive and control conditions. Cognitive performance was also impaired in the negative condition compared to the other two. Contrary to predictions, however, the positive condition did not have a facilitative effect on cognitive performance, but behavioral results indicate that we may not have induced a truly positive affective state. Although we add to evidence that a negative experience can influence subsequent behavior and cognitive performance in nonhuman primates, our work highlights our lack of knowledge about the impact of positive affect, if any, on behavior and cognition. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Scent dog identification of SARS-CoV-2 infections in different body fluids

BackgroundThe main strategy to contain the current SARS-CoV-2 pandemic remains to implement a comprehensive testing, tracing and quarantining strategy until vaccination of the population is adequate. Scent dogs could support current testing strategies.MethodsTen dogs were trained for 8 days to detect SARS-CoV-2 infections in beta-propiolactone inactivated saliva samples. The subsequent cognitive transfer performance for the recognition of non-inactivated samples were tested on three different body fluids (saliva, urine, and sweat) in a randomised, double-blind controlled study.ResultsDogs were tested on a total of 5242 randomised sample presentations. Dogs detected non-inactivated saliva samples with a diagnostic sensitivity of 84% (95% CI: 62.5–94.44%) and specificity of 95% (95% CI: 93.4–96%). In a subsequent experiment to compare the scent recognition between the three non-inactivated body fluids, diagnostic sensitivity and specificity were 95% (95% CI: 66.67–100%) and 98% (95% CI: 94.87–100%) for urine, 91% (95% CI: 71.43–100%) and 94% (95% CI: 90.91–97.78%) for sweat, 82% (95% CI: 64.29–95.24%), and 96% (95% CI: 94.95–98.9%) for saliva respectively.ConclusionsThe scent cognitive transfer performance between inactivated and non-inactivated samples as well as between different sample materials indicates that global, specific SARS-CoV-2-associated volatile compounds are released across different body secretions, independently from the patient’s symptoms. All tested body fluids appear to be similarly suited for reliable detection of SARS-CoV-2 infected individuals.

Insomnia symptom severity and cognitive performance: Moderating role of APOE genotype.

We evaluated whether insomnia symptom severity was associated with cognitive function, and whether this relationship was modified by biomarkers associated with Alzheimer's disease risk. We examined insomnia symptoms and neuropsychological performance 3.4 years later in 511 dementia-free Framingham Heart Study participants (62.65±8.7 years, 50.9%male). Additionally, we explored insomnia symptoms combined with self-reported short habitual sleep duration and effect modification by apolipoprotein E (APOE) ε4 allele status. More severe insomnia symptoms were associated with lower performance on global cognition, and immediate and delayed Logical Memory recall, especially when insomnia symptoms were combined with short sleep duration. The association between insomnia symptoms and poorer memory recall was more pronounced in APOE ε4 allele carriers. Insomnia symptom severity was associated with worse subsequent global cognitive and memory performance, which was especially apparent in APOE ε4 allele carriers, suggesting that poor sleep might be particularly detrimental when the brain is already vulnerable to neurodegeneration.

Duration of subjective poverty in relation to subsequent cognitive performance and decline among adults aged ≥64 in China, 2005–2018

BackgroundThe effects of late-life subjective poverty on brain health are understudied. We aimed to investigate the association between duration of subjective poverty after age 64 and subsequent cognitive function and decline in China. MethodsData were from 4118 adults aged ≥64 at baseline in the population-based China Longitudinal Healthy Longevity Survey (CLHLS), 2005–2018. The duration of subjective poverty was measured from self-rated economic status relative to neighbors in 2005, 2008, and 2011 (never; one time point; two or three time points). Cognitive function was assessed by the Chinese Mini-Mental State Exam (CMMSE; range: 0–30) in 2011, 2014, and 2018. We fitted attrition-weighted, multivariable mixed-effects Tobit regression models to examine the relationship between duration of subjective poverty from 2005 to 2011 and subsequent cognitive function and decline from 2011 to 2018. ResultsA total of 2675 (64.96%) participants never reported subjective poverty over the period 2005–2011, 930 (22.58%) participants reported subjective poverty at one time point, and 513 (12.46%) reported subjective poverty at two or three time points. Compared to those who never reported subjective poverty, participants experiencing subjective poverty at one time point (β = −0.95, 95% CI: −1.48 to −0.41) and two or three time points (β = −2.01; 95% CI: −2.73 to −1.29) had lower CMMSE scores in 2011, indicating a dose-response relationship. Individuals with a longer duration of subjective poverty had a slower rate of decline in CMMSE scores than those never in subjective poverty (β = 1.44; 95% CI: 0.20 to 2.68 for 2018 X Two or three time points). ConclusionSubjective poverty in late life may have unique and cumulative contributions to cognitive aging among older adults in China. The lower level of initial cognitive function but slower rate of cognitive decline observed for those with greater subjective poverty is consistent with theories of cognitive reserve and empirical evidence from Western settings on other socioeconomic markers.

Using historical data to facilitate clinical prevention trials in Alzheimer disease? An analysis of longitudinal MCI (mild cognitive impairment) data sets

BackgroundThe Placebo Group Simulation Approach (PGSA) aims at partially replacing randomized placebo-controlled trials (RPCTs), making use of data from historical control groups in order to decrease the needed number of study participants exposed to lengthy placebo treatment. PGSA algorithms to create virtual control groups were originally derived from mild cognitive impairment (MCI) data of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. To produce more generalizable algorithms, we aimed to compile five different MCI databases in a heuristic manner to create a “standard control algorithm” for use in future clinical trials.MethodsWe compared data from two North American cohort studies (n=395 and 4328, respectively), one company-sponsored international clinical drug trial (n=831) and two convenience patient samples, one from Germany (n=726), and one from Switzerland (n=1558).ResultsDespite differences between the five MCI samples regarding inclusion and exclusion criteria, their baseline demographic and cognitive performance data varied less than expected. However, the five samples differed markedly with regard to their subsequent cognitive performance and clinical development: (1) MCI patients from the drug trial did not deteriorate on verbal fluency over 3 years, whereas patients in the other samples did; (2) relatively few patients from the drug trial progressed from MCI to dementia (about 10% after 4 years), in contrast to the other four samples with progression rates over 30%.ConclusionConventional MCI criteria were insufficient to allow for the creation of well-defined and internationally comparable samples of MCI patients. More recently published criteria for MCI or “MCI due to AD” are unlikely to remedy this situation. The Alzheimer scientific community needs to agree on a standard set of neuropsychological tests including appropriate selection criteria to make MCI a scientifically more useful concept. Patient data from different sources would then be comparable, and the scientific merits of algorithm-based study designs such as the PGSA could be properly assessed.

537 Insomnia Symptoms and Subsequent Cognitive Performance in Older Adults: Are Depressive Symptoms and Vascular Disease Mediators?

Abstract Introduction Alzheimer’s disease and related dementias (ADRD) are growing public health concerns, and poor sleep may represent a modifiable risk factor. However, there is limited research on insomnia as a predictor of subsequent performance in different cognitive domains and mechanisms that might underlie domain-specific associations. The current study examined: (1) which insomnia symptoms predicted performance across five cognitive domains 14 years later, and (2) whether depressive symptoms and/or vascular diseases mediated these associations. Methods Participants included 2,496 adults aged 51+ in the Health and Retirement Study. Insomnia symptoms in 2002 (i.e., “baseline”) were quantified by four self-reported items on frequency of trouble falling asleep, nighttime awakenings, early awakenings, and feeling rested upon awakening. Cognition was assessed in 2016 as part of the Harmonized Cognitive Assessment Protocol and operationalized with five factor scores corresponding to episodic memory, executive function, language, visuoconstruction, and processing speed. Multiple regressions examined associations between baseline insomnia symptoms and subsequent cognitive performance, controlling for sociodemographics and baseline global cognitive performance. Mediation models tested whether associations were explained by self-reported depressive symptoms and/or vascular diseases (i.e., hypertension, heart disease, diabetes, and/or stroke) in 2014, controlling for baseline values. Results Only trouble falling asleep in 2002 was associated with cognition in 2016. Specifically, more frequent trouble falling asleep predicted poorer episodic memory, executive function, language and processing speed performance, but not visuoconstruction. These associations were mediated by depressive symptoms and vascular diseases in 2014 for all domains except episodic memory; only depressive symptoms mediated the association involving memory. After accounting for these mediators, direct effects of trouble falling asleep remained for episodic memory, executive function and language, but not processing speed. Conclusion Difficulty with sleep initiation may be more consequential for later-life cognition than other insomnia symptoms. Depressive symptoms and vascular diseases may partially drive these associations. We speculate that sleep-onset insomnia could mean less total sleep, immune dysfunction, or endocrine effects that worsen mood, vascular health, and cognition. Remaining associations indicate that additional research is needed to characterize other mechanisms through which sleep initiation problems could contribute to later impairments in frontal and temporal cognitive systems, which are implicated early in ADRD. Support (if any):

Breastfeeding Duration Is Associated With Domain-Specific Improvements in Cognitive Performance in 9-10-Year-Old Children.

Significant immunological, physical and neurological benefits of breastfeeding in infancy are well-established, but to what extent these gains persist into later childhood remain uncertain. This study examines the association between breastfeeding duration and subsequent domain-specific cognitive performance in a diverse sample of 9–10-year-olds enrolled in the Adolescent Brain Cognitive Development (ABCD) Study®. The analyses included 9,116 children that attended baseline with their biological mother and had complete neurocognitive and breastfeeding data. Principal component analysis was conducted on data from an extensive battery of neurocognitive tests using varimax-rotation to extract a three-component model encompassing General Ability, Executive Functioning, and Memory. Propensity score weighting using generalized boosted modeling was applied to balance the distribution of observed covariates for children breastfed for 0, 1–6, 7–12, and more than 12 months. Propensity score-adjusted linear regression models revealed significant association between breastfeeding duration and performance on neurocognitive tests representing General Ability, but no evidence of a strong association with Executive Function or Memory. Benefits on General Ability ranged from a 0.109 (1–6 months) to 0.301 (>12 months) standardized beta coefficient difference compared to those not breastfed. Results indicate clear cognitive benefits of breastfeeding but that these do not generalize to all measured domains, with implications for public health policy as it pertains to nutrition during infancy.

Longitudinal Changes in Auditory and Cognitive Function in Middle-Aged and Older Adults.

PurposeThis article aimed to document longitudinal changes in auditory function, including measures of temporal processing, and to examine the associations between observed changes in auditory and cognitive function in middle-aged and older adults.MethodThis was a prospective longitudinal study of 98 adults (66 women) with baseline ages ranging from 40 to 85 years. The mean interval between T1 baseline and T2 follow-up measurements was 8.8 years with a range of 7–11 years. Measures of hearing threshold, gap detection, and auditory temporal-order identification were completed at T1 and T2. Cognitive measures completed at T1 and T2 were the 13 scales of the Wechsler Adult Intelligence Scale–Third Edition. Three approaches were taken to analyze these data: (a) examination of changes over time in group performance, (b) correlations and slopes between auditory and cognitive measures to examine concomitant rates of decline over the 9-year T1-to-T2 period, and (c) regression analyses examining associations between auditory performance at T1 and cognitive performance 9 years later at T2.ResultsFor the group data, there were significant declines in hearing loss, gap-detection thresholds at one frequency, and process-type measures of cognitive function from T1 to T2 matching the trends in the baseline cross-sectional data. Regression analyses of the longitudinal data revealed the strongest connection between auditory temporal-order processing and cognitive processing typically explaining 10%–15% of the variance.ConclusionsA significant amount of variance in rates of cognitive decline, T1 to T2, and subsequent cognitive performance (T2) was explained by measures of auditory function. Although hearing loss occasionally emerged as a significant factor, auditory temporal-order identification emerged much more frequently as the auditory measure most strongly associated with cognitive function.

Supplemental Material for The Effects of Positive and Negative Experiences on Subsequent Behavior and Cognitive Performance in Capuchin Monkeys (Sapajus [Cebus] apella)

Supplemental Material for The Effects of Positive and Negative Experiences on Subsequent Behavior and Cognitive Performance in Capuchin Monkeys (Sapajus [Cebus] apella)

Holocaust exposure and late-life cognitive performance in men with coronary heart disease

BackgroundHolocaust victims experienced extreme physical and mental stress that could lead to prolonged deficits in psychological and physiological well-being. We aimed to examine whether exposure to Holocaust conditions is associated with cognitive function and decline in a sample of old male adults with coronary heart disease (CHD). MethodsThe sample included 346 individuals with CHD who participated in a clinical trial in 1990–1997 (mean age 56.7 ± 6.5 y). During 2004–2008 (mean age 71.8 ± 6.5 y) and 2011–2013 (mean age 77.1 ± 6.4 y) participants underwent computerized cognitive assessments. Exposure to Holocaust conditions was based on self-report at the second assessment. Linear regression and mixed-effect models were conducted to evaluate the associations between Holocaust survivorship and subsequent cognitive performance and rate of cognitive decline. ResultsForty-Three participants (12%) survived concentration camps/ghettos, 69 (20%) were Holocaust survivors who escaped concentration camps/ghettos, and 234 (68%) were not Holocaust survivors. After adjustment for potential confounders, concentration camp/ghetto survivors had poorer global cognitive performance and poorer attention (β = −3.90; 95%CI: 7.11;-0.68 and β = −4.11; 95%CI: 7.83;-0.38, respectively) compared to individuals who were not exposed to Holocaust conditions. Additionally, participants who reported being at concentration camps/ghettoes had increased cognitive decline in global performance and executive function (β = −0.19; 95%CI: 0.37;-0.008 and β = −0.29; 95%CI: 0.53;-0.06, respectively) compared to participants who were not Holocaust survivors. Lastly, those who were Holocaust survivors but not in concentration camps/ghettos had greater decline in attention (β = −0.11; 95%CI: 0.21;-0.01). DiscussionExposure to Holocaust conditions in early-life may be linked with poorer cognitive function and greater cognitive decline decades later in old-adults with CHD.

Worse baseline lung function is associated with worse cognition among older black and white adults

AbstractBackgroundPrior studies indicate that lung function may be an important risk factor for cognitive impairment and decline, but the body of evidence has largely been restricted to cross‐sectional and single‐time point measurement studies in white populations.MethodsWe studied 1128 black and 1641 white participants, mean age 74 years (SD 3), without prevalent dementia at enrollment in the Health Aging and Body Composition (Health ABC) Study. Participants completed spirometry assessments including Forced Expiratory Volume in 1 second (FEV1) at baseline, years 5, 8, and 10. Digit Symbol Substitution Test (DSST) and Modified Mini‐Mental exam (3MS) were used to assess processing speed and global cognitive function at years 5, 8, 10, and 11. We evaluated the association of baseline and rate of change in lung function in relation to baseline and change in cognitive performance (stratified by race) with mixed linear regression models and adjusting for demographics, comorbid health conditions and health behaviors.ResultsCompared to white participants, black participants had less education, lower socioeconomic status, and were more likely to be current smokers. Baseline mean FEV1 was 2300 ml (SD 551) and 1949 ml (SD 640) in white and black participants. During follow‐up lung function decreased by 207 ml (95%CI 199, 215) and 139 ml (95%CI 130, 148) respectively. In multivariable adjusted analyses, higher baseline lung function was associated with better cognitive test scores. One standard deviation (SD) lower baseline FEV1 was associated with worse DSST scores (by 1.50 (95%CI 0.42,2.73) and 0.60 (95%CI ‐1.0, 2.16) points in whites and blacks respectively, p for interaction = 0.04.) In both black and white participants, there were small but not significant effects of decline in lung function on subsequent cognitive performance and decline.ConclusionWhile the magnitude of the association was stronger in whites, we found worse baseline lung function was associated with worse cognitive function up to 10 years later in both black and white participants. Declines in lung and cognitive function vary by population‐level factors. For interventions, it is important to determine if these associations are biological or socially patterned.

Holocaust survivorship and late‐life cognitive performance in men with coronary heart disease

AbstractBackgroundHolocaust victims experienced extreme physical and mental stress that could lead to prolonged deficits in psychological and physiological well‐being. Indeed, some evidence demonstrates a link between Holocaust exposure and higher incidence of post‐traumatic disorder as well as for cardiovascular morbidity and its risk factors, which in turn are associated with increased brain aging. Recent evidence points to increased dementia risk among Holocaust survivors compared to the general population, however data are limited. We aimed to examine whether exposure to Holocaust conditions is associated with cognitive function and decline in old age.MethodThe study sample included 351 individuals (mean age at baseline 56.7±6.5y) with coronary heart disease (CHD) who participated in the secondary prevention Bezafibrate Infarction Prevention trial in 1990‐1997. During 2004‐2008, these participants underwent a computerized cognitive assessment (mean age 71.8±6.5y). A second cognitive assessment was performed during 2011‐2013 (mean age 77.1±6.4y). Exposure to Holocaust conditions was based on self‐report at the second assessment. Linear regression and mixed‐effect models were conducted to evaluate the associations between Holocaust survivorship and subsequent cognitive performance and rate of decline while adjusting for potential confounders.ResultOf the total sample, 45 (12.8%) survived concentration camp/ghettos, 70 (19.9%) were Holocaust survivors who escaped concentration camps/ghettos, and 236 (67.2%) were not Holocaust survivors. After adjustment for potential confounders, concentration camp/ghetto survivors had poorer global cognitive performance and poorer attention (β=‐3.90; 95% CI:‐7.11;‐0.68 and β=‐4.11; 95% CI:‐7.83;‐0.38, respectively) compared to individuals who were not exposed to Holocaust conditions. In the longitudinal analysis, participants who reported being at concentration camps/ghettoes had increased cognitive decline in global performance and executive function (β=‐0.19; 95% CI: ‐0.37;‐0.008 and β=‐0.29; 95% CI: ‐0.53;‐0.06, respectively) compared to participants who were not Holocaust survivors. Lastly, those who were Holocaust survivors but not in concentration camps/ghettos had greater decline in attention (β=‐0.11; 95% CI: ‐0.21;‐0.01). Results remained unchanged after excluding individuals with prevalent stroke and dementia and after utilizing Inverse Probability Weighting to adjust for potential selection bias.ConclusionExposure to Holocaust conditions in early‐life may be linked with poorer cognitive function and greater cognitive decline decades later in old‐adults with (CHD).

Predicting Neuropsychological Impairment in Relapsing Remitting Multiple Sclerosis: The Role of Clinical Measures, Treatment, and Neuropsychiatry Symptoms

This retrospective observational study aimed to define neuropsychological impairment (NI) profiles and determine the influence of clinical, demographic, and neuropsychiatric measures in specific cognitive domains in a cohort of relapsing-remitting multiple sclerosis (RRMS) patients. Ninety-one RRMS patients underwent a neurological examination and a brief neuropsychological assessment. Patients were classified according to the disease-modifying therapies (DMTs) received (platform or high-efficacy). Differences between groups and multiple regression analyses were performed to determine the predictive value of the assessed measures in cognitive performance. More than two-thirds of the patients showed NI. Specifically, mild to moderate NI was presented in approximately half of the participants. Paced Auditory Serial Addition Test (PASAT-3) and Symbol Digit Modalities Test (SDMT) were the most frequently impaired cognitive tests (45.3% and 41.3%, respectively) followed by phonemic verbal fluency (PVF) (27.8%). Expanded Disability Status Scale (EDSS), age, depressive symptoms, and disease duration were the best predictors of SDMT (R2=.34; p<.01), whereas disease duration, EDSS, and anxiety-state levels predicted PASAT-3 (R2=.33, p<.01). Educational level, age, EDSS, and depressive symptoms demonstrated the strongest association with PVF (R2=.31, p<.01). Our results indicated a significant prevalence of NI in RRMS patients that was not dependent on the DMT type. In addition to the meaningful working memory (PASAT-3) and information processing speed (SDMT) impairments found, PVF deficits may also be an important marker of cognitive impairment in RRMS patients. This study supports the relevance of standard clinical measures and reinforces the importance of quantifying clinical and neuropsychiatric symptoms to predict subsequent cognitive performance on a similar multiple sclerosis phenotype and disease stage.

Linked Sources of Neural Noise Contribute to Age-related Cognitive Decline.

Healthy aging is associated with a multitude of structural changes in the brain. These physical age-related changes are accompanied by increased variability in neural activity of all kinds, and this increased variability, collectively referred to as "neural noise," is argued to contribute to age-related cognitive decline. In this study, we examine the relationship between two particular types of neural noise in aging. We recorded scalp EEG from younger (20-30 years old) and older (60-70 years old) adults performing a spatial visual discrimination task. First, we used the 1/f-like exponent of the EEG power spectrum, a putative marker of neural noise, to assess baseline shifts toward a noisier state in aging. Next, we examined age-related decreases in the trial-by-trial consistency of visual stimulus processing. Finally, we examined to what extent these two age-related noise markers are related, hypothesizing that greater baseline noise would increase the variability of stimulus-evoked responses. We found that visual cortical baseline noise was higher in older adults, and the consistency of older adults' oscillatory alpha (8-12 Hz) phase responses to visual targets was also lower than that of younger adults. Crucially, older adults with the highest levels of baseline noise also had the least consistent alpha phase responses, whereas younger adults with more consistent phase responses achieved better behavioral performance. These results establish a link between tonic neural noise and stimulus-associated neural variability in aging. Moreover, they suggest that tonic age-related increases in baseline noise might diminish sensory processing and, as a result, subsequent cognitive performance.

Long-term Change in Physiological Markers and Cognitive Performance in Type 2 Diabetes: The Look AHEAD Study.

The effects of physiological improvements on cognitive function among persons with type 2 diabetes mellitus (T2DM) are not fully understood. To determine whether improvements in physiological markers (body weight, blood sugar control, and physical activity) during intensive lifestyle intervention (ILI) are associated with enhancements in cognitive function in older adults with T2DM. Multisite randomized controlled trial. Academic research centers. Participants were aged 45-76 years, with T2DM. The Action for Health in Diabetes (Look AHEAD) study, a randomized, controlled clinical trial of ILI. Two to 3 cognitive assessments were collected from 1089 participants, the first and last occurring a mean (standard deviation) of 8.6 (1.0) and 11.5 (0.7) years after enrollment. Greater improvement in blood sugar control was associated with better cognitive scores (fasting glucose and Rey Auditory Verbal Learning Test [AVLT]: P = 0.0148; fasting glucose and Digit Symbol Coding (DSC): P = 0.0360; HbA1C and DSC: P = 0.0477); but weight loss had mixed associations with cognitive scores (greater body mass index [BMI] reduction and worse AVLT overall: P = 0.0053; and greater BMI reduction and better DSC scores among those overweight but not obese at baseline: P = 0.010). Associations were strongest among those who were overweight (not obese) at baseline, and among those with a history of cardiovascular disease (CVD) at baseline. Improvements in glycemic control, but not necessarily weight status, during ILI may be associated with better subsequent cognitive performance. These associations may differ by adiposity and CVD history.

Pathways From Social Activities to Cognitive Functioning: The Role of Physical Activity and Mental Health.

Background and ObjectivesOne of the greatest challenges of old age is the risk of cognitive decline. Engagement in social activities has been identified as a possible protective factor. However, it is not yet clear what are the mechanisms underlying this association. This study aims to elucidate the pathways through which social activities impact cognitive functioning, focusing on physical activity and mental health as possible mediators.Research Design and MethodsThe study utilized 3 waves of data—the fourth, fifth, and sixth waves of the Survey of Health, Ageing and Retirement in Europe, collected in 2011, 2013, and 2015, respectively. It focused on respondents aged 60 and older. Cognitive functioning was assessed via immediate recall, delayed recall, and fluency. Social activities were measured by volunteering and attending social clubs. Data were analyzed using a structural equation modeling approach.ResultsThe results indicated a significant direct effect of social activities on cognitive functioning. That is, being socially active at baseline was related to better cognitive function 4 years later. The results also indicated the existence of indirect effects. Engaging in social activities was related to better mental health and more physical activities 2 years later, which were related to better subsequent cognitive performance.Discussion and ImplicationsThese findings highlight the mediating roles of physical activity and mental health in the effects of social activities on cognitive functioning. Understanding these mechanisms can help optimize social activity interventions to improve cognitive aging.

Early Inflammatory Signatures Predict Subsequent Cognition in Long-Term Virally Suppressed Women With HIV.

Immunologic function is an important determinant of cognition. Here we examined the contribution of early immune signatures to cognitive performance among HIV-infected, virally suppressed women (HIV+VS) and in HIV-uninfected (HIV-) women. Specifically, we measured serum inflammatory markers, developed combinatory immune signatures, and evaluated their associations with cognition. Forty-nine HIV+VS women in the Women’s Interagency HIV Study (WIHS) who achieved viral suppression shortly after effective antiretroviral therapy (ART) initiation, and 56 matched HIV− women were selected. Forty-two serum inflammatory markers were measured within 2 years of effective ART initiation for HIV+VS women, and at an initial timepoint for HIV− women. The same inflammatory markers were also measured approximately 1, 7, and 12 years later for all women. Of the 105 women with complete immune data, 83 (34 HIV+VS, 49 HIV−) also had cognitive data available 12 years later at ≥1 time points (median = 3.1). We searched for combinatory immune signatures by adapting a dynamic matrix factorization analytic method that builds upon Tucker decomposition followed by Ingenuity® Pathway Analysis to facilitate data interpretation. Seven combinatory immune signatures emerged based on the Frobenius residual. Three signatures were common between HIV+VS and HIV− women, while four signatures were unique. These inflammatory signatures predicted subsequent cognitive performance in both groups using mixed-effects modeling, but more domain-specific associations were significant in HIV+VS than HIV− women. Leukocyte influx into brain was a major contributor to cognitive function in HIV+VS women, while T cell exhaustion, inflammatory response indicative of depressive/psychiatric disorders, microglial activity, and cytokine signaling predicted both global and domain-specific performance for HIV− women. Our findings suggest that immune signatures may be useful diagnostic, prognostic, and immunotherapeutic targets predictive of subsequent cognitive performance. Importantly, they also provide insight into common and distinct inflammatory mechanisms underlying cognition in HIV− and HIV+VS women.

Abstract P422: Nonalcoholic Fatty Liver Disease and Cognitive Function in Middle-aged Adults: The CARDIA Study

Background: Nonalcoholic fatty liver disease (NAFLD) is an obesity-related condition associated with cardiovascular disease (CVD) and its major risk factors. The latter have been linked to accelerated cognitive decline. Whether NAFLD is associated with decreased cognitive performance in midlife remains uncertain. Methods: Participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study with CT-measured NAFLD and cognitive function assessment at year 25 (2010-2011; n=2,835) were included. Cognitive function was reassessed at year 30 (2015-2016; n=2,388). NAFLD was defined according to liver attenuation and categorized into 3 groups: none [&gt;51 Hounsfield Units (HU)], probable (&gt;40-51 HU), and definite (≤40 HU). Cognitive tests, including the Digit Symbol Substitution Test (DSST), Rey Auditory Verbal Learning Test (RAVLT), and Stroop were analyzed with standardized z scores. Linear models were constructed to examine (a) the cross-sectional association between NAFLD and cognitive scores (year 25) and (b) the predictive role of NAFLD in subsequent (year 30) cognitive scores. Results: The mean age at baseline was 50.1 (SD, 3.6) years (58% women; 48% blacks), with 398 (14%) and 286 (10%) having probable and definite NAFLD, respectively. In unadjusted models, an inverse association was shown between NAFLD and all cognitive tests. For DSST ( P interaction =.047) and RAVLT ( P interaction =.033), the association was stronger in whites than blacks. The association was attenuated after age and sex adjustment, and practically eliminated after further adjustment for sociodemographic and CVD risk factors (Table). NAFLD was not predictive of subsequent cognitive performance in any of the measures once baseline scores were adjusted for (all P &gt;.10). Using liver attenuation as a continuous variable yielded similar results. Conclusion: Among middle-aged adults, an inverse association of NAFLD with cognitive function -evident in whites only- was attenuated by sociodemographic and CVD risk factor adjustment.

Neurodevelopmental shifts in learned value transfer on cognitive control during adolescence

Value-associated cues in the environment often enhance subsequent goal-directed behaviors in adults, a phenomenon supported by the integration of motivational and cognitive neural systems. Given that the interactions among these systems change throughout adolescence, we tested when the beneficial effects of value associations on subsequent cognitive control performance emerge during adolescence. Participants (N = 81) aged 13–20 completed a reinforcement learning task with four cue-incentive pairings that could yield high gain, low gain, high loss, or low loss outcomes. Next, participants completed a Go/NoGo task during fMRI where the NoGo targets comprised the previously learned cues, which tested how prior value associations influence cognitive control performance. Improved accuracy for previously learned high gain relative to low gain cues emerged with age. Older adolescents exhibited enhanced recruitment of the dorsal striatum and ventrolateral prefrontal cortex during cognitive control execution to previously learned high gain relative to low gain cues. Older adolescents also expressed increased coupling between the dorsal striatum and dorsolateral prefrontal cortex for high gain cues, whereas younger adolescents expressed increased coupling between the striatum and ventromedial prefrontal cortex. These findings reveal that learned high value cue-incentive associations enhance cognitive control in late adolescence in parallel with value-selective recruitment of corticostriatal systems.