Inflammatory Biomarkers and Sex Hormones Interact to Predict Ecologically-Assessed Cognitive Performance

Inflammatory biomarkers and sex hormones have been investigated as independent risk and resilience factors for cognitive decline in older adults. Many sex hormones are anti-inflammatory and there is emerging evidence that sex hormones may buffer the risk for cognitive decline associated with higher inflammation. However, few studies have included concurrent examination of inflammation and sex hormones in studies of cognitive performance and cognitive aging. A diverse sample of older adults (N = 245; 65% female, 42% Black, 13% Hispanic; mean age = 76.8 years) had blood drawn before and after a two-week measurement burst that included three cognitive tests (6x per day) assessing working spatial memory, perceptual speed, and feature binding. Testosterone, estradiol, estrone, and six basal cytokine concentrations were quantified. Composite scores of basal inflammation were calculated. Multilevel modeling indicated that heightened inflammation related to poorer spatial working memory performance (B = 0.213, 95%CI[0.11, 0.414], p = .040). In addition, sex hormones moderated the association of cytokine concentration with perceptual speed (e.g., basal cytokines x testosterone: B = 0.13, [-0.24, -0.03], p = 0.013; similar effects evident for estrogens). Decomposition these interactions revealed that heightened inflammation predicted poorer performance, but only among individuals with lower sex-hormone concentrations. This study provides evidence of immune and hormonal-by-immune associations with performance in two cognitive domains in older adults. Examining the functional crosstalk between immune and sex hormone functioning will improve understanding of risk and resilience factors related to cognitive performance and help predict cognitive decline in older adults.

Serum metabolomic biomarkers of perceptual speed in cognitively normal and mildly impaired subjects with fasting state stratification

Cognitive decline is associated with both normal aging and early pathologies leading to dementia. Here we used quantitative profiling of metabolites involved in the regulation of inflammation, vascular function, neuronal function and energy metabolism, including oxylipins, endocannabinoids, bile acids, and steroid hormones to identify metabolic biomarkers of mild cognitive impairment (MCI). Serum samples (n = 212) were obtained from subjects with or without MCI opportunistically collected with incomplete fasting state information. To maximize power and stratify the analysis of metabolite associations with MCI by the fasting state, we developed an algorithm to predict subject fasting state when unknown (n = 73). In non-fasted subjects, linoleic acid and palmitoleoyl ethanolamide levels were positively associated with perceptual speed. In fasted subjects, soluble epoxide hydrolase activity and tauro-alpha-muricholic acid levels were negatively associated with perceptual speed. Other cognitive domains showed associations with bile acid metabolism, but only in the non-fasted state. Importantly, this study shows unique associations between serum metabolites and cognitive function in the fasted and non-fasted states and provides a fasting state prediction algorithm based on measurable metabolites.

Comparing Perceptual Speed Between Educational Contexts

Perceptual speed is a basic component of cognitive functioning that allows people to efficiently process novel visual stimuli and quickly react to them. In educational studies, tests measuring perceptual speed are frequently developed using students from regular schools without considering students with special educational needs. Therefore, it is unclear whether these instruments allow valid comparisons between different school tracks. The present study on N = 3,312 students from the National Educational Panel Study evaluated differential item functioning (DIF) of a short test of perceptual speed between four school tracks in Germany (special, basic, intermediate, and upper secondary schools). Bayesian Rasch Poisson counts modeling identified negligible DIF that did not systematically disadvantage specific students. Moreover, the test reliabilities were comparable between school tracks. These results highlight that perceptual speed can be comparably measured in special schools, thus enabling educational researchers to study schooling effects in the German educational system.

Cognitive Efficiency and Fitness-to-Drive along the Lifespan: The Mediation Effect of Visuospatial Transformations

The way people represent and transform visuospatial information affects everyday activities including driving behavior. Mental rotation and perspective taking have recently been found to predict cognitive prerequisites for fitness-to-drive (FtD). We argue that the relationship between general cognitive status and FtD is mediated by spatial transformation skills. Here, we investigated the performance in the Mental Rotation Test (MRT) and the Perspective-Taking Test (PT) of 175 male active drivers (aged from 18 to 91 years), by administering the Montreal Cognitive Assessment (MoCA) to measure their global cognitive functioning. All participants were submitted to a computerized driving assessment measuring resilience of attention (DT), reaction speed (RS), motor speed (MS), and perceptual speed (ATAVT). Significant results were found for the effect of global cognitive functioning on perceptual speed through the full mediation of both mental rotation and perspective-taking skills. The indirect effect of global cognitive functioning through mental rotation was only found to significantly predict resilience of attention whereas the indirect effect mediated by perspective taking only was found to significantly predict perceptual speed. Finally, the negative effect of age was found on each driving measure. Results presented here, which are limited to male drivers, suggest that general cognitive efficiency is linked to spatial mental transformation skills and, in turn, to driving-related cognitive tasks, contributing to fitness-to-drive in the lifespan.

Metabolic syndrome is associated with poor cognition: a population-based study of 70-year-olds without dementia

Background Individual conditions of metabolic syndrome (MetS) have been related to dementia, however, their combined impact on the preclinical stage is unknown. We investigated the associations between MetS and domain-specific cognitive function as well as the role of sociodemographic, cardiovascular, and genetic factors. Methods Within the Gothenburg H70 Birth Cohort Study-Birth cohort 1944, 1131 dementia-free participants (aged 70 years) were examined during 2014-2016. MetS (central obesity plus at least two factors [reduced HDL-cholesterol, elevated triglycerides, blood pressure, or blood glucose]) was identified according to the International Diabetes Federation criteria. Five cognitive domains (memory, attention/perceptual speed, executive function, verbal fluency, visuospatial abilities) were generated after z-standardizing raw scores from ten neuropsychological tests. Education, heart disease, claudication (indicating peripheral atherosclerosis), and apolipoprotein (APOE) genotype were ascertained by trained staff. Data were analyzed with linear regression models. Results Overall, 618 participants (55%) had MetS. In multi-adjusted linear regressions, MetS was related to poorer performance in attention/perceptual speed (β -0.14 [95% CI -0.25, -0.02]), executive function (β -0.12 [95% CI -0.23, -0.01]), and verbal fluency (β -0.19 [95% CI -0.30, -0.08]). These associations were present only among individuals who did not carry any APOE-ε4 allele or were highly educated. However, among those with MetS, high education was related to better cognitive performance. MetS together with comorbid heart disease or claudication was associated with even worse cognitive performance than each alone. Conclusions MetS is associated with poor attention/perceptual speed, executive function, and verbal fluency performance. Education, APOE-ε4 allele, and comorbid cardiovascular disease influenced the observed associations.

Cognitive and brain cytokine profile of non-demented individuals with cerebral amyloid-beta deposition

Background Brain inflammation has been increasingly associated with early amyloid accumulation in Alzheimer’s disease models; however, evidence of its occurrence in humans remains scarce. To elucidate whether amyloid deposition is associated with neuroinflammation and cognitive deficits, we studied brain inflammatory cytokine expression and cognitive decline in non-demented elderly individuals with and without cerebral amyloid-beta deposition. Methods Global cognition, episodic, working, and semantic memory, perceptual speed, visuospatial ability, and longitudinal decline (5.7 ± 3.6 years) in each cognitive domain were compared between elderly individuals (66–79 years) with and without cerebral amyloid-beta deposition. The expression of 20 inflammatory cytokines was analyzed in frozen temporal, parietal, and frontal cortices and compared between older individuals with and without amyloid-beta deposition in each brain region. Correlation analyses were performed to analyze associations between amyloid-beta load, cytokine expression, and cognitive decline. Results Individuals with cortical amyloid-beta deposition displayed deficits and a faster rate of cognitive decline in perceptual speed as compared with those individuals without amyloid-beta. This decline was positively associated with cortical amyloid-beta levels. Elderly individuals with amyloid-beta deposition had higher levels of IL-1β, IL-6, and eotaxin-3 in the temporal cortex accompanied by an increase in MCP-1 and IL-1β in the parietal cortex and a trend towards higher levels of IL-1β and MCP-1 in the frontal cortex as compared with age-matched amyloid-free individuals. Brain IL-1β levels displayed a positive association with cortical amyloid burden in each brain region. Finally, differential cytokine expression in each cortical region was associated with cognitive decline. Conclusions Elderly individuals with amyloid-beta neuropathology but no symptomatic manifestation of dementia, exhibit cognitive decline and increased brain cytokine expression. Such observations suggest that increased cytokine expression might be an early event in the Alzheimer’s continuum.

A New Look at Retest Learning in Older Adults: Learning in the Absence of Item-Specific Effects

We investigated retest learning (i.e., performance improvement through retest practice) in the absence of itemspecific effects (i.e., learning through memorizing or becoming familiar with specific items) with older adults. Thirty-one older adults (ages 60 – 82 years, M = 71.10, SD = 6.27) participated in an eight-session self-guided retest program. To eliminate item-specific effects, parallel versions of representative psychometric measures for Inductive Reasoning, Perceptual Speed, and Visual Attention were developed and administered across retest sessions. The results showed substantial non-item-specific retest learning, even controlling for anxiety, suggesting that retest learning in older adults can occur at a more conceptual level.

A New Look at Retest Learning in Older Adults: Learning in the Absence of Item-Specific Effects

We investigated retest learning (i.e., performance improvement through retest practice) in the absence of itemspecific effects (i.e., learning through memorizing or becoming familiar with specific items) with older adults. Thirty-one older adults (ages 60 – 82 years, M = 71.10, SD = 6.27) participated in an eight-session self-guided retest program. To eliminate item-specific effects, parallel versions of representative psychometric measures for Inductive Reasoning, Perceptual Speed, and Visual Attention were developed and administered across retest sessions. The results showed substantial non-item-specific retest learning, even controlling for anxiety, suggesting that retest learning in older adults can occur at a more conceptual level.

Free-living standing activity as assessed by seismic accelerometers and cognitive function in community-dwelling older adults: The MIND trial

Background Few older adults are able to achieve recommended levels of moderate-vigorous physical activity despite known cognitive benefits. Alternatively, less intense activities such as standing can be easily integrated into daily life. No existing study has examined the impact of free-living standing activity during daily life as measured by a device on cognition in older adults. Our purpose was to examine the association between free-living standing activity and cognitive function in cognitively healthy older adults. Methods Participants were 98 adult participants aged 65 years or older from the ongoing MIND trial (NCT02817074) without diagnoses or symptoms of mild cognitive impairment or dementia. Linear regression analyses tested cross-sectional associations between standing activity (duration and intensity from the MoveMonitor+ accelerometer/gyroscope) and cognition (4 cognitive domains constructed from 12 cognitive performance tests). Results Participants were on average 69.7 years old (SD = 3.7), 69.4% women, and 73.5% had a college degree or higher. Higher mean intensity of standing activity was significantly associated with higher levels of perceptual speed when adjusting for age, gender, and education level. Each log unit increase in standing activity intensity was associated with 0.72 units higher of perceptual speed (p=.023). When we additionally adjusted for cognitive activities and moderate-vigorous physical activity, and then also for body mass index, depressive symptoms, prescription medication use, and device wear time, the positive association remained. Conclusions These findings should be further explored in longitudinal analyses and interventions for cognition that incorporate small changes to free-living activity in addition to promoting moderate-vigorous physical activity.