Late-life Cognition Research Articles

PROTECT Norge: Online assessment of potentially modifiable risk factors for dementia on cognitive performance in a Norwegian ageing cohort

AbstractBackgroundPROTECT Norge, a fully digital platform, aims to help determine the role of defined genetic, lifestyle and environmental factors on cognition, health and wellbeing in people 50+. Annual questionnaires on demographics, medical conditions and medication use, mental health and lifestyle are completed online. The current study aims to assess whether potentially modifiable risk factors for dementia as presented by the Lancet Commission by Livingston and colleagues (2020) are related to cognitive performance in cognitively healthy people aged 50 and above.MethodA total of 2349 participants completed the PROTECT Cognitive Test System, an online cognitive battery containing six tasks which assess visual episodic memory, spatial and working memory, verbal reasoning, visual attention and task switching. The following risk factors were included in our analysis: physical activity, alcohol use, smoking, social isolation, age, BMI, education, depression, high blood pressure, head trauma and hearing loss. Multiple hierarchical regression analysis was performed. Separate analyses were conducted with the average performance across three sessions for each of the six cognitive measures as the dependent variable. Independent variables were included into the model in a hierarchy based on known risk factors for dementia.ResultResults show that age was associated with reduced cognitive performance for all tasks (p<0.001). In addition, for the digit span test, the risk factors were found to influence the test score were: smoking and previously diagnosed stroke. For the paired associate learning task, the only additional significant risk factor appeared to be gender, with male gender associated with poorer performance. For the grammatical reasoning task, the risk factors associated with lower scores were lower education, older age and smoking. For the switching Stroop test, the risk factors of lower scores were older age, smoking and previously diagnosed depression. For Trail‐making B test, the risk factors of lower scores were age, stroke and the history of heart disease.ConclusionThese preliminary results may improve our understanding of potentially modifiable risk factors for dementia and could inform the design and delivery of interventional trials as a mean to protect cognition in later life and to prevent or slow progression of cognitive decline.

Life course engagement in enriching activities: When and how does it matter for cognitive aging?

Growing evidence suggests that participation in enriching activities (physical, social, and mental) across the life course is beneficial for cognitive functioning in older age. However, few studies have examined the effects of enrichment across the entire life course within the same participants. Using 2,931 participants in the Health and Retirement Study, we linked self-report data from later life and retrospective self-report data from early life and midlife to cognitive performance after Age 65. We categorized participants as having either high (top ∼25%) or average to low (bottom ∼75%) level of enrichment during each life period. Thus, eight groups were identified that reflected unique patterns of enrichment during early, mid, and later life (e.g., high-high-high). Using growth curve modeling, we found that life course enrichment patterns predicted both cognitive functioning and the rate of cognitive decline across five time points spanning 8 years (Aim 1). Groups with high enrichment during at least one life period had higher performance and slower decline in older age, compared to those who had average to low levels of enrichment throughout all three life periods. We also found that high enrichment during each life period independently predicted better cognitive performance and that high enrichment during early and later life also predicted slower cognitive decline (Aim 2). These findings support the idea that high enrichment is beneficial for cognition in later life and that the effects are long-lasting, even when individuals are inconsistent in enrichment engagement throughout the entire life course. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Availability of healthy foods, fruit and vegetable consumption, and cognition among urban older adults

Background. Although prior studies have examined the associations between neighborhood characteristics and cognitive health, little is known about whether local food environments, which are critical for individuals’ daily living, are associated with late-life cognition. Further, little is known about how local environments may shape individuals’ health-related behaviors and impact cognitive health. The aim of this study is to examine whether objective and subjective measures of healthy food availability are associated with ambulatory cognitive performance and whether behavioral and cardiovascular factors mediate these associations among urban older adults.Methods. The sample consisted of systematically recruited, community-dwelling older adults (N = 315, mean age = 77.5, range = 70–91) from the Einstein Aging Study. Objective availability of healthy foods was defined as density of healthy food stores. Subjective availability of healthy foods and fruit/vegetable consumption were assessed using self-reported questionnaires. Cognitive performance was assessed using smartphone-administered cognitive tasks that measured processing speed, short-term memory binding, and spatial working memory performance 6 times a day for 14 days.Results. Results from multilevel models showed that subjective availability of healthy foods, but not objective food environments, was associated with better processing speed (estimate= -0.176, p = .003) and more accurate memory binding performance (estimate = 0.042, p = .012). Further, 14~16% of the effects of subjective availability of healthy foods on cognition were mediated through fruit and vegetable consumption.Conclusions. Local food environments seem to be important for individuals’ dietary behavior and cognitive health. Specifically, subjective measures of food environments may better reflect individuals’ experiences regarding their local food environments not captured by objective measures. Future policy and intervention strategies will need to include both objective and subjective food environment measures in identifying impactful target for intervention and evaluating effectiveness of policy changes.

Associations Between Midlife Menopausal Hormone Therapy Use, Incident Diabetes, and Late Life Memory in the Wisconsin Longitudinal Study.

Prior research suggests a link between menopausal hormone therapy (MHT) use, memory function, and diabetes risk. The menopausal transition is a modifiable period to enhance long-term health and cognitive outcomes, although studies have been limited by short follow-up periods precluding a solid understanding of the lasting effects of MHT use on cognition. We examined the effects of midlife MHT use on subsequent diabetes incidence and late life memory performance in a large, same-aged, population-based cohort. We hypothesized that the beneficial effects of MHT use on late life cognition would be partially mediated by reduced diabetes risk. 1,792 women from the Wisconsin Longitudinal Study (WLS) were included in analysis. We employed hierarchical linear regression, Cox regression, and causal mediation models to test the associations between MHT history, diabetes incidence, and late life cognitive performance. 1,088/1,792 women (60.7%) reported a history of midlife MHT use and 220/1,792 (12.3%) reported a history of diabetes. MHT use history was associated with better late life immediate recall (but not delayed recall), as well as a reduced risk of diabetes with protracted time to onset. Causal mediation models suggest that the beneficial effect of midlife MHT use on late life immediate recall were at least partially mediated by diabetes risk. Our data support a beneficial effect of MHT use on late life immediate recall (learning) that was partially mediated by protection against diabetes risk, supporting MHT use in midlife as protective against late life cognitive decline and adverse health outcomes.

The role of fruit and vegetables in sustaining healthy cognitive function - evidence and issues.

Modifiable lifestyle factors, such as improved nutrition, are crucial in maintaining cognitive health in older age. Fruit and vegetables represent healthy and sustainable sources of nutrients with the potential to prevent age-related cognitive decline. The aim of this review is to synthesise the available evidence, from epidemiological and randomised controlled trials (RCT), regarding the role of fruit and vegetables in sustaining healthy cognitive function. Epidemiological studies of combined fruit and vegetable intake suggest that increased consumption may sustain cognition in later life. The evidence appears to be stronger for an association between vegetables and cognition, particularly for green leafy and cruciferous vegetables. Specific benefits shown for berries, citrus fruits, avocado and nuts suggest fruit is worthy of further investigation in relation to cognition. Data from RCT indicate benefits to differing aspects of cognition following citrus and berry fruits, cocoa and peanuts, but the data are limited and there are a lack of studies exploring effects of vegetables. There is growing evidence for an association between fruit and vegetable intake and cognitive function, but this is not always consistent and the data from RCT are limited. Issues in previous research are highlighted, such as strict exclusion criteria, absence of baseline nutritional status data and lack of consideration of individual differences, which may explain the weaker findings from RCT. Inclusion of those most at risk for cognitive decline is recommended in future nutrition and cognition research.

The Role of Brain Integrity in the Association between Occupational Complexity and Cognitive Performance in Subjects with Increased Risk of Dementia

Introduction: Mechanisms underlying the positive association between occupational mental demands and late-life cognition are poorly understood. The objective of this study was to assess whether the association between occupational complexity and cognition is related to and moderated by brain integrity in individuals at risk for dementia. Brain integrity was appraised throughout structural measures (magnetic resonance imaging, MRI) and amyloid accumulation (Pittsburgh compound B (PiB)-positron emission tomography, PiB-PET). Methods: Participants from the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) neuroimaging sample – MRI (N = 126), PiB-PET (N = 41) – were included in a post hoc cross-sectional analysis. Neuroimaging parameters comprised the Alzheimer’s disease signature (ADS) cortical thickness (FreeSurfer 5.3), medial temporal atrophy (MTA), and amyloid accumulation (PiB-PET). Cognition was assessed using the neuropsychological test battery. Occupational complexity with data, people, and substantive complexity were classified through the Dictionary of Occupational Titles. Linear regression models included cognition as dependent variable, and occupational complexity, measures of brain integrity, and their interaction terms as predictors. Results: Occupational complexity with data and substantive complexity were associated with better cognition (overall cognition, executive function) when adjusting for ADS and MTA (independent association). Significant interaction effects between occupational complexity and brain integrity were also found, indicating that, for some indicators of brain integrity and cognition (e.g., overall cognition, processing speed), the positive association between occupational complexity and cognition occurred only among persons with higher brain integrity (moderated association). Conclusions: Among individuals at risk for dementia, occupational complexity does not seem to contribute toward resilience against neuropathology. These exploratory findings require validation in larger populations.

10 Chronic cadmium exposure is associated with Alzheimer’s Disease-related mortality in adults over age 60 in a representative US sample

OBJECTIVES/GOALS: Cadmium is a widespread neurotoxic metal pollutant; however prior study results of Cd and later-life cognition are mixed. We investigated association of urinary cadmium on Alzheimer’s Disease (AD) mortality risk, accounting for key co-pollutants smoking and lead, in the presence of competing risks. METHODS/STUDY POPULATION: We included 5692 persons, 60 years old from the 1998-2018 National Health and Nutrition Examination Survey. Underlying cause of death was determined via linked 1999-2019 National Death Index data. Urinary cadmium (UCD) reflects prolonged exposure and was adjusted for creatinine. We used multiple imputation (5 iterations) to recapture substantial model observation drop-out (N=782). We used three Cox proportional hazard models to estimate hazard ratios (HR) and 95% confidence interval (CI) per unit increase in UCD and time to AD mortality: a competing risks model, a survey-weighted model, and a baseline model including neither, all adjusted for demographic characteristics, lead, and smoking. RESULTS/ANTICIPATED RESULTS: Follow-up ranged from 0 to 20.8 years (mean 8.2 years), with a total of 1,987 individuals deceased (14,232 person-years at-risk), including 88 individuals dying from AD. Mean UCD was 0.50 μg/g creatinine (standard error=0.01). In baseline and survey-weighted models fully adjusted for NHANES cycle, poverty income ratio, age, race/ethnicity, sex, marital status, education, smoking status, and blood lead levels, a per unit increase in UCD was associated with approximately twice the rate of AD mortality (baseline model HR: 1.92, 95% CI: 1.28, 2.89; survey-weighted model HR: 2.08, 95% CI: 1.42, 3.06). In the competing risks model, this association was attenuated (HR: 1.58, 95% CI 1.06 2.36). DISCUSSION/SIGNIFICANCE: Our study finds chronic cadmium exposure associated with AD mortality even after accounting for competing risks of AD mortality and confounding effects of cigarette smoking and lead exposure, strengthening the evidence that long-term cadmium exposure adversely affects later-life cognitive health.

High school quality is associated with cognition 58 years later.

We leveraged a unique school-based longitudinal cohort-the Project Talent Aging Study-to examine whether attending higher quality schools is associated with cognitive performance among older adults in the United States (mean age=74.8). Participants (n=2,289) completed telephone neurocognitive testing. Six indicators of high school quality, reported by principals at the time of schooling, were predictors of respondents' cognitive function 58 years later. To account for school-clustering, multilevel linear and logistic models were applied. We found that attending schools with a higher number of teachers with graduate training was the clearest predictor of later-life cognition, and school quality mattered especially for language abilities. Importantly, Black respondents (n=239; 10.5 percentage) were disproportionately exposed to low quality high schools. Therefore, increased investment in schools, especially those that serve Black children, could be a powerful strategy to improve later life cognitive health among older adults in the United States.

Lifelong Cognitive Reserve, Imaging Markers of Brain Aging, and Cognitive Function in Dementia-Free Rural Older Adults: A Population-Based Study.

Cognitive reserve (CR) partly explains cognitive variability in the presence of pathological brain aging. We investigated the interplay of lifelong CR with age, sex, and brain aging markers in cognitive phenotypes among older adults with very limited education. This population-based cross-sectional study included 179 dementia-free participants (age ≥65 years; 39.7% women; 67.0% had no or elementary education) examined in 2014-2016. We assessed lacunes and volumes of hippocampus, ventricles, grey matter, white matter (WM), and white matter hyperintensities. Lifelong CR score was generated from six lifespan intellectual factors (e.g., education and social support). We used Mini-Mental State Examination (MMSE) score to assess cognition and Petersen's criteria to define mild cognitive impairment (MCI). Data were analyzed using general linear and logistic models. The association of higher lifelong CR score (range: -4.0-5.0) with higher MMSE score was stronger in women (multivariable-adjusted β-coefficient and 95% CI: 1.75;0.99-2.51) than in men (0.68;0.33-1.03) (pinteraction = 0.006). The association of higher CR with MCI (multivariable-adjusted odds ratio and 95% CI: 0.77;0.60-0.99) did not vary by age or sex. Among participants with low CR (<1.4[median]), greater hippocampal and WM volumes were related to higher MMSE scores with multivariable-adjusted β-coefficients being 1.77(0.41-3.13) and 0.44(0.15-0.74); the corresponding figures in those with high CR were 0.15(-0.76-1.07) and -0.17(-0.41-0.07) (pinteraction <0.01). There was no statistical interaction of CR with MRI markers on MCI. Greater lifelong CR capacity is associated with better late-life cognition among people with limited education, possibly by compensating for impact of neurodegeneration.

Effects of early-life environment and adulthood SES on cognitive change in a multiethnic cohort.

Early-life socioeconomic status (SES) and adversity are associated with late-life cognition and risk of dementia. We examined the association between early-life SES and adversity and late-life cross-sectional cognitive outcomes as well as global cognitive decline, hypothesizing that adulthood SES would mediate these associations. Our sample (N = 837) was a racially and ethnically diverse cohort of non-Hispanic/Latino White (48%), Black (27%), and Hispanic/Latino (19%) participants from Northern California. Participant addresses were geocoded to the level of the census tract, and US Census Tract 2010 variables (e.g., percent with high school diploma) were extracted and combined to create a neighborhood SES composite. We used multilevel latent variable models to estimate early-life (e.g., parental education, whether participant ever went hungry) and adult (participant's education, main occupation) SES factors and their associations with cross-sectional and longitudinal cognitive outcomes of episodic memory, semantic memory, executive function, and spatial ability. Child and adult factors were strongly related to domain-specific cognitive intercepts (0.20-0.48 SD per SD of SES factor); in contrast, SES factors were not related to global cognitive change (0.001-0.01 SD per year per SD of SES factor). Adulthood SES mediated a large percentage (68-75%) of the total early-life effect on cognition. Early-life sociocontextual factors are more strongly associated with cross-sectional late-life cognitive performance compared to cognitive change; this effect is largely mediated through associations with adulthood SES.

Association of Hypertensive Disorders of Pregnancy With Cognition in Later Life.

Studies of hypertensive disorders of pregnancy (HDP), including gestational or chronic hypertension (GH/CH) and preeclampsia/eclampsia (PE/E), suggest associations with early-life and mid-life cognition but have been limited by self-report or use of diagnostic codes, exclusion of nulliparous women, and lack of measurement of cognition in later life. We examined the effects of any HDP, GH/CH, PE/E, and nulliparity on cognition in later life. Participants included 2,239 women (median age 73) enrolled in the Mayo Clinic Study of Aging with medical record-abstracted pregnancy information. A cognitive battery of 9 tests was conducted every 15 months. Global cognitive and domain-specific z scores (memory, executive/attention, visuospatial, and language) were outcomes. Linear mixed-effect models evaluated associations between pregnancy history (all normotensive, any HPD, HPD subtype [GH/CH, PE/E], or nulliparous) and cognitive decline, adjusting for age and education. Additional models adjusted for APOE, smoking, hypertension, dyslipidemia, body mass index (BMI), diabetes, stroke, and heart disease. Interactions between pregnancy history and age or education on cognitive performance were examined. Of the 2,239 women, 1,854 (82.8%) had at least 1 pregnancy (1,607 all normotensive, 100 GH/CH, and 147 PE/E); 385 (17.2%) were nulliparous. Cognitive performance did not cross-sectionally differ for women with a history of any HDP, GH/CH, or PE/E vs women with a history of all normotensive pregnancies; women who were nulliparous had lower global and domain-specific cognition (all p < 0.05) in age- and education-adjusted models. There was an interaction (p = 0.015) between nulliparity and education such that the lower cognitive performance was most pronounced among nulliparous women with ≤12 years of education (beta = -0.42, p < 0.001) vs 12 + years (b = -0.11, p = 0.049). Longitudinally, women with any HDP had greater declines in global cognition and attention/executive z scores compared with women with all normotensive pregnancies. When stratified by HDP type, only women with PE/E had greater declines in global cognition (beta = -0.04, p < 0.001), language (beta = -0.03, p = 0.001), and attention (beta = -0.04, p < 0.001) z scores. Adjustment for vascular risk factors, BMI, smoking, and APOE did not attenuate results. Women with a history of HDP, especially PE/E, are at greater risk of cognitive decline in later life.

Timing of physical activity across adulthood on later-life cognition: 30 years follow-up in the 1946 British birth cohort

BackgroundTo assess how timing, frequency and maintenance of being physically active, spanning over 30 years in adulthood, is associated with later-life cognitive function.MethodsParticipants (n=1417, 53% female) were from the prospective...

Mechanisms of Healthy Aging: An Integrated Neurobiological Perspective on Mood and Cognitive Function

Neurobiological approaches to healthy aging can protect against declines in cognitive function and mood disturbances in older adults. This symposium will focus on health-based mechanisms associated with mood and cognition in late life using an integrated micro- and macro-level perspective. Mechanistic pathways and predictors of healthy aging will be discussed across multiple levels of analysis (genetic, molecular, systems-level neurocircuitry, and behavioral). We will discuss these mechanisms of aging and late-life depression cross-sectionally and in the context of non-pharmacological interventions to identify potential pathways for more personalized treatments.This symposium will take a unique approach to classifying the neurobiology of healthy aging. Dr. Swathi Gujral will present a large study of 108 community-dwelling older adults who completed an exercise intervention and discuss differences in stress and emotional health as a function of exercise condition and APOE e4 carrier status. Dr. Julie Dumas will discuss functioning of the nicotinic cholinergic system in older adults and will present effects of nicotinic stimulation and blockade on brain activation and working memory performance in older adults with and without subjective cognitive decline. Dr. Lauren Oberlin will present neuroimaging features of small vessel disease (SVD) in older adults with and without depression and discuss the association between white matter abnormalities and cognitive decline in late life. Dr. Lindsay Victoria will present neural correlates of negative cognitive bias in late-life depression and their impact on treatment response to psychotherapy in depressed older adults.The unifying goal of these presentations is to characterize mechanistic pathways to precisely target cognitive deficits, improve mood, and promote healthy aging. With an emphasis on individual differences, we will examine predictors of change across a range of domains impacted in aging and late-life depression, including stress, working memory, and executive function. This mechanistic approach has important implications for the development of personalized interventions that emphasize health-based approaches to mood and cognitive function in older adults.

Fingolimod prevents cognitive impairments following hypoxia-induced neonatal seizure by ameliorating the inflammation and oxidative stress in male and female juvenile rats

Hypoxia-induced neonatal seizure (HINS) is associated with cognitive disorders in later life. Since the neuroinflammation following HINS leads to these deleterious effects, in the current study, the short-term outcomes of Fingolimod (FTY720) treatment as an anti-inflammatory agent was investigated in the rat model of HINS. Seizures were induced in postnatal day (P10) by exposure to 5 % O2 for 15 min. Forty-five minutes after the onset of hypoxia, pups received FTY720 (0.3 mg/kg) or normal saline for 12 consecutive days. Then, behavioral functions of the rats were assessed by commonly used tests. Subsequently, hippocampal tissue sampling at P22-P23 was done for biochemical assessments and real-time PCR. The results showed that FTY720 prevents cognitive impairments and related reduction of malondialehyde (MDA) concentration in the hippocampus of both male and female hypoxic animals. Furthermore, FTY720 administration following HINS could not prevent the decreased brain-derived neurotrophic factor (BDNF) concentration, increased nitric oxide (NO) level and decreased Interleukin-4 (IL-4) gene expression in the hippocampus of both male and female hypoxic animals. Interestingly, FTY720 showed significant interaction with sex in hippocampal Tumor necrosis factor alpha (TNF-α) gene expression and BDNF concentration. Taken together, these results suggest that FTY720 administration in the lactation period can prevent the deleterious effects of HINS on cognition in later life by ameliorating inflammation and oxidative stress in the hippocampus of both male and female juvenile rats.

Direct Effect of Life-Course Socioeconomic Status on Late-Life Cognition and Cognitive Decline in the Rush Memory and Aging Project.

The role of socioeconomic status (SES) across the life course in late-life cognition is unclear. We tested the hypotheses that: 1) High SES in childhood, young adulthood, midlife, and late life have independent causal effects on higher cognition level and slower cognitive decline; 2) Compared with stable low SES (referent), stable high SES has the largest estimated effect for higher cognition level and slower decline among life-course SES combinations. The Rush Memory and Aging Project enrolled 1,940 dementia-free older adults in northeastern Illinois (1997-2018). We used inverse probability-weighted marginal structural models to estimate the joint and independent effect of each life-course SES on global and domain-specific cognition. A total of 1,746 participants had, on average, 6 years of follow-up. High SES at each life-course stage starting in young adulthood had a protective estimated effect on global and domain-specific cognition intercepts. Compared with consistently low SES, consistently high SES (β= 0.64, 95% confidence interval: 0.48, 0.93) and high SES beyond childhood (β= 0.64, 95% confidence interval: 0.47, 0.83) had the largest benefit for global cognition intercepts. None of the life-course SES measures influenced rate of global or domain-specific decline. Additional understanding of life-course SES components influencing cognitive level is warranted.

Evaluating interpersonal discrimination and depressive symptoms as partial mediators of the effects of education on cognition: Evidence from the Study of Healthy Aging in African Americans (STAR).

Education is correlated with positive health outcomes, but associations are sometimes weaker among African Americans. The extent to which exposure to discrimination and depressive symptoms attenuates the education-cognition link has not been investigated. Study of Healthy Aging in African Americans (STAR) participants (n=764; average age 69 years) completed the Spanish and English Neuropsychological Assessment Scales. We assessed everyday and major lifetime discrimination and depressive symptoms as mediators of education effects on cognition using G-estimation with measurement error corrections. Education was correlated with greater major lifetime and everyday discrimination but lower depressive symptoms. Accounting for discrimination and depressive symptoms slightly reduced the estimated effect of education on cognition. The estimated total effect of graduate education (vs<Bachelor's) was 0.66 (95% confidence interval [CI]: 0.62, 0.68), and the direct effect not mediated by discrimination or depressive symptoms was 0.60 (95% CI: 0.43, 0.76). Education has robust effects on later-life cognition after controlling multiple mediating pathways and offsetting mechanisms.

Gender, Personality, and Cognitive Resilience Against Early-Life Disadvantage.

Early-life disadvantage (ELD) relates to lower late-life cognition. However, personality factors, including having an internal locus of control (LOC) or a conscientious personality, relate to resilience and effective stress coping. We explore whether personality factors convey resilience against the negative effects of ELD on cognition, by gender, in Mexico. Using the 2015 Mexican Health and Aging Study, we estimated expected cognition using multiple ELD markers to identify a subsample in the lowest quartile of expected cognition given ELD (n=2,086). In this subsample, we estimated cross-sectional associations between personality and having above-median observed cognitive ability (n=522) using logistic regression. Among those in the lowest quartile of expected cognition, a more internal LOC (β=0.32 [men] and β=0.44 [women]) and conscientious personality (β=0.39 [men] and β=0.17 [women]) were significantly associated with having above-median cognitive ability in models adjusted for demographic confounders. Larger benefits of conscientiousness were observed for men than women. Associations between personality and having above-median cognitive ability remained statistically significant after further adjustment for health, stress, and cognitive stimulation variables, regardless of gender. Personality factors may convey resilience among individuals who experienced ELD, potentially breaking the link between ELD and worse late-life cognition. Structural factors and gender roles may affect how much women benefit from personality factors.

Early- to late-life environmental factors and late-life global cognition in septuagenarian and octogenarians: The SONIC study

This study aimed to evaluate cognitively stimulating environments throughout life and to examine direct and indirect associations between these environments and late-life cognition. Early-life education, three domains of work complexity (data, people, and things) based on the longest-held occupation, and engagement in late-life leisure activities (LAs) were assessed. A structural equation model was developed using cross-sectional data of 1721 Japanese older adults in 70 ± 1 and 80 ± 1 years. The model confirmed significant direct effects of work complexity with data and late-life LAs on late-life cognitive performance. The associations of education and work complexity with late-life cognition were mediated through the subsequent environment(s). However, the total effects of work complexity with people and things on late-life cognition were insignificant. The findings suggest that cognitively stimulating activities in adulthood and beyond may lead to individual differences in late-life global cognition. In addition, antecedent complex environments might make subsequent life environments more cognitively stimulating. The results are discussed from the perspectives of cognitive plasticity and environmental complexity.

Fetal anemia and elevated hepcidin in a mouse model of fetal alcohol spectrum disorder.

Prenatal alcohol exposure (PAE) impairs offspring growth and cognition, and this is worsened by concurrent iron deficiency. Alcohol disrupts fetal iron metabolism and produces functional iron deficiency, even when maternal iron status is adequate. We used a mouse model of moderate PAE to investigate the mechanisms underlying this dysregulated iron status. C57BL/6J female mice received 3 g/kg alcohol daily from embryonic day (E) 8.5-17.5 and were assessed at E17.5. Alcohol reduced fetal hemoglobin, hematocrit, and red blood cell counts, despite elevated erythropoietin production. Alcohol suppressed maternal hepcidin expression and the upstream iron-sensing BMP/SMAD pathway, consistent with its effects in the nonpregnant state. In contrast, alcohol elevated fetal hepcidin, although this was not accompanied by an upregulation of the BMP/SMAD or proinflammatory IL-6/STAT3 pathways. Fetal expression of hepatic genes contributing to hemoglobin synthesis and iron metabolism were unaffected by alcohol, whereas those affecting ribosome biogenesis were suppressed, suggesting a novel candidate effector for this fetal anemia. These data confirm and extend prior observations that PAE disrupts maternal and fetal iron metabolism and impairs the fetus's ability to regulate iron status. We propose this dysregulation increases gestational iron needs and represents a conserved response to PAE. Prenatal alcohol exposure causes a functional iron deficiency in a model that also impairs cognition in later life. Prenatal alcohol exposure causes fetal anemia. This fetal anemia is accompanied by elevated hepcidin and erythropoietin. Findings are consistent with prior observations that prenatal alcohol exposure increases maternal-fetal iron requirements during pregnancy.

Body Mass Index and Cognition: Associations Across Mid- to Late Life and Gender Differences.

Higher mid-life body mass index (BMI) is associated with lower late-life cognition. Associations between later-life BMI and cognition are less consistent; evidence suggests reverse causation may play a role. We aimed to characterize associations between BMI and cognition across a wide age range during mid- to late life (55-85years) and examine whether associations vary by gender. We used data from the Health and Retirement Study (HRS) (N=39,153) to examine the association between BMI and 3 cognitive outcomes: cognitive level, cognitive decline, and cognitive impairment. We used a series of linear regression, mixed effects regression, and logistic regression models, adjusting for potential confounders. Higher BMI before age 65 (midlife) was associated with lower cognitive performance, faster rates of cognitive decline, and higher odds of cognitive impairment in late life. Averaging across analyses assessing associations between BMI measured before age 60 and late-life cognition, a 5-unit higher level of BMI was associated with a 0.26 point lower cognitive score. Beyond age 65, associations flipped, and higher BMI was associated with better late-life cognitive outcomes. Associations in both directions were stronger in women. Excluding those with BMI loss attenuated findings among women in older ages, supporting the reverse causation hypothesis. In this sample, age 65 represented a critical turning point between mid- and late life for the association between BMI and cognition, which has important implications for recruitment strategies for studies focused on risk factors for late-life cognitive outcomes. Evidence of gender differences raises the need to further investigate plausible mechanisms.