Higher baseline inflammatory marker levels predict greater cognitive decline in older people with type 2 diabetes: year 10 follow-up of the Edinburgh Type 2 Diabetes Study

Aims/hypothesis We aimed to determine the longitudinal association of circulating markers of systemic inflammation with subsequent long-term cognitive change in older people with type 2 diabetes. Methods The Edinburgh Type 2 Diabetes Study is a prospective cohort study of 1066 adults aged 60 to 75 years with type 2 diabetes. Baseline data included C-reactive protein, IL-6, TNF-α fibrinogen and neuropsychological testing on major cognitive domains. Cognitive testing was repeated after 10 years in 581 participants. A general cognitive ability score was derived from the battery of seven individual cognitive tests using principal component analysis. Linear regression was used to determine longitudinal associations between baseline inflammatory markers and cognitive outcomes at follow-up, with baseline cognitive test results included as covariables to model cognitive change over time. Results Following adjustment for age, sex and baseline general cognitive ability, higher baseline fibrinogen and IL-6 were associated with greater decline in general cognitive ability (standardised βs = −0.059, p=0.032 and −0.064, p=0.018, respectively). These associations lost statistical significance after adjustment for baseline vascular and diabetes-related covariables. When assessing associations with individual cognitive tests, higher IL-6 was associated with greater decline in tests of executive function and abstract reasoning (standardised βs = 0.095, p=0.006 and −0.127, p=0.001, respectively). Similarly, raised fibrinogen and C-reactive protein levels were associated with greater decline in processing speed (standardised βs = −0.115, p=0.001 and −0.111, p=0.001, respectively). These associations remained statistically significant after adjustment for the diabetes- and vascular-related risk factors. Conclusions/interpretation Higher baseline levels of inflammatory markers, including plasma IL-6, fibrinogen and C-reactive protein, were associated with subsequent cognitive decline in older people with type 2 diabetes. At least some of this association appeared to be specific to certain cognitive domains and to be independent of vascular and diabetes-related risk factors. Graphical abstract

Reduced contextual information during future thinking in Alzheimer’s Disease

Objective: This study assessed the ability of patients with Alzheimer’s Disease (AD) to produce “when, where, and who” information during future thinking. Methods: AD patients and control participants were invited to imagine future scenarios. Future thinking was analyzed with respect to the number of “when, where, and who” details. Analysis showed fewer “when, where, and who” details in AD participants than in control participants. Fewer “when” than “where” details and fewer “where” than “who” details were observed in AD and control participants. Results: Production of temporal information in participants with AD was found to be associated with general cognitive functioning, as assessed with the Mini Mental State Exam. Future thinking in AD is mainly associated with reduced contextual information. Conclusion : The diminished ability to construct time-related details during future thinking in AD can be mainly associated with the diminished general cognitive ability in AD, and probably with hippocampal compromise in the disease. We also propose a socio-emotional account according to which, confronted with a limited-time perspective during future thinking, AD patients may tend to maximize their emotional well-being by avoiding time-related information and thinking about friends, family and beloved ones.

Acculturation moderates cognitive performance in adults at risk of autosomal dominant Alzheimer's Disease

Acculturative processes via persistent exposure to a set of cultural practices and behaviors can influence cognitive functioning (Park & Huang, 2010). The impact of acculturation on populations at risk for Alzheimer’s disease (AD), however, remains understudied. Persons with or at-risk for early-onset autosomal dominant AD (ADAD) offer a known AD pathogenesis and the opportunity to study whether acculturation moderates their cognitive performance. The present study used a latent variable model to test whether effects of latent cognitive ability on observable cognitive performance depend on acculturation. Participants included 119 adults with or at-risk for ADAD, the majority of whom were of Mexican origin with various levels of U.S. acculturation. Participants completed the Cognitive Abilities Screening Instrument (CASI) and the Acculturation Rating Scale for Mexican Americans-II (ARSMA-II). Confirmatory factor analysis was used to estimate a latent general cognitive ability factor from nine domains (e.g., attention, abstraction and judgment). The ARSMA-II was used to test whether factor loadings depended on level of acculturation, covarying for mutation status. Results revealed ARSMA-II scores nearly significantly moderated the effects of general cognitive ability on abstraction and judgment (λ = 0.20, SE = 0.11, p = .070). Individual differences in general cognitive ability at lower levels of acculturation likely predict lower abstraction and judgment performance. Cognitive assessments may not equally represent true cognitive ability in Mexican-Americans. Although the CASI was developed as a cross-cultural measure of cognitive functioning, caution should be exercised in inferring true cognitive functioning in Mexican-Americans who may not be acculturated to the U.S.

Bilingualism and Healthy Aging: Onset Age of Bilingualism as a Predictor of Older Adult Theory of Mind

The ability to understand and speak more than one language (i.e., bilingualism) may protect against age-related cognitive deterioration (Abutalebi et al., 2015). While there is mounting evidence suggesting that bilingualism confers advantages in domain-general cognitive abilities in late adulthood (see Bialystok, 2017, for a review), few studies have investigated the influences of bilingualism on socio-cognitive abilities such as theory of mind (ToM) in the normal aging process. Thus, in this study, we examine how bilingualism factors (i.e., onset age of bilingualism, language balance, and diversity in language use) are associated with individual differences in ToM in healthy older adult bilinguals aged 58-79 (N=44). ToM abilities were assessed using the Theory-of-Mind Task Battery (Hutchins et al., 2008), where participants viewed vignettes and answered questions about the protagonists’ cognitive and affective mental states. All participants completed a self-report language background questionnaire and the Montreal Cognitive Assessment (MoCA) test as a measure of general cognitive ability. Results revealed that better ToM was negatively correlated with participants’ chronological age (r=-.43, p=.004) and the onset age of second-language acquisition (r=-.41, p=.006), but not language balance and diversity (ps>.40). Partial regression analyses showed that earlier onset age of bilingualism predicted better ToM performance (β=-.40, p=.009), even after controlling for age, education, and general cognitive ability. These findings suggest that bilingual language experience, particularly earlier exposure to a second language, may provide benefits to older adults in preserving their ability to understand others’ mental states, acting as a cognitive reserve against age-related declines in socio-cognitive functions.

Preliminary evidence for the Matrix Matching Test as a valid and reliable measure of general cognitive ability in adolescents

Introduction: In research, a simple measure of general cognitive ability is often required. One method is the Matrix Matching Test, a brief, free-to-use, language-free assessment of general cognitive ability or intelligence in adults, which taps both fluid and crystalized processes. We investigated its reliability and validity with adolescent participants. Method:The Matrix Matching Test was administered to 111 participants, aged 12 to 17 (46% female).Subsamples also completed two standard measures of cognitive ability: Vocabulary (crystalized) and Matrix Reasoning (fluid) tests from the Wechsler Intelligence Scale for Children IV (WISC-IV). Results: The Matrix Matching Test was found to have acceptable internal consistency and good retest reliability. Criterion validity was indicated by its ability to distinguish between psychosocially deprived participants living in foster care (n = 40) and controls, and by its positive correlation with grade point average. There were large positive correlations between the Matrix Matching Test and the standard measures of Vocabulary, and Matrix Reasoning, suggesting convergent validity. Conclusions: Our preliminary evidence suggests that The Matrix Matching Test is a reliable and valid measure of general cognitive ability for ages 12 to 17.

Brain-wide functional connectivity patterns support general cognitive ability and mediate effects of socioeconomic status in youth

General cognitive ability (GCA) is an individual difference dimension linked to important academic, occupational, and health-related outcomes and its development is strongly linked to differences in socioeconomic status (SES). Complex abilities of the human brain are realized through interconnections among distributed brain regions, but brain-wide connectivity patterns associated with GCA in youth, and the influence of SES on these connectivity patterns, are poorly understood. The present study examined functional connectomes from 5937 9- and 10-year-olds in the Adolescent Brain Cognitive Development (ABCD) multi-site study. Using multivariate predictive modeling methods, we identified whole-brain functional connectivity patterns linked to GCA. In leave-one-site-out cross-validation, we found these connectivity patterns exhibited strong and statistically reliable generalization at 19 out of 19 held-out sites accounting for 18.0% of the variance in GCA scores (cross-validated partial η2). GCA-related connections were remarkably dispersed across brain networks: across 120 sets of connections linking pairs of large-scale networks, significantly elevated GCA-related connectivity was found in 110 of them, and differences in levels of GCA-related connectivity across brain networks were notably modest. Consistent with prior work, socioeconomic status was a strong predictor of GCA in this sample, and we found that distributed GCA-related brain connectivity patterns significantly statistically mediated this relationship (mean proportion mediated: 15.6%, p < 2 × 10−16). These results demonstrate that socioeconomic status and GCA are related to broad and diffuse differences in functional connectivity architecture during early adolescence, potentially suggesting a mechanism through which socioeconomic status influences cognitive development.