The Reference Ability Neural Network Study: Motivation, Design, and Initial Feasibility Analyses

We introduce and describe the Reference Ability Neural Network Study and provide initial feasibility data. Based on analyses of large test batteries administered to individuals ranging from young to old, four latent variables, or reference abilities (RAs) that capture the majority of the variance in age-related cognitive change have been identified: episodic memory, fluid reasoning, perceptual speed, and vocabulary. We aim to determine whether spatial fMRI networks can be derived that are uniquely associated with the performance of each reference ability. We plan to image 375 healthy adults (50 per decade from age 20 to 50; 75 per decade from age 50 to 80) while performing a set of 12 cognitive tasks. Data on 174 participants are reported here. Three tasks were grouped a priori into each of the four reference ability domains. We first assessed to what extent both cognitive task scores and activation patterns readily show convergent and discriminant validity, i.e. increased similarity between tasks within the same domain and decreased similarity between tasks between domains, respectively. Block-based time-series analysis of each individual task was conducted for each participant via general linear modeling. We partialled activation common to all tasks out of the imaging data. For both test scores and activation topographies, we then calculated correlations for each of 66 possible pairings of tasks, and compared the magnitude of correlation of tasks within reference ability domains to that of tasks between domains. For the behavioral data, globally there were significantly stronger inter-task correlations within than between domains. When examining individual abilities, 3 of the domains also met these criteria but memory reached only borderline significance. Overall there was greater topographic similarity within reference abilities than between them (p<0.0001), but when examined individually, statistical significance was reached only for episodic memory and perceptual speed. We then turned to a multivariate technique, linear indicator regression analysis, to derive four unique linear combinations of Principal Components (PC) of imaging data that were associated with each RA. We investigated the ability of the identified PCs to predict the reference domain associated with the activation of individual subjects for individual tasks. Median accuracy rates for associating component task activation with a particular reference ability were quite good: memory: 82%; reasoning: 87%; speed: 84%; vocabulary: 77%. These results demonstrate that even using basic GLM analysis, the topography of activation of tasks within a domain is more similar than tasks between domains. The follow-up regression analyses suggest that all tasks with each RA rely on a common network, unique to that RA. Our ultimate goal is to better characterize these RA neural networks and then study how their expression changes across the age span. Our hope is that by focusing on these networks associated with key features of cognitive aging, as opposed to task-related activation associated with individual tasks, we will be able to advance our knowledge regarding the key brain changes that underlie cognitive aging

Making Cognitive Latent Variables Manifest: Distinct Neural Networks for Fluid Reasoning and Processing Speed

Cognitive psychologists posit several specific cognitive abilities that are measured with sets of cognitive tasks. Tasks that purportedly tap a specific underlying cognitive ability are strongly correlated with one another, whereas performances on tasks that tap different cognitive abilities are less strongly correlated. For these reasons, latent variables are often considered optimal for describing individual differences in cognitive abilities. Although latent variables cannot be directly observed, all cognitive tasks representing a specific latent ability should have a common neural underpinning. Here, we show that cognitive tasks representing one ability (i.e., either perceptual speed or fluid reasoning) had a neural activation pattern distinct from that of tasks in the other ability. One hundred six participants between the ages of 20 and 77 years were imaged in an fMRI scanner while performing six cognitive tasks, three representing each cognitive ability. Consistent with prior research, behavioral performance on these six tasks clustered into the two abilities based on their patterns of individual differences and tasks postulated to represent one ability showed higher similarity across individuals than tasks postulated to represent a different ability. This finding was extended in the current report to the spatial resemblance of the task-related activation patterns: The topographic similarity of the mean activation maps for tasks postulated to reflect the same reference ability was higher than for tasks postulated to reflect a different reference ability. Furthermore, for any task pairing, behavioral and topographic similarities of underlying activation patterns are strongly linked. These findings suggest that differences in the strengths of correlations between various cognitive tasks may be because of the degree of overlap in the neural structures that are active when the tasks are being performed. Thus, the latent variable postulated to account for correlations at a behavioral level may reflect topographic similarities in the neural activation across different brain regions

Gene Expression Profiling and Molecular Characterization of Antimony Resistance in Leishmania amazonensis

Leishmania are unicellular microorganisms that can be transmitted to humans by the bite of sandflies. They cause a spectrum of diseases called leishmaniasis, which are classified as neglected tropical diseases by the World Health Organization. The treatment of leishmaniasis is based on the administration of antimony-containing drugs. These drugs have been used since 1947 and still constitute the mainstay for leishmaniasis treatment in several countries. One of the problems with these compounds is the emergence of resistance. Our work seeks to understand how these parasites become resistant to the drug. We studied antimony-resistant Leishmania amazonensis mutants. We analyzed gene expression at the whole genome level in antimony-resistant parasites and identified mechanisms used by Leishmania for resistance. This work could help us in developing new strategies for treatment in endemic countries where people are unresponsive to antimony-based chemotherapy. The identification of common mechanisms among different species of resistant parasites may also contribute to the development of diagnostic kits to identify and monitor the spread of resistance

Indicators of subjective social status: Differential associations across race and sex

Background: Subjective social status (SSS), or perception of rank on the social hierarchy, is an important indicator of various health outcomes. However, the psychosocial influences on this construct are unclear, and how these influences vary across different sociodemographic groups is poorly understood. Methods: Participants were 2077 African-American and Whites (M age=47.85; 57% female; 58% African American, and 58% above poverty) from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study. Multiple regression analyses examined (1) hypothesized psychosocial indicators of SSS and (2) the moderating effect of race and sex on the variables associated with SSS. Results: In addition to the traditional measures of SES (i.e. income, employment, and education), psychosocial variables (i.e. depressive symptomatology, neighborhood satisfaction, and self-rated health) were significantly associated with SSS. However, some of these indicators varied with respect to race and sex. Three significant interactions were found: sex by employment, race by employment, and race by education, wherein objective measures of SES were more associated with SSS for Whites and men compared to African Americans and women. Conclusion: Psychosocial measures may influence individuals’ perceptions of themselves on the social hierarchy. Additionally, SSS may vary by demographic group. When considering the impact of SSS on health, it is important to consider the unique interpretations that various demographic groups have when perceiving themselves on the social hierarchy. Keywords: Subjective social status, Socioeconomic status, Race, Sex, Social hierarch

Modification of everyday activities and its association with self-awareness in cognitively diverse older adults.

Cognitive impairment (CI) in older adults is frequently accompanied by difficulty performing complex everyday activities (e.g., managing finances). However, it is unclear if and how older adults with CI modify their activities (i.e., Do individuals continue, monitor, seek help with, change their approach to, or stop different activities?). In the current study, we examined if older adults with CI are concerned about their ability to carry out complex activities, if and how they modify activities based on their concern, and the factors associated with activity modification. We hypothesized that older adults with CI will more frequently be concerned about, and modify, everyday activities than cognitively healthy (HE) older adults, and that higher awareness of memory loss in the CI group would relate to more frequent modification. The sample included 81 older adults (51 HEs; mean age 70.02 (7.34) and 30 CI; mean age 75.97 (8.12)). Compared to HEs, the CI group reported having more concern about, F(3,77) = 5.50, p = 0.02, and modifying a greater number of activities, F(3,77) = 5.02, p = 0.03. Medication management (30%) and completing taxes (33.3%) were among the most frequently modified activities for the CI and HE groups, respectively. In the CI group, higher memory awareness was associated with more concern (r = .53, p = .005) and activity modification (r = 0.55, p = .003). Findings provide novel information about how cognitively diverse older adults navigate complex activities in daily life. We propose a preliminary theoretical model by which self-awareness may influence navigation of everyday activities in the context of CI

Association of Antioxidant Vitamins A, C, E and Carotenoids with Cognitive Performance over Time: A Cohort Study of Middle-Aged Adults

Carotenoids may strengthen the association of antioxidant vitamins A, C, and E with favorable cognitive outcomes over time, though a few prospective studies have examined this hypothesis. We evaluated the longitudinal data from 1251 participants in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study (Age at visit 1 in 2004&ndash;2009 (v1): 30&ndash;65 years). Vitamins A, C, and E dietary intakes and total and individual dietary carotenoids were computed using two 24-h recalls at v1. Cognitive tests, covering global mental status and domains of memory/learning, attention, psychomotor speed, visuo-spatial, language/verbal, and executive function were conducted at v1 and/or v2 (2009&ndash;2013); mean &plusmn; SD follow-up: 4.66 &plusmn; 0.93 years. Mixed-effects linear regression models detected an interaction between vitamin E and total (and individual) carotenoids for three of 11 cognitive tests at v1, with only one meeting the statistical significance upon multiple testing correction whereby vitamin E was linked with greater verbal memory performance in the uppermost total carotenoid tertile (&gamma;0a = +0.26 &plusmn; 0.08, p = 0.002), a synergism largely driven by carotenoid lycopene. Vitamins A and C showed no consistent interactions with carotenoids. In conclusion, we provide partial evidence for synergism between vitamin E and carotenoids in relation to better baseline cognitive performance, pending further studies with time-dependent exposures and randomized trials directly examining this synergism

The right insula contributes to memory awareness in cognitively diverse older adults

Unawareness of memory loss is a challenging characteristic of Alzheimer’s disease (AD) and other age-related neurodegenerative conditions at their earliest stages, adversely affecting important outcomes such as patient decision making and safety. The basis of this metacognitive disturbance has been elusive; however it is almost certainly determined in part by compromise to brain regions critical for self-assessment. The subjectivity of traditional measurements of selfawareness in dementia has likely limited the rigor with which its neuroanatomic correlates can be established. Here we objectively measure memory awareness (metamemory) using a Feeling of Knowing (FOK) task in a group of cognitively diverse older adults, including 14 with mild AD and 20 cognitively healthy older adults. Performance on the metamemory task was examined in relation to the structural integrity of 14 bilateral neuroanatomic regions hypothesized to support self-awareness. Less accurate metamemory was associated only with reduced right insular volume (r = .41, p = .019). Implications of the current findings for models of metacognitive aging are discussed, with attention to the role of the insula in the conscious detection of errors