Towards validation of a new computerised test of goal neglect: preliminary evidence from clinical and neuroimaging pilot studies

Objective: Goal neglect is a significant problem following brain injury, and is a target for rehabilitation. It is not yet known how neural activation might change to reflect rehabilitation gains. We developed a computerised multiple elements test (CMET), suitable for use in neuroimaging paradigms. Design: Pilot correlational study and event-related fMRI study. Methods: In Study 1, 18 adults with acquired brain injury were assessed using the CMET, other tests of goal neglect (Hotel Test; Modified Six Elements Test) and tests of reasoning. In Study 2, 12 healthy adults underwent fMRI, during which the CMET was administered under two conditions: self-generated switching and experimenter-prompted switching. Results: Among the clinical sample, CMET performance was positively correlated with both the Hotel Test (r = 0.675, p = 0.003) and the Modified Six Elements Test (r = 0.568, p = 0.014), but not with other clinical or demographic measures. In the healthy sample, fMRI demonstrated significant activation in rostro-lateral prefrontal cortex in the self-generated condition compared with the prompted condition (peak 40, 44, 4; ZE = 4.25, p(FWEcorr) = 0.026). Conclusions: These pilot studies provide preliminary evidence towards the validation of the CMET as a measure of goal neglect. Future studies will aim to further establish its psychometric properties, and determine optimum pre- and post-rehabilitation fMRI paradigms

Managing laboratory automation: integration and informatics in drug discovery

Drug discovery today requires the focused use of laboratory automation and other resources in combinatorial chemistry and high-throughput screening (HTS). The ultimate value of both combinatorial chemistry and HTS technologies and the lasting impact they will have on the drug discovery process is a chapter that remains to be written. Central to their success and impact is how well they are integrated with each other and with the rest of the drug discovery processes-informatics is key to this success. This presentation focuses on informatics and the integration of the disciplines of combinatorial chemistry and HTS in modern drug discovery. Examples from experiences at Neurogen from the last five years are described

Computational chemistry, data mining, high-throughput synthesis and screening - informatics and integration in drug discovery

Drug discovery today includes considerable focus of laboratory automation and other resources on both combinatorial chemistry and high-throughput screening, and computational chemistry has been a part of pharmaceutical research for many years. The real benefit of these technologies is beyond the exploitation of each individually. Only recently have significant efforts focused on effectively integrating these and other discovery disciplines to realize their larger potential. This technical note will describe one example of these integration efforts

Differing Effects of Education on Cognitive Decline in Diverse Elders with Low Versus High Educational Attainment

OBJECTIVE: In light of growing debate over whether and how early life educational experiences alter late-life cognitive trajectories, this study sought to more thoroughly investigate the relationship between educational attainment and rates of late-life cognitive decline in a racially, ethnically, and educationally diverse population. METHOD: Older adults (N = 3,435) in the community-based Washington Heights-Inwood Columbia Aging Project were administered neuropsychological tests of memory, language, visuospatial function, and processing speed at approximate 24-month intervals for up to 18 years. Second-order latent growth curves estimated direct and indirect (through income) effects of educational attainment on rates of global cognitive decline separately in individuals with low (0-8 years) and high (9-20 years) educational attainment. RESULTS: More years of education were associated with higher cognitive level and slower cognitive decline in individuals with low or high educational attainment. The association between having more than 9 years of education and exhibiting slower cognitive decline was fully mediated by income. Although having additional years of education up to 8 years was also associated with higher income, this did not explain associations between education and cognitive change in the low-education group. CONCLUSIONS: Early education (i.e., up to 8 years) may promote aspects of development during a sensitive period of childhood that protect against late-life cognitive decline independent of income. In contrast, later education (i.e., 9 years and beyond) is associated with higher income, which may influence late-life cognitive health through multiple, nonmutually exclusive pathways

Literacy and Memory Decline among Ethnically Diverse Elders

Literacy may be a more powerful indicator of brain reserve than years of education. Literacy level may be a proxy for native intellectual capacity or life experience that can compensate for brain damage or provide brain reserve. Alternately, the experience of acquiring literacy skills may in itself change the organization of the brain and increase protection against cognitive decline. However, because people with low levels of literacy obtain poor scores on most cognitive measures, only longitudinal studies can elucidate the role of reading ability in reserve. We determined whether literacy skills could predict cognitive change in a sample of 136 English-speaking African American, Caucasian, and Hispanic elders selected from a longitudinal aging study in New York City. According to a physician’s independent examination, all participants were nondemented throughout the four longitudinal assessments. Literacy level was assessed using the WRAT-3 reading subtest. After accounting for age at baseline and years of education, GEE analyses showed that elders with low levels of literacy had a steeper decline in both immediate and delayed recall of a word list over time as compared to high literacy elders. Our findings suggest that literacy skills are protective against memory decline among nondemented elders

Functional Status in the Young-Old: Establishing a Working Prototype of an Extended-Instrumental Activities of Daily Living Scale

BACKGROUND: Instrumental activities of daily living (IADLs) exhibit strong predictive power for the presence of dementia and mild cognitive impairment. However, IADLs are often less effective in younger cohorts or in healthy community-dwelling samples, presenting with large ceiling effects. This study aimed to construct an IADL scale with an extended range. An effort was made to incorporate leisure activity tasks that were more stimulating, and potentially more challenging, into a set of traditional IADLs. METHODS: Beginning with a set of IADL and leisure activity items, nonparametric item response theory methodology was used to construct a scale with appropriate dimensionality, monotonicity, item discrimination power, and scalability within a large cohort of young-old (aged 65-75). Dimensionality was further scrutinized by principal component analysis of the residuals. The predictive validity of the resulting scale for poor cognitive performance was evaluated using logistic regression. RESULTS: A reliable (rho = .73) unidimensional construct was established, meeting the Mokken item response theory criteria of medium scalability. Excluding demented participants, the adjusted model proved sensitive to relatively subtle cognitive deficits; each additional task endorsed (nine-item scale) significantly decreased the odds of being in the bottom quarter of composite domains relating to processing speed (odds ratio = 0.73 [confidence interval: 0.56-0.97], p < .05) and visuospatial ability (odds ratio = 0.70 [confidence interval: 0.73-0.87], p < .01). CONCLUSIONS: A reliable extended-IADL scale was constructed meeting item response theory assumptions relating to unidimensionality, monotonicity, and invariant item ordering. The range of measurement extends well beyond traditional IADL scales. Finally, the scale appears to be sensitive to cognitive differences within the normal spectrum

Racial differences in neurocognitive outcomes post-stroke: The impact of healthcare variables

AbstractObjectives:The present study examined differences in neurocognitive outcomes among non-Hispanic Black and White stroke survivors using the NIH Toolbox-Cognition Battery (NIHTB-CB), and investigated the roles of healthcare variables in explaining racial differences in neurocognitive outcomes post-stroke.Methods:One-hundred seventy adults (91 Black; 79 White), who participated in a multisite study were included (age:M=56.4;SD=12.6; education:M=13.7;SD=2.5; 50% male; years post-stroke: 1–18; stroke type: 72% ischemic, 28% hemorrhagic). Neurocognitive function was assessed with the NIHTB-CB, using demographically corrected norms. Participants completed measures of socio-demographic characteristics, health literacy, and healthcare use and access. Stroke severity was assessed with the Modified Rankin Scale.Results:An independent samplesttest indicated Blacks showed more neurocognitive impairment (NIHTB-CB Fluid Composite T-score:M=37.63;SD=11.67) than Whites (Fluid T-score:M=42.59,SD=11.54;p=.006). This difference remained significant after adjusting for reading level (NIHTB-CB Oral Reading), and when stratified by stroke severity. Blacks also scored lower on health literacy, reported differences in insurance type, and reported decreased confidence in the doctors treating them. Multivariable models adjusting for reading level and injury severity showed that health literacy and insurance type were statistically significant predictors of the Fluid cognitive composite (p&lt;.001 andp=.02, respectively) and significantly mediated racial differences on neurocognitive impairment.Conclusions:We replicated prior work showing that Blacks are at increased risk for poorer neurocognitive outcomes post-stroke than Whites. Health literacy and insurance type might be important modifiable factors influencing these differences. (JINS, 2017,23, 640–652)</jats:p

Influence of Leisure Activity on the Incidence of Alzheimer's Disease

OBJECTIVE: To determine whether leisure activities modify the risk for incident dementia. BACKGROUND: Although high educational and occupational attainments have been associated with reduced risk of incident dementia, the relation between leisure activities and dementia risk has not been adequately investigated. METHODS: A total of 1,772 nondemented individuals aged 65 years or older, living in northern Manhattan, New York, were identified and followed longitudinally in a community-based cohort incidence study. Subjects' leisure activities at baseline were assessed, annual examinations with the same standardized neurologic and neuropsychological measures were performed for up to 7 years (mean 2.9 years), and incident dementia was assessed as the main outcome measure. Cox proportional hazards models, adjusting for age, ethnic group, education, and occupation, were used to estimate the relative risk (RR) of incident dementia associated with high leisure activities. RESULTS: Of the 1,772 subjects, 207 became demented. The risk of dementia was decreased in subjects with high leisure activities (RR, 0.62; 95% CI 0.46 to 0.83). The association of high leisure with decreased RR of incident dementia was present even when baseline cognitive performance, health limitations interfering with desired leisure activities, cerebrovascular disease, and depression were considered. CONCLUSIONS: The data suggest that engagement in leisure activities may reduce the risk of incident dementia, possibly by providing a reserve that delays the onset of clinical manifestations of the diseas