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Matt Huentelman

Publications and source records attributed to Matt Huentelman.

3 recordsLinked to original sources

Individual Differences in Cognitive Aging Rodent Datasets (ID-CARD): A collaborative platform for behavioral analysis across the lifespan.

Understanding cognitive aging requires approaches that capture individual variability while enabling integration across studies. In rodent models, behavioral data are central to this effort, yet cross-laboratory differences in experimental design limit comparability and constrain secondary analysis. To address this gap, we developed the Individual Differences in Cognitive Aging Rodent Datasets (ID-CARD), a first-of-its-kind collaborative repository aggregating trial-level Morris water maze data from multiple laboratories. ID-CARD is designed to support large-scale, integrative analyses and to facilitate secondary use of existing behavioral data in alignment with emerging data-sharing and transparency initiatives. Rather than imposing retrospective harmonization of experimental protocols, we implemented a normalization and modeling framework that enables comparison of learning trajectories while preserving meaningful variation across studies. Behavioral data from > 5000 rats spanning common strains, both sexes, and multiple ages were normalized in training and performance domains and fit with a logarithmic function to derive an error accumulation rate coefficient (EARC) as a measure of spatial learning. Age was strongly associated with increased EARC, indicating attenuated learning, even after adjusting for non-spatial cue performance. Analyses of goodness of fit revealed systematic structure in learning dynamics, where age was associated with reduced learning-curve conformity after accounting for overall performance. Inter-individual variability in spatial learning also increased with age, with strain-specific interactions. These findings demonstrate that integrated analysis of heterogeneous behavioral datasets can yield robust, individual-level insights into cognitive aging. ID-CARD provides a scalable resource and analytic framework to advance discovery in behavioral neuroscience by enabling reuse, integration, and comparative analysis of existing data.

Cognitive aging

Heterogeneity Analysis of Associations Involving the Large-Scale Online MindCrowd Survey Memory Test.

INTRODUCTION: Alzheimer's disease and related disorders (ADRDs), as well as general age-related cognitive decline, are known to be multifactorial with heterogeneous etiologies. Identifying and accommodating heterogeneity in any one ADRD-related data set can be pursued using different analytical techniques, each with different assumptions or purposes. For example, whereas a great deal of research has explored clustering individuals or variables that exhibit greater similarity in some way, little research has explored evidence for heterogeneity in the relationships between relevant outcomes, such as performance on a memory test, and risk factors such as environmental exposures, behaviors, or genetic factors among individuals. METHODS: We explored evidence of heterogeneity in the relationships between ability on a memory test, specifically the paired associate learning (PAL) test, and multiple social and demographic risk factors using the large MindCrowd study database (n > 90,000 individuals). We focused on mixtures of regression models but compared models assuming many interaction effects among independent variables as well as random effects. RESULTS: We ultimately find substantial evidence for heterogeneity and offer an intuitive explanation for it involving individual motivation for participating in the MindCrowd study. Basically, we argue that our mixture of regression model analysis results suggest that a smaller group of individuals (∼16%) likely participated in the MindCrowd study out of a concern for their cognitive abilities as they exhibit stronger and statistically significant negative associations between age, number of medications they are on, some ancestries, and the number correct on the PAL test. They also exhibit stronger positive associations between education and PAL test results in a dose-dependent manner suggesting that a "cognitive reserve" associated with greater education could benefit them. Analysis models assuming interaction terms and random effects suggested that other forms of heterogeneity in the relationships between variables exist in the data set, but their results do not carry with them the same intuitive explanation that the results of the mixture model analyses do. CONCLUSION: We find evidence for heterogeneity in the relationships between social and demographic variables and PAL test results in the large MindCrowd study database. This heterogeneity is likely due to individuals with and without concerns for their cognitive abilities participating in the study. We also find other types of evidence in the data set. Our results should motivate caution in the use of large epidemiological study or survey-oriented data sets to build predictive models of clinical or subclinical pathologies without exploring or accommodating heterogeneity. Our results also suggest that one should include questions about motivation to participate in large epidemiological studies since different motivations may impact important relationships between independent and dependent variables.

Humans

Sex-specific genetic predictors of Alzheimer's disease biomarkers.

Cerebrospinal fluid (CSF) levels of amyloid-&#x3b2; 42 (A&#x3b2;42) and tau have been evaluated as endophenotypes in Alzheimer's disease (AD) genetic studies. Although there are sex differences in AD risk, sex differences have not been evaluated in genetic studies of AD endophenotypes. We performed sex-stratified and sex interaction genetic analyses of CSF biomarkers to identify sex-specific associations. Data came from a previous genome-wide association study (GWAS) of CSF A&#x3b2;42 and tau (1527 males, 1509 females). We evaluated sex interactions at previous loci, performed sex-stratified GWAS to identify sex-specific associations, and evaluated sex interactions at sex-specific GWAS loci. We then evaluated sex-specific associations between prefrontal cortex (PFC) gene expression at relevant loci and autopsy measures of plaques and tangles using data from the Religious Orders Study and Rush Memory and Aging Project. In A&#x3b2;42, we observed sex interactions at one previous and one novel locus: rs316341 within SERPINB1 (p&#x2009;=&#x2009;0.04) and rs13115400 near LINC00290 (p&#x2009;=&#x2009;0.002). These loci showed stronger associations among females (&#x3b2;&#x2009;=&#x2009;-&#x2009;0.03, p&#x2009;=&#x2009;4.25&#x2009;&#xd7;&#x2009;10-8; &#x3b2;&#x2009;=&#x2009;0.03, p&#x2009;=&#x2009;3.97&#x2009;&#xd7;&#x2009;10-8) than males (&#x3b2;&#x2009;=&#x2009;-&#xa0;0.02, p&#x2009;=&#x2009;0.009; &#x3b2;&#x2009;=&#x2009;0.01, p&#x2009;=&#x2009;0.20). Higher levels of expression of SERPINB1, SERPINB6, and SERPINB9 in PFC was associated with higher levels of amyloidosis among females (corrected p values&#x2009;<&#x2009;0.02) but not males (p&#x2009;>&#x2009;0.38). In total tau, we observed a sex interaction at a previous locus, rs1393060 proximal to GMNC (p&#x2009;=&#x2009;0.004), driven by a stronger association among females (&#x3b2;&#x2009;=&#x2009;0.05, p&#x2009;=&#x2009;4.57&#x2009;&#xd7;&#x2009;10-10) compared to males (&#x3b2;&#x2009;=&#x2009;0.02, p&#x2009;=&#x2009;0.03). There was also a sex-specific association between rs1393060 and tangle density at autopsy (pfemale&#x2009;=&#x2009;0.047; pmale&#x2009;=&#x2009;0.96), and higher levels of expression of two genes within this locus were associated with lower tangle density among females (OSTN p&#x2009;=&#x2009;0.006; CLDN16 p&#x2009;=&#x2009;0.002) but not males (p&#x2009;&#x2265;&#x2009;0.32). Results suggest a female-specific role for SERPINB1 in amyloidosis and for OSTN and CLDN16 in tau pathology. Sex-specific genetic analyses may improve understanding of AD's genetic architecture.

Aged, 80 and over