Determinants of fluid intelligence in healthy aging: Omega-3 polyunsaturated fatty acid status and frontoparietal cortex structure.

INTRODUCTION: Accumulating evidence indicates that cognitive decline depends not only upon changes in brain health, but critically, also upon nutritional status. Decline in fluid intelligence, one of the most debilitating aspects of cognitive aging, has been linked to omega-3 polyunsaturated fatty acid (PUFA) status; however, it is not known whether this phenomenon results from specific omega-3 PUFAs acting on particular aspects of brain health. Therefore, this study aims to explore whether particular patterns of omega-3 PUFAs influence fluid intelligence by supporting specific neural structures. METHODS: We measured six plasma phospholipid omega-3 PUFAs, fluid intelligence, and regional gray matter volume in the frontal and parietal cortices in 100 cognitively intact older adults (65-75 years old). A four-step mediation analysis was implemented using principal component analysis and multivariate linear regressions, adjusted for age, gender, education, and body mass index. RESULTS: The mediation analysis revealed that one pattern of omega-3 PUFAs, consisting of alpha-linolenic acid, stearidonic acid, and eicosatrienoic acid, was linked to fluid intelligence, and that total gray matter volume of the left frontoparietal cortex (FPC) fully mediated the relationship between this omega-3 PUFA pattern and fluid intelligence. DISCUSSION: These data demonstrate that fluid intelligence may be optimally supported by specific omega-3 PUFAs through preservation of FPC gray matter structure in cognitively intact older adults. This report provides novel evidence for the benefits of particular omega-3 PUFA patterns on fluid intelligence and underlying gray matter structure.

Aerobic Fitness Explains Individual Differences in the Functional Brain Connectome of Healthy Young Adults.

A wealth of neuroscience evidence demonstrates that aerobic fitness enhances structural brain plasticity, promoting the development of gray matter volume and maintenance of white matter integrity within networks for executive function, attention, learning, and memory. However, the role of aerobic fitness in shaping the functional brain connectome remains to be established. The present work therefore investigated the effects of aerobic fitness (as measured by VO2max) on individual differences in whole-brain functional connectivity assessed from resting state fMRI data. Using a connectome-wide association study, we identified significant brain-fitness relationships within a large sample of healthy young adults (N = 242). The results revealed several regions within frontal, temporal, parietal, and cerebellar cortex, having significant association with aerobic fitness. We further characterized the influence of these regions on 7 intrinsic connectivity networks, demonstrating the greatest association with networks that are known to mediate the beneficial effects of aerobic fitness on executive function (frontoparietal network), attention and learning (dorsal and ventral attention network), and memory (default mode network). In addition, we provide evidence that connectivity strength between these regions and the frontoparietal network is predictive of individuals' fluid intelligence.

Predictors of Memory in Healthy Aging: Polyunsaturated Fatty Acid Balance and Fornix White Matter Integrity.

Recent evidence demonstrates that age and disease-related decline in cognition depends not only upon degeneration in brain structure and function, but also on dietary intake and nutritional status. Memory, a potential preclinical marker of Alzheimer's disease, is supported by white matter integrity in the brain and dietary patterns high in omega-3 and omega-6 polyunsaturated fatty acids. However, the extent to which memory is supported by specific omega-3 and omega-6 polyunsaturated fatty acids, and the degree to which this relationship is reliant upon microstructure of particular white matter regions is not known. This study therefore examined the cross-sectional relationship between empirically-derived patterns of omega-3 and omega-6 polyunsaturated fatty acids (represented by nutrient biomarker patterns), memory, and regional white matter microstructure in healthy, older adults. We measured thirteen plasma phospholipid omega-3 and omega-6 polyunsaturated fatty acids, memory, and regional white matter microstructure in 94 cognitively intact older adults (65 to 75 years old). A three-step mediation analysis was implemented using multivariate linear regressions, adjusted for age, gender, education, income, depression status, and body mass index. The mediation analysis revealed that a mixture of plasma phospholipid omega-3 and omega-6 polyunsaturated fatty acids is linked to memory and that white matter microstructure of the fornix fully mediates the relationship between this pattern of plasma phospholipid polyunsaturated fatty acids and memory. These results suggest that memory may be optimally supported by a balance of plasma phospholipid omega-3 and omega-6 polyunsaturated fatty acids through the preservation of fornix white matter microstructure in cognitively intact older adults. This report provides novel evidence for the benefits of plasma phospholipid omega-3 and omega-6 polyunsaturated fatty acid balance on memory and underlying white matter microstructure.

Nutritional status, brain network organization, and general intelligence.

The high energy demands of the brain underscore the importance of nutrition in maintaining brain health and further indicate that aspects of nutrition may optimize brain health, in turn enhancing cognitive performance. General intelligence represents a critical cognitive ability that has been well characterized by cognitive neuroscientists and psychologists alike, but the extent to which a driver of brain health, namely nutritional status, impacts the neural mechanisms that underlie general intelligence is not understood. This study therefore examined the relationship between the intrinsic connectivity networks supporting general intelligence and nutritional status, focusing on nutrients known to impact the metabolic processes that drive brain function. We measured general intelligence, favorable connective architecture of seven intrinsic connectivity networks, and seventeen plasma phospholipid monounsaturated and saturated fatty acids in a sample of 99 healthy, older adults. A mediation analysis was implemented to investigate the relationship between empirically derived patterns of fatty acids, general intelligence, and underlying intrinsic connectivity networks. The mediation analysis revealed that small world propensity within one intrinsic connectivity network supporting general intelligence, the dorsal attention network, was promoted by a pattern of monounsaturated fatty acids. These results suggest that the efficiency of functional organization within a core network underlying general intelligence is influenced by nutritional status. This report provides a novel connection between nutritional status and functional network efficiency, and further supports the promise and utility of functional connectivity metrics in studying the impact of nutrition on cognitive and brain health.

Parahippocampal Cortex Mediates the Relationship between Lutein and Crystallized Intelligence in Healthy, Older Adults.

Introduction: Although, diet has a substantial influence on the aging brain, the relationship between dietary nutrients and aspects of brain health remains unclear. This study examines the neural mechanisms that mediate the relationship between a carotenoid important for brain health across the lifespan, lutein, and crystallized intelligence in cognitively intact older adults. We hypothesized that higher serum levels of lutein are associated with better performance on a task of crystallized intelligence, and that this relationship is mediated by gray matter structure of regions within the temporal cortex. This investigation aims to contribute to a growing line of evidence, which suggests that particular nutrients may slow or prevent aspects of cognitive decline by targeting specific features of brain aging. Methods: We examined 76 cognitively intact adults between the ages of 65 and 75 to investigate the relationship between serum lutein, tests of crystallized intelligence (measured by the Wechsler Abbreviated Scale of Intelligence), and gray matter volume of regions within the temporal cortex. A three-step mediation analysis was implemented using multivariate linear regressions to control for age, sex, education, income, depression status, and body mass index. Results: The mediation analysis revealed that gray matter thickness of one region within the temporal cortex, the right parahippocampal cortex (Brodmann's Area 34), partially mediates the relationship between serum lutein and crystallized intelligence. Conclusion: These results suggest that the parahippocampal cortex acts as a mediator of the relationship between serum lutein and crystallized intelligence in cognitively intact older adults. Prior findings substantiate the individual relationships reported within the mediation, specifically the links between (i) serum lutein and temporal cortex structure, (ii) serum lutein and crystallized intelligence, and (iii) parahippocampal cortex structure and crystallized intelligence. This report demonstrates a novel structural mediation between lutein status and crystallized intelligence, and therefore provides further evidence that specific nutrients may slow or prevent features of cognitive decline by hindering particular aspects of brain aging. Future work should examine the potential mechanisms underlying this mediation, including the antioxidant, anti-inflammatory, and membrane modulating properties of lutein.

Inferior Prefrontal Cortex Mediates the Relationship between Phosphatidylcholine and Executive Functions in Healthy, Older Adults.

Objectives: This study examines the neural mechanisms that mediate the relationship between phosphatidylcholine and executive functions in cognitively intact older adults. We hypothesized that higher plasma levels of phosphatidylcholine are associated with better performance on a particular component of the executive functions, namely cognitive flexibility, and that this relationship is mediated by gray matter structure of regions within the prefrontal cortex (PFC) that have been implicated in cognitive flexibility. Methods: We examined 72 cognitively intact adults between the ages of 65 and 75 in an observational, cross-sectional study to investigate the relationship between blood biomarkers of phosphatidylcholine, tests of cognitive flexibility (measured by the Delis-Kaplan Executive Function System Trail Making Test), and gray matter structure of regions within the PFC. A three-step mediation analysis was implemented using multivariate linear regressions and we controlled for age, sex, education, income, depression status, and body mass index. Results: The mediation analysis revealed that gray matter thickness of one region within the PFC, the left inferior PFC (Brodmann's Area 45), mediates the relationship between phosphatidylcholine blood biomarkers and cognitive flexibility. Conclusion: These results suggest that particular nutrients may slow or prevent age-related cognitive decline by influencing specific structures within the brain. This report demonstrates a novel structural mediation between plasma phosphatidylcholine levels and cognitive flexibility. Future work should examine the potential mechanisms underlying this mediation, including phosphatidylcholine-dependent cell membrane integrity of the inferior PFC and phosphatidylcholine-dependent cholinergic projections to the inferior PFC.

Covariance based outlier detection with feature selection.

The present covariance based outlier detection algorithm selects from a candidate set of feature vectors that are best at identifying outliers. Features extracted from biomedical and health informatics data can be more informative in disease assessment and there are no restrictions on the nature and number of features that can be tested. But an important challenge for an algorithm operating on a set of features is for it to winnow the effective features from the ineffective ones. The powerful algorithm described in this paper leverages covariance information from the time series data to identify features with the highest sensitivity for outlier identification. Empirical results demonstrate the efficacy of the method.

Efficient Blockwise Permutation Tests Preserving Exchangeability.

In this paper, we present a new blockwise permutation test approach based on the moments of the test statistic. The method is of importance to neuroimaging studies. In order to preserve the exchangeability condition required in permutation tests, we divide the entire set of data into certain exchangeability blocks. In addition, computationally efficient moments-based permutation tests are performed by approximating the permutation distribution of the test statistic with the Pearson distribution series. This involves the calculation of the first four moments of the permutation distribution within each block and then over the entire set of data. The accuracy and efficiency of the proposed method are demonstrated through simulated experiment on the magnetic resonance imaging (MRI) brain data, specifically the multi-site voxel-based morphometry analysis from structural MRI (sMRI).

QTest: Quantitative Testing of Theories of Binary Choice.

The goal of this paper is to make modeling and quantitative testing accessible to behavioral decision researchers interested in substantive questions. We provide a novel, rigorous, yet very general, quantitative diagnostic framework for testing theories of binary choice. This permits the nontechnical scholar to proceed far beyond traditionally rather superficial methods of analysis, and it permits the quantitatively savvy scholar to triage theoretical proposals before investing effort into complex and specialized quantitative analyses. Our theoretical framework links static algebraic decision theory with observed variability in behavioral binary choice data. The paper is supplemented with a custom-designed public-domain statistical analysis package, the QTest software. We illustrate our approach with a quantitative analysis using published laboratory data, including tests of novel versions of "Random Cumulative Prospect Theory." A major asset of the approach is the potential to distinguish decision makers who have a fixed preference and commit errors in observed choices from decision makers who waver in their preferences.

Multivariate Voronoi Outlier Detection for Time Series.

Outlier detection is a primary step in many data mining and analysis applications, including healthcare and medical research. This paper presents a general method to identify outliers in multivariate time series based on a Voronoi diagram, which we call Multivariate Voronoi Outlier Detection (MVOD). The approach copes with outliers in a multivariate framework, via designing and extracting effective attributes or features from the data that can take parametric or nonparametric forms. Voronoi diagrams allow for automatic configuration of the neighborhood relationship of the data points, which facilitates the differentiation of outliers and non-outliers. Experimental evaluation demonstrates that our MVOD is an accurate, sensitive, and robust method for detecting outliers in multivariate time series data.