Nutrient biomarker patterns, cognitive function, and fMRI measures of network efficiency in the aging brain.

A central aim of research in the psychological and brain sciences is to establish therapeutic interventions to promote healthy brain aging. Accumulating evidence indicates that diet and the many bioactive substances present in food are reasonable interventions to examine for dementia prevention. However, interdisciplinary research that applies methods from nutritional epidemiology and network neuroscience to investigate the role of nutrition in shaping functional brain network efficiency remains to be conducted. The present study therefore sought to combine methods across disciplines, applying nutrient biomarker pattern (NBP) analysis to capture the effects of plasma nutrients in combination and to examine their collective influence on measures of functional brain network efficiency (small-world propensity). We examined the contribution of NBPs to multiple indices of cognition and brain health in non-demented elders (n = 116), investigating performance on measures of general intelligence, executive function, and memory, and resting-state fMRI measures of brain network efficiency within seven intrinsic connectivity networks. Statistical moderation investigated whether NBPs influenced network efficiency and cognitive outcomes. The results revealed five NBPs that were associated with enhanced cognitive performance, including biomarker patterns high in plasma: (1) ω-3 and ω-6 polyunsaturated fatty acids (PUFAs), (2) lycopene, (3) ω-3 PUFAs, (4) carotenoids, and (5) vitamins B (riboflavin, folate, B12) and D. Furthermore, three NBPs were associated with enhanced functional brain network efficiency, including biomarker patterns high in plasma: (1) ω-6 PUFAs, (2) ω-3 PUFAs, and (3) carotene. Finally, ω-3 PUFAs moderated the fronto-parietal network and general intelligence, while ω-6 PUFAs and lycopene moderated the dorsal attention network and executive function. In sum, NBPs account for a significant proportion of variance in measures of cognitive performance and functional brain network efficiency. The results motivate a multidisciplinary approach that applies methods from nutritional epidemiology (NBP analysis) and cognitive neuroscience (functional brain network efficiency) to characterize the impact of nutrition on human health, aging, and disease.

Nutrient biomarkers shape individual differences in functional brain connectivity: Evidence from omega-3 PUFAs.

A wealth of neuroscience evidence demonstrates that diet and nutrition play an important role in structural brain plasticity, promoting the development of gray matter volume and maintenance of white matter integrity across the lifespan. However, the role of nutrition in shaping individual differences in the functional brain connectome remains to be well established. We therefore investigated whether nutrient biomarkers known to have beneficial effects on brain structure (i.e., the omega-3 polyunsaturated fatty acids; ω-3 PUFAs), explain individual differences in functional brain connectivity within healthy older adults (N = 96). Our findings demonstrate that ω-3 PUFAs are associated with individual differences in functional connectivity within regions that support executive function (prefrontal cortex), memory (hippocampus), and emotion (amygdala), and provide key evidence that the influence of these regions on global network connectivity reliably predict general, fluid, and crystallized intelligence. The observed findings not only elucidate the role of ω-3 PUFAs in functional brain plasticity and intelligence, but also motivate future studies to examine their impact on psychological health, aging, and disease.

Prospective memory intervention using visual imagery in individuals with brain injury.

Prospective memory deficits are common after brain injury and can create impediments to independent living. Most approaches to management of such deficits are compensatory, such as the use of notebooks or electronic devices. While these can be effective, a restorative approach, in theory, could lead to greater generalisation of treatment. In the current study a metacognitive technique, using visual imagery, was employed under conditions of rote repetition and spaced retrieval. Treatment was provided in an AB-BA crossover design with A as the active treatment and B as a no-treatment attention control to 20 individuals with brain injury. A group of 20 healthy participants served to control for effects of re-testing. Individuals with brain injury demonstrated improvement on the main outcome measure of prospective memory, the Memory for Intentions Screening Test, only after the active treatment condition. In addition, some generalisation of treatment was measured in daily life. Moreover, treatment gains were maintained for one year after treatment was completed.

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.

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.

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.

Effects of drinking patterns on prospective memory performance in college students.

OBJECTIVE: Traditional college students are at a critical juncture in the development of prospective memory (PM). Their brains are vulnerable to the effects of alcohol. METHOD: There were 123 third and fourth year college students, 19-23 years old, who completed the Self-Rating Effects of Alcohol (SREA), Modified Timeline Follow-back (TFLB), Brief Young Adult Alcohol Consequences Scale (BYAACS), and Alcohol Effects Questionnaire (AEQ) once per month on a secure online database, as reported elsewhere (Dager et al., 2013). Data from the 6 months immediately before memory testing were averaged. In a single testing session participants were administered the Mini International Neuropsychiatric Interview-Diagnostic and Statistical Manual for Mental Disorders-Fourth Edition-Text Revision (MINI-DSM-IV-TR), measures of PM (event-based and time-based), and retrospective memory (RM). Based on the average score of six consecutive monthly responses to the SREA, TLFB, and AEQ, students were classified as nondrinkers, light drinkers, or heavy drinkers (as defined previously; Dager et al., 2013). Alcohol-induced amnesia (blackout) was measured with the BYAACS. RESULTS: We found a relationship between these alcohol use classifications and time-based PM, such that participants who were classified as heavier drinkers were more likely to forget to perform the time-based PM task. We also found that self-reported alcohol-induced amnesia (blackouts) during the month immediately preceding memory testing was associated with lower performance on the event-based PM task. Participants' ability to recall the RM tasks suggested the PM items were successfully encoded even when they were not carried out, and we observed no relationship between alcohol use and RM performance. CONCLUSION: Heavy alcohol use in college students may be related to impairments in PM. (PsycINFO Database Record

Nutritional Cognitive Neuroscience: Innovations for Healthy Brain Aging.

Nutritional cognitive neuroscience is an emerging interdisciplinary field of research that seeks to understand nutrition's impact on cognition and brain health across the life span. Research in this burgeoning field demonstrates that many aspects of nutrition-from entire diets to specific nutrients-affect brain structure and function, and therefore have profound implications for understanding the nature of healthy brain aging. The aim of this Focused Review is to examine recent advances in nutritional cognitive neuroscience, with an emphasis on methods that enable discovery of nutrient biomarkers that predict healthy brain aging. We propose an integrative framework that calls for the synthesis of research in nutritional epidemiology and cognitive neuroscience, incorporating: (i) methods for the precise characterization of nutritional health based on the analysis of nutrient biomarker patterns (NBPs), along with (ii) modern indices of brain health derived from high-resolution magnetic resonance imaging (MRI). By integrating cutting-edge techniques from nutritional epidemiology and cognitive neuroscience, nutritional cognitive neuroscience will continue to advance our understanding of the beneficial effects of nutrition on the aging brain and establish effective nutritional interventions to promote healthy brain aging.

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.

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.

Anterior cingulate cortex mediates the relationship between O3PUFAs and executive functions in APOE e4 carriers.

INTRODUCTION: Although diet has a substantial influence on the aging brain, the relationship between biomarkers of diet and aspects of brain health remains unclear. This study examines the neural mechanisms that mediate the relationship between omega-3 polyunsaturated fatty acids (O3PUFAs) and executive functions in at-risk (APOE e4 carriers), cognitively intact older adults. We hypothesized that higher levels of O3PUFAs are associated with better performance in a particular component of the executive functions, namely cognitive flexibility, and that this relationship is mediated by gray matter volume of a specific region thought to be important for cognitive flexibility, the anterior cingulate cortex. METHODS: We examined 40 cognitively intact adults between the ages of 65 and 75 with the APOE e4 polymorphism to investigate the relationship between biomarkers of O3PUFAs, tests of cognitive flexibility (measured by the Delis-Kaplan Executive Function System Trail Making Test), and gray matter volume within regions of the prefrontal cortex (PFC). RESULTS: A mediation analysis revealed that gray matter volume within the left rostral anterior cingulate cortex partially mediates the relationship between O3PUFA biomarkers and cognitive flexibility. CONCLUSION: These results suggest that the anterior cingulate cortex acts as a mediator of the relationship between O3PUFAs and cognitive flexibility in cognitively intact adults thought to be at risk for cognitive decline. Through their link to executive functions and neuronal measures of PFC volume, O3PUFAs show potential as a nutritional therapy to prevent dysfunction in the aging brain.

Prospective memory in schizophrenia: relationship to medication management skills, neurocognition, and symptoms in individuals with schizophrenia.

OBJECTIVE: Impaired adherence to medication regimens is a serious concern for individuals with schizophrenia linked to relapse and poorer outcomes. One possible reason for poor adherence to medication is poor ability to remember future intentions, labeled prospective memory skills. It has been demonstrated in several studies that individuals with schizophrenia have impairments in prospective memory that are linked to everyday life skills. However, there have been no studies, to our knowledge, examining the relationship of a clinical measure of prospective memory to medication management skills, a key element of successful adherence. METHODS: In this Study 41 individuals with schizophrenia and 25 healthy adults were administered a standardized test battery that included measures of prospective memory, medication management skills, neurocognition, and symptoms. RESULTS: Individuals with schizophrenia demonstrated impairments in prospective memory (both time and event-based) relative to healthy controls. Performance on the test of prospective memory was correlated with the standardized measure of medication management in individuals with schizophrenia. Moreover, the test of prospective memory predicted skills in medication adherence even after measures of neurocognition were accounted for. CONCLUSIONS: This suggests that prospective memory may play a key role in medication management skills and thus should be a target of cognitive remediation programs.