Elevated Serum C-Reactive Protein Relates to Increased Cerebral Myoinositol Levels in Middle-Aged Adults

C-reactive protein (CRP), a systemic marker of inflammation, is a risk factor for late life cognitive impairment and dementia, yet the mechanisms that link elevated CRP to cognitive decline are not fully understood. In this study we examined the relationship between CRP and markers of neuronal integrity and cerebral metabolism in middle-aged adults with intact cognitive function, using proton magnetic resonance spectrocospy. We hypothesized that increased levels of circulating CRP would correlate with changes in brain metabolites indicative of early brain vulnerability. Thirty-six individuals, aged 40 to 60, underwent neuropsychological assessment, a blood draw for CRP quantification, and 1H MRS examining N-acetyl-aspartate, myo-inositol, creatine, choline, and glutamate concentrations in occipito-parietal grey matter. Independent of age, sex and education, serum CRP was significantly related to higher cerebral myo-inositol/creatine ratio (F(4,31) = 4.74, P = 0.004), a relationship which remained unchanged after adjustment for cardiovascular risk (F(5,30) = 4.356, CRP β = 0.322, P = 0.045). Because these biomarkers are detectable in midlife they may serve as useful indicators of brain vulnerability during the preclinical period when mitigating intervention is still possible

Overlap of phonetic features as a determinant of the between-stream phonological similarity effect

Serial recall from working memory is known to be impaired by the presence of irrelevant background speech, but several prior studies have concluded that the magnitude of the impairment is independent of the phonological relationship between to-be-remembered (TBR) and to-be-ignored (TBI) sources of information. In the present study, we examined the influence of between-stream phonological similarity in serial recall while attending to a heretofore uncontrolled variable, the phonetic feature. We found that TBI items sharing many phonetic features with TBR items produced significantly stronger working-memory impairments than TBI items with minimal phonetic feature overlap. In addition, participants were more likely to report remembering incorrect items that incorporated phonological characteristics of the TBI stream in the high-overlap condition. These findings provide evidence for subphonemic between-stream interactions and suggest that multiple parallel processes contribute to the irrelevant speech effect. We propose that a 2-component model, which combines the assumptions of process- and content-based accounts for the irrelevant speech effect, offers the best explanation for these findings. © 2011 American Psychological Association

Indirect effects of elevated body mass index on memory performance through altered cerebral metabolite concentrations

OBJECTIVE: Elevated body mass index (BMI) at midlife is associated with increased risk of cognitive decline in later life. The goal of the current study was to assess mechanisms of early brain vulnerability by examining if higher BMI at midlife affects current cognitive performance through alterations in cerebral neurochemistry. METHODS: Fifty-five participants, aged 40 to 60 years, underwent neuropsychological testing, health screen, and proton magnetic resonance spectroscopy examining N-acetylaspartate, creatine (Cr), myo-inositol (mI), choline, and glutamate concentrations in occipitoparietal gray matter. Concentrations of N-acetylaspartate, choline, mI, and glutamate were calculated as a ratio over Cr and examined in relation to BMI using multivariate regression analyses. Structural equation modeling was used to determine if BMI had an indirect effect on cognition through cerebral metabolite levels. RESULTS: Higher BMI was associated with elevations in mI/Cr (F(5,45) = 3.843, p =.006, β = 0.444, p =.002), independent of age, sex, fasting glucose levels, and systolic blood pressure. Moreover, a χ difference test of the direct and indirect structural equation models revealed that BMI had an indirect effect on global cognitive performance (Δχ = 19.939, df = 2, p \u3c.001). Subsequent follow-up analyses revealed that this effect was specific to memory (Δχ = 22.027, df = 2, p \u3c.001). CONCLUSIONS: Higher BMI was associated with elevations in mI/Cr concentrations in the occipitoparietal gray matter and indirectly related to poorer memory performance through mI/Cr levels, potentially implicating plasma hypertonicity and neuroinflammation as mechanisms underlying obesity-related brain vulnerability. Copyright © 2012 by the American Psychosomatic Society

Functional magnetic resonance imaging of working memory reveals frontal hypoactivation in middle-aged adults with cognitive complaints

Older adults with cardiovascular disease (CVD) often complain about cognitive difficulties including reduced processing speed and attention. On cross-sectional examination, such reports relate more closely to mood than to cognitive performance; yet, in longitudinal studies, these complaints have foreshadowed cognitive decline over time. To test the hypothesis that self-reported cognitive difficulties reflect early changes in brain function, we examined cognitive complaints and depression in relation to blood oxygen level dependent (BOLD) response to a cognitive task in middle-aged adults at risk for CVD. Forty-nine adults (ages 40 to 60 years) completed a measure of perceived cognitive dysfunction (Cognitive Difficulties Scale), medical history questionnaire, neuropsychological assessment and functional magnetic resonance imaging (fMRI) during a working memory task. Increased report of cognitive difficulties was significantly associated with weaker task-related activation in the right superior frontal/middle frontal gyrus (F(4,44) = 3.26; p =.020, CDS = 0.39; p =.009) and the right inferior frontal gyrus (F(4,44) = 3.14; p =.024, CDS = 0.45; p =.003), independent of age, education, and self-reported depressive symptoms. Lower activation intensity in the right superior frontal gyrus was related to trends toward poorer task performance. Thus, self-reported cognitive difficulties among cognitively normal middle-aged adults may provide important clinical information about early brain vulnerability that should be carefully monitored. © 2011 The International Neuropsychological Society

Inflammation as a mediator of the relationship between cortical thickness and metabolic syndrome

Metabolic Syndrome (MetS), the clustering of obesity, high blood pressure, and disordered glucose and lipid/lipoprotein metabolism within a single individual, is associated with poorer cognitive function. It has been hypothesized that cognitive impairment in MetS occurs primarily within the context of inflammation. MetS risk factors are also associated with thinning of the cerebral cortex. However, the mechanisms by which MetS and inflammation affect the brain are poorly understood. The present study used statistical mediation to examine the relationship between MetS risk factors, cortical thickness in a priori regions of interest (ROIs) and inflammation. ROIs were chosen from the previous literature. Forty-three adults between the ages of 40 and 60 years underwent a health screen, neuropsychological testing and structural magnetic resonance imaging. Serum levels of pro-inflammatory markers (interleukin 1, interleukin 2, interleukin 6 and C-Reactive Protein) were measured using enzyme-linked immunosorbent assays. A higher number of MetS risk factors were associated with thinning in the inferior frontal ROI (β = −0.35, p = 0.019) as well as higher levels of serum interleukin 2 (β = 0.31, p = 0.04). A higher level of serum interleukin 2 was also associated with reduced thickness in the inferior frontal gyrus (β = −0.41, p = 0.013). After accounting for the effects of interleukin 2, the number of MetS risk factors was no longer associated with cortical thickness in the inferior frontal gyrus indicating successful statistical mediation. The results indicate a potentially important role for inflammation in linking MetS to cortical thinning and cognitive vulnerability

Baseline Characteristics of the 2015-2019 First Year Student Cohorts of the NIH Building Infrastructure Leading to Diversity (BUILD) Program.

ObjectiveThe biomedical/behavioral sciences lag in the recruitment and advancement of students from historically underrepresented backgrounds. In 2014 the NIH created the Diversity Program Consortium (DPC), a prospective, multi-site study comprising 10 Building Infrastructure Leading to Diversity (BUILD) institutional grantees, the National Research Mentoring Network (NRMN) and a Coordination and Evaluation Center (CEC). This article describes baseline characteristics of four incoming, first-year student cohorts at the primary BUILD institutions who completed the Higher Education Research Institute, The Freshmen Survey between 2015-2019. These freshmen are the primary student cohorts for longitudinal analyses comparing outcomes of BUILD program participants and non-participants.DesignBaseline description of first-year students entering college at BUILD institutions during 2015-2019.SettingTen colleges/universities that each received <$7.5mil/yr in NIH Research Project Grants and have high proportions of low-income students.ParticipantsFirst-year undergraduate students who participated in BUILD-sponsored activities and a sample of non-BUILD students at the same BUILD institutions. A total of 32,963 first-year students were enrolled in the project; 64$30,000/yr and 25% were their family's first generation in college.Planned outcomesPrimary student outcomes to be evaluated over time include undergraduate biomedical degree completion, entry into/completion of a graduate biomedical degree program, and evidence of excelling in biomedical research and scholarship.ConclusionsThe DPC national evaluation has identified a large, longitudinal cohort of students with many from groups historically underrepresented in the biomedical sciences that will inform institutional/national policy level initiatives to help diversify the biomedical workforce

Current Serum Lipoprotein Levels and fMRI Response to Working Memory in Midlife

Aims: Given that high cholesterol levels at midlife are a risk factor for future cognitive decline, the goal of the current study was to determine if cholesterol-related alterations in the cerebrovascular response to cognition could be detected at midlife. Methods: Forty adults, aged 40-60 years, performed a 2-Back working memory task during fMRI. The associations between serum total cholesterol, HDL-cholesterol, and total cholesterol/HDL-cholesterol concentrations to task-related activation intensity were modeled using multivariate multiple regression (two-tailed p \u3c 0.02). Results: Higher levels of total cholesterol/HDL-cholesterol related to reduced working memory-related activation intensity in the left inferior parietal lobe, right superior frontal gyrus, and right middle frontal gyrus. Conclusion: These data provide preliminary support for a deleterious effect of elevated total cholesterol/HDL-cholesterol ratio on cerebrovascular support for cognition in midlife. Copyright © 2011 S. Karger AG, Basel