The common genetic influence over processing speed and white matter microstructure: Evidence from the Old Order Amish and Human Connectome Projects

Speed with which brain performs information processing influences overall cognition and is dependent on the white matter fibers. To understand genetic influences on processing speed and white matter FA, we assessed processing speed and diffusion imaging fractional anisotropy (FA) in related individuals from two populations. Discovery analyses were performed in 146 individuals from large Old Order Amish (OOA) families and findings were replicated in 485 twins and siblings of the Human Connectome Project (HCP). The heritability of processing speed was h(2)=43% and 49% (both p\u3c0.005), while the heritability of whole brain FA was h(2)=87% and 88% (both p\u3c0.001), in the OOA and HCP, respectively. Whole brain FA was significantly correlated with processing speed in the two cohorts. Quantitative genetic analysis demonstrated a significant degree to which common genes influenced joint variation in FA and brain processing speed. These estimates suggested common sets of genes influencing variation in both phenotypes, consistent with the idea that common genetic variations contributing to white matter may also support their associated cognitive behavior

ASSOCIATION BETWEEN CUMULATIVE LIFETIME STRESS, COGNITIVE FUNCTION AND SLEEP: THE MODERATING EFFECTS OF RESILIENCE

Stress is multidimensional and can be labeled as acute, chronic, or cumulative. Cumulative lifetime stress encompasses the exposure to stressors occurring over the course of the lifetime, instead of focusing on a specific time point. Not surprisingly, exposure to stress over the lifetime can pose significant negative effects on one’s physical, mental, and emotional wellbeing. It has further been suggested that exposure to cumulative lifetime stress can have varying effects on cognitive function and sleep. While some studies have previously examined these relationships, more research is needed. As such, the goal of the current study was to examine the relationship between cumulative lifetime stress and cognitive function, the relationship between cumulative lifetime stress and sleep function, and the role of resilience as a moderator in the stress-cognitive function and stress-sleep relationships in a college student sample (n = 153). Linear regressions and moderation analyses were used to ascertain those relationships. Results demonstrated that cumulative lifetime stress did not predict variables of cognitive function, except for working memory, where greater cumulative lifetime stress was associated with better working memory task performance. In contrast, cumulative lifetime stress predicted sleep outcomes, with greater cumulative lifetime stress associated with more sleep quality disturbances, and greater insomnia severity, and daytime sleepiness. In both analyses, resilience as a moderator did not influence those relationships. Findings from the current study underscore the detrimental effects of lifetime stress exposure on health outcomes, further adding to existing literature

The common genetic influence over processing speed and white matter microstructure: Evidence from the Old Order Amish and Human Connectome Projects.

Speed with which brain performs information processing influences overall cognition and is dependent on the white matter fibers. To understand genetic influences on processing speed and white matter FA, we assessed processing speed and diffusion imaging fractional anisotropy (FA) in related individuals from two populations. Discovery analyses were performed in 146 individuals from large Old Order Amish (OOA) families and findings were replicated in 485 twins and siblings of the Human Connectome Project (HCP). The heritability of processing speed was h(2)=43% and 49% (both p<0.005), while the heritability of whole brain FA was h(2)=87% and 88% (both p<0.001), in the OOA and HCP, respectively. Whole brain FA was significantly correlated with processing speed in the two cohorts. Quantitative genetic analysis demonstrated a significant degree to which common genes influenced joint variation in FA and brain processing speed. These estimates suggested common sets of genes influencing variation in both phenotypes, consistent with the idea that common genetic variations contributing to white matter may also support their associated cognitive behavior

Cardiovascular risks impact human brain N -acetylaspartate in regionally specific patterns

Cardiovascular risk factors such as dyslipidemia and hypertension increase the risk for white matter pathology and cognitive decline. We hypothesize that white matter levels of -acetylaspartate (NAA), a chemical involved in the metabolic pathway for myelin lipid synthesis, could serve as a biomarker that tracks the influence of cardiovascular risk factors on white matter prior to emergence of clinical changes. To test this, we measured levels of NAA across white matter and gray matter in the brain using echo planar spectroscopic imaging (EPSI) in 163 individuals and examined the relationship of regional NAA levels and cardiovascular risk factors as indexed by the Framingham Cardiovascular Risk Score (FCVRS). NAA was strongly and negatively correlated with FCVRS across the brain, but, after accounting for age and sex, the association was found primarily in white matter regions, with additional effects found in the thalamus, hippocampus, and cingulate gyrus. FCVRS was also negatively correlated with creatine levels, again primarily in white matter. The results suggest that cardiovascular risks are related to neurochemistry with a predominantly white matter pattern and some subcortical and cortical gray matter involvement. NAA mapping of the brain may provide early surveillance for the potential subclinical impact of cardiovascular and metabolic risk factors on the brain