Can structural MRI indices of cerebral integrity track cognitive trends in executive control function during normal maturation and adulthood?

We explored the relationship between structural neuroimaging-based indices of cerebral integrity and executive control function (ECF) in two groups of healthy subjects: A maturing group (33 subjects; 19-29 years) and a senescing group (38 adults; 30-90 years). ECF was assessed using the Executive Interview (EXIT) battery. Cortical indices of cerebral integrity included GM thickness, intergyral span, and sulcal span, each measured for five cortical regions per hemisphere. Subcortical indices included fractional anisotropy (FA), measured using track-based-spatial-statistics (TBSS), and the volume of T2-hyperintense WM (HWM). In the maturing group, no significant relationships between neuroanatomical changes and ECF were found; however, there were hints that late-term maturation of cerebral WM influenced variability in ECF. In the senescing group, the decline in ECF corresponded to atrophic changes in cerebral WM (sulcal and intergyral span) primarily in the superior frontal and anterior cingulate regions. A large fraction of the variability in ECF (62%) can be explained by variability in the structural indices from these two regions.

Prevalence of prediabetes and diabetes and metabolic profile of patients with nonalcoholic fatty liver disease (NAFLD).

OBJECTIVE: Prediabetes and type 2 diabetes mellitus (T2DM) are believed to be common and associated with a worse metabolic profile in patients with nonalcoholic fatty liver disease (NAFLD). However, no previous study has systematically screened this population. RESEARCH DESIGN AND METHODS: We studied the prevalence and the metabolic impact of prediabetes and T2DM in 118 patients with NAFLD. The control group comprised 20 subjects without NAFLD matched for age, sex, and adiposity. We measured 1) plasma glucose, insulin, and free fatty acid (FFA) concentration during an oral glucose tolerance test; 2) liver fat by magnetic resonance spectroscopy (MRS); 3) liver and muscle insulin sensitivity (euglycemic insulin clamp with 3-[(3)H]glucose); and 4) indexes of insulin resistance (IR) at the level of the liver (HIR(i)= endogenous glucose production × fasting plasma insulin [FPI]) and adipose tissue (Adipo-IR(i)= fasting FFA × FPI). RESULTS: Prediabetes and T2DM was present in 85% versus 30% in controls (P < 0.0001), all unaware of having abnormal glucose metabolism. NAFLD patients were IR at the level of the adipose tissue, liver, and muscle (all P < 0.01-0.001). Muscle and liver insulin sensitivity were impaired in patients with NAFLD to a similar degree, whether they had prediabetes or T2DM. Only adipose tissue IR worsened in T2DM and correlated with the severity of muscle (r = 0.34; P < 0.001) and hepatic (r = 0.57; P < 0.0001) IR and steatosis by MRS (r = 0.35; P < 0.0001). CONCLUSIONS: Patients with NAFLD may benefit from early screening for T2DM, because the prevalence of abnormal glucose metabolism is much higher than previously appreciated. Regardless of glucose tolerance status, severe IR is common. In patients with T2DM, adipose tissue IR appears to play a major role in the severity of NAFLD.

Genetic analysis of cortical thickness and fractional anisotropy of water diffusion in the brain.

OBJECTIVES: The thickness of the brain's cortical gray matter (GM) and the fractional anisotropy (FA) of the cerebral white matter (WM) each follow an inverted U-shape trajectory with age. The two measures are positively correlated and may be modulated by common biological mechanisms. We employed four types of genetic analyses to localize individual genes acting pleiotropically upon these phenotypes. METHODS: Whole-brain and regional GM thickness and FA values were measured from high-resolution anatomical and diffusion tensor MR images collected from 712, Mexican American participants (438 females, age = 47.9 ± 13.2 years) recruited from 73 (9.7 ± 9.3 individuals/family) large families. The significance of the correlation between two traits was estimated using a bivariate genetic correlation analysis. Localization of chromosomal regions that jointly influenced both traits was performed using whole-genome quantitative trait loci (QTL) analysis. Gene localization was performed using SNP genotyping on Illumina 1M chip and correlation with leukocyte-based gene-expression analyses. The gene-expressions were measured using the Illumina BeadChip. These data were available for 371 subjects. RESULTS: Significant genetic correlation was observed among GM thickness and FA values. Significant logarithm of odds (LOD ≥ 3.0) QTLs were localized within chromosome 15q22-23. More detailed localization reported no significant association (p < 5·10(-5)) for 1565 SNPs located within the QTLs. Post hoc analysis indicated that 40% of the potentially significant (p ≤ 10(-3)) SNPs were localized to the related orphan receptor alpha (RORA) and NARG2 genes. A potentially significant association was observed for the rs2456930 polymorphism reported as a significant GWAS finding in Alzheimer's disease neuroimaging initiative subjects. The expression levels for RORA and ADAM10 genes were significantly (p < 0.05) correlated with both FA and GM thickness. NARG2 expressions were significantly correlated with GM thickness (p < 0.05) but failed to show a significant correlation (p = 0.09) with FA. DISCUSSION: This study identified a novel, significant QTL at 15q22-23. SNP correlation with gene-expression analyses indicated that RORA, NARG2, and ADAM10 jointly influence GM thickness and WM-FA values.

Relationship among neuroimaging indices of cerebral health during normal aging.

Sensitive measures of brain aging show great promise for gauging factors that affect aging and degenerative processes, such as risk genes or therapy. Here we examined age-related trends for three indices of cerebral health: gyral gray matter (GM) thickness, dilation of sulcal spaces with CSF, and the volume of T2-hyperintense white matter (HWM) lesions. The study involved 31 healthy adults age 57-82 years old. Measurements of average GM thickness, average sulcal span and HWM volume were performed using high-resolution 3D T1- and T2-weighted brain MR images. Age-related trends for the three cerebral health indices were consistent with previously published work though the analysis of their covariance led to a previously unreported relationship. Simultaneous multiple regression found that dilation of cortical sulci were primarily (t = 2.59, P < 0.01) related to the increases in HWM volume and secondarily related (t = -2.51, P < 0.01) to the reductions of the cortical GM thickness. The are-corrected correlation between reduction in GM thickness and increases in HWM volume, was not significant (P = 0.34). These findings are of interest in designing quantitative measures of brain aging for monitoring individual patients and in large-scale clinical trials.