Andreana P. Haley

Socioeconomic Status Modifies Heritability of IQ in Young Children

Scores on the Wechsler Intelligence Scale for Children were analyzed in a sample of 7-year-old twins from the National Collaborative Perinatal Project. A substantial proportion of the twins were raised in families living near or below the poverty level. Biometric analyses were conducted using models allowing for components attributable to the additive effects of genotype, shared environment, and non-shared environment to interact with socioeconomic status (SES) measured as a continuous variable. Results demonstrate that the proportions of IQ variance attributable to genes and environment vary nonlinearly with SES. The models suggest that in impoverished families, 60% of the variance in IQ is accounted for by the shared environment, and the contribution of genes is close to zero; in affluent families, the result is almost exactly the reverse.

Differential functional magnetic resonance imaging response to food pictures in successful weight-loss maintainers relative to normal-weight and obese controls

BACKGROUND Prior research indicates that successful weight-loss maintainers (SWLs) work harder than people of normal weight to maintain their weight loss, including greater dietary restriction of fat and higher physical activity levels. However, little work to date has examined how SWLs differ biologically from normal-weight (NW) and obese controls. OBJECTIVE The objective was to compare the brain responses of SWLs to food pictures with those of NW and obese controls. DESIGN Blood oxygen level-dependent responses to high- and low-energy food pictures were measured in 18 NW controls, 16 obese controls, and 17 SWLs. RESULTS Group differences were identified in 4 regions, which indicated significant change in activation in response to the food pictures. SWLs showed greater activation in the left superior frontal region and right middle temporal region than did NW and obese controls-a pattern of results confirmed in exploratory voxel-wise analyses. Obese controls also showed greater activation in a bilateral precentral region. CONCLUSIONS These results suggest that SWLs show greater activation in frontal regions and primary and secondary visual cortices-a pattern consistent with greater inhibitory control in response to food cues and greater visual attention to the food cues. A greater engagement of inhibitory control regions in response to food cues as well as a greater monitoring of foods may promote control of food intake and successful weight-loss maintenance.

Endothelial function and white matter hyperintensities in older adults with cardiovascular disease.

Background and Purpose— The presence of white matter hyperintensities on brain MRI is common among elderly individuals. Previous research suggests that cardiovascular risk factors are associated with increased white matter hyperintensities. Examining the role of direct physiological measures of vascular function will help to clarify the vascular mechanisms related to white matter hyperintensities. The aim of the present study was to examine the association between endothelial-dependent and endothelial-independent vasodilatation and white matter hyperintensity volume. Methods— Twenty-five older adults with a range of cardiovascular diseases underwent brain MRI and completed assessments of blood vessel integrity using endothelial-dependent and independent flow-mediated dilation of the brachial artery. A semi-automated pixel-based method was used to quantify total brain volume and white matter hyperintensity volume, with white matter hyperintensity volume corrected for total brain volume. The association between measures of flow-mediated dilation and log-transformed white matter hyperintensities was examined. Results— Correlation analysis revealed that endothelial-dependent vasodilatation was significantly and inversely associated with white matter hyperintensity volume. In contrast, endothelial-independent vasodilatation was not associated with white matter hyperintensities. Neither endothelial-dependent nor endothelial-independent vasodilatation was associated with total brain volume. Conclusions— These data provide preliminary evidence that the integrity of the vascular endothelium is associated with white matter hyperintensities in older adults with cardiovascular disease. Impaired vascular function may be one mechanism that contributes to the development of white matter hyperintensities in the brain. Additional longitudinal research combining measures of vessel function, neuroimaging and cognition will be helpful in clarifying this potential mechanism.

Vascular and cognitive functions associated with cardiovascular disease in the elderly.

This study examines the relationship between systemic vascular function, neurocognitive performance, and structural brain abnormalities on magnetic resonance imaging (MRI) among geriatric outpatients with treated, stable cardiovascular disease and no history of neurological illness (n = 88, ages 56–85 years). Vascular function was assessed by cardiac ejection fraction and output, sequential systolic and diastolic blood pressures, flow mediated brachial artery reactivity (BAR), and carotid intima media thickness (IMT). White matter hyperintensities (WMH) on MRI were quantified and examined relative to cognitive and vascular function. Principal component analysis revealed two primary vascular components: one associated with cardiac function, the other with atherosclerotic burden/endothelial dysfunction. Both factors were significantly associated with cognitive function and WMH volume. Reduced systolic variability and increased IMT were most strongly related to reduced attention, executive function, and information-processing speed. These findings suggest the possibility that systemic vascular indices may provide proxy measures of cerebrovascular dysfunction and reinforce the importance of achieving greater understanding of interaction between systemic vascular disease and brain dysfunction among elderly people with cardiovascular disease.

Insulin sensitivity as a mediator of the relationship between BMI and working memory-related brain activation.

Midlife obesity is associated with cognitive deficits and cerebral atrophy in older age. However, little is known about the early signs of these deleterious brain effects or the physiological mechanisms that underlie them. Functional magnetic resonance imaging (fMRI) allows us to detect early changes in brain response to cognitive challenges while behavioral performance is still intact. Accordingly, we examined the impact of obesity on functional activation during a 2‐Back task in 32 cognitively normal middle‐aged adults, who were classified into normal, overweight, and obese groups according to BMI. Additionally, we examined insulin sensitivity as a potential mediator of the relationship between BMI and brain activation. Insulin sensitivity is of special interest because insulin is strongly associated with both obesity and central nervous system functioning. Group differences in task‐related brain activation were examined in a priori regions of interest (ROIs) using ANOVA. The obese BMI group displayed significantly lower task‐related activation in the right parietal cortex, BA 40/7, (F(2,29) = 5.26, P = 0.011) than the normal (P = 0.016) and overweight (P = 0.047) BMI groups. Linear regression and bootstrapping methods for assessing indirect effects indicated that insulin sensitivity fully mediated the relationship between task‐related activation in the right parietal cortex and BMI ((F(3,28) = 9.03, P = 0.000), β = 0.611, P = 0.001, 95% confidence interval: −2.548 to −0.468). In conclusion, obesity in middle age was related to alterations in brain activation during a cognitive challenge and this association appeared to be mediated by insulin sensitivity.

Probiotics in prevention and treatment of obesity: a critical view.

The worldwide prevalence of obesity more than doubled between 1980 and 2014. The obesity pandemic is tightly linked to an increase in energy availability, sedentariness and greater control of ambient temperature that have paralleled the socioeconomic development of the past decades. The most frequent cause which leads to the obesity development is a dysbalance between energy intake and energy expenditure. The gut microbiota as an environmental factor which influence whole-body metabolism by affecting energy balance but also inflammation and gut barrier function, integrate peripheral and central food intake regulatory signals and thereby increase body weight. Probiotics have physiologic functions that contribute to the health of gut microbiota, can affect food intake and appetite, body weight and composition and metabolic functions through gastrointestinal pathways and modulation of the gut bacterial community.

Relationship between testosterone supplementation and insulin-like growth factor-I levels and cognition in healthy older men.

BACKGROUND Our laboratory has previously reported that testosterone (T) administration to older men significantly improves cognitive function. This study examined potential changes in insulin-like growth factor (IGF) IGF-I, IGF-II and IGF-related binding proteins in response to T administration in older men and their relationship to cognitive functioning. METHODS Twenty-five healthy community dwelling volunteers, ranging in age from 50-80 years were randomized to receive weekly intra-muscular (i.m.) injections of either 100 mg T enanthate or placebo (saline) for 6 weeks. Serum hormone levels and cognitive functioning was assessed at baseline and twice during treatment. RESULTS Significant positive associations between IGF-I and IGF-II and spatial memory, spatial reasoning, and verbal fluency were observed after 6 weeks of T administration. Increased serum T levels from treatment were positively associated with improvement in spatial reasoning performance, whereas estradiol was associated with a decline in divided attention performance. Serum IGF-I, IGF-II and IGFBPs did not change in response to T treatment. CONCLUSIONS Our results suggest that T, estradiol and IGF-I may have independent and selective effects on cognitive functioning. Positive associations between T levels and cognition are consistent with an effect of androgen treatment, whereas positive associations between IGF-I levels and cognition are reflective of a relationship between endogenous IGF-I levels and cognition.

Central artery stiffness, neuropsychological function, and cerebral perfusion in sedentary and endurance-trained middle-aged adults.

Background: Midlife vascular disease risk is a strong risk factor for late-life dementia. Central arterial stiffness, a hallmark of vascular aging, is associated with accelerated brain aging and cognitive decline. Habitual aerobic exercise is an effective lifestyle strategy to reduce central arterial stiffness and is related to lower risk of cognitive impairment. Objective: To determine the associations among cardiopulmonary fitness, neuropsychological function, central arterial stiffness, and cerebral perfusion in the sedentary and endurance-trained middle-aged adults. Methods: Twenty-six sedentary and 32 endurance-trained middle-aged adults were measured for maximal oxygen consumption, central arterial stiffness determined by aortic pulse wave velocity and carotid ultrasound, neuropsychological function, and regional cerebral blood flow assessed by MRI. Results: There were no group differences in age, sex, ethnicity, education, blood pressure, and carotid intima–media wall thickness (all P > 0.05). Neuropsychological performance and occipitoparietal perfusion were greater, and central arterial stiffness was lower in endurance-trained individuals than in sedentary individuals (all P < 0.05). Greater cardiopulmonary fitness was related to better cognitive composite scores, including memory and attention-executive function (r = 0.28–0.40, P < 0.05). Lower carotid arterial stiffness was associated with better neuropsychological outcome independent of age, sex, and education (r = −0.32 to −0.35, P < 0.05), and correlated with greater occipitoparietal blood flow (r = −0.37 to −0.51, P < 0.05). Conclusion: Lower carotid artery stiffness in endurance-trained adults is associated with better neuropsychological outcome and greater occipitoparietal perfusion.

Association between central elastic artery stiffness and cerebral perfusion in deep subcortical gray and white matter.

BACKGROUND Central elastic artery stiffness can increase vascular resistance and induce hypertrophic remodeling of cerebral arterioles and, in turn, may increase the risk of cerebral hypoperfusion. In this study, we examined whether central artery stiffness was directly associated with cerebral perfusion. METHODS Thirty-five adults (15 men and 20 women; 49 ± 7 years) were studied. Central artery stiffness was determined by carotid-femoral pulse wave velocity (cfPWV). Regional cerebral perfusion in deep subcortical white and gray matter was measured using arterial spin labeling (ASL). RESULTS Participants were divided into two groups created by a median split of pooled subjects (median cfPWV = 1,090 cm/s). The group with high cfPWV showed significantly lower cerebral perfusion in frontal (29.9 ± 3.6 vs. 50.7 ± 3.7 ml/100 g/min, P = 0.001) and parietal (33.4 ± 6.0 vs. 57.5 ± 5.7 ml/100 g/min, P < 0.01) white matter and hippocampus (44.4 ± 4.4 vs. 60.1 ± 6.1 ml/100 g/min, P = 0.04) than the low cfPWV group. Simple correlation analysis revealed that cfPWV is significantly associated with cerebral perfusion in frontal (r = -0.64, P < 0.001) and parietal (r = -0.36, P = 0.03) white matter. Multiple linear regression analysis further indicated that 11% of the variability in frontal white matter perfusion (ΔR(2) = 0.11, P = 0.03) is explained by cfPWV (β = -0.54, P = 0.03), independent of age, sex, race, heart rate, blood pressure, and cardiovascular medication. CONCLUSIONS Central elastic artery stiffness is inversely and significantly associated with cerebral perfusion in deep subcortical frontal white matter, independent of potential confounding factors.

Subjective cognitive complaints relate to white matter hyperintensities and future cognitive decline in patients with cardiovascular disease.

OBJECTIVE Elderly patients with cardiovascular disease (CVD) often report cognitive difficulties including reduced cognitive processing speed and attention. On cross-sectional examination, such reports relate more closely to mood than to objective measures of cognitive performance, thus questioning the validity of subjective cognitive complaints as a marker of neurodegenerative processes. This study examined the longitudinal relationship among self-reported cognitive difficulties, depression, and performance on objective tests of global cognition in patients with CVD. PARTICIPANTS AND METHODS Forty-seven patients with CVD (aged 55-85 years) completed a measure of perceived cognitive dysfunction (Cognitive Difficulties Scale [CDS]), a medical history questionnaire, the Dementia Rating Scale (DRS), and the Beck Depression Inventory (BDI) at baseline and 12 months later. Baseline brain imaging was available on a small subsample (N = 17). RESULTS Hierarchical linear regression revealed that increased report of cognitive difficulties at baseline was significantly associated with poorer DRS performance at follow-up (F[3, 43] = 4.45, p = 0.008, CDS partial r = -0.30, p = 0.048), independent of age, education, baseline DRS, and BDI scores. Greater perceived cognitive dysfunction at baseline also related to higher level of white matter lesions (r = 0.53, df = 15, p = 0.028). CONCLUSIONS Self-reported cognitive difficulties may reflect early changes in cognitive aging that are difficult to detect using global cognitive screening measures at a single time point. However, these perceived difficulties relate to objectively measured cognitive decline over time. Thus, they may provide important clinical information about early neurodegenerative processes that should be carefully monitored.