Biomedical subjects

John Gunstad

Publications and source records attributed to John Gunstad.

At least 19 recordsLinked to original sources

PubMed2007

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.

Aged↗

PubMed2006

Carotid artery intima-media thickness and cognition in cardiovascular disease.

BACKGROUND: Increased carotid artery intima-media thickness (IMT) is a non-invasive marker of systemic arterial disease. Increased IMT has been associated with atherosclerosis, abnormal arterial mechanics, myocardial infarction, and stroke. Given evidence of a relationship between cardiovascular health and attention-executive-psychomotor functioning, the purpose of this study was to examine IMT in relation to neuropsychological test performance in patients with a variety of cardiovascular diagnoses. METHODS: One hundred and nine participants, ages 55 to 85, underwent neuropsychological assessment and B-mode ultrasound of the left common carotid artery. IMT was calculated using an automated algorithm based on a validated edge-detection technique. The relationship between IMT and measures of language, memory, visual-spatial abilities and attention-executive-psychomotor functioning was modeled using hierarchical linear regression analyses adjusted for age, education, sex, cardiovascular risk, current systolic blood pressure, and history of coronary artery disease (CAD). RESULTS: Increased IMT was associated with significantly lower performance in the attention-executive-psychomotor domain (IMT beta=-0.26, p<.01), independent of age, education, sex, cardiovascular risk, current systolic blood pressure, and CAD (F(10,100)=3.61, p<.001). IMT was not significantly related to language, memory, or visual-spatial abilities. CONCLUSIONS: Our findings suggest that, in patients with cardiovascular disease, IMT may be associated with the integrity of frontal subcortical networks responsible for attention-executive-psychomotor performance. Future studies are needed to clarify the mechanisms by which IMT affects cognition and examine potential interactions between increased IMT and other measures of cardiovascular health such as blood pressure variability, cardiac systolic performance, and systemic perfusion.

Aged↗

PubMed2006

Dissociation of the component processes of attention in healthy adults.

Cohen's [Cohen, R. (1993). The Neuropsychology of Attention. New York: Plenum Publishing] model of attention proposes four interrelated processes, namely Sensory Selective Attention, Response Selection/Control, Focus/Capacity, and Sustained Attention. Though this model has been supported in patient samples, it has not been examined in a healthy adult cohort. Using Principal Components Analysis, we examined the explanatory power of this model in 342 adults screened for significant medical and psychiatric history. The four derived components accounted for 58.7% of the total variance. Results were generally supportive of Cohen's [Cohen, R. (1993). The Neuropsychology of Attention. New York: Plenum Publishing] model, though further clarification of the relationship between processing speed and more complex aspects of attention (e.g. working memory, set shifting) is needed. These findings support the notion that attention is not a unitary process, but instead comprised of distinct components. Future studies including both neuropsychological testing and functional neuroimaging may provide important insight into the underpinnings of attentional processes.

Adolescent↗

PubMed2006

Elevated body mass index is associated with executive dysfunction in otherwise healthy adults.

There is growing evidence that obesity is linked to adverse neurocognitive outcome, including reduced cognitive functioning and Alzheimer disease. However, no study to date has determined whether the relationship between body mass index (BMI) and cognitive performance varies as a function of age. We examined attention and executive function in a cross-section of 408 healthy persons across the adult life span (20-82 years). Bivariate correlation showed that BMI was inversely related to performance on all cognitive tests. After controlling for possible confounding factors, overweight and obese adults (BMI > 25) exhibited poorer executive function test performance than normal weight adults (BMI, 18.5-24.9). No differences emerged in attention test performance, and there was no evidence of a BMI x age interaction for either cognitive domain. These results provide further evidence for the relationship between elevated BMI and reduced cognitive performance and suggest that this relationship does not vary with age. Further research is needed to identify the etiology of these deficits and whether they resolve after weight loss.

Adolescent↗

PubMed2006

Relation of brain natriuretic peptide levels to cognitive dysfunction in adults > 55 years of age with cardiovascular disease.

Cardiovascular disease (CVD) is associated with cognitive deficits long before the onset of stroke or dementia. Recent work has extended these findings and shown that patients with congestive heart failure also exhibit reduced cognitive performance. Brain natriuretic peptide (BNP) is used to help diagnose heart failure, but no study has examined whether BNP predicts cognitive dysfunction in older patients with CVD. BNP values and performance on the Dementia Rating Scale were assessed in 56 older adults with documented CVD. Forty-eight percent of the participants were women, and their average age was 70 +/- 8 years. All participants had Mini-Mental State Examination scores greater than the cutoff for dementia and no histories of neurologic or severe psychiatric disorders. The average BNP level was 122 +/- 202 pg/ml. Hierarchical regression analyses showed that log-transformed BNP levels predicted Dementia Rating Scale total score after adjusting for possible demographic and medical confounders (DeltaR2 = 0.09, F[1, 44] = 6.14, p = 0.017). Partial correlation analysis adjusting for these possible confounders showed a particularly strong relation to the conceptualization subtest (r = -0.44, p = 0.002), a measure of verbal and nonverbal abstraction abilities. In conclusion, the results of the present study provide the first evidence for an independent relation between BNP and cognitive dysfunction in older adults with CVD.

Age Factors↗

PubMed2006

C-reactive protein, but not homocysteine, is related to cognitive dysfunction in older adults with cardiovascular disease.

Cardiovascular disease (CVD) is a risk factor for cognitive impairment and dementia. Recent studies implicate homocysteine (HCY) and C-reactive protein (CRP) in this increased risk, as both are associated with cognitive dysfunction in demented and non-demented patients. However, it remains unclear whether they confer added risk in older adults with CVD. A total of 126 older CVD patients underwent blood and neuropsychological evaluation as part of a prospective examination of the neurocognitive consequences of CVD. A subset of these participants (n=37) also underwent neuroimaging to quantify the degree of white matter disease. After adjusting for demographic and medical factors, no significant relationship emerged between HCY and cognitive performance. In contrast, CRP showed significant independent relationships to test performance, including global cognitive performance, attention/psychomotor function, executive function, memory, and visuospatial abilities. Neither HCY nor CRP was related to extent of white matter disease or whole brain volume on magnetic resonance imaging. Further study is needed to identify mechanisms by which inflammatory processes impact on cognitive function and to determine whether reducing circulating levels of inflammatory markers results in improved cognition.

Aged↗

PubMed2006

Exposure to early life trauma is associated with adult obesity.

Exposure to traumatic events during childhood is associated with an elevated risk of adult obesity. It has been hypothesized that the psychological sequelae from childhood trauma account for this risk, though no study has examined whether an increased risk of obesity is found in persons without psychological disorders. We examined exposure to early life stressors and body mass index (BMI) in 696 adults without significant medical or psychiatric history. Bivariate correlation showed that the total number of early life stressors (r=0.08), age (r=0.19), and sex (r=0.16) were significantly related to adult BMI. Given the relationship between sex and BMI, we examined the contribution of early life stressors to adult obesity separately for men and women. In men, hierarchical regression showed that exposure to early life stressors predicted adult obesity. Specifically, history of being bullied/rejected (Obese 31%, Normal weight, 9%) and emotional abuse (Obese, 17%; Normal weight, 2%) predicted adult obesity after controlling for the effects of age. In women, no relationship between early life stressors and adult obesity was found. These findings suggest that multiple processes mediate the relationship between early life stress and adult obesity and that their relative contributions may differ between men and women.

Adult↗

PubMed2006

BDNF Val66Met polymorphism is associated with body mass index in healthy adults.

Although recent studies suggest a possible relationship between the brain-derived neurotrophic factor Val66Met polymorphism and eating disorders, no study has examined the possibility that the Met-Met genotype is associated with a lower body mass index (BMI) in healthy individuals. We examined this possibility in 481 adults (age range 18-82 years) without significant medical or psychiatric history. After adjusting for gender, analysis of covariance showed that persons with the Met-Met genotype had a lower BMI than those with the Val-Met/Val-Val genotypes (22.28 +/-3.77 vs. 24.72+/-4.81). A similar, though nonsignificant, trend emerged when comparing all three genotypes separately. These findings suggest a possible relationship between Val66Met polymorphism and BMI in healthy adults. Further work is needed to clarify possible mechanisms for this relationship.

Adolescent↗

PubMed2006

Early life stress and morphometry of the adult anterior cingulate cortex and caudate nuclei.

BACKGROUND: Early life stress (ELS) is linked to adult psychopathology and may contribute to long-term brain alterations, as suggested by studies of women who suffered childhood sexual abuse. We examine whether reported adverse ELS defined as stressful and/or traumatic adverse childhood events (ACEs) is associated with smaller limbic and basal ganglia volumes. METHOD: 265 healthy Australian men and women without psychopathology or brain disorders were studied. ACEs were assessed by the ELSQ and current emotional state by the DASS. Anterior cingulate cortex (ACC), hippocampus, amygdala, and caudate nucleus volumes were measured from T1-weighted MRI. Analyses examined ROI volumetric associations with reported ACEs and DASS scores. RESULTS: Participants with greater than two ACEs had smaller ACC and caudate nuclei than those without ACEs. A significant association between total ACEs and ROI volumes for these structures was observed. Regression analysis also revealed that ELS was more strongly associated than current emotional state (DASS) with these ROI volumes. CONCLUSIONS: Reported ELS is associated with smaller ACC and caudate volumes, but not the hippocampal or amygdala volumes. The reasons for these brain effects are not entirely clear, but may reflect the influence of early stress and traumatic events on the developing brain.

Adolescent↗

PubMed2006

Cognitive status of young and older cigarette smokers: data from the international brain database.

Previous studies that have examined the impact of cigarette smoking on cognition have revealed mixed results; some studies report no impact and others report detrimental effects, especially in older individuals. Few studies, however, have examined the effects of cigarette smoking on both young and old healthy individuals using highly robust and standardized methods of cognitive assessment. This study draws on an international database to contrast cognitive differences between younger and older individuals who regularly smoke cigarettes and non-smokers. Data were sampled from 1000 highly screened healthy individuals free of medical or psychiatric health complications. A cohort of 62 regular smokers (n = 45 < 45 years of age; n = 1745 years) with a Fagerstrom nicotine dependency score of 1 or more were identified and matched to a cohort of 62 healthy nonsmokers (n = 43 < 45 years; n = 1945 years) on demographic variables and estimated intelligence. Performances on cognitive measures of attention, reaction time, cognitive flexibility, psychomotor speed, and memory were considered for analysis. As a group, smokers performed more poorly than nonsmokers on one measure of executive function. A significant age and smoking status interaction was identified with older smokers performing more poorly than older nonsmokers and younger smokers on a measure of long-delayed recall of new information. Cigarette smoking is associated with isolated and subtle cognitive difficulties among very healthy individuals.

Adult↗

PubMed2006

The relationship between frontal gray matter volume and cognition varies across the healthy adult lifespan.

OBJECTIVE: Age-associated decline in gray matter brain volume and cognitive function in healthy adults has been reported in the literature. The goal of the current study is to examine the relationship between age-related changes in regional gray matter volumes and cognitive function in a large, cross-sectional sample of healthy adults across the lifespan. METHODS: Magnetic resonance imaging and cognitive assessment were conducted on 148 adults aged 21-76 years. Multiple regression analyses examining the effect of age were performed on magnetic resonance image-derived gray matter brain volumes and standardized cognitive summary scores of attention and executive function. Regression was also performed to test the effect of age, gray matter volumes, and their interaction on the prediction of cognitive performance. RESULTS: Age significantly predicted performance on tests of attention (F [1, 146]=50.97, p <0.01, R2=0.26) and executive function (F [1, 146]=126.19, p <0.01, R2=0.46) and gray matter volumes for frontal subregions (lateral, medial, orbital), hippocampus, amygdala, and putamen (F [2, 145]=45.34-23.96, p <0.01-0.02). Lateral frontal (beta=-1.53, t=-2.16, df=131, p <0.03) and orbital frontal (beta=1.24, t=2.08, df=131, p <0.04) regions significantly predicted performance on tests of attention. Lateral frontal (beta=-1.69, t=-2.83, df=131, p <0.01) and the interaction between age and lateral frontal volume (beta=3.76, t=2.49, df=131, p <0.02) significantly predicted executive function. CONCLUSIONS: The findings confirm age-associated decline in cognitive function and gray matter volumes, particularly in anterior cortical brain regions. Furthermore, the association between lateral frontal gray matter volume and the ability to successfully plan, organize, and execute strategies varies as a function of age across the healthy adult lifespan.

Adult↗

PubMed2006

An obsessive-compulsive subtype of schizotypy: evidence from a nonclinical sample.

Obsessive-compulsive (OC) and schizotypal symptoms are highly correlated in clinical samples. The current study investigated the presence of schizotypal and OC symptomatology in a large undergraduate sample using factor and cluster analysis and t test comparison of cluster groups. Separate clusters of individuals reporting high levels of schizotypal and OC symptoms versus purely schizotypal symptoms emerged and demonstrated different overall symptom profiles. Individuals with high levels of pure schizotypy symptoms demonstrated a prevalence of interpersonal symptoms, including restricted affect, and few close friends. In contrast, those with high levels of both schizotypy and OC symptoms demonstrated higher cognitive/perceptual symptoms, including ideas of reference and suspiciousness. Consistent with research in clinical populations, results suggest greater prevalence of positive symptoms in individuals experiencing both schizotypal and OC disorder symptoms.

Adolescent↗

PubMed2006

Age effects in time estimation: relationship to frontal brain morphometry.

Compared with many other cognitive functions, relatively little is known about time representation in the brain. Recent work shows disrupted timing and time estimation in older adults, although it is unclear whether these effects are the result of normal aging or disease-related processes. The present study examined time estimation in persons across the adult lifespan who were free from significant medical or psychiatric history. Results showed older adults exhibited greater variability in time estimation, but no evidence for systematic acceleration or slowing emerged. This variability was correlated with performance on a variety of cognitive tests including attention, working memory and executive function. Although no relationship emerged between time estimation and EEG indices from central regions, multiple MRI indices were significantly correlated with time estimation. Stepwise regression showed volume of the supplementary motor area predicted variability in time estimation. These results indicate that healthy aging is associated with altered time estimation and suggest that changes in frontal brain regions mediate these effects.

Adolescent↗

PubMed2006

Cognitive reserve and the relationship between depressive symptoms and awareness of deficits in dementia.

Depression and low cognitive reserve are linked to impaired awareness in dementia, although their relative contributions are unknown. The authors investigated the impact of depressive symptoms and cognitive reserve on awareness in questionable and mild dementia. Sixty-six patients completed measures of cognitive reserve, awareness, and depressive symptoms. Cognitive reserve and its interaction with depressive symptoms accounted for significant proportions of variance in awareness; depressive symptoms alone did not. Depressive symptoms and awareness were positively related in high, but not low, cognitive reserve groups. Findings suggest cognitive reserve moderates the depression/awareness relationship in dementia, which may explain previously discrepant findings.

Aged↗

PubMed2006

Patterns of cognitive performance in middle-aged and older adults: A cluster analytic examination.

Cognitive decline in speeded abilities, executive function, and memory is believed to typify normal aging. However, there is significant variability in cognitive function with advanced age and some reports of relatively intact cognitive function among a subset of older individuals. The present study consists of a cluster analysis to examine the patterns of cognitive function in middle-aged and older individuals. Analyses revealed 3 clusters of middle-aged adults, including an intact group, persons with poor motor speed, and a group with reduced executive function. Three clusters were also identified for older adults, including a group with poor executive function, persons with reduced speed performance (attention, executive function, motor), and a group with global cognitive decline. No evidence emerged for a cluster of older adults with intact performance in all domains or with isolated memory deficits. Findings generally support the frontal aging hypothesis and may provide important information about healthy cognitive aging.

Adult↗

PubMed2006

Early life stress and adult emotional experience: an international perspective.

Early life stress (ELS) has been linked to adult psychopathology, though few studies have examined the universality of specific adverse childhood events (ACEs) in healthy adults. We examined the co-occurrence of specific ACEs and their relationship to current emotional distress in an international sample of adults without psychopathology. Participants were 1659 men and women recruited for an international neurocognitive-neuroimaging database from sites in the United States, Australia, England, and the Netherlands. Participants had no current or prior diagnosis of major depression, anxiety, substance abuse, or neurological brain disorder. The occurrence and age on onset of 19 ACEs was assessed by a self-report questionnaire (ELSQ), and current symptoms of stress, depression, and anxiety by the Depression Anxiety Stress Scale (DASS). The relationship of specific ACEs to DASS symptoms was examined. Participants reported relatively high prevalence of ACEs. Only 27.6% of the sample reported no ACEs, while 39.5% reported one or two significant experiences and 32.9% reported more than two ACEs. Rates of most ACEs were quite similar across the three continents. Various ACEs were significantly associated with current DASS severity, particularly ACEs involving emotional abuse, neglect, and family conflict, violence, and breakup. Finding nearly one-third of the sample reported three or more ACEs suggest a high prevalence of ELS in otherwise healthy "normal" adults around the world. Associations between ELS and current emotional distress suggest that these events have functional relevance and deserve further investigation.

Adult↗

PubMed2005

Neuroimaging and cardiac correlates of cognitive function among patients with cardiac disease.

In the present study, we examined the relationships between whole brain volume (WBV), subcortical hyperintensities (SH), indices of cardiac disease and cognitive function in nondemented cardiac patients with evidence of mild cerebrovascular disease. A total of 27 individuals with evidence of cardiac disease underwent neuropsychological examination, neuroimaging, and cardiac assessment. Cognition was assessed with the Dementia Rating Scale-2 (DRS). WBV and SH were quantified using a semi-automated thresholding program based on MRI. Correlational analyses revealed that WBV predicted performance on the overall DRS score, the attention subscale and the initiation/perseveration scale. SH were significantly associated with performance on the attention subscale, and the initiation/perseveration subscale. Regression analyses revealed that SH accounted for most of the variance in the initiation/perseveration scale, whereas WBV accounted for most of the variance in the attention scale. The only cardiac structural or functional variable related to the neurological indices was aortic diameter, which was strongly related to both neuroimaging variables, as well as performances on the DRS attention and initiation/perseveration subscales. Our results highlight the importance of overall brain parenchyma in determining cognitive status among patients at risk for cognitive decline and suggest that select indices of structural cardiac morphology may be related to the early phases of cerebrovascular disease and cognitive status.

Aged↗

PubMed2005

Progressive morphometric and cognitive changes in vascular dementia.

Evidence for progressive cognitive decline in vascular dementia (VaD) is mixed, with some studies showing little or no decline over time. One possible explanation for these inconsistent findings is the heterogeneity of pathology encompassed by the VaD diagnosis. It is possible that subtypes of VaD (i.e. those resulting from different lesion distributions) show different patterns of cognitive decline. In the present study, a heterogeneous VaD group demonstrated cognitive decline from baseline to 12-month follow-up. Although this decline was coincident to morphometric changes (i.e. increased subcortical hyperintensities (SH), decreased whole brain volume (WBV)), no relationship emerged between cognitive decline and morphometric changes. Preliminary examination of VaD subtypes revealed patients with subcortical infarct or SH-only exhibited greater decline than VaD patients with cortical lesions. Further research is needed to determine whether this observed decline is attributable to differential lesion distribution or statistical artifact.

Aged↗