David F. Tate

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.

Obesity is associated with memory deficits in young and middle-aged adults

Recent findings suggest obesity is associated with reduced memory performance in older adults. The present study examined whether similar deficits also exist in younger adults and the degree to which the relationship between body mass index (BMI) and memory varies as a function of age. Prior to inclusion, participants were rigorously screened and excluded for medical conditions known to impact cognitive functioning, including neurological disorders, head injury, cardiovascular disease, and diabetes. A total of 486 healthy adults completed a verbal list-learning task. Participants were categorized into normal weight, overweight, and obese groups based on their BMI. Performance on learning, delayed recall, and recognition performance were compared across BMI groups. Results showed obese individuals had poorer memory performance when comparing persons across the adult lifespan (age 21–82 yr), but also when examining only younger and middle-aged adults (age 21–50 yr). Regression analyses found no evidence of an interaction between BMI and age on any memory variable, suggesting the relationship between BMI and memory does not vary with age. These findings provide further support for an independent relationship between obesity and reduced memory performance and suggest these effects are not limited to older adults. Further research is needed to identify etiological factors.

Relationship Between Body Mass Index and Brain Volume in Healthy Adults

There is a growing evidence that elevated body mass index (BMI) is associated with adverse neurocognitive outcome, though no study has examined whether morphometric differences are found in persons across the adult life span. We compared 201 healthy individuals in normal weight, overweight, and obese groups (aged 17–79). After correcting for demographic differences, obese individuals showed smaller whole brain and total gray matter volume than normal weight and overweight individuals. These findings support an independent relationship between BMI and brain structure and demonstrate that these differences are not limited to older adults.

Regional white matter and neuropsychological functioning across the adult lifespan

BACKGROUND The current study utilized magnetic resonance imaging (MRI) to more fully elucidate the relationship among age, regional white matter, and neuropsychological functioning. METHODS One hundred ninety-nine neurologically healthy adults received MRI and standardized neuropsychological assessment. MR images were spatially normalized and segmented by tissue type; relative white matter values in each of the four cerebral lobes in each hemisphere were computed. Subjects were divided into Younger (ages 21-30), Middle (ages 31-54), and Older (ages 55-79) age groups. RESULTS The Older group had significantly less overall relative white matter than the Middle group, who had significantly less overall relative white matter than the Younger participants (F (2, 193) = 5.42, p = 0.005). Differences in frontal lobe white matter were of largest magnitude, followed by temporal lobe (F (6, 579) = 3.32, p = 0.003). Age and frontal and temporal lobe white matter were primarily associated with performance on neuropsychological tests of executive functioning and memory. Mediational analysis suggested that frontal lobe white matter mediated the relationship between age and performance on tasks of executive functioning and memory. CONCLUSIONS The results confirm age-associated decline in frontal and temporal white matter, and age-related cognitive decline in several domains. Decline in neuropsychological functioning is, in part, mediated by a relative age-related reduction in frontal white matter.

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.

The Impact of Apathy and Depression on Quality of Life in Patients Infected with HIV

Apathy refers to decreased self-initiation and goal-directed behavior. Apathy is a relatively common neuropsychiatric symptom associated with HIV, yet the impact of apathy on health-related quality of life (QOL) has not been investigated. We examined the relationship between apathy, depression, and QOL among individuals infected with HIV. Apathy was quantified using the Marin Apathy scale and QOL was measured with the Medical Outcomes Study Short-Form 36 (SF-36). Results of the study revealed that both apathy and depression were more common among patients with HIV than healthy control subjects. Twenty-six percent of the patients with HIV reported clinically significant apathy while 80% of the patients reported clinically significant depression. Apathy did not relate to ratings of overall QOL, but it was modestly associated with ratings of mental health and role disruption secondary to mental health. By contrast, ratings of depression were strongly related to overall QOL and most indices of SF-36. Regression equations revealed that depression and apathy independently contributed to mental health and role disruption secondary to mental health. Importantly, ratings of depression accounted for the majority of variance for ratings of QOL. The findings indicate that while apathy is more common among individuals with HIV compared to healthy control subjects, the impact of apathy on QOL is less significant than depression. Clinicians should continue to focus on depression as an important neuropsychiatric symptom associated with HIV.

Reliability and validity of MRI-based automated volumetry software relative to auto-assisted manual measurement of subcortical structures in HIV-infected patients from a multisite study

The automated volumetric output of FreeSurfer and Individual Brain Atlases using Statistical Parametric Mapping (IBASPM), two widely used and well published software packages, was examined for accuracy and consistency relative to auto-assisted manual (AAM) tracings (i.e., manual correction of automated output) when measuring the caudate, putamen, amygdala, and hippocampus in the baseline scans of 120 HIV-infected patients (86.7% male, 47.3+/-6.3y.o., mean HIV duration 12.0+/-6.3years) from the NIH-funded HIV Neuroimaging Consortium (HIVNC) cohort. The data was examined for accuracy and consistency relative to auto-assisted manual tracing, and construct validity was assessed by correlating automated and AAM volumetric measures with relevant clinical measures of HIV progression. When results were averaged across all patients in the eight structures examined, FreeSurfer achieved lower absolute volume difference in five, higher sensitivity in seven, and higher spatial overlap in all eight structures. Additionally, FreeSurfer results exhibited less variability in all measures. Output from both methods identified discrepant correlations with clinical measures of HIV progression relative to AAM segmented data. Overall, FreeSurfer proved more effective in the context of subcortical volumetry in HIV-patients, particularly in a multisite cohort study such as this. These findings emphasize that regardless of the automated method used, visual inspection of segmentation output, along with manual correction if necessary, remains critical to ensuring the validity of reported results.

Lower Cardiac Output Is Associated with Greater White Matter Hyperintensities in Older Adults with Cardiovascular Disease

OBJECTIVES: To preliminarily examine the association between cardiac output, a measure of systemic blood flow, and structural brain magnetic resonance imaging indices of white matter hyperintensities (WMHs).

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.

Reduced hippocampal volume in alcohol and substance naïve Vietnam combat veterans with posttraumatic stress disorder.

ObjectiveThis pilot study was undertaken to exclude the effects of alcohol and other substances on brain morphology in posttraumatic stress disorder. BackgroundPosttraumatic stress disorder and alcohol use are among the conditions associated with decreased hippocampal volume. The possible confounding contribution of alcohol and other substances of abuse to decreased hippocampal volume in posttraumatic stress disorder has not been previously explored directly. MethodIn this pilot study, magnetic resonance imaging scans of 4 substance naive subjects with combat-related posttraumatic stress disorder and of 4 controls were quantified. ResultsBilateral hippocampal volumes were significantly smaller in posttraumatic stress disorder subjects. No significant differences were found between posttraumatic stress disorder subjects and the comparison group for total brain, gray and white matter, and ventricular volumes. ConclusionsThese findings suggest that posttraumatic stress disorder in the absence of alcohol and other substance abuse may be associated with reduced hippocampal volume. The significance of reduced hippocampal volume in posttraumatic stress disorder is discussed.