Robert H. Paul

Early Life Stress and Morphometry of the Adult Anterior Cingulate Cortex and Caudate Nuclei

BACKGROUNDnEarly 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.nnnMETHODn265 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.nnnRESULTSnParticipants 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.nnnCONCLUSIONSnReported 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.

THE TEST-RETEST RELIABILITY OF A STANDARDIZED NEUROCOGNITIVE AND NEUROPHYSIOLOGICAL TEST BATTERY: “NEUROMARKER”

NeuroMarker combines EEG and ERP measures with neurocognitive tests in a fully computerized and standardized testing system. It is designed for use across the lifespan and has a large normative database of over 1,000 subjects. This study was a preliminary evaluation of “NeuroMarker” in subjects spanning four decades. Twenty-one healthy subjects (12–57 years) were tested at baseline and four weeks later. From the “Neuromarker” battery, the authors analyzed EEG data (eyes open and closed) and ERPs elicited during auditory oddball (N100, P200, N200, P300) and working memory (P150, P300) tasks. Concomitant neuropsychological data, acquired using a touch-screen system, comprised measures of sensori-motor, attention, verbal, executive, and memory function. Test-retest data were examined using analyses of variance and correlational procedures (corrected for multiple comparisons), with parallel analyses of age. EEG data did not differ across sessions, and showed high test-retest reliability (.71–.95), particularly for theta and delta (>.85). ERP components also showed sound reliability, particularly for sites where components are maximal: fronto-central N100 (.76–.77), centro-parietal P300 (.78–.81) to oddball targets, N100 and P200 (.74–.86) to oddball non-targets, and P150 amplitude and latency (.84–.93) to working memory stimuli. Neuropsychological tests showed a similarly sound level of consistency (on average, .70), with the most consistent tests tapping simple motor function, estimated intelligence, switching of attention (Part 2), verbal interference response time and memory intrusions (.71–.89). Age and sex did not have a differential impact on reliability for EEG, ERP, or neuropsychology measures. These findings provide preliminary evidence that the “NeuroMarker” battery is reliable for test-retest assessments. The results suggest that the standardized approach has utility for providing sensitive clinical and treatment evaluations across age groups.

Preliminary validity of "integneuro": a new computerized battery of neurocognitive tests.

The purpose of this study was to examine the preliminary validity of a newly developed battery of computerized cognitive measures, IntegNeuroTM. This standardized and semi-automated computerized battery assesses sensori-motor function, attention, new learning and memory, language fluency, executive function, and estimated intelligence. A total of 50 healthy individuals (aged 22–80 years) were included in the study. Correlational analyses revealed highly significant associations between the two cognitive batteries. These results support the use of IntegNeuroTM as a computerized cognitive system. Additional studies are needed to examine the clinical utility of the battery.

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

BACKGROUNDnThe current study utilized magnetic resonance imaging (MRI) to more fully elucidate the relationship among age, regional white matter, and neuropsychological functioning.nnnMETHODSnOne 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.nnnRESULTSnThe 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.nnnCONCLUSIONSnThe 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.

Demographic, Clinical, and Cognitive Characteristics of Multiple Sclerosis Patients Who Continue to Work

To determine the factors that contribute to maintaining employment by MS patients, we compared thirty-eight patients who were still working to sixty-four patients who retired prematurely. The employed group was younger, better educated, had less severe physical disability, a shorter duration of disease, an earlier age at diagnosis, and per formed significantly better on nearly all neuropsychological variables examined. Mul tiple regression analysis indicated that walking ability, age, two measures of memory, and one test of verbal fluency, taken together, accounted for 49% of the variance in employment status. Although most patients who maintained employment had only mild to moderate physical and cognitive impairments, nine patients who continued to work were impaired on three or more of the seven cognitive domains tested. Implications for more effective rehabilitation are considered.

Systemic hypoperfusion is associated with executive dysfunction in geriatric cardiac patients

The present study examines the relationship between systemic hypoperfusion via cardiac output (CO) and neuropsychological performances emphasizing executive function in an aging cohort. Geriatric outpatients with treated, stable cardiovascular disease (CVD) and no history of neurological illness (n=72, ages 56-85) were administered cognitive measures with an emphasis on executive functioning. Echocardiogram findings were used to stratify participants into two groups: low CO (<4.0 L/min) and normal CO (> o r=4.0 L/min). Between-group comparisons were made using ANCOVAs adjusting for systolic blood pressure. The low CO group performed significantly worse than the normal CO group on DKEFS Tower Test and DKEFS Trail Making Test. No significant between-group differences were noted for any of the other cognitive indices. Findings suggest that reduced CO is associated with poorer executive functioning among geriatric outpatients with stable CVD, as the cognitive profile emphasizes a relationship between systemic hypoperfusion and problems with sequencing and planning. The executive dysfunction profile may be secondary to reduced blood flow to vulnerable subcortical structures implicated in frontal-subcortical circuitry.

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.

Neurocognitive performance enhanced by highly active antiretroviral therapy in HIV-infected women

ObjectiveTo determine whether highly active retroviral therapy (HAART) is associated with better neurocognitive outcome over time among HIV-infected women with severely impaired immune function. MethodsA semiannual neurocognitive examination on four tasks was administered: Color Trail Making, Controlled Oral Word Association, Grooved Pegboard and Four-Word Learning. This protocol was initiated in the HIV Epidemiological Research study (HERS) study when a womans CD4 cell count fell to < 100 × 106 cells/l. Immune function (CD4), viral load status and depression severity (CESD) were also assessed semi-annually, along with an interview to determine medication intake and illicit drug use. ResultsHAART was not available to any participant at the time of enrollment (baseline), while 44% reported taking HAART at their most recent visit (mean duration of HAART 36.3 ± 12.6 months). HAART-treated women had improved neurocognitive performance compared with those not treated with HAART. Women taking HAART for 18 months or more showed the strongest neurocognitive performance with improved verbal fluency, psychomotor and executive functions. These functions worsened among women not taking HAART. Substance abuse status, severity of depressive symptoms, age and educational level did not influence the HAART treatment effects on neurocognitive performance. Neurocognitive improvements were strongly associated with the magnitude of CD4 cell count increases. ConclusionsHAART appeared to produce beneficial effect on neurocognitive functioning in HIV-infected women with severely impaired immune systems. Benefits were greatest for women who reported receiving HAART for more than 18 months.