Maheen M. Adamson

Neuropsychiatric diagnosis and management of chronic sequelae of war-related mild to moderate traumatic brain injury

Soldiers with a traumatic brain injury (TBI) present with an array of neuropsychiatric symptoms that can be grouped into nosological clusters: (1) cognitive dysfunctions: difficulties in memory, attention, language, visuospatial cognition, sensory-motor integration, affect recognition, and/or executive function typically associated with neocortical damage; (2) neurobehavioral disorders: mood, affect, anxiety, posttraumatic stress, and psychosis, as well as agitation, sleep problems, and libido loss, that may have been caused by damage to the cortex, limbic system, and/or brain stem monoaminergic projection systems; (3) somatosensory disruptions: impaired smell, vision, hearing, equilibrium, taste, and somatosensory perception frequently caused by trauma to the sensory organs or their projections through the brain stem to central processing systems; (4) somatic symptoms: headache and chronic pain; and (5) substance dependence. TBI-related cognitive impairment is common in veterans who have served in recent conflicts in the Middle East and is often related to blasts from improvised explosive devices. Although neurobehavioral disorders such as depression and posttraumatic stress disorder commonly occur after combat, the presentation of such disorders in those with head injury may pass undetected with use of current diagnostic criteria and neuropsychological instruments. With a multidimensional approach (such as the biopsychosocial model) applied to each symptom cluster, psychological, occupational, and social dysfunction can be delineated and managed.

APOE-epsilon4 and aging of medial temporal lobe gray matter in healthy adults older than 50 years.

Atrophy of the hippocampus and surrounding temporal regions occurs in Alzheimers disease (AD). APOE ε4, the major genetic risk factor for late-onset AD, has been associated with smaller volume in these regions before amyloidosis can be detected by AD biomarkers. To examine APOE ε4 effects in relation to aging, we performed a longitudinal magnetic resonance imaging study involving cognitively normal adults (25 APOE ε4 carriers and 31 ε3 homozygotes), initially aged 51-75 years. We used growth curve analyses, which can provide information about APOE ε4-related differences initially and later in life. Hippocampal volume was the primary outcome; nearby medial temporal regions were secondary outcomes. Brain-derived neurotrophic factor, val66met was a secondary covariate. APOE ε4 carriers had significantly smaller initial hippocampal volumes than ε3 homozygotes. Rate of hippocampal atrophy was not greater in the APOE ε4 group, although age-related atrophy was detected in the overall sample. The findings add to the growing evidence that effects of APOE ε4 on hippocampal size begin early in life, underscoring the importance of early interventions to increase reserve.

Apolipoprotein E ɛ4 influences on episodic recall and brain structures in aging pilots

The apolipoprotein (APOE) epsilon4 allele is associated with cognitive deficits and hippocampal atrophy in nondemented middle-aged and older adults. It is not known to what extent this genetic risk factor for Alzheimers disease (AD) impacts performance in late middle-aged and older workers in cognitively demanding occupations. This cross-sectional analysis examines brain-cognitive-genetic relationships in actively flying general aviation pilots, half of whom are APOE epsilon4 carriers. Fifty pilots were studied with structural MRI and memory tasks. Average visual paired associate memory recall performance was lower in APOE epsilon4 carriers than non-carriers. Memory performance correlated positively with hippocampal volume, but no structural differences were found in hippocampal or frontal volumes with respect to APOE epsilon4 allele. These results were evident in healthy professionals without any presenting memory problems and without selection for a family history of AD. These findings point to basic memory testing as a sensitive tool for detecting APOE epsilon4-related influences on memory in aging workers.

Reduced hippocampal activity during encoding in cognitively normal adults carrying the APOE ɛ4 allele.

Apolipoprotein (APOE) ɛ4-related differences in memory performance have been detected before age 65. The hippocampus and the surrounding medial temporal lobe (MTL) structures are the first site affected by Alzheimers disease (AD) and the MTL is the seat of episodic memory, including visuo-spatial memory. While reports of APOE ɛ4-related differences in these brain structures are not consistent in either cross-sectional or longitudinal structural and functional magnetic resonance imaging (fMRI) studies, there is increasing evidence that brain activity at baseline (defined as activity during fixation or rest) may differ in APOE ɛ4 carriers compared to non-carriers. In this fMRI study, cognitively normal APOE ɛ4 carriers and non-carriers engaged in a perspective-dependent spatial learning task (Shelton & Gabrieli, 2002) previously shown to activate MTL structures in older participants (Borghesani et al., 2008). A low-level, visually engaging dot-control task was used for comparison, in addition to fixation. APOE ɛ4 carriers showed less activation than non-carriers in the hippocampus proper during encoding. Specifically, when spatial encoding was contrasted against the dot-control task, encoding-related activation was significantly lower in carriers than non-carriers. By contrast, no ɛ4-related differences in the hippocampus were found when spatial encoding was compared with fixation. Lower activation, however, was not global since encoding-related activation in early visual cortex (left lingual gyrus) was not different between APOE ɛ4 carriers and non-carriers. The present data document APOE ɛ4-related differences in the hippocampus proper during encoding and underscore the role of low-level control contrasts for complex encoding tasks. These results have implications for fMRI studies that investigate the default-mode network (DMN) in middle-aged to older APOE ɛ4 carriers to help evaluate AD risk in this otherwise cognitively normal population.

MR Spectroscopy for Assessment of Memantine Treatment in Mild to Moderate Alzheimer Dementia

OBJECTIVES Magnetic Resonance Spectroscopy (MRS) may provide a precise and reliable assessment of the extent and severity of neural tissue loss caused by various diseases. In particular, the N-Acetyl Aspartate (NAA) and Creatine (Cr) ratio has been found to be an indicator of the degree of neuronal loss in Alzheimers disease (AD). Memantine is thought to benefit the AD brain by stabilizing the NMDA receptors on neurons in turn reducing excitotoxicity. Despite its effectiveness in treating moderate to severe AD, memantine has not had similar success in the treatment of mildly demented AD patients. The objective of this study was to test whether memantine would slow or prevent the loss of neurons in mild to moderate AD patients. METHODS A double-blind placebo-controlled study was designed to measure the effect of a year-long course of memantine in patients with a probable AD diagnosis with mild to moderate dementia. The primary outcome measure was stipulated to be change in MRS NAA/Cr ratio in inferior parietal cortex in memantine relative to the placebo treatment condition. The secondary outcome measures were changes in cognitive and function scale scores. RESULTS This pilot study failed to demonstrate a benefit of memantine on the primary outcome measure, the inferior parietal NAA/Cr ratio, or the secondary outcome measures. CONCLUSIONS More studies are needed to determine the effect of memantine on regions of the brain significantly affected by AD pathology.

The impact of depression on veterans with PTSD and traumatic brain injury: a diffusion tensor imaging study

A significant proportion of military personnel deployed in support of Operation Enduring Freedom and Operation Iraqi Freedom were exposed to war-zone events associated with traumatic brain injury (TBI), depression (DEP) and posttraumatic stress disorder (PTSD). The co-occurrence of TBI, PTSD and DEP in returning Veterans has recently increased research and clinical interest. This study tested the hypothesis that white matter abnormalities are further impacted by depression. Of particular relevance is the uncinate fasciculus (UF), which is a key fronto-temporal tract involved in mood regulation, and the cingulum; a tract that connects to the hippocampus involved in memory integration. Diffusion tensor imaging (DTI) was performed on 25 patients with a combination of PTSD, TBI and DEP and 20 patients with PTSD and TBI (no DEP). Microstructural changes of white matter were found in the cingulum and UF. Fractional anisotropy (FA) was lower in Veterans with DEP compared to those without DEP.

Imaging the Alzheimer Brain

This supplement to the Journal of Alzheimers Disease contains more than half of the chapters from The Handbook of Imaging the Alzheimer Brain, which was first presented at the International Conference on Alzheimers Disease in Paris, in July, 2011. While the Handbook contains 27 chapters that are modified articles from 2009, 2010, and 2011 issues of the Journal of Alzheimers Disease, this supplement contains the 31 new chapters of that book and an introductory article drawn from the introductions to each section of the book. The Handbook was designed to provide a multilevel overview of the full field of brain imaging related to Alzheimers disease (AD). The Handbook, as well as this supplement, contains both reviews of the basic concepts of imaging, the latest developments in imaging, and various discussions and perspectives of the problems of the field and promising directions. The Handbook was designed to be useful for students and clinicians interested in AD as well as scientists studying the brain and pathology related to AD.

Initial Cognitive Performance Predicts Longitudinal Aviator Performance

OBJECTIVES The goal of the study was to improve prediction of longitudinal flight simulator performance by studying cognitive factors that may moderate the influence of chronological age. METHOD We examined age-related change in aviation performance in aircraft pilots in relation to baseline cognitive ability measures and aviation expertise. Participants were aircraft pilots (N = 276) aged 40-77.9. Flight simulator performance and cognition were tested yearly; there were an average of 4.3 (± 2.7; range 1-13) data points per participant. Each participant was classified into one of the three levels of aviation expertise based on Federal Aviation Administration pilot proficiency ratings: least, moderate, or high expertise. RESULTS Addition of measures of cognitive processing speed and executive function to a model of age-related change in aviation performance significantly improved the model. Processing speed and executive function performance interacted such that the slowest rate of decline in flight simulator performance was found in aviators with the highest scores on tests of these abilities. Expertise was beneficial to pilots across the age range studied; however, expertise did not show evidence of reducing the effect of age. DISCUSSION These data suggest that longitudinal performance on an important real-world activity can be predicted by initial assessment of relevant cognitive abilities.

The impact of brain size on pilot performance varies with aviation training and years of education

Previous studies have consistently reported age-related changes in cognitive abilities and brain structure. Previous studies also suggest compensatory roles for specialized training, skill, and years of education in the age-related decline of cognitive function. The Stanford/VA Aviation Study examines the influence of specialized training and skill level (expertise) on age-related changes in cognition and brain structure. This preliminary report examines the effect of aviation expertise, years of education, age, and brain size on flight simulator performance in pilots aged 45-68 years. Fifty-one pilots were studied with structural magnetic resonance imaging, flight simulator, and processing speed tasks. There were significant main effects of age (p < .01) and expertise (p < .01), but not of whole brain size (p > .1) or education (p > .1), on flight simulator performance. However, even though age and brain size were correlated (r = -0.41), age differences in flight simulator performance were not explained by brain size. Both aviation expertise and education were involved in an interaction with brain size in predicting flight simulator performance (p < .05). These results point to the importance of examining measures of expertise and their interactions to assess age-related cognitive changes.

Exploring interhemispheric collaboration in older compared to younger adults

Physical and Name Identity letter-matching tasks were used to explore differences in interhemispheric collaboration in younger and older adults. To determine whether other factors might also be related to across/within-hemisphere processing or visual field asymmetries, neuropsychological tests measuring frontal/executive functioning were administered, and comparisons were made for participants split into low and high efficiency groups based on performance on the letter-matching tasks. A Task by Across/Within interaction was found for both groups, but with a stronger within-hemisphere advantage for the Physical Task and a weaker across-hemisphere advantage for the Name Task for older participants. More efficient groups and better performers on several neuropsychological tasks showed a reduced across-hemisphere advantage for the Name Identity task. Findings suggest that computational complexity, specific task demands, and perhaps trade-offs between age-related changes in gray and white matter all contribute to whether processing loads are distributed across or within hemispheres as we age.