Center for Imaging of Neurodegenerative Diseases

San Francisco, CA, United States

Center for Imaging of Neurodegenerative Diseases

San Francisco, CA, United States
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Chao L.,University of California at San Francisco | Chao L.,Center for Imaging of Neurodegenerative Diseases | Weiner M.,University of California at San Francisco | Weiner M.,Center for Imaging of Neurodegenerative Diseases | And 2 more authors.
Psychiatry Research - Neuroimaging | Year: 2013

We previously reported that hippocampal volume was associated with current, but not lifetime posttraumatic stress disorder (PTSD) symptom severity. In the present study, we test the hypothesis that like the hippocampus, the volumes of other brain regions previously implicated in PTSD, are also negatively related to current, but not lifetime PTSD symptom severity. One hundred ninety-one veterans underwent structural magnetic resonance imaging (MRI) on a 4. T scanner. Seventy-five veterans were trauma unexposed, 43 were trauma exposed without PTSD, 39 were trauma exposed with current PTSD, and 34 were trauma exposed veterans with remitted PTSD. Hippocampal, amygdala, rostral and caudal anterior cingulate, insula, and corpus callosum volumes, quantified with Freesurfer version 4.5, were analyzed by group using multivariate analysis of covariance. Veterans with PTSD had smaller hippocampal, caudal anterior cingulate, insula, and corpus callosum volumes than the unexposed controls (p≤0.009); smaller hippocampal, caudal anterior cingulate, insula (p≤0.009) and marginally smaller corpus callosum (p=0.06) than veterans with remitted PTSD; and smaller hippocampal and caudal anterior cingulate volumes than veterans without PTSD (p≤0.04). In contrast, there was no significant volume differences between veterans with remitted PTSD compared to those without PTSD or unexposed controls. The finding that current but not lifetime PTSD accounts for the volumes of multiple brain regions suggests that either smaller brain volume is a vulnerability factor that impedes recovery from PTSD or that recovery from PTSD is accompanied by a wide-spread restoration of brain tissue. © 2013 Elsevier Ireland Ltd.

Kuceyeski A.,New York Medical College | Meyerhoff D.J.,University of California at San Francisco | Meyerhoff D.J.,Center for Imaging of Neurodegenerative Diseases | Durazzo T.C.,University of California at San Francisco | And 2 more authors.
Human Brain Mapping | Year: 2013

A recently developed measure of structural brain connectivity disruption, the loss in connectivity (LoCo), is adapted for studies in alcohol dependence. LoCo uses independent tractography information from young healthy controls to project the location of white matter (WM) microstructure abnormalities in alcohol-dependent versus nondependent individuals onto connected gray matter (GM) regions. LoCo scores are computed from WM abnormality masks derived at two levels: (1) groupwise differences of alcohol-dependent individuals (ALC) versus light-drinking (LD) controls and (2) differences of each ALC individual versus the LD control group. LoCo scores based on groupwise WM differences show that GM regions belonging to the extended brain reward system (BRS) network have significantly higher LoCo (i.e., disconnectivity) than those not in this network (t = 2.18, P = 0.016). LoCo scores based on individuals' WM differences are also higher in BRS versus non-BRS (t = 5.26, P = 3.92 × 10-6) of ALC. These results suggest that WM alterations in alcohol dependence, although subtle and spatially heterogeneous across the population, are nonetheless preferentially localized to the BRS. LoCo is shown to provide a more sensitive estimate of GM involvement than conventional volumetric GM measures by better differentiating between brains of ALC and LD controls (rates of 89.3% vs. 69.6%). However, just as volumetric measures, LoCo is not significantly correlated with standard metrics of drinking severity. LoCo is a sensitive WM measure of regional cortical disconnectivity that uniquely characterizes anatomical network disruptions in alcohol dependence.© 2012 Wiley Periodicals, Inc.

Durazzo T.C.,Center for Imaging of Neurodegenerative Diseases | Durazzo T.C.,University of California at San Francisco | Meyerhoff D.J.,Center for Imaging of Neurodegenerative Diseases | Meyerhoff D.J.,University of California at San Francisco | Nixon S.J.,University of Florida
Drug and Alcohol Dependence | Year: 2012

Background: The majority of studies investigating the neurocognitive consequences of chronic smoking have been conducted with adults 60 years and older. Therefore, the scope of neurocognitive dysfunction associated with chronic cigarette smoking in middle age (i.e., 30-60 age range) has not been fully delineated. Methods: Twenty-seven (44 ± 9 years of age; 4 females) non-smoking and 30 smoking (49 ± 8 years of age; 4 females) participants completed a comprehensive neurocognitive battery and measures of fine motor dexterity and postural stability. All participants were free of biomedical or psychiatric conditions that may have influenced neurocognitive and motor function. Results: Smokers performed significantly worse than non-smokers on the following domains: auditory-verbal and visuospatial learning, visuospatial memory, cognitive efficiency, executive skills, general intelligence, processing speed, fine motor dexterity and postural stability. The differences between smokers and non-smokers evidenced moderate to strong effect sizes and were not mediated by age, education, vocational level, estimated verbal intelligence or alcohol consumption. In smokers, a greater number of lifetime years of smoking was related to poorer performance on measures of cognitive efficiency, processing speed and visuospatial skills. Conclusions: Results from this middle-aged cohort replicated previous research and provides novel findings indicating that chronic smoking was associated with inferior performance on measures of general intelligence, visuospatial learning and memory and fine motor dexterity. Research that relates measures of neurobiological function/integrity to neurocognition is needed to better understand the mechanisms contributing to the poorer performance across multiple domains demonstrated by smokers. © 2011.

Mueller S.G.,Center for Imaging of Neurodegenerative Diseases | Schuff N.,Center for Imaging of Neurodegenerative Diseases | Yaffe K.,The Medical Memory | Madison C.,The Medical Memory | And 2 more authors.
Human Brain Mapping | Year: 2010

Background: Histopathological studies and animal models suggest that hippocampal subfields may be differently affected by aging, Alzheimer's disease (AD), and other diseases. High-resolution images at 4 Tesla depict details of the internal structure of the hippocampus allowing for in vivo volumetry of different subfields. The aims of this study were as follows: (1) to determine patterns of volume loss in hippocampal subfields in normal aging, AD, and amnestic mild cognitive impairment (MCI). (2) To determine if measurements of hippocampal subfields provide advantages over total hippocampal volume for differentiation between groups. Methods: Ninety-one subjects (53 controls (mean age: 69.3 ± 7.3), 20 MCI (mean age: 73.6 ± 7.1), and 18 AD (mean age: 69.1 ± 9.5) were studied with a high-resolution T2 weighted imaging sequence aimed at the hippocampus. Entorhinal cortex (ERC), subiculum, CA1, CA1-CA2 transition zone (CA1-2), CA3 & dentate gyrus (CA3&DG) were manually marked in the anterior third of the hippocampal body. Hippocampal volume was obtained from the Freesurfer and manually edited. Results: Compared to controls, AD had smaller volumes of ERC, subiculum, CA1, CA1-2, and total hippocampal volumes. MCI had smaller CA1-2 volumes. Discriminant analysis and power analysis showed that CA1-2 was superior to total hippocampal volume for distinction between controls and MCI. Conclusion: The patterns of subfield atrophy in AD and MCI were consistent with patterns of neuronal cell loss/reduced synaptic density described by histopathology. These preliminary findings suggest that hippocampal subfield volumetry might be a better measure for diagnosis of early AD and for detection of other disease effects than measurement of total hippocampus. © 2010 Wiley-Liss, Inc.

Durazzo T.C.,Center for Imaging of Neurodegenerative Diseases | Durazzo T.C.,University of California at San Francisco | Meyerhoff D.J.,Center for Imaging of Neurodegenerative Diseases | Meyerhoff D.J.,University of California at San Francisco | Nixon S.J.,University of Florida
Drug and Alcohol Dependence | Year: 2013

Background: Previous cross-sectional MRI studies with healthy, young-to-middle-aged adults reported no significant differences between smokers and non-smokers on total hippocampal volume. However, these studies did not specifically test for greater age-related volume loss in the total hippocampus or hippocampal subregions in smokers, and did they did not examine relationships between hippocampal and subfield volumes and episodic learning and memory performance. Methods: Healthy, young-to-middle-aged (45. ±. 12 years of age) smokers (n= 39) and non-smokers (n= 43) were compared on total hippocampal and subfield volumes derived from high-resolution 4. Tesla MRI, emphasizing testing for greater age-related volume losses in smokers. Associations between hippocampal volumes and measures of episodic learning and memory were examined. Results: Smokers showed significantly smaller volumes, as well as greater volume loss with increasing age than non-smokers in the bilateral total hippocampus and multiple subfields. In smokers, greater pack-years were associated with smaller volumes of the total hippocampus, presubiculum, and subiculum. In the entire cohort, performance on measures of learning and memory was related to larger total hippocampal and several subfield volumes, predominately in the left hemisphere. Conclusions: Chronic cigarette smoking in this young-to-middle aged cohort was associated with smaller total hippocampal and subfield volumes, which were exacerbated by advancing age. Findings also indicated an adverse smoking dose/duration response (i.e., pack-years) with total hippocampal and select subfield volumes. These hippocampal volume abnormalities in smokers may be related to the deficiencies in episodic learning and memory in young-to-middle-aged smokers reported in previous studies. © 2013 Elsevier Ireland Ltd.

Meyerhoff D.J.,Center for Imaging of Neurodegenerative Diseases | Mon A.,Center for Imaging of Neurodegenerative Diseases | Metzler T.,University of California at San Francisco | Neylan T.C.,University of California at San Francisco
Sleep | Year: 2014

Study Objectives: To test if posttraumatic stress disorder (PTSD) is associated with low brain gamma-Aminobutyric acid (GABA) levels and if reduced GABA is mediated by poor sleep quality. Design: Laboratory study using in vivo proton magnetic resonance spectroscopy (1H MRS) and behavioral testing. Setting: VA Medical Center Research Service, Psychiatry and Radiology. Patients or Participants: Twenty-seven patients with PTSD (PTSD+) and 18 trauma-exposed controls without PTSD (PTSD?), recruited from United States Army reservists, Army National Guard, and mental health clinics. Interventions: None. Measurements and Results: 1H MRS at 4 Tesla yielded spectra from three cortical brain regions. In parieto-occipital and temporal cortices, PTSD+ had lower GABA concentrations than PTSD?. As expected, PTSD+ had higher depressive and anxiety symptom scores and a higher Insomnia Severity Index (ISI) score. Higher ISI correlated with lower GABA and higher glutamate levels in parieto-occipital cortex and tended to correlate with lower GABA in the anterior cingulate. The relationship between parieto-occipital GABA and PTSD diagnosis was fully mediated through insomnia severity. Lower N-Acetylaspartate and glutamate concentrations in the anterior cingulate cortex correlated with higher arousal scores, whereas depressive and anxiety symptoms did generally not influence metabolite concentrations. Conclusions: Low brain gamma-Aminobutyric acid (GABA) concentration in posttraumatic stress disorder (PTSD) is consistent with most findings in panic and social anxiety disorders. Low GABA associated with poor sleep quality is consistent with the hyperarousal theory of both primary insomnia and PTSD. Our data demonstrate that poor sleep quality mediates low parieto-occipital GABA in PTSD. The findings have implications for PTSD treatment approaches.

Mon A.,University of California at San Francisco | Mon A.,Center for Imaging of Neurodegenerative Diseases | Durazzo T.C.,University of California at San Francisco | Durazzo T.C.,Center for Imaging of Neurodegenerative Diseases | And 2 more authors.
Drug and Alcohol Dependence | Year: 2012

Background: Little is known about the effects of alcohol dependence on cortical concentrations of glutamate (Glu) or gamma aminobutyric acid (GABA). We used proton magnetic resonance spectroscopy (MRS) to study cross-sectionally and longitudinally the concentrations of these in alcohol dependent individuals (ALC) during early abstinence from alcohol. Methods: Twenty ALC were studied at about one week of abstinence from alcohol (baseline) and 36 ALC at five weeks of abstinence and compared to 16 light/non-drinking controls (LD). Eleven ALC were studied twice during abstinence. Participants underwent clinical interviewing, blood work, neuropsychological testing, structural imaging and single-volume proton MRS at 4Tesla. Absolute concentrations of Glu, GABA and those of other 1H MRS-detectable metabolites were measured in the anterior cingulate (ACC), parieto-occipital cortex (POC) and dorso-lateral prefrontal cortex (DLPFC). Relationships of metabolite levels to drinking severity and neurocognition were also assessed. Results: ALC at baseline had lower concentrations of Glu, N-acetylaspartate (NAA), choline- (Cho) and creatine-containing metabolites (Cr) than LD in the ACC, but had normal GABA and myo-inositol (mI) levels. At five weeks of abstinence, metabolite concentrations were not significantly different between groups. Between one and five weeks of abstinence, Glu, NAA and Cho levels in the ACC increased significantly. Higher cortical mI concentrations in ALC related to worse neurocognitive outcome. Conclusion: These MRS data suggest compromised and regionally specific bioenergetics/metabolism in one-week-abstinent ALC that largely normalizes over four weeks of sustained abstinence. The correlation between mI levels and neurocognition affirms the functional relevance of this putative astrocyte marker. © 2012 .

Veitch D.P.,Center for Imaging of Neurodegenerative Diseases | Friedl K.E.,U.S. Army | Weiner M.W.,University of California at San Francisco
Current Alzheimer Research | Year: 2013

Delayed neurological health consequences of environmental exposures during military service have been generally underappreciated. The rapidly expanding understanding of Alzheimer's disease (AD) pathogenesis now makes it possible to quantitate some of the likely long-term health risks associated with military service. Military risk factors for AD include both factors elevated in military personnel such as tobacco use, traumatic brain injury (TBI), depression, and post-traumatic stress disorder (PTSD) and other nonspecific risk factors for AD including, vascular risk factors such as obesity and obesity-related diseases (e.g., metabolic syndrome), education and physical fitness. The degree of combat exposure, Vietnam era Agent Orange exposure and Gulf War Illness may also influence risk for AD. Using available data on the association of AD and specific exposures and risk factors, the authors have conservatively estimated 423,000 new cases of AD in veterans by 2020, including 140,000 excess cases associated with specific military exposures. The cost associated with these excess cases is approximately $5.8 billion to $7.8 billion. Mitigation of the potential impact of military exposures on the cognitive function of veterans and management of modifiable risk factors through specifically designed programs will be instrumental in minimizing the impact of AD in veterans in the future decades. © 2013 Bentham Science Publishers.

Chao L.L.,Center for Imaging of Neurodegenerative Diseases
Journal of Occupational and Environmental Medicine | Year: 2016

OBJECTIVE:: The aim of this study was to examine the relationship between the self-reported frequencies of hearing chemical alarms during deployment and visuospatial function in Gulf War (GW) veterans. METHODS:: The relationship between the self-reported frequency of hearing chemical alarms, neurobehavioral, and volumetric brain imaging data was examined with correlational, regression, and mediation analyses. RESULTS:: The self-reported frequency of hearing chemical alarms was inversely associated with and significantly predicted performance on a visuospatial task (ie, Block Design) over and above potentially confounding variables, including concurrent, correlated GW-related exposures. This effect was partially mediated by the relationship between hearing chemical alarms and lateral occipital cortex volume. CONCLUSIONS:: Exposure to substances that triggered chemical alarms during GW deployment likely had adverse effects on veterans’ brain structure and function, warranting further investigation of whether these GW veterans are at an increased risk for dementia. Copyright © 2016 by the American College of Occupational and Environmental Medicine

Mueller S.G.,Center for Imaging of Neurodegenerative Diseases | Bateman L.M.,Columbia University | Laxer K.D.,California Pacific Medical Center
NeuroImage: Clinical | Year: 2014

The symptoms witnessed in unexplained death in epilepsy (SUDEP) suggest a breakdown of central autonomic control. Since the brainstem plays a crucial role in autonomic control, the objectives of this study were 1. To investigate if temporal lobe epilepsy (TLE) is associated with brainstem atrophy and to characterize it using graph Analysis 2. To compare the findings with those in two probable TLESUDEP. T1 images were obtained from 17 controls, 30 TLE (16 with mesial-temporal-sclerosis (TLE-MTS) and 14 without (TLE-no)) and from 2 patients who died of SUDEP. The brainstem was extracted, warped onto a brainstem atlas and Jacobian determinants maps (JDM) calculated. SPM8 was used to compare the JDMs at the group level, z-score maps were calculated for single subject analysis. Brainstem regions encompassing autonomic structures were identified based on macroscopic landmarks and mean z-scores from 5 × 5 × 5 voxel cubes extracted to calculate a new measure called atrophy-similarity index (ASI) for graph analysis. TLE-MTS had volume loss in the dorsal mesencephalon. The SUDEP cases had severe and more extensive volume loss in the same region. Nodal degrees and participation coefficients were decreased and local efficiency increased in SUDEP compared to controls. TLE is associated with volume loss in brainstem regions involved in autonomic control. Structural damage in these regions might increase the risk for a fatal dysregulation during situations with increased demand such as following severe seizures. © 2014 The Authors.

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