Jagust, William

AbstractBoth traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are common problems resulting from military service, and both have been associated with increased risk of cognitive decline and dementia resulting from Alzheimer's disease (AD) or other causes. This study aims to use imaging techniques and biomarker analysis to determine whether traumatic brain injury (TBI) and/or PTSD resulting from combat or other traumas increase the risk for AD and decrease cognitive reserve in Veteran subjects, after accounting for age. Using military and Department of Veterans Affairs records, 65 Vietnam War veterans with a history of moderate or severe TBI with or without PTSD, 65 with ongoing PTSD without TBI, and 65 control subjects are being enrolled in this study at 19 sites. The study aims to select subject groups that are comparable in age, gender, ethnicity, and education. Subjects with mild cognitive impairment (MCI) or dementia are being excluded. However, a new study just beginning, and similar in size, will study subjects with TBI, subjects with PTSD, and control subjects with MCI. Baseline measurements of cognition, function, blood, and cerebrospinal fluid biomarkers; magnetic resonance images (structural, diffusion tensor, and resting state blood‐level oxygen dependent (BOLD) functional magnetic resonance imaging); and amyloid positron emission tomographic (PET) images with florbetapir are being obtained. One‐year follow‐up measurements will be collected for most of the baseline procedures, with the exception of the lumbar puncture, the PET imaging, and apolipoprotein E genotyping. To date, 19 subjects with TBI only, 46 with PTSD only, and 15 with TBI and PTSD have been recruited and referred to 13 clinics to undergo the study protocol. It is expected that cohorts will be fully recruited by October 2014. This study is a first step toward the design and statistical powering of an AD prevention trial using at‐risk veterans as subjects, and provides the basis for a larger, more comprehensive study of dementia risk factors in veterans.

AbstractBackgroundApolipoprotein E (APOE) ε4 allele's role as a modulator of the relationship between soluble plasma amyloid beta (Aβ) and fibrillar brain Aβ measured by Pittsburgh compound B positron emission tomography ([11C]PiB PET) has not been assessed.MethodsNinety‐six Alzheimer's Disease Neuroimaging Initiative participants with [11C]PiB scans and plasma Aβ1–40 and Aβ1–42 measurements at the time of PET scanning were included. Regional and voxelwise analyses of [11C]PiB data were used to determine the influence of APOE ε4 allele on association of plasma Aβ1–40, Aβ1–42, and Aβ1–40/Aβ1–42 with [11C]PiB uptake.ResultsIn APOE ε4− but not ε4+ participants, positive relationships between plasma Aβ1–40/Aβ1–42 and [11C]PiB uptake were observed. Modeling the interaction of APOE and plasma Aβ1–40/Aβ1–42 improved the explained variance in [11C]PiB binding compared with using APOE and plasma Aβ1–40/Aβ1–42 as separate terms.ConclusionsThe results suggest that plasma Aβ is a potential Alzheimer's disease biomarker and highlight the importance of genetic variation in interpretation of plasma Aβ levels.

AbstractBackgroundThere is epidemiological evidence that cardiovascular risk factors (CVRF) also are risk factors for Alzheimer's disease, but there is limited information on this from neuropathological studies, and even less from in vivo studies. Therefore, we examined the relationship between CVRF and amyloid‐β (Aβ) brain burden measured by Pittsburgh Compound B‐positron emission tomography (PiB‐PET) studies in the Alzheimer's Disease Neuroimaging Initiative.MethodsNinety‐nine subjects from the Alzheimer's Disease Neuroimaging Initiative cohort who had a PiB‐PET study measure, apolipoprotein E genotyping data, and information available on CVRF (body mass index [BMI], systolic blood pressure, diastolic blood pressure [DBP], and cholesterol and fasting glucose test results) were included. Eighty‐one subjects also had plasma cortisol, C‐reactive protein, and superoxide dismutase 1 measurements. Stepwise regression models were used to assess the relation between the CVRF and the composite PiB‐PET score.ResultsThe first model included the following as baseline variables: age, clinical diagnosis, number of apolipoprotein ε4 alleles, BMI (P = .023), and DBP (P = .012). BMI showed an inverse relation with PiB‐PET score, and DBP had a positive relation with PiB‐PET score. In the second adjusted model, cortisol plasma levels were also associated with PiB‐PET score (P = .004). Systolic blood pressure, cholesterol, or impaired fasting glucose were not found to be associated with PiB‐PET values.ConclusionIn this cross‐sectional study, we found an association between Aβ brain burden measured in vivo and DBP and cortisol, indicating a possible link between these CVRF and Aβ burden measured by PiB‐PET. These findings highlight the utility of biomarkers to explore potential pathways linking diverse Alzheimer's disease risk factors.