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Browsing by Author "Landau, Susan M."
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Item Effects of traumatic brain injury and posttraumatic stress disorder on development of Alzheimer's disease in Vietnam Veterans using the Alzheimer's Disease Neuroimaging Initiative: Preliminary report(Elsevier, 2017-06) Weiner, Michael W.; Harvey, Danielle; Hayes, Jacqueline; Landau, Susan M.; Aisen, Paul S.; Petersen, Ronald C.; Tosun, Duygu; Veitch, Dallas P.; Jack, Clifford R., Jr.; Decarli, Charles; Saykin, Andrew J.; Grafman, Jordan; Neylan, Thomas C.; Department of Radiology and Imaging Sciences, IU School of MedicineIntroduction Traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) have previously been reported to be associated with increased risk of Alzheimer's disease (AD). We are using biomarkers to study Vietnam Veterans with/without mild cognitive impairment with a history of at least one TBI and/or ongoing PTSD to determine whether these contribute to the development of AD. Methods Potential subjects identified by Veterans Administration records underwent an initial telephone screen. Consented subjects underwent clinical evaluation, lumbar puncture, structural magnetic resonance imaging, and amyloid positron emission tomography (PET) scans. Results We observed worse cognitive functioning in PTSD and TBI + PTSD groups, worse global cognitive functioning in the PTSD group, lower superior parietal volume in the TBI + PTSD group, and lower amyloid positivity in the PTSD group, but not the TBI group compared to controls without TBI/PTSD. Medial temporal lobe atrophy was not increased in the PTSD and/or TBI groups. Discussion Preliminary results do not indicate that TBI or PTSD increase the risk for AD measured by amyloid PET. Additional recruitment, longitudinal follow-up, and tau-PET scans will provide more information in the future.Item Head injury is associated with tau deposition on PET in MCI and AD patients(Wiley, 2021-08-24) Risacher, Shannon L.; West, John D.; Deardorff, Rachael; Gao, Sujuan; Farlow, Martin R.; Brosch, Jared R.; Apostolova, Liana G.; McAllister, Thomas W.; Wu, Yu-Chien; Jagust, William J.; Landau, Susan M.; Weiner, Michael W.; Saykin, Andrew J.; Radiology and Imaging Sciences, School of MedicineIntroduction: Head injuries (HI) are a risk factor for dementia, but the underlying etiology is not fully known. Understanding whether tau might mediate this relationship is important. Methods: Cognition and tau deposition were compared between 752 individuals with (impaired, n = 302) or without cognitive impairment (CN, n = 450) with amyloid and [18F]flortaucipir positron emission tomography, HI history information, and cognitive testing from the Alzheimer's Disease Neuroimaging Initiative and the Indiana Memory and Aging Study. Results: Sixty-three (38 CN, 25 impaired) reported a history of HI. Higher neuropsychiatric scores and poorer memory were observed in those with a history of HI. Tau was higher in individuals with a history of HI, especially those who experienced a loss of consciousness (LOC). Results were driven by impaired individuals, especially amyloid beta-positive individuals with history of HI with LOC. Discussion: These findings suggest biological changes, such as greater tau, are associated with HI in individuals with cognitive impairment. Small effect sizes were observed; thus, further studies should replicate and extend these results.Item Increasing participant diversity in AD research: Plans for digital screening, blood testing, and a community-engaged approach in the Alzheimer's Disease Neuroimaging Initiative 4(Wiley, 2023) Weiner, Michael W.; Veitch, Dallas P.; Miller, Melanie J.; Aisen, Paul S.; Albala, Bruce; Beckett, Laurel A.; Green, Robert C.; Harvey, Danielle; Jack, Clifford R., Jr.; Jagust, William; Landau, Susan M.; Morris, John C.; Nosheny, Rachel; Okonkwo, Ozioma C.; Perrin, Richard J.; Petersen, Ronald C.; Rivera-Mindt, Monica; Saykin, Andrew J.; Shaw, Leslie M.; Toga, Arthur W.; Tosun, Duygu; Trojanowski, John Q.; Alzheimer's Disease Neuroimaging Initiative; Radiology and Imaging Sciences, School of MedicineIntroduction: The Alzheimer's Disease Neuroimaging Initiative (ADNI) aims to validate biomarkers for Alzheimer's disease (AD) clinical trials. To improve generalizability, ADNI4 aims to enroll 50-60% of its new participants from underrepresented populations (URPs) using new biofluid and digital technologies. ADNI4 has received funding from the National Institute on Aging beginning September 2022. Methods: ADNI4 will recruit URPs using community-engaged approaches. An online portal will screen 20,000 participants, 4000 of whom (50-60% URPs) will be tested for plasma biomarkers and APOE. From this, 500 new participants will undergo in-clinic assessment joining 500 ADNI3 rollover participants. Remaining participants (∼3500) will undergo longitudinal plasma and digital cognitive testing. ADNI4 will add MRI sequences and new PET tracers. Project 1 will optimize biomarkers in AD clinical trials. Results and discussion: ADNI4 will improve generalizability of results, use remote digital and blood screening, and continue providing longitudinal clinical, biomarker, and autopsy data to investigators.Item The Alzheimer's Disease Neuroimaging Initiative in the era of Alzheimer's disease treatment: A review of ADNI studies from 2021 to 2022(Wiley, 2024) Veitch, Dallas P.; Weiner, Michael W.; Miller, Melanie; Aisen, Paul S.; Ashford, Miriam A.; Beckett, Laurel A.; Green, Robert C.; Harvey, Danielle; Jack, Clifford R., Jr.; Jagust, William; Landau, Susan M.; Morris, John C.; Nho, Kwangsik T.; Nosheny, Rachel; Okonkwo, Ozioma; Perrin, Richard J.; Petersen, Ronald C.; Rivera Mindt, Monica; Saykin, Andrew; Shaw, Leslie M.; Toga, Arthur W.; Tosun, Duygu; Alzheimer’s Disease Neuroimaging Initiative; Radiology and Imaging Sciences, School of MedicineThe Alzheimer's Disease Neuroimaging Initiative (ADNI) aims to improve Alzheimer's disease (AD) clinical trials. Since 2006, ADNI has shared clinical, neuroimaging, and cognitive data, and biofluid samples. We used conventional search methods to identify 1459 publications from 2021 to 2022 using ADNI data/samples and reviewed 291 impactful studies. This review details how ADNI studies improved disease progression understanding and clinical trial efficiency. Advances in subject selection, detection of treatment effects, harmonization, and modeling improved clinical trials and plasma biomarkers like phosphorylated tau showed promise for clinical use. Biomarkers of amyloid beta, tau, neurodegeneration, inflammation, and others were prognostic with individualized prediction algorithms available online. Studies supported the amyloid cascade, emphasized the importance of neuroinflammation, and detailed widespread heterogeneity in disease, linked to genetic and vascular risk, co-pathologies, sex, and resilience. Biological subtypes were consistently observed. Generalizability of ADNI results is limited by lack of cohort diversity, an issue ADNI-4 aims to address by enrolling a diverse cohort.Item Traumatic brain injury and post-traumatic stress disorder are not associated with Alzheimer's disease pathology measured with biomarkers(Wiley, 2022-06-29) Weiner, Michael W.; Harvey, Danielle; Landau, Susan M.; Veitch, Dallas P.; Neylan, Thomas C.; Grafman, Jordan H.; Aisen, Paul S.; Petersen, Ronald C.; Jack, Clifford R., Jr.; Tosun, Duygu; Shaw, Leslie M.; Trojanowski, John Q.; Saykin, Andrew J.; Hayes, Jacqueline; DeCarli, Charles; Alzheimer’s Disease Neuroimaging Initiative; Department of Defense Alzheimer's Disease Neuroimaging Initiative; Radiology and Imaging Sciences, School of MedicineIntroduction: Epidemiological studies report an association between traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) and clinically diagnosed Alzheimer's disease (AD). We examined the association between TBI/PTSD and biomarker-defined AD. Methods: We identified 289 non-demented veterans with TBI and/or PTSD and controls who underwent clinical evaluation, cerebrospinal fluid (CSF) collection, magnetic resonance imaging (MRI), amyloid beta (Aβ) and tau positron emission tomography, and apolipoprotein E testing. Participants were followed for up to 5.2 years. Results: Exposure groups (TBI, PTSD, and TBI + PTSD) had higher prevalence of mild cognitive impairment (MCI: P < .0001) and worse Mini-Mental State Examination scores (PTSD: P = .008; TBI & PTSD: P = .009) than controls. There were no significant differences in other cognitive scores, MRI volumes, Aβ or tau accumulation, or in most longitudinal measures. Discussion: TBI and/or PTSD were not associated with elevated AD biomarkers. The poorer cognitive status of exposed veterans may be due to other comorbid pathologies.Item Using the Alzheimer's Disease Neuroimaging Initiative to improve early detection, diagnosis, and treatment of Alzheimer's disease(Wiley, 2022) Veitch, Dallas P.; Weiner, Michael W.; Aisen, Paul S.; Beckett, Laurel A.; DeCarli, Charles; Green, Robert C.; Harvey, Danielle; Jack, Clifford R., Jr.; Jagust, William; Landau, Susan M.; Morris, John C.; Okonkwo, Ozioma; Perrin, Richard J.; Petersen, Ronald C.; Rivera-Mindt, Monica; Saykin, Andrew J.; Shaw, Leslie M.; Toga, Arthur W.; Tosun, Duygu; Trojanowski, John Q.; Alzheimer’s Disease Neuroimaging Initiative; Radiology and Imaging Sciences, School of MedicineIntroduction: The Alzheimer's Disease Neuroimaging Initiative (ADNI) has accumulated 15 years of clinical, neuroimaging, cognitive, biofluid biomarker and genetic data, and biofluid samples available to researchers, resulting in more than 3500 publications. This review covers studies from 2018 to 2020. Methods: We identified 1442 publications using ADNI data by conventional search methods and selected impactful studies for inclusion. Results: Disease progression studies supported pivotal roles for regional amyloid beta (Aβ) and tau deposition, and identified underlying genetic contributions to Alzheimer's disease (AD). Vascular disease, immune response, inflammation, resilience, and sex modulated disease course. Biologically coherent subgroups were identified at all clinical stages. Practical algorithms and methodological changes improved determination of Aβ status. Plasma Aβ, phosphorylated tau181, and neurofilament light were promising noninvasive biomarkers. Prognostic and diagnostic models were externally validated in ADNI but studies are limited by lack of ethnocultural cohort diversity. Discussion: ADNI has had a profound impact in improving clinical trials for AD.