Browsing by Author "Jones, David T."

Now showing 1 - 6 of 6
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    Baseline neuropsychiatric symptoms and psychotropic medication use midway through data collection of the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS) cohort
    (Wiley, 2023) Polsinelli, Angelina J.; Wonderlin, Ryan J.; Hammers, Dustin B.; Pena Garcia, Alex; Eloyan, Anii; Taurone, Alexander; Thangarajah, Maryanne; Beckett, Laurel; Gao, Sujuan; Wang, Sophia; Kirby, Kala; Logan, Paige E.; Aisen, Paul; Dage, Jeffrey L.; Foroud, Tatiana; Griffin, Percy; Iaccarino, Leonardo; Kramer, Joel H.; Koeppe, Robert; Kukull, Walter A.; La Joie, Renaud; Mundada, Nidhi S.; Murray, Melissa E.; Nudelman, Kelly; Soleimani-Meigooni, David N.; Rumbaugh, Malia; Toga, Arthur W.; Touroutoglou, Alexandra; Vemuri, Prashanthi; Atri, Alireza; Day, Gregory S.; Duara, Ranjan; Graff-Radford, Neill R.; Honig, Lawrence S.; Jones, David T.; Masdeu, Joseph; Mendez, Mario F.; Womack, Kyle; Musiek, Erik; Onyike, Chiadi U.; Riddle, Meghan; Rogalski, Emily; Salloway, Steven; Sha, Sharon J.; Turner, Raymond S.; Wingo, Thomas S.; Wolk, David A.; Carrillo, Maria C.; Dickerson, Bradford C.; Rabinovici, Gil D.; Apostolova, Liana G.; LEADS Consortium; Neurology, School of Medicine
    Introduction: We examined neuropsychiatric symptoms (NPS) and psychotropic medication use in a large sample of individuals with early-onset Alzheimer's disease (EOAD; onset 40-64 years) at the midway point of data collection for the Longitudinal Early-onset Alzheimer's Disease Study (LEADS). Methods: Baseline NPS (Neuropsychiatric Inventory - Questionnaire; Geriatric Depression Scale) and psychotropic medication use from 282 participants enrolled in LEADS were compared across diagnostic groups - amyloid-positive EOAD (n = 212) and amyloid negative early-onset non-Alzheimer's disease (EOnonAD; n = 70). Results: Affective behaviors were the most common NPS in EOAD at similar frequencies to EOnonAD. Tension and impulse control behaviors were more common in EOnonAD. A minority of participants were using psychotropic medications, and use was higher in EOnonAD. Discussion: Overall NPS burden and psychotropic medication use were higher in EOnonAD than EOAD participants. Future research will investigate moderators and etiological drivers of NPS, and NPS differences in EOAD versus late-onset AD. Keywords: early-onset Alzheimer's disease; early-onset dementia; mild cognitive impairment; neuropharmacology; neuropsychiatric symptoms; psychotropic medications.
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    Classification of Intrinsically Disordered Regions and Proteins
    (American Chemical Society, 2014-07-09) van der Lee, Robin; Buljan, Marija; Lang, Benjamin; Weatheritt, Robert J.; Daughdrill, Gary W.; Dunker, A. Keith; Fuxreiter, Monika; Gough, Julian; Gsponer, Joerg; Jones, David T.; Kim, Philip M.; Kriwacki, Richard W.; Oldfield, Christopher J.; Pappu, Rohit V.; Tompa, Peter; Uversky, Vladimir N.; Wright, Peter E.; Babu, M. Madan; Department of Biochemistry & Molecular Biology, IU School of Medicine
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    Longitudinal Clinical, Neuropsychological, and Neuroimaging Characterization of a Kindred with a 12-Octapeptide Repeat Insertion in PRNP: The Next Generation
    (Taylor & Francis, 2020-08) Townley, Ryan A.; Polsinelli, Angelina J.; Fields, Julie A.; Machulda, Mary M.; Jones, David T.; Graff-Radford, Jonathan; Kantarci, Kejal M.; Lowe, Val J.; Rademakers, Rosa V.; Baker, Matt C.; Kumar, Neeraj; Boeve, Bradley F.; Neurology, School of Medicine
    Background: Highly penetrant inherited mutations in the prion protein gene (PRNP) offer a window to study the pathobiology of prion disorders. Method: Clinical, neuropsychological, and neuroimaging characterization of a kindred. Results: Three of four mutation carriers have progressed to a frontotemporal dementia phenotype. Declines in neuropsychological function coincided with changes in FDG-PET at the identified onset of cognitive impairment. Conclusions and relevance: Gene silencing treatments are on the horizon and when they become available, early detection will be crucial. Longitudinal studies involving familial mutation kindreds can offer important insights into the initial neuropsychological and neuroimaging changes necessary for early detection.
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    New Insights into Atypical Alzheimer’s Disease in the Era of Biomarkers
    (Elsevier, 2021) Graff-Radford, Jonathan; Yong, Keir X.X.; Apostolova, Liana G.; Bouwman, Femke H.; Carrillo, Maria; Dickerson, Bradford C.; Rabinovici, Gil D.; Schott, Jonathan M.; Jones, David T.; Murray, Melissa E.; Neurology, School of Medicine
    Most patients with Alzheimer's disease present with amnestic problems; however, a substantial proportion, over-represented in young-onset cases, have atypical phenotypes including predominant visual, language, executive, behavioural, or motor dysfunction. In the past, these individuals often received a late diagnosis; however, availability of CSF and PET biomarkers of Alzheimer's disease pathologies and incorporation of atypical forms of Alzheimer's disease into new diagnostic criteria increasingly allows them to be more confidently diagnosed early in their illness. This early diagnosis in turn allows patients to be offered tailored information, appropriate care and support, and individualised treatment plans. These advances will provide improved access to clinical trials, which often exclude atypical phenotypes. Research into atypical Alzheimer's disease has revealed previously unrecognised neuropathological heterogeneity across the Alzheimer's disease spectrum. Neuroimaging, genetic, biomarker, and basic science studies are providing key insights into the factors that might drive selective vulnerability of differing brain networks, with potential mechanistic implications for understanding typical late-onset Alzheimer's disease.
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    Temporal order of clinical and biomarker changes in familial frontotemporal dementia
    (Springer Nature, 2022) Staffaroni, Adam M.; Quintana, Melanie; Wendelberger, Barbara; Heuer, Hilary W.; Russell, Lucy L.; Cobigo, Yann; Wolf, Amy; Goh, Sheng-Yang Matt; Petrucelli, Leonard; Gendron, Tania F.; Heller, Carolin; Clark, Annie L.; Taylor, Jack Carson; Wise, Amy; Ong, Elise; Forsberg, Leah; Brushaber, Danielle; Rojas, Julio C.; VandeVrede, Lawren; Ljubenkov, Peter; Kramer, Joel; Casaletto, Kaitlin B.; Appleby, Brian; Bordelon, Yvette; Botha, Hugo; Dickerson, Bradford C.; Domoto-Reilly, Kimiko; Fields, Julie A.; Foroud, Tatiana; Gavrilova, Ralitza; Geschwind, Daniel; Ghoshal, Nupur; Goldman, Jill; Graff-Radford, Jonathon; Graff-Radford, Neill; Grossman, Murray; Hall, Matthew G. H.; Hsiung, Ging-Yuek; Huey, Edward D.; Irwin, David; Jones, David T.; Kantarci, Kejal; Kaufer, Daniel; Knopman, David; Kremers, Walter; Lago, Argentina Lario; Lapid, Maria I.; Litvan, Irene; Lucente, Diane; Mackenzie, Ian R.; Mendez, Mario F.; Mester, Carly; Miller, Bruce L.; Onyike, Chiadi U.; Rademakers, Rosa; Ramanan, Vijay K.; Ramos, Eliana Marisa; Rao, Meghana; Rascovsky, Katya; Rankin, Katherine P.; Roberson, Erik D.; Savica, Rodolfo; Tartaglia, M. Carmela; Weintraub, Sandra; Wong, Bonnie; Cash, David M.; Bouzigues, Arabella; Swift, Imogen J.; Peakman, Georgia; Bocchetta, Martina; Todd, Emily G.; Convery, Rhian S.; Rowe, James B.; Borroni, Barbara; Galimberti, Daniela; Tiraboschi, Pietro; Masellis, Mario; Finger, Elizabeth; van Swieten, John C.; Seelaar, Harro; Jiskoot, Lize C.; Sorbi, Sandro; Butler, Chris R.; Graff, Caroline; Gerhard, Alexander; Langheinrich, Tobias; Laforce, Robert; Sanchez-Valle, Raquel; de Mendonça, Alexandre; Moreno, Fermin; Synofzik, Matthis; Vandenberghe, Rik; Ducharme, Simon; Le Ber, Isabelle; Levin, Johannes; Danek, Adrian; Otto, Markus; Pasquier, Florence; Santana, Isabel; Kornak, John; Boeve, Bradley F.; Rosen, Howard J.; Rohrer, Jonathan D.; Boxer, Adam L.; Frontotemporal Dementia Prevention Initiative (FPI) Investigators; Medicine, School of Medicine
    Unlike familial Alzheimer’s disease, we have been unable to accurately predict symptom onset in presymptomatic familial frontotemporal dementia (f-FTD) mutation carriers, which is a major hurdle to designing disease prevention trials. We developed multimodal models for f-FTD disease progression and estimated clinical trial sample sizes in C9orf72, GRN, and MAPT mutation carriers. Models included longitudinal clinical and neuropsychological scores, regional brain volumes, and plasma neurofilament light chain (NfL) in 796 carriers and 412 non-carrier controls. We found that the temporal ordering of clinical and biomarker progression differed by genotype. In prevention-trial simulations employing model-based patient selection, atrophy and NfL were the best endpoints, whereas clinical measures were potential endpoints in early symptomatic trials. F-FTD prevention trials are feasible but will likely require global recruitment efforts. These disease progression models will facilitate the planning of f-FTD clinical trials, including the selection of optimal endpoints and enrollment criteria to maximize power to detect treatment effects.
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    The Longitudinal Early-onset Alzheimer’s Disease Study (LEADS): Framework and methodology
    (Wiley, 2021) Apostolova, Liana G.; Aisen, Paul; Eloyan, Ani; Fagan, Anne; Fargo, Keith N.; Foroud, Tatiana; Gatsonis, Constantine; Grinberg, Lea T.; Jack, Clifford R., Jr.; Kramer, Joel; Koeppe, Robert; Kukull, Walter A.; Murray, Melissa E.; Nudelman, Kelly; Rumbaugh, Malia; Toga, Arthur; Vemuri, Prashanthi; Trullinger, Amy; Iaccarino, Leonardo; Day, Gregory S.; Graff-Radford, Neill R.; Honig, Lawrence S.; Jones, David T.; Masdeu, Joseph; Mendez, Mario; Musiek, Erik; Onyike, Chiadi U.; Rogalski, Emily; Salloway, Steve; Wolk, David A.; Wingo, Thomas S.; Carrillo, Maria C.; Dickerson, Bradford C.; Rabinovici, Gil D.; LEADS Consortium; Neurology, School of Medicine
    Patients with early‐onset Alzheimer's disease (EOAD) are commonly excluded from large‐scale observational and therapeutic studies due to their young age, atypical presentation, or absence of pathogenic mutations. The goals of the Longitudinal EOAD Study (LEADS) are to (1) define the clinical, imaging, and fluid biomarker characteristics of EOAD; (2) develop sensitive cognitive and biomarker measures for future clinical and research use; and (3) establish a trial‐ready network. LEADS will follow 400 amyloid beta (Aβ)‐positive EOAD, 200 Aβ‐negative EOnonAD that meet National Institute on Aging–Alzheimer's Association (NIA‐AA) criteria for mild cognitive impairment (MCI) or AD dementia, and 100 age‐matched controls. Participants will undergo clinical and cognitive assessments, magnetic resonance imaging (MRI), [18F]Florbetaben and [18F]Flortaucipir positron emission tomography (PET), lumbar puncture, and blood draw for DNA, RNA, plasma, serum and peripheral blood mononuclear cells, and post‐mortem assessment. To develop more effective AD treatments, scientists need to understand the genetic, biological, and clinical processes involved in EOAD. LEADS will develop a public resource that will enable future planning and implementation of EOAD clinical trials.