Dadar, Mahsa
Mayo Clinic
Douglas Mental Health University Institute
Citations 2
Olfactory decline in aging: longitudinal trajectories and associations with cognitive decline and postmortem neuropathology
Tremblay, Cécilia , Driver-Dunckley, Erika, Alasmar, Zaki , Serrano, Geidy E, Shill, Holly A. , Mehta, SH, Ho, Andrew, Fereshtehnejad, Seyed-Mohammad , Shprecher, David, Lorenzini, Ileana , Belden, Christine M. , Atri, Alireza, Adler, Charles H, Beach, Thomas G, Dadar, Mahsa, Zeighami, Yashar, Choudhury, Parichita , Driver‐Dunckley, Erika , Serrano, Geidy E. , Mehta, Shyamal H. , Ho, Andrew H, Shprecher, David , Atri, A., Adler, Charles H. , Beach, Thomas G. , Dadar, Mahsa , Zeighami, Yashar
No container title available | April 28, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Importance Decline in olfactory function may be used as a predictor of cognitive decline, to enhance early detection models, improve risk stratification, and enable early intervention. Objective To assess the longitudinal association between olfactory decline, cognitive decline, and postmortem neuropathology. Design, setting and participants Retrospective longitudinal analysis with clinicopathological correlations of a prospective population-based cohort study using data from the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND) and its Brain and Body Donation Program. Participants included cognitively unimpaired individuals without parkinsonism that converted to mild cognitive impairment (MCI) and/or dementia or remained cognitively stable. Main Outcomes and Measures longitudinal change in olfaction, neuropsychiatric symptoms, motor function and memory, conversion to MCI/dementia, postmortem neuropathology Results Over a mean follow-up period of 7.7 ± 5.4 years, out of 922 participants who were cognitively unimpaired at the first cognitive conference, 643 remained cognitively unimpaired, 279 converted to MCI, and 82 developed dementia. Of these, 633 individuals had at least 2 olfactory tests. Converters showed reduced olfactory function (t=-12.6, p <0.0001), faster progression in neuropsychiatric symptom burden (t=3.42, p < 0.001), and faster decline in memory (t= -7.33, p <0.0001) prior to conversion while no significant differences were observed in motor scores between converters and non-converters. Using ROC analysis, olfactory decline, increased neuropsychiatric symptom burden, as well as motor and memory decline predicted conversion to MCI with a consistent accuracy of ∼ 70% up to 5 years before conversion, while UPSIT alone had an accuracy of ∼ 60%. Longitudinal decline in olfaction was associated with a higher burden of a-synuclein (t= -8.21, p <0.0005), tau tangle (t= -2.66, p < 0.01) and amyloid plaque burden (t= -2.85, p < 0.005) and a faster decline over time was associated with a higher burden of tau (t=5.66, p<0.0001). Conclusions and Relevance A reduction in olfactory identification ability is observed up to a decade prior to conversion to MCI and is associated with underlying burden of neuropathology markers, underscoring the value of incorporating olfactory testing in cognitively unimpaired individuals to identify those at-risk of future cognitive decline.
Frequency and Clinical Outcomes Associated With Tau Positron Emission Tomography Positivity
Raghavan, Sheelakumari, Costoya‐Sánchez, Alejandro , Mainta, Ismini , Rodríguez-Fonseca, Omar Darío, Perissinotti, Andrés , Gu, Yuna , Yun, Jihwan, Peretti, Débora Elisa , Aguiar, Pablo , Bischof, Gérard N. , Seo, Sang Won , Villeneuve, Sylvia , O’Brien, John T. , Jagust, William, Frisoni, Giovanni B. , Soleimani‐Meigooni, David N. , Carrillo, Marı́a C., Joie, Renaud La , Rabinovici, Gil D. , Apostolova, Liana G. , Pontecorvo, Michael J. , Johnson, Keith A. , Weiner, Michael W. , Petersen, Ronald C., Jack, Clifford R. , Schöll, Michael , Labonté, Anne , Faubert, Anne‐Marie, Mathieu, Axel, Madjar, Cécile , Carrier, Charles Edouard, Kazazian, Christina, Lepage, Claude, Maillet, David , Michaud, Diane, Couture, Doris, Dea, Doris, Courcot, Blandine, Debacker, Clément , Fontaine, David, Knopman, David S. , Multhaup, Gerhard, Maltais, Jean‐Robert, Breitner, John C.S. , Poirier, Judes, Cheewakriengkrai, Laksanun, Sager, Mark A., Dauar‐Tedeschi, Marina, Rajah, Natasha, Aisen, Paul, Toussaint, Paule‐Joanne , Pierre, Bellec, Kostopoulos, Penelope, Étienne, Pierre , Tariot, Pierre N. , Orban, Pierre , Hoge, Rick, Thomas, Ronald J. , Gauthier, Serge , Craft, Suzanne , Montine, Thomas J. , Nair, Vasavan, Bohbot, Véronique D. , Venugopalan, Vinod, Ituria‐Medina, Yasser, Khachaturian, Zaven S., Teigner, Eduard, Anthal, Elena, Yu, Elsa, Ferdinand, Fabiola, Pogossova, Galina, Mayrand, Ginette, Duclair, Guerda, Gagné, Guylaine, Newbold‐Fox, Holly, Leppert, Illana, Tremblay‐Mercier, Jennifer , Frenette, Joanne, Frappier, Josée, Kat, Justin, Miron, Justin , Wan, Karen, Mahar, Laura, Carmo, Leopoldina, Théroux, Louise, Dufour, Marianne, Lafaille‐Magnan, Marie‐Élyse, Savard, Mélissa, Tuwaig, Miranda, Petkova, Mirela, Rioux, Pierre, Meyer, P.T., El‐Khoury, Rana, Gordon, Renee, Giles, Renuka, Das, Samir, Wang, Seqian, Tabrizi, Shirin , Mathotaarachchi, Sulantha , Dubuc, Sylvie, Lee, Tanya , Beaudry, Thomas, Gervais, Valérie, Pagé, Véronique, Desautels, René, Benbouhoud, Fatiha, Saint‐Fort, Eunice Farah, Verfaillie, Sander C.J. , Farzin, Sarah , Salaciak, Alyssa , Tullo, Stéphanie , Daoust, Leslie‐Ann, Köbe, Theresa , McSweeney, Melissa, Nilsson, Nathalie , Pishnamazi, Morteza, Bedetti, Christophe , Hudon, Louise, Greco, Claudia, Chapleau, Marianne , St‐Onge, Frédéric , Boutin, Sophie , Geddes, Maiya R. , Ducharme, Simon , Jean, Gabriel, Sylvain, Elisabeth, Élie, Marie‐Josee, Leblond‐Baccichet, Gloria, Soucy, Jean‐Paul , Ozlen, Hazal , Bailly, Julie, Mohammediyan, Béry, Chen, Yalin , Remz, Jordana, Rentz, Dorene M., Amariglio, Rebecca E. , Blacker, Deborah , Chhatwal, Jasmeer P. , Dickerson, Brad C., Donovan, Nancy J. , Farrell, Michelle E. , Gómez, Cristina Lois, Marshall, Gad A. , Oaoo, Kate, Price, Julie, Prokopiou, Prokopis C. , Reynolds, Gretchen , Skylar-Scott, Irina A., Vila‐Castelar, Clara , Yang, Hyun‐Sik , Trojanowki, John Q., Green, Robert C, Perrin, Richard J. , Shaw, Leslie M. , Potter, William Z. , Bernard, Marie , Jackson, Jonathan, Masliah, Eliezer , Masterman, Donna, Okonkwo, Ozioma, Ryan, Laurie, Silverberg, Nina, Fleisher, Adam , Fockler, Juliet , Conti, Cat, Jin, Chengshi , Nosheny, Rachel L. , Ashford, Mariam, Flenniken, Derek , Kormos, Adrienne, Montine, Tom, Rafii, Michael, Raman, Rema , Gessert, Devon, Salazar, Jennifer, Zimmerman, Caileigh, Cabrera, Yuliana, Walter, Sarah , Miller, Garrett, Coker, Godfrey, Clanton, Taylor, Hergesheimer, Lindsey, Smith, Stephanie , Adegoke, Olusegun, Mahboubi, Payam, Moore, Shelley, Pizzola, Jeremy, Shaffer, Elizabeth , Harvey, Danielle, Forghanian-Arani, Arvin, Borowski, Bret, Ward, Chad, Gunter, Jeff, Kantarci, Kejal, Thompson, Paul , Jahanshad, Neda , DeCarli, Charles , Knaack, Alexander , Fletcher, Evan, Chen, Stephanie R, Choe, Mark, Crawford, Karen , Yuschkevich, Paul A, Reiman, Eric M. , Mathis, Chet, Landau, Susan , Cairns, Nigel J. , Householder, Erin, Franklin, Erin , Bernhardt, Haley, Taylor‐Reinwald, Lisa, Korecka, Magdalena , Figurski, Michal, Neu, Scott, Nho, Kwangsik, Foroud, Tatiana M., Faber, Kelley , Wilmes, Kristi, Thal, Leon J., Dage, Jeffrey L. , Eloyan, Ani , Hammers, Dustin B. , Kirby, Kala, Kramer, Joel, Legarde, Julien, Murray, Melissa E., Newell, Kathy L. , Taurone, Alexander, Thangarajah, Maryanne, Touroutoglou, Alexandra , Clark, David , Day, Gregory S, Duara, Ranjan , Graff-Radford, Neill R, Grant, Ian , Masdeu, Joseph C. , Mendez, Mario F. , Onyike, Chiadi U. , Riddle, Meghan , Rogalskı, Emily , Salloway, Steven, Sha, Sharon J. , Carrillo, María C. , O'Brien, John Tiernan , Jack, Clifford R , Schöll, Michael , La Joie, Renaud , Rabinovici, Gil D , Dage, Jeffrey L , Rial, Alexis Moscoso , Heeman, Fiona , Raghavan, Sheelakumari , Essen, Martijn van , Camacho, Valle , Silva‐Rodríguez, Jesús , Ribaldi, Federica , Coomans, Emma M. , Brum, Wagner Scheeren , Grothe, Michel J. , Drzezga, Alexander E. , Malpetti, Maura , Rowe, James B. , Giessen, Elsmarieke van de , Ossenkoppele, Rik , Smith, Ruben , Hansson, Oskar , Garibotto, Valentina , Dickerson, Bradford Clark , LaMontagne, Pamela , Sperling, Reisa Anne , Vemuri, Prashanthi , Tam, Angela , Binette, Alexa Pichet , Dansereau, Christian , Picard, Cynthia , Michaud, Diane, Couture, Doris, Cuello, A. Claudio , Barkun, Alan , Evans, Alan Charles , Tardif, Christine Lucas , Knopman, David S. , Near, Jamie , Leoutsakos, Jeannie‐Marie , Brandt, Jason , Pruessner, Jens C. , Morris, John C. , Collins, D. Louis , Chakravarty, M. Mallar , Eisenberg, Mark Jeffrey , Rajah, Maria Natasha , Rosa-Neto, Pedro , Bellec, Pierre , Thomas, Ronald, Fonov, Vladimir , Vallee, Isabelle, Vogel, Jacob W. , Dadar, Mahsa , Appleby, Melissa , Meyer, Pierre‐François, Gonneaud, Julie , Pascoal, Tharick Ali , Vachon‐Presseau, Étienne , Spreng, R. Nathan , Rentz, Dorene M. , Buckley, Rachel F. , Gagliardi, Geoffroy Pierre , Gatchel, Jennifer R. , Guzmán‐Vélez, Edmarie , Jacobs, Heidi I.L. , Jutten, Roos J. , Pardilla‐Delgado, Enmanuelle , Price, Julie C. , Quiroz, Yakeel T. , Schultz, Aaron P. , Schultz, Stephanie A. , Sepulcre, Jorge , Vannini, Patrizia , Toga, Arthur W. , Beckett, Laurel , Saykin, Andrew J. , Potter, William, Barnes, Lisa L. , Gonzalez, Hector, Ho, Carole , Hsiao, John , Jackson, Jonathan , Veitch, Dallas P. , Neuhaus, John M , Rafii, Michael S. , Jimenez‐Maggiora, Gustavo Adolfo , Donohue, Michael , Arani, Arvin , Schwarz, Christopher G. , Jones, David T. , Kantarci, Kejal , Senjem, Matthew L. , Reid, Robert I. , Fox, Nick C. , Malone, Ian B. , Thomopoulos, Sophia I. , Nir, Talia M. , Tosun, Duygu , Das, Sandhitsu R. , Koeppe, Robert A. , Chen, Kewei , Risacher, Shannon L. , Shen, Li , Nudelman, Kelly , Ghetti, Bernardino , Grinberg, Lea T. , Hammers, Dustin B , Kirby, Kala, Kukull, Walter A. , Murray, Melissa E. , Polsinelli, Angelina J. , Atri, Alireza , Duara, Ranjan , Graff‐Radford, Neill R. , Honig, Lawrence S. , Johnson, Erik C. B. , Masdeu, Joseph C , Musiek, Erik , Salloway, Steve , Turner, Raymond Scott , Wingo, Thomas S , Wolk, S. J. , Womack, Kyle
JAMA | June 16, 2025 | Volume: 334 | Issue: 3 | Pages: 229
Importance Tau positron emission tomography (PET) allows in vivo detection of neurofibrillary tangles, a core neuropathologic feature of Alzheimer disease (AD). Objective To provide estimates of the frequency of tau PET positivity and its associated risk of clinical outcomes. Design, Setting, and Participants Longitudinal study using data pooled from 21 cohorts, comprising a convenience sample of 6514 participants from 13 countries, collected between January 2013 and June 2024. Cognitively unimpaired individuals and patients with a clinical diagnosis of mild cognitive impairment (MCI), AD dementia, or other neurodegenerative disorders were included. Exposures Tau PET with flortaucipir F 18, amyloid-β (Aβ) PET, and clinical examinations. Tau PET scans were visually rated as positive according to a US Food and Drug Administration– and European Medicines Agency–approved method, designed to indicate the presence of advanced neurofibrillary tangle pathology (Braak stages V-VI). Main Outcomes and Measures Frequency of tau PET positivity and absolute risk of clinical progression (eg, progression to MCI or dementia). Results Among the 6514 participants (mean age, 69.5 years; 50.5% female), median follow-up time ranged from 1.5 to 4.0 years. Of 3487 cognitively unimpaired participants, 349 (9.8%) were tau PET positive; the estimated frequency of tau PET positivity was less than 1% in those aged younger than 50 years, and increased from 3% (95% CI, 2%-4%) at 60 years to 19% (95% CI, 16%-24%) at 90 years. Tau PET positivity frequency estimates increased across MCI and AD dementia clinical diagnoses (43% [95% CI, 41%-46%] and 79% [95% CI, 77%-82%] at 75 years, respectively). Most tau PET–positive individuals (92%) were also Aβ PET positive. Cognitively unimpaired participants who were positive for both Aβ PET and tau PET had a higher absolute risk of progression to MCI or dementia over the following 5 years (57% [95% CI, 45%-71%]) compared with both Aβ PET–positive/tau PET–negative (17% [95% CI, 13%-22%]) and Aβ PET–negative/tau PET–negative (6% [95% CI, 5%-8%]) individuals. Among participants with MCI at the time of the tau PET scan, an Aβ PET–positive/tau PET–positive profile was associated with a 5-year absolute risk of progression to dementia of 70% (95% CI, 59%-81%). Conclusions and Relevance In a large convenience sample, a positive tau PET scan occurred at a nonnegligible rate among cognitively unimpaired individuals, and the combination of Aβ PET positivity and tau PET positivity was associated with a high risk of clinical progression in both preclinical and symptomatic stages of AD. These findings underscore the potential of tau PET as a biomarker for staging AD pathology.