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Comparison of the Melbourne rapid fields-web device-independent online perimeter and the octopus 600 perimeter in glaucoma patients
Kong, George Y. X., Vingrys, Algis, Ambawat, Manisha, Mahboob, Md, Bano, Shakira, Dorairaj, Syril, Bhartiya, Shibal

Frontiers in Ophthalmology | October 12, 2026 | Volume: 6 | Issue: No issue available | Pages: No page available

10.3389/fopht.2026.1961375 Get It

Introduction The purpose of this study is to evaluate the agreement, repeatability, and testing efficiency of Melbourne Rapid Fields-Web (MRF-Web), a browser-based, device-independent perimeter, compared with the Octopus 600 perimeter in glaucoma patients. Methods This retrospective, cross-sectional, single-center observational study included 113 patients undergoing routine visual field assessment for glaucoma or glaucoma suspicion at Marengo Asia Hospitals, Gurgaon, India. MRF-Web testing was performed on a calibrated 14-inch laptop with Hindi voice guidance. Agreement between MRF-Web and Octopus 600 for Mean Deviation (MD) and pattern-based global indices was assessed using intraclass correlation coefficients (ICCs) and Bland–Altman analysis. Test-retest repeatability was evaluated in 51 patients who underwent repeat MRF-Web testing. Results MRF-Web showed strong group-level concordance with Octopus 600 for MD, with an ICC of 0.88 (95% CI, 0.81–0.92), Bland–Altman bias of -0.78 dB, and 95% limits of agreement from -4.72 to 3.17 dB. Concordance for the pattern-based indices was moderate, with an ICC of 0.72 (95% CI, 0.58–0.81), bias of -0.59 dB, and 95% limits of agreement from -4.41 to 3.24 dB. MRF-Web demonstrated good test-retest concordance, with an ICC of 0.86 (95% CI, 0.69–0.94). Mean per-eye test duration was significantly shorter with MRF-Web than with Octopus 600 (232.9 ± 49.8 versus 342.4 ± 94.4 seconds). Conclusions MRF-Web demonstrated strong group-level concordance with Octopus 600 MD measurements and shorter per-eye testing times in this predominantly mild-disease cohort. The limits of agreement indicate that measurements from the two platforms should not be regarded as directly interchangeable, and further study is required in moderate and advanced glaucoma.
Smartphone Passive Digital Phenotyping in Frontotemporal Lobar Degeneration
Paolillo, Emily W. , Dhanam, Sreya , Taylor, Jack C. , Sanderson-Cimino, Mark, Fregly, Ray, Saloner, Rowan, Casaletto, Kaitlin B, Kramer, Joel H, Miller, Bruce L, Seeley, William W, Gorno-Tempini, Maria Luisa, Ljubenkov, Peter A. , Rojas, Julio C, Lee, Suzee, Sturm, Virginia, Appleby, Brian, Bayram, Ece, Clark, David, Considine, Ciaran , Darby, R. Ryan , Day, Gregory S, Vito, Alyssa , Eldaief, Mark, Fields, Julie A. , Ghoshal, Nupur , Huey, Edward D, Irwin, David J, Kantarci, Kejal, Kwan, Justin , Mackenzie, Ian R. , Masdeu, Joseph C, Onyike, Chiadi U, Pantelyat, Alexander, Pascual, Belén , Popli, Tanav, Rascovsky, Katya, Rezaii, Neguine , Scholz, Sonja W. , Snyder, Allison , Tartaglia, Maria Carmela , Traynor, Bryan J, Wong, Bonnie, Kornak, John , Kremers, Walter K. , Forsberg, Leah K. , Heuer, Hilary W. , Boeve, Bradley F. , Rosen, Howard J, Boxer, Adam L, Staffaroni, Adam M. , Sanderson‐Cimino, Mark , Saloner, Rowan , Casaletto, Kaitlin B. , Kramer, Joel H. , Miller, Bruce L. , Seeley, William W. , Gorno‐Tempini, Maria Luisa , Rojas, Julio C. , Sturm, Virginia E. , Appleby, Brian S. , Day, Gregory S, Vito, Alyssa De, Eldaief, Mark C. , Huey, Edward D. , Irwin, David J. , Kantarci, Kejal , Masdeu, Joseph, Onyike, Chiadi U. , Popli, Tanav A. , Tartaglia, Maria Carmela , Traynor, Bryan J. , Rosen, Howard J. , Boxer, Adam L.

No container title available | September 22, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.64898/2026.09.18.26363439 Get It

Introduction: Frontotemporal lobar degeneration (FTLD) is a devastating disease that commonly results in early onset dementia, yet its rarity and heterogeneity limit large-scale research and clinical trials. Remote monitoring via low-burden digital health tools may overcome these barriers. We evaluated clinical utility of passive smartphone monitoring in FTLD using a multi-domain mobile assessment platform. Methods: Participants were 567 adults (53% clinically normal, 21% prodromal FTLD, 26% symptomatic FTLD) who completed an in-person study visit and downloaded the ALLFTD Mobile App on their personal smartphones. The app delivered unsupervised cognitive tests and passively collected continuous data on battery percentage (proxy for smartphone use) and step count. Longitudinal follow-up included smartphone monitoring and annual in-person study visits. Primary analyses examined associations between passive smartphone features and markers of disease severity at baseline and longitudinally, and tested whether passive features added incremental value beyond app-based cognitive testing. Results: Passive smartphone features were feasible to collect and showed excellent reliability with <2 weeks of monitoring (ICCs>0.9). Features capturing smartphone use and movement demonstrated sensitivity to gold-standard clinical measures of disease severity both at baseline and longitudinally. A classification model combining passive features, the app-based cognitive composite score, and demographics detected longitudinal functional decline (AUC=0.89); passive features alone (AUC=0.84) performed comparably to a cognitive screener (AUC=0.85). Discussion: Passive smartphone monitoring is a valid, zero-burden measure of disease severity and progression in FTLD that adds modest incremental value beyond app-based cognitive testing. Findings support its use as a scalable digital endpoint in longitudinal FTLD research.
Feasibility of remote self-administered cognitive assessment in an Alzheimer’s disease treatment clinic
Kaser, Alyssa N , Stricker, John L. , Corriveau‐Lecavalier, Nick , Boots, Elizabeth A. , Machulda, Mary M. , Fields, Julie A. , Jones, David T. , McCarter, Stuart J. , Botha, Hugo , Coburn, Ryan P , Bermudez, Camilo , Neth, Bryan J., Graff‐Radford, Jonathan , Ramanan, Vijay K. , Stricker, Nikki H. , Hughes, Morgan A , Corriveau-Lecavalier, Nick , Boots, Elizabeth A , Machulda, Mary M , Jones, David T , Botha, Hugo , Coburn, Ryan P , Bermudez, Camilo , Graff-Radford, Jonathan , Ramanan, Vijay K , Stricker, Nikki H

No container title available | September 17, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.64898/2026.09.15.26362283 | PMID 42779999 Get It

Abstract Introduction Remote cognitive assessments offer an accessible, scalable way to support clinical characterization and longitudinal monitoring of cognition. This study evaluates the feasibility of implementing Mayo Test Drive (MTD), a remote, self-administered digital cognitive assessment, within a specialized clinic focused on eligibility assessments for anti-amyloid therapies for Alzheimer’s disease (AD). Method Two-hundred and nine ( N =209) patients (M age =71.2, 53% female) were evaluated through the Mayo Clinic Rochester Alzheimer’s Disease Treatment Clinic (ADTC) and had the opportunity to complete MTD, either as a remote, patient-initiated session through a patient-facing healthcare portal or during an in-clinic neuropsychological evaluation. Results Clinical diagnoses included 55.2% mild cognitive impairment (MCI), 31.0% mild dementia, and 11.6% moderate dementia, in addition to 2.2% cognitively unimpaired (CU), as determined by neurology consensus at a multidisciplinary case conference. Among those who initiated MTD ( n =197/209), 97.5% completed a session (70.6% remotely, 26.9% in clinic). Completion rates were high across diagnostic groups and did not significantly differ by clinical severity ( p =.12): CU (100%), MCI (99.1%), mild dementia (97.0%), and moderate dementia (89.5%). Remote completion rates overall were high (97.9%). Among completers, administration setting (remote vs. in-clinic) did not significantly differ by clinical stage, χ²(3)=2.37, p =.49. Reasons for non-initiation included not receiving or opening portal messages and other/unknown factors. Discussion Remote digital cognitive assessment is feasible within the context of clinic eligibility evaluations for AD therapies. The high completion rates of MTD across clinical impairment levels in this setting support development of paths for broader use in cognitive characterization in AD care.
Out‐of‐pocket costs are not the bottom line in financial toxicity
Fields, Brittany C. , Afolaranmi, Oluwasegun , Ohlsen, Timothy J. D. , Okoroh, Juliet S. , Lumati, Juliet S , Afolaranmi, Oluwasegun

Cancer | August 6, 2026 | Volume: 132 | Issue: 16 | Pages: No page available

10.1002/cncr.70561 | PMID 42559663 Get It

Health care–related out‐of‐pocket and indirect costs may create financial barriers to initial and/or continued receipt of care among patients with cancer, and subsequent financial toxicity is associated with worse oncologic and quality of life outcomes. Recognition and mitigation of risk factors for financial toxicity are essential to the provision of equitable, high‐quality care.
Resting Metabolic Rate in Collegiate Male Wrestlers: Cross-validation and Development of Prediction Equations
Dobbs, Ward C. , Magee, Meghan K., Ja, Fields, Sims, Jesse N. L., Saine, Noelle D., Jones, Margaret T., Jagim, Andrew R. , Fields, Jennifer B.

Medicine & Science in Sports & Exercise | July 23, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.1249/mss.0000000000004071 | PMID 42492233 Get It

Purpose: The purpose of the current study was to cross-validate previously developed RMR prediction equations using laboratory measurements of RMR as a criterion. Methods: National Collegiate Athletic Association (NCAA) Division I (n = 60) and III (n = 113) male wrestlers participated in the current study (n = 173; Age: 19.6 ± 1.5 yrs.; Height: 176.3 ± 6.3 cm; Weight: 76.6 ± 10.9 kg; Body Fat: 11.4 ± 3.0%). Indirect calorimetry was used to measure RMR and Skinfold thickness was used to estimate body fat percentage (BF%) during the preseason period under standardized dress (underwear only), fasting, and resting conditions. Results: Mean measured RMR was 2102±341 kcal·d −1 . All body mass-based RMR prediction equations significantly underestimated the measured RMR, with the exception of the Jagim and Schofield equations. The Tinsley fat-free mass (FFM) equation and the Cunningham equation had the lowest constant error (CE) values when compared to measured RMR (mean bias ± standard error: 80 ± 20 kcal and 126 ± 20 kcal·d −1 , respectively). Linear regression indicated the Tinsley FFM (R 2 = 0.422, RMSE = 279 kcals, %RMSE = 13.3%), and Cunningham FFM equations had the closest agreement to measured RMR (R 2 = 0.422, RMSE = 301 kcals, %RMSE = 14.3%), along with the Jagim equation for a body mass-based prediction equation (R 2 = 0.377, RMSE = 338 kcals, %RMSE = 16.1%). The standard error of the estimate (SEE) ranged from 260 to 272 kcal·day −1 across equations. Coefficients of determination (R 2 ) ranged from 37% to 42%. The new body mass and FFM-based equations exhibited good agreement based on the CE (26 and -13 kcal·day −1 ), RMSE (274 and 252 kcal·day −1 ), respectively. Conclusions: The newly developed equations demonstrated mean bias <2% of measured RMR.
Outcomes and Costs After Robotic vs Laparoscopic Complex Elective Cholecystectomy
Caldwell, Katharine E., Threlkeld, Edie, Litrel, Joseph, Brocke, Tiffany, Fields, Ryan C., Panni, Roheena Z., Nguyen, Trang, Leigh, Natasha, Sanford, Dominic E., Caldwell, Katharine E. , Threlkeld, Edie, Litrel, Joseph, Brocke, Tiffany K , Fields, Ryan C., Panni, Roheena Z. , Leigh, Natasha L. , Sanford, Dominic E.

JAMA Surgery | July 15, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.1001/jamasurg.2026.2650 | PMID 42455567 Get It

Importance As the use of robotic cholecystectomy increases, its value remains poorly defined for complex elective cholecystectomy (CEC), where complex gallbladder pathology results in increased technical difficulty. Objective To determine whether a robotic approach is associated with improved clinical outcomes and altered total hospital cost as compared with a laparoscopic approach for patients undergoing CEC. Design, Setting, and Participants This cohort study analyzed data from an academic hepatobiliary referral center for patients who underwent cholecystectomy from August 2018 to August 2024. CEC was defined by preoperative criteria: prior aborted or partial cholecystectomy, presence of a cholecystostomy tube, and/or history of gallbladder perforation or fistula. Exposure Robotic-assisted vs laparoscopic cholecystectomy. Main Outcomes and Measures The primary outcome was a composite of an unplanned postoperative endoscopic retrograde cholangiopancreatography or interventional radiology procedure. Secondary outcomes included operative time, postoperative complications, and operative and total hospital costs. Results A total of 863 patients underwent cholecystectomy and met inclusion criteria; 525 (60.8%) were female and 338 (39.2%) were male, and their median (IQR) age was 61 (45-71) years. Among patients undergoing CEC, the laparoscopic approach was independently associated with an increased need for unplanned endoscopic or percutaneous intervention compared with the robotic group (odds ratio, 4.24; 95% CI, 1.24-14.52; P = .02). There were no significant differences in postoperative outcomes between the laparoscopic and robotic groups in patients undergoing non-CEC. Patients undergoing the laparoscopic approach had significantly reduced operating room costs when compared with patients undergoing a robotic approach in both the CEC ($7720 vs $8936, respectively) and non-CEC groups ($6368 vs $ 8351, respectively). However, there was no difference in the overall total cost of care between laparoscopic CEC and robotic CEC groups ($14 309 vs $14 476, respectively). The overall total cost of care was significantly higher for patients undergoing robotic non-CEC as compared with laparoscopic non-CEC ($11 416 vs $9925, respectively). Conclusions and Relevance This study found that for complex gallbladder disease, robotic cholecystectomy offers a clinical advantage, reducing complications and downstream interventions without increasing the overall costs of care. These findings suggest strategic application of the robotic platform may offer clinical advantages in high-complexity gallbladder surgery, maximizing patient benefit and resource efficiency.
Longitudinal Modeling of Pitching Workload and Countermovement Jump Performance as Determinants of Fastball Velocity and Consistency in Collegiate Baseball Pitchers
Burke, Adam A. , Saine, Noelle D., King, Erica L. , Ja, Fields, Miller, Angela D. , Green, Bowling, Jones, Margaret T. , Jones, Margaret T , Fields, Jennifer B., Jagim, Andrew R.

Journal of Strength & Conditioning Research | July 9, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.1519/jsc.0000000000005602 | PMID 42423608 Get It

Abstract Burke, AA, Saine, ND, King, EL, Fields, JB, Jagim, AR, Miller, AD, Green, BC, and Jones, MT. Longitudinal modeling of pitching workload and countermovement jump performance as determinants of fastball velocity and consistency in collegiate baseball pitchers. J Strength Cond Res XX(X): 000–000, 2026—Maintenance of four-seam fastball (FSFB) velocity across the baseball season is critical, yet the extent to which workload and neuromuscular status relate to velocity is unclear. Thus, aims of the current study were to assess the relationship between external pitching workload metrics and FSFB velocity; quantify within-season FSFB velocity; and examine how countermovement jump (CMJ) performance predicts FSFB velocity. Collegiate pitchers ( n = 8) completed weekly CMJ testing during a 15-week, 53-game season. Countermovement jump metrics included jump height (JH), reactive strength index–modified (RSImod), peak braking force, and peak propulsive force normalized to body mass. Workload variables (innings, total pitches, FSFB pitches) and FSFB velocity were evaluated via repeated measures correlation (RMCORR). A longitudinal heat map visualized velocity trends, and a hierarchical location–scale model assessed predictors of mean velocity and variance. Repeated measures correlation showed weak negative associations between FSFB velocity and innings ( r = −0.15, p = 0.11), total pitches ( r = −0.18, p = 0.05), and FSFB pitches ( r = −0.18, p = 0.05). Heat map analysis identified 3 distinct velocity clusters. Location model results indicated no predictors of mean velocity. The scale model showed JH ( γ = −0.060, p = 0.001) predicted reduced velocity variance, and RSImod ( γ = 3.800, p < 0.001) predicted increased variance. Findings suggest that velocity patterns varied across athletes, where greater workloads were negatively associated with FSFB pitch velocity. Further, CMJ performance related to velocity stability rather than mean velocity. Routine longitudinal monitoring and continued strength-power training are recommended to support FSFB velocity.
Clinical Associations of Cerebrospinal Fluid TMEM106B in Familial and Sporadic Frontotemporal Dementia
Olzinski, Molly, Downer, Joshua, Rajbanshi, Binita, Li, Jingyao, Loureiro, Joseph, Heuer, Hilary, Ljubenkov, Peter, Vandevrede, Lawren, Staffaroni, Adam, Lario‐Lago, Argentina, Leichter, Dana, Wolf, Amy, Wise, Amy, Sanderson-Cimino, Mark, Barragan, Eden, Spina, S, Grinberg, Lea T., Seeley, William W., Casaletto, Kaitlin B., Kramer, Joel, Ramos, Eilana, Geschwind, Daniel, Cook, Casey, Petrucelli, L, Forsberg, Leah K., Gendron, Tania, Boeve, Bradley F., Rademakers, Rosa, Rosen, Howard J., Saloner, Rowan, Boxer, Adam L., Rojas, Julio C., Abdullah, M. Samy, Apostolova, Liana, Appleby, Brian, Bayram, Ece, Hp, Botha, Bozoki, Andrea, Brushaber, Danielle, Clark, David, Considine, Ciaran M., Darby, R. Ryan, Day, Gregory S., Dickerson, Bradford C., Dickson, Dennis, Domoto-Reilly, Kimiko, Dwosh, Emily, Faber, Kelley M., Fields, Julie A. , Fong, Jamie C., Foroud, Tatiana, Galasko, Douglas R., Gavrilova, Ralitza, Ghoshal, Nupur , Goldman, Jill, Graff-Radford, Jonathan, Graff-Radford, Neill, Grant, Ian M., Cn, Hales, Honig, Lawrence S., Gd, Hsiung, Huey, Edward D, Irwin, David, Jones, David T., Kantarci, Kejal, Knopman, David, Kolander, Tyler , Kornak, J M, Kremers, W., Kwan, Justin , Lapid, Maria, Lee, Suzee, Litvan, Irene, Lucente, Diane, Mackenzie, Ian R., Masdeu, J C, Massimo, Lauren, McGinnis, Scott, McMillan, Corey T., Mendez, Mario F., Mester, Carly, Miyagawa, Toji , Molden, Joie, Onyike, Chiadi, Pantelyat, Alexander, Pascual, Belen, Paulson, Henry, Ramanan, Vijay, Rankin, Katherine P., Rascovsky, Katya, Rhoads, Kristoffer , Savica, Rodolfo, Snyder, Allison, Sullivan, A. Campbell, Syrjanen, Jeremy, Tartaglia, M, Taylor, Jack, Tipton, P E, WEINTRAUB, S, Wint, Dylan, Wong, Bonnie, Yokoyama, Jennifer, Paulson, Henry L. , Barmada, Sami J. , Paulson, Henry L , Barmada, Sami , Cobigo, Yann , Worringer, Kathleen A. , Heuer, Hilary W. , VandeVrede, Lawren , Staffaroni, Adam M. , Wolf, Amy , Wise, Amy B. , Sanderson‐Cimino, Mark , Barragan, Eden V. , Grinberg, Lea T. , Seeley, William W. , Casaletto, Kaitlin B. , Kramer, Joel, Ramos, Eliana Marisa , Geschwind, Daniel H. , Forsberg, Leah K. , Gendron, Tania F. , Boeve, Bradley F. , Perneel, Jolien , Rademakers, Rosa , Rosen, Howard J. , Saloner, Rowan , Boxer, Adam L. , Rojas, Julio C. , Appleby, Brian S. , Barmada, Sami, Bayram, Ece , Botha, Hugo, Bozoki, Andrea C , Brushaber, Danielle , Clark, David, Considine, Ciaran , Dickerson, Bradford Clark , Dickson, Dennis, Domoto‐Reilly, Kimiko , Dwosh, Emily , Foroud, Tatiana, Graff‐Radford, Jonathan , Graff-Radford, Neill, Hales, Chadwick M., Honig, Lawrence S. , Hsiung, Ging-Yuek R., Huey, Edward D. , Jones, David T., Kantarci, Kejal , Kornak, John , Kremers, Walter, Kwan, Justin, Léger, Gabriel C. , Litvan, Irene , Lucente, Diane , Mackenzie, Ian R. , Massimo, Lauren , McGinnis, Scott, McMillan, Corey T. , Mendez, Mario F. , Mester, Carly , Pascual, Belén , Ramanan, Vijay, Rankin, Katherine P. , Roberson, Erik D. , Savica, Rodolfo , Snyder, Allison , Sullivan, A. Campbell , Syrjanen, Jeremy A. , Taylor, Jack C. , Tipton, Philip W., Vandebergh, Marijne , Weıntraub, Sandra , Wint, Dylan

JAMA Neurology | June 22, 2026 | Volume: 83 | Issue: 8 | Pages: 778

10.1001/jamaneurol.2026.1927 | PMID 42329632 Get It

Importance TMEM106B is a frontotemporal lobar degeneration (FTLD) genetic susceptibility factor, and TMEM106B protein aggregates are a feature of aging and neurodegeneration. Whether TMEM106B protein levels are associated with clinical features is unknown. Objective To investigate the clinical associations of cerebrospinal fluid (CSF) TMEM106B in FTLD. Design, Setting, and Participants This cross-sectional study was conducted in 2 independent frontotemporal dementia (FTD) cohorts (recruitment from April 2009 through July 2023, with analyses from January 2025 through April 2026), with a 2-year follow up. This multicenter clinical study integrated clinical, genetic, biomarker, and neuroimaging data. Individuals were recruited through the University of California, San Francisco (n = 3733), or ALLFTD (n = 2343). Participants with available CSF were included. A discovery cohort (n = 271) included participants with sporadic neuropathology-confirmed FTLD; presymptomatic or symptomatic carriers of pathogenic variants in C9orf72 , GRN , or MAPT ; or controls. An independent validation cohort (n = 383) included participants with clinically diagnosed sporadic FTD, Alzheimer disease (AD), and controls. Exposures CSF samples for TMEM106B quantification with aptamer proteomics (SomaScan version 3.0 [discovery cohort] and SomaScan version 4.1 [validation cohort]). Main Outcomes and Measures Parametric tests compared the primary outcome, CSF TMEM106B, by disease severity, TMEM106B rs1990622 genotype, sex, clinical syndrome, pathological diagnosis, and pathogenic variant and determined associations with brain volume. Results In the discovery (n = 271; 136 women [51%]; median [IQR] age, 59 [38-80] years) and validation (n = 383; 183 women [48%]; median [IQR] age, 64 [50-78] years) cohorts, lower CSF TMEM106B was associated with more severe disease (β, −0.15; 95% CI, −0.24 to −0.04; P = .003), lower frontotemporal brain volumes (β, 0.42; 95% CI, 0.24-0.61; P &amp;lt; .001), and faster clinical progression (β, −2.21; 95% CI, −3.70 to −0.72; P = .001). Associations of TMEM106B with clinical disease severity were independent of those with neurofilament light chain. TMEM106B levels were influenced by TMEM106B rs1990622 genotype, where individuals with the protective G/G genotype had lower levels than the risk A/A genotype. CSF TMEM106B levels did not differentiate between FTLD subtypes or between FTLD and AD. Conclusions and Relevance Per the results of this cross-sectional study, TMEM106B is detectable in CSF and levels reflect disease severity in sporadic and genetic FTLD and AD, but levels are also influenced by the TMEM106B rs1990622 genotype. CSF TMEM106B could support further studies to understand the mechanisms of disease and develop clinical tools in FTLD and other neurodegenerative diseases.
Trajectories of brain structure and function in young adult carriers of genetic frontotemporal dementia variants
So, Isis , Staffaroni, Adam M. , Coleman, Kristy , Bouzigues, Arabella , Ferry‐Bolder, Eve , Cullen, Eva , Russell, Lucy L. , Foster, Phoebe H. , Farley, Sophie , Thompson, Alexander, Ber, Isabelle Le , Körtvelyessy, Péter , Schroeter, M., Uzelac, Željko , Kruger, Johanna S. W. , Langheinrich, Tobias , Ducharme, Simon , Santana, Isabel J., Tartaglia, Carmela, Mendonca, Alexandre de, Morenoizco, Fermin, Brushaber, Danielle, Considine, Ciaran , Faber, Kelley, Fagan, Anne, Fields, Julie, Foroud, Tatiana, Forsberg, Leah K. , Geschwind, Daniel, Heuer, Hilary W. , Huang, Eric, Kantarci, Kejal, Kolander, Tyler , Lago, Argentina Lario , Lavigne, Shannon B., Mester, Carly , Molden, Joie, Petrucelli, Leonard , Rademakers, Rosa , Ramos, Eilana, Rankin, Katherine P., Rascovsky, Katya, Rhoads, Kristoffer , Weintraub, Sandra, Wong, Bonnie, Boxer, Adam L. , Rosen, Howard J. , Lee, Suzee E. , Lombardi, Jolina , Staffaroni, Adam M , Coleman, Kristy K L , Bouzigues, Arabella , Ferry-Bolder, Eve , Cullen, Eva , Russell, Lucy L , Foster, Phoebe H , Farley, Sophie , Convery, Rhian , Van Swieten, John C , Jiskoot, Lize C , Seelaar, Harro , Galimberti, Daniela , Vandenberghe, Rik , Laforce, Robert , Bruffaerts, Rose , Bertoux, Maxime , Lebouvier, Thibaud , Solje, Eino , Xiong, Chengjie , di Fede, Giuseppe , Le Ber, Isabelle , Migliaccio, Raffaella Lara , Körtvélyessy, Peter , Logroscino, Giancarlo , Otto, Markus , Uzelac, Zeljko , Illán-Gala, Ignacio , Krüger, Johanna , Nacmias, Benedetta , Gerhard, Alexander , Langheinrich, Tobias , Ducharme, Simon , Masellis, Mario , Rowe, James B , Graff, Caroline , Synofzik, Matthis , Borroni, Barbara , Sánchez-Valle, Raquel , Considine, Ciaran M , Forsberg, Leah K , Gendron, Tania F , Heuer, Hilary W , Huang, Eric , Kolander, Tyler , Mester, Carly , Petrucelli, Leonard , Rademakers, Rosa , Vandebergh, Marijne , Boeve, Brad , Boxer, Adam , Rosen, Howard J , Lee, Suzee E , Rohrer, Jonathan D , Finger, Elizabeth C. , Lombardi, Jolina , Swieten, John C. van , Jiskoot, Lize C. , Seelaar, Harro , Galimberti, Daniela , Vandenberghe, Rik , Laforce, Robert , Lebouvier, Thibaud , Xiong, Chengjie , Thompson, Alexander G. , Logroscino, Giancarlo , Otto, Markus , Illán‐Gala, Ignacio , Nacmias, Benedetta , Tartaglia, Carmela M., de Mendonça, Alexandre , Rowe, James B. , Graff, Caroline , Moreno, Fermín , Synofzik, Matthis , Borroni, Barbara , Sánchez‐Valle, Raquel , Brushaber, Danielle , Fagan, Anne M. , Gendron, Tania F. , Geschwind, Daniel, Kantarci, Kejal , Ramos, Eliana Marisa , Rankin, Katherine P. , Vandebergh, Marijne , Weıntraub, Sandra , Boeve, Bradley F. , Rohrer, Jonathan D.

No container title available | June 11, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.64898/2026.06.08.26355165 | PMID 42326777 Get It

ABSTRACT Background and Objectives Converging evidence hints at neurodevelopmental effects in genetic frontotemporal degeneration (FTD). In cross-sectional studies, for some genes, young adult FTD variant carriers show differences in brain volumes and cognition compared to familial non-carriers. However, longitudinal trajectories may more sensitively capture FTD-related neurodevelopmental vs. neurodegenerative changes than cross-sectional approaches. This study examined longitudinal trajectories of brain volumes, executive function, and plasma biomarkers in young adult carriers compared to familial non-carriers, as measures of neurodevelopmental and neurodegenerative outcomes of FTD-causing variants. Methods This longitudinal cohort study comprised participants, aged 18-30 years, from the FTD Prevention Initiative across Europe, Canada, and the USA. Genetic groups included C9orf72 (47%), MAPT (30%), and GRN (23%). Linear mixed-effects models were computed to assess longitudinal outcomes across age between groups, controlling for sex, scanner (for brain volumes), and education (for executive function); random effects accounted for between-subject variability nested within family membership. Results Variant carriers ( n =147) and familial non-carriers ( n =113) did not differ in age (mean±SD, 25.9±3.2 years), sex (53% female), or number of visits (2.1±1.7). Young adult C9orf72 repeat expansion carriers exhibited smaller thalamic volumes than non-carriers at the reference age of 26 years ( b =-982.8mm 3 , SE=317.0, p= 0.0046, f 2 =0.32), with relatively stable trajectories across ages 18-30 (i.e., no change over time). Trajectories of rostral anterior cingulate volumes differed in C9orf72 carriers and non-carriers across age, where carriers showed relatively stable trajectories and non-carriers showed age-appropriate declines ( b =64.4mm 3 , SE=29.9, p= 0.035, f 2 =0.07). For MAPT and GRN , there were little to no differences in total brain, cortical, or subcortical volumes between groups and over time. No longitudinal differences were observed between carriers and non-carriers in executive function, or plasma NfL or GFAP for any genetic group. Discussion C9orf72 repeat expansions were linked to smaller average thalamic volumes and stable trajectories between ages 18 to 30, supporting potential neurodevelopmental origins. The modest evidence supporting an absence of difference in neurodegenerative biomarkers and executive function suggests minimal early neurodegeneration and functional preservation in young adulthood.