@article{pmid42479994,

title = {Association Between Plasma GFAP and Medial Temporal Atrophy and Cognition in Amyloid-Negative Cerebrovascular Disease},

author = {Markley Silva Oliveira-Junior and Matheus Scarpatto Rodrigues and Livia Amaral and Guilherme Povala and Andreia Rocha and Marina Scop Medeiros and Sarah Abbas and João Pedro Ferrari-Souza and Pampa Saha and Firoza Z Lussier and Pamela C L Ferreira and Guilherme Bauer-Negrini and Carolina Soares and Hyun Woong Roh and Eduardo Rigon Zimmer and Thomas Karikari and Helmet Karim and Pedro Rosa-Neto and Chang Hyung Hong and Dana Tudorascu and Sang Joon Son and Bruna Bellaver and Tharick Pascoal},

doi = {10.1212/WNL.0000000000218336},

issn = {1526-632X},

year  = {2026},

date = {2026-08-01},

journal = {Neurology},

volume = {107},

number = {3},

pages = {e218336},

abstract = {BACKGROUND AND OBJECTIVES: Plasma glial fibrillary acidic protein (GFAP), a marker of astrocyte reactivity, is elevated across multiple neurodegenerative conditions, including Alzheimer disease. However, its role in neurodegeneration and cognitive decline driven by cerebrovascular pathology, independent of β-amyloid (Aβ) copathology, remains poorly characterized. We investigated whether plasma GFAP is associated with medial temporal atrophy and cognition across a spectrum of cerebrovascular burden in Aβ-negative cognitively impaired individuals.nnMETHODS: In this cross-sectional multicenter study, Aβ PET-negative cognitively impaired participants were recruited from South Korean memory clinics. Plasma GFAP was measured using ultrasensitive Simoa assays. White matter hyperintensity burden was graded using the Fazekas scale and stratified into low (LVP: Fazekas 1) and high (HVP: Fazekas 2-3) cerebrovascular burden groups. Medial temporal gray matter density was assessed using voxel-based morphometry, and hippocampal and amygdalar volumes were derived from T1-weighted MRI adjusted for intracranial volume. Linear regression, interaction, and bootstrap mediation models were used to assess associations among GFAP, brain structure, and cognition.nnRESULTS: A total of 324 participants were included (LVP n = 203; HVP n = 121; median age 73 years [interquartile range 66-78]; 67.9% female). Compared with LVP, HVP participants were older (75 vs 71 years;  < 0.0001), had lower Mini-Mental State Examination (MMSE) scores (22.7 vs 24.5;  = 0.005), and higher plasma GFAP (136.7 vs 112.1 pg/mL;  = 0.001). Higher GFAP was associated with lower medial temporal gray matter density in HVP (β = -0.311;  = 0.001) but not LVP (β = -0.012;  = 0.858), with a significant GFAP-vascular burden interaction (β = -0.309;  = 0.008). In HVP, higher GFAP was associated with smaller hippocampal (β = -0.179;  = 0.044) and amygdalar volumes (β = -0.169;  = 0.049) and lower MMSE (β = -0.194;  = 0.039). Medial temporal atrophy statistically explained the GFAP-MMSE association (indirect β = -0.071, 95% CI -0.140 to -0.010;  = 0.016). Vascular comorbidities (diabetes, dyslipidemia, hypertension) did not modify the GFAP-cognition association.nnDISCUSSION: In Aβ-negative cognitively impaired individuals with high cerebrovascular burden, elevated plasma GFAP is associated with medial temporal atrophy and cognitive decline, suggesting GFAP may capture astrocyte-reactivity relevant to vascular cognitive impairment beyond amyloid pathology. These cross-sectional findings require confirmation in longitudinal and ethnically diverse cohorts.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid42168643,

title = {Visual versus quantitative tau-PET Braak staging in Alzheimer's disease using [F]MK6240},

author = {Arthur C Macedo and Karine Provost and Jean-Paul Soucy and Arlette Haeger and Joseph Therriault and Lydia Trudel and Nesrine Rahmouni and Jaime Fernandez-Arias and Étienne Aumont and Aurélie Lebrun and Tevy Chan and Seyyed Ali Hosseini and Gleb Bezgin and Cécile Tissot and Stijn Servaes and Brandon Hall and Jenna Stevenson and Robert Hopewell and Chris Hung-Hsin Hsiao and Gallen Triana-Baltzer and Hartmuth C Kolb and Andréa L Benedet and Gassan Massarweh and Jesse Klostranec and Paolo Vitali and Tharick A Pascoal and Pedro Rosa-Neto},

doi = {10.1007/s00259-026-07886-3},

issn = {1619-7089},

year  = {2026},

date = {2026-08-01},

journal = {Eur J Nucl Med Mol Imaging},

volume = {53},

number = {10},

pages = {5644--5658},

abstract = {PURPOSE: The 2024 Alzheimer's Association Workgroup research framework designates tau proteinopathy (T) as a key element for Alzheimer's disease (AD) staging, but optimal staging approaches have yet to be determined. Here, we compared visual and quantitative tau-PET-based Braak staging as candidate strategies to implement T biological staging in vivo.nnMETHODS: We included 140 participants from the TRIAD cohort who underwent [⁸F]MK6240 tau-PET. Quantitative Braak staging (qBraak) was derived from regional SUVR thresholds, whereas visual Braak staging (vBraak) was independently performed by three nuclear medicine physicians using an adapted interpretation algorithm. Inter-rater and inter-method agreement were assessed using Cohen's and Fleiss' κ statistics. Associations with clinical severity, cortical thickness, plasma pTau217, and cortical tau extent were examined. Diagnostic performance for identifying amyloid-positive cognitively impaired individuals was evaluated.nnRESULTS: vBraak demonstrated substantial to nearly perfect inter-rater agreement (κ = 0.65-0.93). Agreement between vBraak and qBraak was moderate when stages were treated categorically (κ = 0.51), but substantial when their ordinal nature was considered (weighted κ up to 0.73). Both strategies showed comparable associations with clinical severity and neurodegeneration. vBraak was more sensitive to amyloid-β-positive cognitive impairment and identified intermediate-stage involvement at lower global tau extent. Visual-quantitative discordant cases were primarily attributable to off-target binding or spatially heterogeneous tau patterns.nnCONCLUSION: Both vBraak and qBraak staging provide complementary and largely concordant approaches for operationalizing T staging. Quantitative methods enable scalable, group-level analyses, whereas visual assessment remains essential for identifying atypical tau patterns and informing clinically relevant decision-making.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid42521309,

title = {Protecting the brain from post-stroke cognitive impairment and dementia with multimodal exercise training: study protocol for a Bayesian adaptive trial (PROTECT)},

author = {Kevin Moncion and Lynden Rodrigues and Ashanté Bon and Adam Sutoski and Kira Sikorska and Elric Y Allison and Juliano Abreu and Shirin Golchi and Nathalie Arbour and Claudine Gauthier and Caroline Paquette and Pedro Rosa-Neto and Ilana Leppert and Christopher Rowley and Christine L Tardiff and Alexander Thiel and Baraa Al-Khazraji and Ada Tang and Marc Roig},

doi = {10.1136/bmjopen-2026-123336},

issn = {2044-6055},

year  = {2026},

date = {2026-07-01},

journal = {BMJ Open},

volume = {16},

number = {7},

pages = {e123336},

abstract = {INTRODUCTION: Stroke triggers acute vascular and inflammatory mechanisms that predispose the brain to rapid neurodegeneration. Up to 52% of stroke survivors develop cognitive impairment within 6 months and 20% receive a clinical diagnosis of dementia within 5 years. The subacute phase (<6 months) represents a critical window in which the brain may be most responsive to neuroprotective interventions. Multimodal aerobic and resistance training improves cognition in chronic stroke, but whether it improves cognition, neuroimaging markers and blood biomarkers of dementia risk when delivered during this early window remains unknown. The PROTECT trial will compare the effects of 12 weeks of multimodal exercise (moderate-to-high-intensity resistance and aerobic training) versus a low-intensity exercise comparator on cognition, neuroimaging outcomes, blood biomarkers of cognitive decline and dementia risk in people with subacute stroke.nnMETHODS AND ANALYSIS: The PROTECT trial is a 12-week, Phase 3, assessor-blinded, multisite Bayesian adaptive randomised controlled trial (RCT) following a two-arm parallel group sequential design with 6-month and 12-month follow-up (NCT07445841). Participants will be randomised to multimodal training or the comparator using concealed allocation with permuted blocks of varying sizes. The primary outcome is cognition, measured using the 13-item Alzheimer's Disease Assessment Scale-Cognitive assessment (ADAS-Cog-13). Secondary outcomes include ADAS-Cog-Plus, structural and perfusion neuroimaging and blood biomarkers of inflammation and neurodegeneration. Tertiary outcomes include cardiorespiratory fitness, functional mobility, muscle strength, body composition, neuropsychological status, patient-reported cognition, quality of life, fatigue and healthcare utilisation. Outcomes will be assessed at baseline, post-intervention (primary endpoint) and at 6-month and 12-month follow-up. Sample size was estimated via 20 000 Monte Carlo simulations using an ADAS-Cog effect size of Cohen's d=0.63 from a previous exercise RCT. The target was ≥80% power to detect this treatment effect at a one-sided type I error rate of 2.5%, using a weakly informative prior centred at zero with a variance of 100. The minimum required was 45 completers per arm (N=90) and accounting for 25% attrition, up to 120 participants (60 per arm) will be enrolled. Pre-planned adaptive features include: (1) two interim analyses at 50% and 75% of completers; (2) early stopping for efficacy and futility; and (3) sample size re-estimation.nnETHICS AND DISSEMINATION: Ethical approval to conduct this study has been granted by the Centre de recherche interdisciplinaire en réadaptation du Montréal métropolitain (CRIR MP-50-2025-2294) and Hamilton Integrated Research Board (HIREB 19222). Any protocol amendments will be submitted to the appropriate ethics boards. Written informed consent to participate in this study will be obtained from all participants by study coordinators or assistants. Study results will be published and reported in peer-reviewed journal following Adaptive Designs Consolidated Standards of Reporting Trials extension guidelines.nnTRIAL REGISTRATION NUMBER: NCT07445841.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid42422935,

title = {Validation and normative data for the Multilingual Naming Test (MINT) in French-speaking Quebec adults over 40},

author = {Felix-Etienne Colpron-Larin and Etienne Aumont and Samantha Schwartz and Laura-Maria Perez and Nesrine Rahmouni and Arthur Casa Macedo and Lydia Trudel and Delphine Oliva Lopez and Brandon Hall and Anna Marier and Thomas Carrier and Marie-Anne St-Georges and Jean-Christophe Maranda and Jenna Stevenson and Paolo Vitali and Maxime Montembeault and Pedro Rosa-Neto},

doi = {10.1080/23279095.2026.2700399},

issn = {2327-9109},

year  = {2026},

date = {2026-07-01},

journal = {Appl Neuropsychol Adult},

pages = {1--12},

abstract = {Picture naming tests are critical tools for assessing language and semantic memory deficits in dementia, but must be adapted to local cultural context. This study aimed to develop and validate a Quebec French version of the Multilingual Naming Test (MINT), including determining norms and assessing diagnostic accuracy of mild cognitive impairment (MCI) and dementia. Quebec French-speaking participants ( = 224) were drawn from the TRIAD Montreal cohort and the DEVOCS study and stratified into three subgroups using a double-threshold of quantitative (Montreal Cognitive Assessment) and qualitative (consensus diagnosis) assessments. Linear models were used to create norms and compare diagnostic groups; correspondence with the Boston Naming Test (BNT) used the equipercentile method. Item-specific analysis revealed that naming of three items was sex-dependent. We found significant effects of sex and education, and an interaction trend, on uncued MINT scores. The MINT showed high comparability to the BNT, and Receiver Operating Characteristic curves corroborated their similar diagnostic ability. The MINT performed better at discriminating dementia from cognitively unimpaired participants than at identifying MCI. Correcting for education and sex was necessary to obtain accurate scores. Our results show that the MINT is adequately valid and effective to replace the BNT in neuropsychological assessment in the Quebec French population.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41392092,

title = {In vivo-measured Lewy body pathology is associated with neuropsychiatric symptoms across the Alzheimer's disease continuum},

author = {Douglas Teixeira Leffa and Guilherme Povala and Pamela C L Ferreira and João Pedro Ferrari-Souza and Guilherme Bauer-Negrini and Matheus Scarpatto Rodrigues and Livia Amaral and Firoza Z Lussier and Marina Scop Medeiros and Carolina Soares and Cristiano Schaffer Aguzzoli and Arthur C Macedo and Joseph Therriault and Pedro Rosa-Neto and Dana L Tudorascu and Eduardo R Zimmer and Bruna Bellaver and Tharick A Pascoal},

doi = {10.1038/s41380-025-03400-7},

issn = {1476-5578},

year  = {2026},

date = {2026-05-01},

journal = {Mol Psychiatry},

volume = {31},

number = {5},

pages = {2472--2480},

abstract = {Intracellular alpha-synuclein aggregates, known as Lewy bodies (LB), are commonly observed in Alzheimer's disease (AD) dementia. Post-mortem studies have shown a higher frequency of neuropsychiatric symptoms among individuals with AD and LB co-pathology. However, the effects of in vivo-measured LB pathology on neuropsychiatric symptoms in AD remain underexplored. This study aimed to evaluate cross-sectional and longitudinal effects of in vivo-measured LB pathology on neuropsychiatric symptoms across the AD continuum. We analyzed data from 1169 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Participants had in vivo measures of LB pathology (assessed using an alpha-synuclein seed amplification assay), amyloid-beta (Aβ) and phosphorylated tau (p-tau) levels in cerebrospinal fluid, and neuropsychiatric symptoms evaluated using the Neuropsychiatric Inventory-Questionnaire (NPI-Q). Logistic and Cox proportional hazards regression models were used to assess cross-sectional and longitudinal effects, respectively, adjusting for age, sex, and cognitive status. Participants had a mean baseline age of 73.05 (SD 7.22) years, 47.13% were women, 426 (36.44%) cognitively unimpaired, and 743 (63.56%) cognitively impaired. In cross-sectional analyses, LB pathology was associated with higher rates of anxiety, apathy, motor disturbances, and appetite disturbances. In longitudinal analyses, LB pathology increased the risk of developing psychosis and anxiety. These effects were independent of Aβ and p-tau. Our results suggest that in vivo-measured LB pathology is closely associated with neuropsychiatric symptoms across the AD continuum. These findings underscore the potential of in vivo LB detection as a marker for identifying individuals at increased risk of neuropsychiatric symptoms, both in clinical trials and in clinical practice.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41978994,

title = {Elevation in network dynamics amplifies amyloid-dependent tau pathology},

author = {Jieying Li and Yang Yi and Lin Gan and Gleb Bezgin and Tevy Chan and Nesrine Rahmouni and Yi-Ting Wang and Etienne Aumont and Seyyed Ali Hosseini and Brandon J Hall and Lydia Trudel and Joseph Therriault and Arthur C Macedo and Kely Monica Quispialaya Socualaya and Jaime Fernandez Arias and Yansheng Zheng and Delphine Olivia-Lopez and Robert Hopewell and Chris Hung-Hsin Hsiao and Ting Zou and Jean-Paul Soucy and Serge Gauthier and Paolo Vitali and Tharick A Pascoal and Qolamreza R Razlighi and Maxime Montembeault and Rong Li and Pedro Rosa-Neto},

doi = {10.1002/alz.71354},

issn = {1552-5279},

year  = {2026},

date = {2026-04-01},

journal = {Alzheimers Dement},

volume = {22},

number = {4},

pages = {e71354},

abstract = {INTRODUCTION: The role of brain network dynamics in relation to amyloid beta (Aβ) and tau pathology across Braak stages remains unclear.nnMETHODS: In this cross-sectional study of 216 participants from Translational Biomarkers of Aging and Dementia (TRIAD) cohort, we analyzed resting-state functional magnetic resonance imaging using a multilayer modularity algorithm to assess brain network dynamics across 10 predefined functional networks, stratified by amyloid and tau positron emission tomography biomarkers and Braak stages.nnRESULTS: Switching rates were significantly elevated in Aβ-positive/tau-positive individuals relative to Aβ-negative/tau-negative individuals, and increased progressively with advancing Braak stages. Elevated switching rates were strongly correlated with Aβ and tau burden in dorsal attention network and sensorimotor network, as well as with cognitive severity. Importantly, the interaction between network switching rate and Aβ burden synergistically contributed to accelerated tau accumulation in Braak stage III to V regions.nnDISCUSSION: These findings support the framework that increased network switching may amplify Aβ-related tau load and cognitive deterioration in Alzheimer's disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41981379,

title = {Analytical and clinical validation of the Lumipulse G plasma p-tau217 assay for clinical implementation},

author = {Burak Arslan and Johan Gobom and Ulf Andreasson and Laia Montoliu-Gaya and Andrea L Benedet and Anna Dittrich and Silke Kern and Ingmar Skoog and Nicholas J Ashton and Tevy Chan and Nesrine Rahmouni and Pedro Rosa-Neto and Kaj Blennow and Henrik Zetterberg and Hlin Kvartsberg},

doi = {10.1002/alz.71374},

issn = {1552-5279},

year  = {2026},

date = {2026-04-01},

journal = {Alzheimers Dement},

volume = {22},

number = {4},

pages = {e71374},

abstract = {INTRODUCTION: Although several plasma tau phosphorylated at threonine 217 (p-tau217) immunoassays are now available, comprehensive analytical validation remains limited. We therefore evaluated the Lumipulse G plasma p-tau217 assay and verified established cutoffs for clinical implementation.nnMETHODS: This study was conducted in two phases: (1) analytical validation of the Lumipulse G plasma p-tau217 assay, assessing precision, lower limit of quantification (LLoQ), selectivity, stability, and interference; and (2) verification of previously established cutoffs using a two-threshold approach in 37 samples with confirmed cerebrospinal fluid (CSF) Aβ42/Aβ40 status.nnRESULTS: The assay demonstrated strong analytical performance, with repeatability and intermediate precision (%CV < 7%) and an LLoQ of 0.12 pg/mL. The p-tau217 was stable across freeze-thaw cycles but less so at 4°C, and hemolysis > 2% introduced variability. Cutoff verification showed 97% reproducibility with excellent agreement (ρ = 0.99, p < 0.0001).nnDISCUSSION: The Lumipulse assay showed robust analytical performance and reproducibility, supporting clinical use, though certified reference materials are still needed for standardization.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41722275,

title = {Estimated prevalence of underdiagnosed dementia in a multiethnic community-based study},

author = {Lydia Trudel and Joseph Therriault and Arthur C Macedo and Meredith N Braskie and Karin L Meeker and Arthur W Toga and Serge Gauthier and Paolo Vitali and Sid E O'Bryant and Pedro Rosa-Neto},

doi = {10.1016/j.tjpad.2026.100510},

issn = {2426-0266},

year  = {2026},

date = {2026-04-01},

journal = {J Prev Alzheimers Dis},

volume = {13},

number = {4},

pages = {100510},

abstract = {Dementia frequently goes undetected in community settings, particularly among socially disadvantaged populations. Here, we estimated the prevalence of underdiagnosed dementia across diverse sociodemographic determinants of health in the Health and Aging Brain Study-Health Disparities (HABS-HD), a community-based cohort of adults recruited through community outreach in Fort Worth, Texas. We estimated age-specific probabilities of underdiagnosis using Poisson regression models with a log link, including age and sex as covariates. Robust (sandwich) variance estimators were used to obtain standard errors and 95% confidence intervals (CI). Group differences or trends for continuous measures were assessed using robust variance estimates. The prevalence of underdiagnosed dementia was higher among individuals without physician access (98.1% vs. 78.1%, p<.0001), non-English speakers (97.9% vs. 76.8%, p<.0001), and the uninsured (91.5% vs. 79.5%, p=.03). Black and Hispanic participants also showed higher prevalence (85.8% and 90.9%) compared to non-Hispanic White participants (64.9%; p=.02 and p=.002, respectively). Each additional year of education was associated with a 2.5% lower risk of underdiagnosis (p<.0001). No differences were observed by sex, marital status, income or social support. Our results highlight that several sociodemographic factors contribute to the likelihood of living with undiagnosed dementia.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41650358,

title = {Association of Cortical Free Water With Brain Tau Tangle Load in the Alzheimer Disease Continuum},

author = {Brandon J Hall and Etienne Aumont and Seyyed Ali Hosseini and Jaime Fernandez Arias and Arnaud Boré and Gleb Bezgin and Lydia Trudel and Tevy Chan and Joseph Therriault and Arthur C Macedo and Marcel Seungsu Woo and Delphine Oliva-Lopez and Nesrine Rahmouni and Yansheng Zheng and Stijn Servaes and Jenna Stevenson and Serge Gauthier and Andrea L Benedet and Matthieu Dumont and Jean-Christophe Houde and Gallen Triana-Baltzer and Hartmuth Christian Kolb and Nicholas J Ashton and Henrik Zetterberg and Yasser Iturria Medina and Paolo Vitali and Maxime Descoteaux and Jesse Michael Klostranec and Tharick Pascoal and Pedro Rosa-Neto},

doi = {10.1212/WNL.0000000000214606},

issn = {1526-632X},

year  = {2026},

date = {2026-03-01},

journal = {Neurology},

volume = {106},

number = {5},

pages = {e214606},

abstract = {BACKGROUND AND OBJECTIVES: Neurofibrillary tangles (NFTs) progressively damage gray matter in Alzheimer disease (AD). Resulting cortical microstructural alterations might not be detectable using macrostructural metrics but may be studied using isotropic water diffusion, as it reflects extracellular free water content. The aim of this study was to examine the effect of NFTs on cortical microstructure by investigating whether cortical free water increases as a function of tau load. We also investigated whether phosphorylated tau in blood plasma also indicated cortical microstructural abnormalities.nnMETHODS: For this cross-sectional study, we sampled participants with T1 MRI, multishell diffusion-weighted MRI, amyloid PET ([F]AZD4694), tau PET, and plasma phosphorylated tau 217+ (p-tau217) from the Translational biomarkers in Aging and Dementia cohort at McGill University; participants were recruited between 2017 and 2024. We used the Neurite Orientation Dispersion and Density Imaging algorithm to calculate isotropic free water images ("free water"). FreeSurfer was used to calculate cortical thickness in the entorhinal, fusiform, inferior temporal, and middle temporal gyri regions of interest ("meta-ROI"); Automatic Segmentation of Hippocampal Subfields was used to calculate hippocampal volumes. We grouped participants by amyloid PET positivity (A), plasma p-tau217 positivity (T1), and tau PET positivity (T2). We performed voxel-wise correlation analyses between free water and these proteinopathy markers, as well as ROI-based analyses in the meta-ROI.nnRESULTS: A total of 303 participants (mean age 67 years, 58.7% female) were included in this study (168 cognitively normal individuals, 43 with mild cognitive impairment, 23 with AD dementia, 68 not diagnosed). Tau PET was positively correlated with free water in gray matter predominantly in the temporal lobe (partial  = 0.39,  < 0.001), and the correlation of p-tau217 with the meta-ROI free water was entirely mediated by tau PET ( < 0.001). In addition, medial temporal and hippocampal free water was negatively correlated with Montreal Cognitive Assessment scores in the A-T+ and A+T+ groups. The strongest ROI-based multilinear models for predicting temporal gray matter and hippocampal tau PET burden used both cortical thickness and free water as predictors (temporal gray matter partial  = 0.62; hippocampal partial  = 0.64).nnDISCUSSION: In AD-relevant regions, increased free water correlates with tau load independently of macrostructural metrics or amyloid load. Free water may serve as an imaging marker for microstructural changes in gray matter resulting from NFT accumulation, complementary to macrostructural metrics.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41816928,

title = {Language deficits across PET-based Braak stages of tau accumulation in Alzheimer's disease},

author = {Anna Marier and Jaime Fernández Arias and Étienne Aumont and Brandon J Hall and Arthur C Macedo and Nesrine Rahmouni and Gleb Bezgin and Paolo Vitali and Pedro Rosa-Neto and Maxime Montembeault},

doi = {10.1002/alz.71286},

issn = {1552-5279},

year  = {2026},

date = {2026-03-01},

journal = {Alzheimers Dement},

volume = {22},

number = {3},

pages = {e71286},

abstract = {INTRODUCTION: Language complaints in cognitively unimpaired (CU) individuals may reflect Alzheimer's Disease (AD) pathology and future objective impairments.nnMETHODS: 211 participants (138 CU, 45 with mild cognitive impairment (MCI), and 28 with dementia) from the TRIAD cohort underwent F-MK-6240 tau-PET and F-AZD-4694 amyloid-PET. Word-finding complaints, confrontation naming, semantic fluency, phonemic fluency and word-knowledge were evaluated.nnRESULTS: Complaints about forgetting the names of objects appeared in early tau stages (Braak 1-2), followed by naming difficulties (Braak 3-4), and widespread language impairments in later stages (Braak 5-6). Across the biologically-defined AD continuum, lower language performance was associated with tau accumulation predominantly in left-temporal language regions. In CU, only subjective word-finding complaints related to tau, indicating language concerns could reflect underlying pathology before measurable cognitive decline.nnDISCUSSION: Language measures support early detection and staging of AD pathophysiology and contribute to better align cognitive assessment with biological definitions of the disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41856988,

title = {Amygdala and hippocampal contributions to broad autism phenotype: Project Ice Storm},

author = {Xinyuan Li and Muhammad Naveed Iqbal Qureshi and David P Laplante and Guillaume Elgbeili and Sherri Lee Jones and Suzanne King and Pedro Rosa-Neto},

doi = {10.1038/s41398-026-03918-6},

issn = {2158-3188},

year  = {2026},

date = {2026-03-01},

journal = {Transl Psychiatry},

volume = {16},

number = {1},

abstract = {Prenatal maternal stress (PNMS) increases the risk for autism, and individuals with autism inconsistently exhibit increased or decreased volumes and functional connectivity of the whole amygdala and the whole hippocampus. Given heterogeneous structures of the amygdala and hippocampus and the heterogeneity of autism symptoms, it is worth examining how their subregions contribute to different autism phenotypes. T1-weighted and resting-state functional MRI data were acquired from 32 young adults of mothers who were pregnant during, or within 3 months of, the 1998 Quebec ice storm. Their broad autism phenotype (BAP) was self-reported, including aloof personality, pragmatic language impairment and rigid personality. This sample has a wide range of scores on the BAP Questionnaire. Volumes of the amygdala nuclei and hippocampal subfields were calculated. Seed-to-voxel analysis was applied to examine functional connectivity of the amygdala nuclei and hippocampal subfields with the rest of the brain, and linear regressions were implemented to examine associations of volume and functional connectivity with the three autism phenotypes. Primarily, we found that 1) rigid personality was associated with decreased left hippocampal cornu ammonis (CA)1 volume; 2) pragmatic language impairment was associated with decreased left hippocampal CA1 connectivity with the supplementary motor area, and increased right hippocampal CA4 connectivity with the left putamen; and 3) rigid personality was associated with increased right central amygdala connectivity with the left inferior lateral occipital cortex (LOC); and increased left hippocampal CA3 connectivity with the right superior parietal lobule, increased right hippocampal CA4 connectivity with the left superior LOC, and increased right hippocampal dentate gyrus connectivity with the left superior LOC. In contrast, we found no associations with aloof personality. Our results suggest that, within a sample exposed to PNMS, amygdala and hippocampal structure and function contribute differently to two different autistic-like characteristics, with hippocampus-motor connectivity explaining variance in communication impairment, and with hippocampal volume, amygdala- and hippocampus- sensory connectivity sharing the common mechanism in rigid behaviors. Given these links between brain and autistic-like traits, future research should examine whether brain volumes and connectivity mediate associations between PNMS and autistic-like traits in young adulthood.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41668114,

title = {Functional network phenotypes of mild behavioural impairment: cognitive effects moderated by amyloid},

author = {Kok Pin Ng and Joanna Su Xian Chong and Firoza Lussier and Joseph Therriault and Nesrine Rahmouni and Melissa Savard and Jenna Stevenson and Tharick Pascoal and Serge Gauthier and Pedro Rosa-Neto and Juan Helen Zhou},

doi = {10.1186/s13195-026-01980-2},

issn = {1758-9193},

year  = {2026},

date = {2026-02-01},

journal = {Alzheimers Res Ther},

volume = {18},

number = {1},

abstract = {BACKGROUND: Mild behavioural impairment (MBI) is a neurobehavioural syndrome that represents an at-risk state for incident cognitive decline. No study to date has systematically investigated whole-brain within- and between- network functional connectivity (FC) disruptions in MBI and their effects on cognitive performance in dementia-free individuals. Hence, we sought to evaluate the whole-brain functional network phenotypes associated with MBI and its subdomains, and their relationships with amyloid and tau pathology in predicting future cognition and function in dementia-free older adults.nnMETHODS: We studied 203 dementia-free individuals aged between 55 and 90 years (77 males) from the Translational Biomarkers in Aging and Dementia (TRIAD) cohort with baseline functional MRI, amyloid-β [18 F]AZD4694 and tau [18 F]MK6240 PET imaging, and longitudinal neuropsychological assessments up to 32 months. Multivariate associations between MBI-Checklist (MBI-C) subdomain scores and whole-brain FC matrices were examined using partial least squares correlation. We then assessed how these MBI-related network phenotypes were associated with baseline and longitudinal changes in global cognition (via Montreal Cognitive Assessment (MoCA) scores) and functional performance (via clinical dementia rating (CDR) sum of boxes), and whether they interacted with baseline Alzheimer’s disease pathology (global amyloid uptake and tau temporal meta-region-of-interest uptake via PET) to influence future outcomes using linear regression models.nnRESULTS: We identified an MBI-related functional network phenotype characterized by greater MBI severity and widespread dysfunctions particularly in higher-order networks. Greater expression of this phenotype was associated with poorer baseline global cognition, as well as greater functional impairment at baseline and over time. Further, baseline global amyloid uptake, but not temporal tau uptake, moderated the effects of baseline MBI-related FC disruptions on longitudinal global cognition changes in dementia-free older adults. Specifically, individuals with higher amyloid burden and greater MBI-related FC disruptions showed accelerated cognitive decline over time. In contrast, the MBI-C total score did not show independent or interactive effects with amyloid and tau burden on longitudinal cognitive and functional outcomes.nnCONCLUSIONS: Our findings demonstrated a global MBI-related functional network phenotype in dementia-free individuals that was associated with impaired cognition and function. Moreover, this phenotype interacts with amyloid burden to accelerate cognitive decline, underscoring its relevance in preclinical Alzheimer’s disease.nnSUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13195-026-01980-2.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41656561,

title = {Quantitative susceptibility mapping of the brain is associated with inflammatory changes in Alzheimer's disease related areas},

author = {Seyyed Ali Hosseini and Stijn Servaes and Arthur C Macedo and Etienne Aumont and Nesrine Rahmouni and Tevy Chan and Joseph Therriault and Lydia Trudel and Brandon Hall and Yi-Ting Wang and Jaime Fernandez Arias and Gleb Bezgin and Yansheng Zheng and Marina P Gonçalves and Kely Quispialaya Socualaya and Marcel S Woo and Cécile Tissot and Delphine Oliva-Lopez and Jieying Li and Stuart Mitchell and Aurélie Lebrun and Robert Hopewell and Sanjeev Chawla and Vladimir Fonov and Gassan Massarweh and Yasser Iturria Medina and Jean-Paul Soucy and Maxime Montembeault and Paolo Vitali and Kaj Blennow and Thomas K Karikari and Andréa L Benedet and Nicholas J Ashton and Henrik Zetterberg and Tharick A Pascoal and Serge Gauthier and Jesse Klostranec and Hangwei Zhuang and Junghun Cho and D Louis Collins and Yi Wang and David A Rudko and Pedro Rosa-Neto},

doi = {10.1177/0271678X261417193},

issn = {1559-7016},

year  = {2026},

date = {2026-02-01},

journal = {J Cereb Blood Flow Metab},

pages = {271678X261417193},

abstract = {Accumulation of paramagnetic substances in brain tissue may constitute a feature of Alzheimer's disease (AD) associated with inflammatory processes. This study employed MRI quantitative susceptibility mapping (QSM), as an index of paramagnetic load, to assess its association with brain Aβ and tau aggregates, as well as inflammatory biomarkers. We assessed QSM and T1-weighted MRI scans from 315 participants in the TRIAD cohort, including young-controls and individuals across the AD spectrum. Imaging was performed at baseline, with follow-up assessments at 12 and 24 months. Mean-cortical and subcortical susceptibility values were measured, and correlations with AD-relevant plasma and CSF inflammatory biomarkers. At baseline, AD patients had significantly greater QSM than age-matched controls in the posterior cingulate cortex, precuneus, and basal ganglia. After 24 months, QSM increased in the anterior cingulate in MCI, while dementia cases showed increase in the pallidum and hippocampus. Multiple comparison analysis indicated correlation between QSM and immune biomarkers IL-10RB, PD-L1, SCF, TWEAK, CSF-1, CXCL9, HGF, and CD40, but not with brain Aβ or tau-related biomarkers. Our findings reveal that the magnitude of tissue susceptibility load, as measured by QSM, reflects tissue inflammation rather than protein aggregation. QSM provides new insights into tissue dysfunction, with potential applications in AD therapeutic development.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41738400,

title = {Choroidal-ventricular system abnormalities are linked to amyloid-β aggregation in Alzheimer's disease},

author = {Seyyed Ali Hosseini and Etienne Aumont and Nesrine Rahmouni and Marcel S Woo and Arthur C Macedo and Brandon Hall and Tevy Chan and Joseph Therriault and Lydia Trudel and Yansheng Zheng and Gleb Bezgin and Aurélie Lebrun and Jaime Fernandez Arias and Kely Quispialaya Socualaya and Cécile Tissot and Stijn Servaes and Yi-Ting Wang and Delphine Oliva-Lopez and Stuart Mitchell and Robert Hopewell and Chris Hung-Hsin Hsiao and Catherine Saleh and Jenna Stevenson and Firoza Lussier and Liyong Wu and Min Chu and Sanjeev Chawla and Vladimir Fonov and Gassan Massarweh and Yasser Iturria Medina and Jean-Paul Soucy and Karine Provost and David A Rudko and Thomas Karikari and Andréa Lessa Benedet and Nicholas J Ashton and Henrik Zetterberg and Maxime Montembeault and Paolo Vitali and Kaj Blennow and Serge Gauthier and D Louis Collins and Jesse Klostranec and Tharick A Pascoal and Pedro Rosa-Neto},

doi = {10.1002/alz.71205},

issn = {1552-5279},

year  = {2026},

date = {2026-02-01},

journal = {Alzheimers Dement},

volume = {22},

number = {2},

pages = {e71205},

abstract = {INTRODUCTION: Enlargement of the choroidal-ventricular system occurs in aging and Alzheimer's disease (AD), but emerging evidence links these abnormalities to amyloid beta (Aβ) aggregation. We tested this hypothesis by assessing associations between AD pathophysiology and choroidal-ventricular system measures across the AD continuum.nnMETHODS: Ventricular volume, choroid-plexus volume, and ventricular radioactivity after positron emission tomography (PET) tracer injections were analyzed in 385 Translational Biomarkers in Aging and Dementia (TRIAD) and 282 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants using linear models and partial correlations. A composite score combining these measures was also tested against established AD biomarkers.nnRESULTS: With advancing AD stages, ventricular and choroid-plexus volumes increased while ventricular radioactivity declined. These measures were interrelated, and abnormalities appeared even in amyloid-negative elderly. Across cohorts, they correlated with amyloid- and tau-PET, cerebrospinal fluid (CSF) and plasma p-tau isoforms, glial fibrillary acidic protein (GFAP), and cognition. Voxel-wise analyses showed strong associations with cortical Aβ, mediating downstream tau effects.nnDISCUSSION: Changes in the choroidal-ventricular system are mutually correlated and carry an additive-effect on cortical Aβ load.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41853044,

title = {Ventricular enlargement is associated with early Alzheimer's disease pathophysiology},

author = {Seyyed Ali Hosseini and Etienne Aumont and Nesrine Rahmouni and Marcel S Woo and Arthur C Macedo and Brandon Hall and Lydia Trudel and Tevy Chan and Jaime Fernandez Arias and Yi-Ting Wang and Stijn Servaes and Joseph Therriault and Yansheng Zheng and Kely Quispialaya Socualaya and Gleb Bezgin and Cécile Tissot and Delphine Oliva-Lopez and Robert Hopewell and Chris Hung-Hsin Hsiao and Catherine Saleh and Jenna Stevenson and Firoza Lussier and Liyong Wu and Min Chu and Sanjeev Chawla and Vladimir Fonov and Gassan Massarweh and Yasser Iturria-Medina and Jean-Paul Soucy and David A Rudko and Serge Gauthier and Thomas Karikari and Andréa Lessa Benedet and Nicholas J Ashton and Henrik Zetterberg and Maxime Montembeault and Paolo Vitali and Kaj Blennow and D Louis Collins and Jesse Klostranec and Tharick A Pascoal and Pedro Rosa-Neto},

doi = {10.1093/braincomms/fcag066},

issn = {2632-1297},

year  = {2026},

date = {2026-01-01},

journal = {Brain Commun},

volume = {8},

number = {2},

pages = {fcag066},

abstract = {Alzheimer's disease (AD) is characterized by progressive brain changes, including protein aggregation and structural changes. Cerebrospinal fluid (CSF) system abnormalities, such as ventricular dilation, increased choroid plexus volume or positron emission tomography (PET) ligand uptake in the CSF, have also been consistently described. We aimed to examine whether changes in CSF production and clearance might be associated with brain protein aggregation across biological stages of Alzheimer's disease. We hypothesized an association between brain protein aggregation and changes on the CSF system. We examined 378 individuals from the Translational Biomarkers in Aging and Dementia (TRIAD) cohort with T1-weighted magnetic resonance imaging (MRI), amyloid-PET and tau-PET assessments. We assessed the lateral ventricle and choroid plexus volumes, both corrected for intracranial volume, in the MRI native space. Non-specific ventricular tracer standardized uptake value ratio (SUVR), derived from amyloid- and tau-PET images, was used as an indirect marker of choroid plexus-related clearance activity and served as a metric of CSF dynamics. Linear models tested associations amongst lateral ventricular volume (reflecting CSF space enlargement), choroid plexus volume (reflecting secretory tissue morphology) and ventricular SUVR (reflecting tracer activity within the CSF compartment and serving as an indirect marker of choroid plexus-related clearance function and CSF dynamics) with Aβ and tau aggregations. Analyses were restricted to within-modality associations, relating ventricular radioactivity to cortical pathology for each PET tracer. We found that when considered independently, larger ventricular and choroid plexus volumes were associated with higher neocortical Aβ-PET SUVR, particularly in the precuneus and cingulate cortices. Additionally, lower ventricular radioactivity (derived from amyloid-PET) showed strong negative associations in the dorsal apex of the neocortex. However, when all three ventricular parameters were included in the same model, these effects were mediated by ventricular volume. By contrast, the effect of the ventricular parameters on tau load was mediated by Aβ in the neocortex. Therefore, ventricular enlargement appears to be associated with Aβ load. Distinct from neurodegeneration, changes in ventricular parameters, particularly ventricular volume, are associated with upstream Alzheimer's disease pathophysiology. While ventricular volume significantly mediated ventricular amyloid clearance, no such effect was observed for tau, suggesting distinct clearance mechanisms for these pathologies in Alzheimer's disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41722502,

title = {Subcortical microglial inflammation is uniquely linked to subpial cortical demyelination in multiple sclerosis},

author = {Risavarshni Thevakumaran and Stephan Blinder and Marcus Couch and Alexey Kostikov and Rozalia Arnaoutelis and Sridar Narayanan and Pedro Rosa-Neto and Douglas L Arnold and David A Rudko},

doi = {10.1016/j.nicl.2026.103962},

issn = {2213-1582},

year  = {2026},

date = {2026-01-01},

journal = {Neuroimage Clin},

volume = {49},

pages = {103962},

abstract = {BACKGROUND: In multiple sclerosis (MS), pathology of both the subpial cortex and subependymal parenchyma has been strongly linked to compartmentalized meningeal inflammation. The topographical distribution of subpial demyelination can be appraised in vivo using surface-based mapping of magnetization transfer saturation (MTsat) in the cortex with 7T MRI. We combined 7T cortical MTsat mapping with [C]PBR28 PET molecular imaging of microglia to study the potential influence of subcortical microglial inflammation on cortical pathology.nnMETHODS: Thirty-eight MS patients (median EDSS: 4.0) and 21 healthy controls (HCs) underwent high resolution 7T MRI and [C]PBR28 PET. Principal component analysis of [C]PBR28 PET data was used to phenotype patients as having high (MSHigh) or low (MSLow) subcortical inflammation. Quantitative, surface-based measures of cortical myelin were obtained by sampling MTsat maps at 25%-50%-75% depths from the pial surface.nnRESULTS: MSHigh patients presented substantially greater, diffuse reductions in MTsat at all three cortical depths relative to HCs (P < 0.05). Areas of significantly reduced MTsat were greatest at 25% depth in the frontal, parietal and cingulate cortices, occupying nearly 70% of total cortical area and providing evidence of extensive subpial demyelination. Importantly, MSHigh patients presented increased microstructural abnormalities in subcortical regions (P < 0.05), alongside higher Expanded Disability Status Score (EDSS) (P = 0.02), increased odds of progressive MS (odds ratio = 4.85:1 [1.20, 23.26], P = 0.03) and significant cortical atrophy (P = 0.009).nnDISCUSSION: We provide in vivo evidence of a relationship between subcortical microglial inflammation and subpial demyelination in MS that is associated with increased clinical disability.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41528514,

title = {Inter-individual variability of neurotransmitter receptor and transporter density in the human brain},

author = {Justine Y Hansen and Jouni Tuisku and Jarkko Johansson and Zeyu Chang and Colm J McGinnity and Vincent Beliveau and Synthia Guimond and Melanie Ganz and Martin Nørgaard and Marian Galovic and Gleb Bezgin and Sylvia M L Cox and Jarmo Hietala and Marco Leyton and Eliane Kobayashi and Pedro Rosa-Neto and Thomas Funck and Nicola Palomero-Gallagher and Gitte M Knudsen and Paul Marsden and Alexander Hammers and Lauri Nummenmaa and Lauri Tuominen and Bratislav Misic},

doi = {10.1007/s00429-025-03069-2},

issn = {1863-2661},

year  = {2026},

date = {2026-01-01},

journal = {Brain Struct Funct},

volume = {231},

number = {1},

pages = {13},

abstract = {Neurotransmitter receptors guide the propagation of signals between brain regions. Mapping receptor distributions in the brain is therefore necessary for understanding how neurotransmitter systems mediate the link between brain structure and function. Normative receptor density can be estimated using group averages from Positron Emission Tomography (PET) imaging. However, the generalizability and reliability of group-average receptor maps depends on the inter-individual variability of receptor density, which is currently unknown. Here we collect group standard deviation brain maps of PET-estimated protein abundance for 12 different neurotransmitter receptors and transporters across 7 neurotransmitter systems, including dopamine, serotonin, acetylcholine, glutamate, GABA, cannabinoid, and opioid. We illustrate how cortical and subcortical inter-individual variability of receptor and transporter density varies across brain regions and across neurotransmitter systems. We complement inter-individual variability with inter-regional variability, and show that receptors that vary more across brain regions than across individuals also demonstrate greater out-of-sample spatial consistency. Altogether, this work quantifies how receptor systems vary in healthy individuals, and provides a means of assessing the generalizability of PET-derived receptor density quantification.nnSUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00429-025-03069-2.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41556545,

title = {Clinical-biological Alzheimer's disease stage concordance: insights from cohorts and autopsy data},

author = {Lydia Trudel and Joseph Therriault and Arthur C Macedo and Seyyed A Hosseini and Jaime Fernandez-Arias and Tevy Chan and Nesrine Rahmouni and Gleb Bezgin and Cécile Tissot and Marcel S Woo and Étienne Aumont and Yansheng Zheng and Brandon Hall and Delphine Oliva-Lopez and Stuart W Mitchell and Robert Hopewell and Chris Hung-Hsin Hsiao and Arthur W Toga and Meredith N Braskie and Karin L Meeker and Jean-Paul Soucy and Marie-Christine Guiot and Serge Gauthier and Paolo Vitali and Sid E O'Bryant and Tharick A Pascoal and Pedro Rosa-Neto},

doi = {10.1093/brain/awag018},

issn = {1460-2156},

year  = {2026},

date = {2026-01-01},

journal = {Brain},

abstract = {Alzheimer's disease (AD) is defined by its characteristic neuropathologic changes, which allow for diagnosis and assessment of severity. Recently, the Alzheimer's Association proposed a framework to stage Alzheimer's disease biologically based on tau-PET. Furthermore, the framework hypothesizes a degree of alignment between biological Alzheimer's disease severity and clinical symptom severity. We aimed to investigate the concordance between clinical and biological stages of Alzheimer's disease and explore factors contributing to discordance using in vivo and postmortem neuropathological data. Data from 768 amyloid-β positive individuals were drawn from four observational cross-sectional in vivo cohorts-TRIAD, ADNI, HABS-HD, and SCAN-as well as a postmortem autopsy dataset from the National Alzheimer's Coordinating Center (NACC; n = 3,188). All in vivo participants had tau-PET imaging, clinical diagnosis, and neurobehavioral assessments. Participants were assigned a biological Alzheimer's disease stage based on their tau-PET scan according to the Alzheimer's Association revised criteria stages. The autopsy dataset included individuals with moderate-to-frequent neuritic plaques (CERAD scores 2-3), along with premortem clinical and neurobehavioral data. Clinical-biological concordance was quantified using squared-weighted Cohen's Kappa. Ordinal and linear regression models assessed associations between biological stage and clinical severity (CDR-Sum of Boxes, MMSE), adjusting for age, sex, and cohort. Postmortem analyses evaluated the impact of comorbid neuropathologies on clinical-biological discordance using adjusted odds ratios and ordinal regression. Overall concordance between clinical and biological Alzheimer's disease staging was moderate (Cohen's Kappa=0.52, p < 0.001). Approximately 70% of individuals classified as cognitively unimpaired or with dementia exhibited biological stages consistent with their clinical diagnoses. In contrast, transitional decline and mild cognitive impairment (MCI) groups were more heterogenous. Notably, 25% of Aβ-positive individuals with MCI demonstrated no detectable tau-PET abnormality. Nonetheless, advanced tau-PET stage was reliably associated with clinical impairment. In the NACC autopsy dataset, nearly all individuals with more severe clinical stage than their proposed biological stage exhibited comorbid neuropathologies, including FTLD-TDP-43, FTLD-tau, Lewy bodies, LATE, and cerebrovascular disease. The number of comorbid pathologies was strongly associated with increased odds of clinical dementia (t = 8.45, p < 0.001). While there is moderate agreement between clinical and biological stages of Alzheimer's disease across the entire disease spectrum, strong agreement is found in clinically unimpaired and dementia stages. Comparison of clinical and biological Alzheimer's disease stages provides a framework for understanding the large contributions of non-AD neurodegenerative diseases to dementia in Aβ-positive individuals. Our results have important implications for clinical trial recruitment strategies and highlight the urgent need for biomarkers for non-AD pathological processes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41433447,

title = {Alzheimer's Imaging Consortium},

author = {Stuart William Mitchell and Tevy Chan and Lydia Trudel and Seyyed Ali Hosseini and Arthur C Macedo and Marina P Gonçalves and Nesrine Rahmouni and Brandon J Hall and Kely Monica Quispialaya Socualaya and Joseph Therriault and Stijn Servaes and Gleb Bezgin and Yansheng Zheng and Etienne Aumont and Yi-Ting Wang and Jaime Fernandez Arias and Ana Paula Bernardes Real and Wan Lu Jia and Robert Hopewell and Chris Hsiao and Jean-Paul Soucy and Paolo Vitali and Tharick A Pascoal and Pedro Rosa-Neto},

doi = {10.1002/alz70862_109868},

issn = {1552-5279},

year  = {2025},

date = {2025-12-01},

journal = {Alzheimers Dement},

volume = {21 Suppl 8},

number = {Suppl 8},

pages = {e109868},

abstract = {BACKGROUND: Brain and cognitive resilience (BR, CR) reflect the capacity to maintain structural integrity and cognitive function despite pathological tau deposition in Alzheimer's disease (AD). Tau pathology can be characterized in terms of spatial extent of tauopathy (SEOT) or load using standardized uptake value ratio (SUVR). The aim was to compare SEOT and SUVR in their association with BR and CR. To replicate findings from Ossenkoppele et al. (2020) using MK-6240 PET imaging and evaluate demographic, genetic, and imaging factors associated with BR and CR. The objective of this study is to assess the value of SEOT metrics in resilience models and compare their predictive power to standardized uptake value ratio (SUVR) and to evaluate cross sectional interactions between tau pathology, cognitive resilience, and cognitive decline.nnMETHOD: We assessed 126 amyloid-β-positive participants TRIAD cohort with tau-PET using [F]MK6240 and cognitive assessments (MMSE). SEOT was quantified as the proportion of voxels considered as abnormal relative to young controls. We used Participants recruited from TRIAD cohort, including individuals with mild cognitive impairment (MCI) or AD, positive amyloid-β biomarkers, MK-6240 PET imaging data.nnRESULT: Higher Whole Cortex MK SUVR is associated with lower MMSE scores, showing increased tau pathology correlates with cognitive decline. MCI patients maintain higher MMSE scores despite some tau accumulation, while AD patients show greater variability and decline. The negative trend suggests tau deposition contributes to cognitive impairment, but other factors may also play a role. 2. Whole Cortex MK SUVR vs. MMSE the negative correlation between Whole Cortex SEOT and MMSE appears stronger, with a more pronounced decline in cognitive function (MMSE scores) as SEOT increases, suggesting SEOT may be a more sensitive marker of disease progression in AD patients.nnCONCLUSION: Whole Cortex SEOT exhibits a stronger negative correlation with MMSE compared to Whole Cortex MK-6240 SUVR, indicating that SEOT may serve as a more sensitive marker of cognitive decline in Alzheimer's disease and mild cognitive impairment. Further research is needed to validate SEOT's potential as a diagnostic or prognostic biomarker in neurodegenerative conditions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41433453,

title = {Alzheimer's Imaging Consortium},

author = {Shaney Flores and Thomas Hunter Smith and Jalen Scott and Danielle Gray and Yi Su and Diana A Hobbs and Sarah J Keefe and Jacqueline Rizzo and Hope Shimony and Tammie L S Benzinger and David N Soleimani-Meigooni and Hwamee Oh and Juan Fortea and Belen Pascual and Pedro Rosa-Neto and Tharick A Pascoal and Suzanne L Baker and Brian A Gordon},

doi = {10.1002/alz70862_109929},

issn = {1552-5279},

year  = {2025},

date = {2025-12-01},

journal = {Alzheimers Dement},

volume = {21 Suppl 8},

number = {Suppl 8},

pages = {e109929},

abstract = {BACKGROUND: Tau tangle deposition is associated with Alzheimer disease (AD) clinical symptomology and cognitive decline. Such deposition can be measured in vivo using positron emission tomography (PET). Off-target signal from extra-cerebral sources, such as skull or meninges, may bias quantification but the impact is currently unknown. Here, we investigate off-target sources in individuals with crossover 18F-AV-1451 and 18F-MK-6240 tau PET scans within the HEAD study.nnMETHOD: T1-weighted magnetic resonance imaging (MRI), Pittsburgh Compound B (PiB) amyloid PET, and tau PET were acquired for 42 participants. Tau PET scans were quantified using body-weighted standardized uptake values (SUV) and SUV ratios (SUVRs) with cerebellar grey as the reference region. To isolate skull bone, CT scans from each participant were aligned to their own T1 image and threshold using a Hounsfield units cutoff derived from applying Gaussian mixture modeling on the average of all CT images to identify a skull bone compartment. For meninges, MNI-152 aligned 18F-MK-6240 SUVR images were averaged and thresholded to identify voxels that potentially were meninges. This template was then transformed back into participant space and masked using the skull bone image and a brain mask to isolate those voxels that were neither bone nor brain but fell in-between, producing a subject-specific meningeal mask (Figure 1). Group average SUV images were created between amyloid negative and positive individuals.nnRESULT: Average age of participants was 66 (21-88) years. 25 were biologically female and 15 were amyloid positive. Group average SUV images show extra-cerebral off-target signal was more pronounced in 18F-MK-6240 for both amyloid negative and positive individuals compared to 18F-AV-1451 (Figure 2). The extra-cerebral 18F-MK-6240 signal appeared across the entire cortical surface and posterior cerebellum, potentially impacting a cerebellar reference for tau PET SUVR quantification.nnCONCLUSION: While off-target extra-cerebral signal appears in both tau PET tracers, it was more pronounced and wide-spread in 18F-MK-6240. Subject-specific skull and meningeal masks can parse this signal to aid in cause determination. Additional work is needed to explore factors contributing to this signal, such as demographic, health, and genetic.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}