@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{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{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{pmid41804764,

title = {Longitudinal association between sleep and Alzheimer's pathology},

author = {Bery Mohammediyan and Andrée-Ann Baril and Alfonso Fajardo Valdez and Frédéric St-Onge and Alexa Pichet Binette and Julie Carrier and Maiya R Geddes and Simon Ducharme and Maxime Montembeault and Jean-Paul Soucy and John Breitner and Judes Poirier and Sylvia Villeneuve and },

doi = {10.1002/alz.71228},

issn = {1552-5279},

year  = {2026},

date = {2026-03-01},

journal = {Alzheimers Dement},

volume = {22},

number = {3},

pages = {e71228},

abstract = {INTRODUCTION: Since sleep disturbance is a modifiable risk factor for Alzheimer's disease (AD), we tested associations between sleep and AD pathology in cognitively unimpaired (CU) persons.nnMETHODS: We included 223 participants from the PREVENT-AD cohort with self-reported measures of sleep, objective actigraphy measures of sleep, and positron emission tomography (PET) scans for AD pathology quantification. Repeated PET scans (mean follow-up: 4.31 ± 0.55 years) were available for 103 participants. We conducted robust linear models (RLM) for cross-sectional analyses and RLMs using the annual change in AD pathology for longitudinal analyses.nnRESULTS: All actigraphy-based sleep variability measures were associated with tau burden (duration: β = 0.121 [95% confidence interval {CI} = 0.010; 0.232], p = 0.034; efficiency: 0.122 [0.010; 0.235], 0.033; fragmentation: 0.115 [0.010; 0.221], 0.033). Greater variability in sleep fragmentation was also associated with amyloid burden (0.074 [0.008; 0.140], 0.028), and variability in sleep efficiency portended amyloid burden and faster accumulation over time (0.075 [0.009; 0.141], 0.026; 0.164 [0.008; 0.320], 0.039; respectively).nnDISCUSSION: Irregularity in sleep patterns is associated with higher pathological burden and faster amyloid accumulation.},

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{pmid41646781,

title = {Multimodal semantic knowledge of emotion concepts in frontotemporal dementia},

author = {Maxime Montembeault and Valentina Borghesani and Zachary A Miller and Maria Luisa Mandelli and Janhavi Pillai and Sheila Tran and Rian Bogley and Carly Millanski and Zoe Ezzes and Buddhika Ratnasiri and Eleanor R Palser and Hulya Ulugut and Kyan Younes and Michelle Shiota and Dacher Keltner and Alan Cowen and Maya L Henry and Katherine P Rankin and Virginia E Sturm and Maria Luisa Gorno-Tempini},

doi = {10.64898/2026.01.12.26343893},

year  = {2026},

date = {2026-01-01},

journal = {medRxiv},

abstract = {BACKGROUND: Recent work has delineated the semantic behavioral variant of frontotemporal dementia (sbvFTD; or right temporal variant of FTD, which is thought to preferentially impair semantic knowledge for emotional concepts. However, this proposed core feature has not yet been empirically validated, and no clinical tool exists to assess it. Establishing reliable markers is essential to clinically differentiate sbvFTD from behavioral variant FTD (bvFTD), which is critical given their overlapping behavioral symptoms but divergent underlying pathologies. Furthermore, contrasting sbvFTD with semantic variant primary progressive aphasia (svPPA) can advance our understanding of semantic memory, revealing how the right and left anterior temporal lobes (ATLs) support emotion- versus tool-related knowledge, highlighting the graded, lateralized organization of the semantic system.nnMETHODS: We studied 15 patients with sbvFTD, 15 with svPPA, 18 with bvFTD, and 37 healthy controls. A novel multimodal semantic battery, the Fear and Spider Test (FST), which assesses tool- and emotion-related concepts across word-based semantic associations, picture-based semantic associations, and sound-to-picture matching, was administered. Stimuli were matched on psycholinguistic and perceptual features, and emotional items were drawn from multicultural facial expressions validated with the Facial Action Coding System. Neural correlates of semantic performance were investigated using voxel-based morphometry.nnRESULTS: As expected, patients with both sbvFTD and svPPA showed greater deficits in all semantic tasks compared to controls and bvFTD, and bilateral anterior temporal lobe (ATL) volumes were broadly associated with performance across all semantic tasks. Interactions between modality and categories were necessary for the emergence of differences between sbvFTD and svPPA and right and left ATL atrophy: performance on the Words-Tools condition was more impaired in svPPA and correlated with left ATL volume, while performance on the Pictures-Emotions condition was more impaired in sbvFTD and correlated with right ATL volume.nnCONCLUSION: The FST provides the first clear dissociation of sbvFTD from bvFTD, a distinction of critical clinical importance given their divergent pathological substrates and the absence of frontotemporal lobar degeneration specific biomarkers. The study also refines our understanding of semantic memory: contrasting sbvFTD with svPPA reveals complementary roles of the right and left ATLs in supporting emotion and tool knowledge, underscoring the graded, lateralized organization of the semantic system.},

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{pmid41457063,

title = {The impact of sex on clinical profiles of patients with behavioral variant frontotemporal dementia},

author = {Parsa Afrooz and Marie-Anne St-Georges and Thomas Carrier and Yashar Zeighami and Mahsa Dadar and Maxime Montembeault},

doi = {10.1002/alz.70996},

issn = {1552-5279},

year  = {2025},

date = {2025-12-01},

journal = {Alzheimers Dement},

volume = {21},

number = {12},

pages = {e70996},

abstract = {INTRODUCTION: Sex differences in behavioral variant frontotemporal dementia (bvFTD) remain understudied, especially when controlling for sex differences already existing in the general population.nnMETHODS: Clinical features were analyzed in 620 bvFTD participants. Sex-diagnosis interactions were examined in 1029 bvFTD and 1029 healthy control (HC) participants for neuropsychiatric symptoms, and in 1109 bvFTD and 1109 HC participants for cognitive, behavioral, and language measures.nnRESULTS: Males with bvFTD showed greater-than-expected loss of empathy and nighttime behavioral symptoms relative to females, based on sex-by-diagnosis interactions. They also exhibited higher-than-expected punishment sensitivity. In contrast, females with bvFTD showed greater-than-expected impairments in semantic fluency and picture naming relative to HC females.nnDISCUSSION: Findings reveal that males with bvFTD present with more prominent behavioral disturbances, while females with bvFTD experience greater language impairments. This work is an important step toward integrating social determinants of health, such as sex, into the diagnostic and care paradigms for bvFTD.nnHIGHLIGHTS: Males with behavioral variant frontotemporal dementia (bvFTD) show more empathy loss and nighttime behavioral symptoms Females with bvFTD have greater deficits in naming and semantic fluency Findings support including sex in diagnostic and care models for bvFTD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41573346,

title = {Psychometric Properties of the UCSF Fein MAC Educational & Developmental History Questionnaire:: A Novel Screening Tool for Capturing Early Life Learning Profiles Across Healthy Aging and Dementia Populations},

author = {Ezra Mauer and Isabel E Allen and Rian Bogley and Ryan Newbury and Valentina Diaz and Kaitlin B Casaletto and Maxime Montembeault and Katherine P Rankin and Renaud La Joie and Jacob Ziontz and William J Jagust and Gil D Rabinovici and Howard J Rosen and Joel H Kramer and Bruce L Miller and Maria Luisa Gorno-Tempini and Zachary A Miller},

doi = {10.64898/2025.11.30.25341313},

year  = {2025},

date = {2025-12-01},

journal = {medRxiv},

abstract = {BACKGROUND: Increasing evidence suggests that neurodevelopmental differences substantially alter the expression and course of later-life neurodegenerative diseases. Standard approaches for determining early-life neurodevelopmental differences in aging populations rely largely on chart-based reviews, which poses a methodological challenge due to the varied quality and completeness of medical records. To overcome this limitation, we created the novel Educational & Developmental History (EDevHx) form, a retrospective questionnaire designed to capture early developmental features. Here, we evaluated its psychometric properties among a large sample of cognitively unimpaired, aging adults.nnMETHODS: The EDevHx was completed by 677 clinically normal adults aged 46-95 years who underwent standard evaluations to establish their cognitively healthy status.nnRESULTS: EDevHx items grouped into hypothesized domains (Language, Motor, Visuospatial/Mathematical, Attention, Social) significantly loaded onto their associated domains via confirmatory factor analysis. For each factor, the associated items significantly related to the factor while holding other items constant, indicating a lack of redundancy. Multidimensional scaling analysis showed items were visually grouped within hypothesized domains. Each factor demonstrated acceptable internal consistency. Test-retest reliability ranged from moderate to good, except for the Social factor's, which was poor. Each factor (as well as two items theorized not to map onto any hypothesized domain) demonstrated convergent/divergent validity with validated questionnaires/neurocognitive tests.nnCONCLUSION: The EDevHx tool represents an easily scalable and robust method for capturing early developmental features among aging populations. The present study demonstrates its strong psychometric properties, supporting its immediate and widespread integration into clinical and research practices alike.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41387629,

title = {Clinical recognition of frontotemporal dementia with right temporal predominance: a consensus statement from the International Working Group},

author = {Hulya Ulugut and Kyan Younes and Maxime Montembeault and Maxime Bertoux and Muireann Irish and Fiona Kumfor and Giorgio G Fumagalli and Bedia Samanci and Ignacio Illán-Gala and Jennifer C Thompson and Alexander F Santillo and Elisabet Englund and Maria Landqvist Waldö and Lina Riedl and Jan Van den Stock and Mathieu Vandenbulcke and Rik Vandenberghe and Robert Laforce and Simon Ducharme and Peter S Pressman and Paulo Caramelli and Leonardo Cruz de Souza and Leonel T Takada and Hakan Gurvit and Janine Diehl-Schmid and Daniela Galimberti and Florence Pasquier and Sandra Weintraub and Bruce L Miller and Virginia E Sturm and Jennifer L Whitwell and Bradley Boeve and Jonathan D Rohrer and Olivier Piguet and Maria Luisa Gorno-Tempini and Keith A Josephs and Julie Snowden and James B Rowe and Jason D Warren and Katherine P Rankin and Yolande A L Pijnenburg and },

doi = {10.1038/s43856-025-01252-4},

issn = {2730-664X},

year  = {2025},

date = {2025-12-01},

journal = {Commun Med (Lond)},

volume = {5},

number = {1},

pages = {523},

abstract = {Accurate diagnosis of frontotemporal dementia (FTD) with right anterior temporal lobe (RATL) predominance remains challenging due to lack of clinical characterization, and standardized terminology. The recent research of the International Working Group (IWG) identified common symptoms but also unveiled broad terminologies lacking precision and operationalization, with risk of misdiagnoses, inappropriate referrals and poor clinical management. Based on the published evidence (91267 articles screened) and expert opinion (105 FTD specialists across 52 centers) by using the nominal group technique, the IWG delineates three primary domains of impairment causing behavioral, memory and language problems: (i) multimodal knowledge of non-verbal information including people, living beings, landmarks, flavors/odors, sounds, bodily sensations, emotions and social cues; (ii) socioemotional behavior encompassing emotion expression, social response and motivation; and (iii) prioritization for focus on specific interests, hedonic valuation and personal preferences. This study establishes a consensus on clinical profile, phenotypic nomenclature, and future directions to enhance diagnostic precision and therapeutic interventions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41350737,

title = {International consensus for the assessment of social cognition in neurocognitive disorders: framework definition and clinical recommendations of the SIGNATURE initiative},

author = {Alessandra Dodich and Andrea Panzavolta and Giulia Funghi and Claudia Meli and Cristina Festari and Thanos Chatzikostopoulos and Christian Chicherio and Florencia Clarens and Fabricio Ferreira de Oliveira and Marco Filardi and Agustin Ibanez and Laura Invernizzi and Thibaud Lebouvier and Giancarlo Logroscino and Sarah E MacPherson and Riccardo Manca and Camillo Marra and Jordi A Matias-Guiu and Maxime Montembeault and Costanza Papagno and Simone Pomati and Mario Possenti and Olivier Piguet and Leonardo Sacco and Ann-Katrin Schild and Marc Sollberger and Miguel Tábuas-Pereira and Marianna Tsatali and Magda Tsolaki and Esther van den Berg and Stefano F Cappa and Maxime Bertoux and Fiona Kumfor and Jan Van den Stock and Marina Boccardi and Kathleen Anne Welsh-Bohmer and Chiara Cerami and },

doi = {10.1186/s13195-025-01908-2},

issn = {1758-9193},

year  = {2025},

date = {2025-12-01},

journal = {Alzheimers Res Ther},

volume = {18},

number = {1},

pages = {6},

abstract = {BACKGROUND: Socio-cognitive assessment in neurocognitive disorders (NCDs) is rare in clinical practice and no consensus exists as to a uniform operationalization of socio-cognitive measures for NCDs in memory clinics. The SIGNATURE initiative aims to optimize the use of socio-cognitive measures in memory clinics, defining expert recommendations. We report consortium guidelines for the use of socio-cognitive measures in NCDs based on available evidence from the literature and the current state of practices in memory clinics.nnMETHODS: Using a Delphi consensus method supported by a literature review and the results of an international survey, 22 specialists defined recommendations for the context of use, relevance in NCD diagnosis, priorities for future research and facilitators/obstacles of socio-cognitive assessment in major and mild NCDs.nnRESULTS: Overall, panelists recommended social cognition testing in routine diagnostic assessment to evaluate both socio-cognitive and socio-behavioral alterations. A set of clinical, methodological, implementation and external factors facilitating or hampering the use of socio-cognitive tasks was identified.nnCONCLUSIONS: This is the first focused endeavor to favor the implementation of socio-cognitive assessment, which is required by DSM-5 but seldom performed despite clear evidence of its clinical relevance for diagnosis and care. Our results provide an initial set of recommendations, refinable through the future actions of the SIGNATURE initiative. Future collaborative clinical research projects should overcome current limitations and foster the use of ecological and cross-culturally validated measures in clinics.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41266593,

title = {APOE ε4 potentiates tau related reactive astrogliosis assessed by cerebrospinal fluid YKL40 in Alzheimer's disease},

author = {Lydia Trudel and Joseph Therriault and Arthur C Macedo and Marcel S Woo and Nesrine Rahmouni and Étienne Aumont and Stijn Servaes and Seyyed Ali Hosseini and João Pedro Ferrari-Souza and Bruna Bellaver and Pamela L Ferreira and Tevy Chan and Yi-Ting Wang and Jaime Fernandez-Arias and Yansheng Zheng and Brandon Hall and Jenna Stevenson and Robert Hopewell and Chris Hung-Hsin Hsiao and Maxime Montembeault and Jesse Klostranec and Yasser Iturria-Medina and Paolo Vitali and Thomas K Karikari and Andrea L Benedet and Nicholas J Ashton and Eduardo Zimmer and Serge Gauthier and Tharick A Pascoal and Henrik Zetterberg and Kaj Blennow and Pedro Rosa-Neto},

doi = {10.1038/s43856-025-01171-4},

issn = {2730-664X},

year  = {2025},

date = {2025-11-01},

journal = {Commun Med (Lond)},

volume = {5},

number = {1},

pages = {484},

abstract = {BACKGROUND: Glial responses are involved in neurodegenerative processes, with tau pathology often associated with increased glial inflammatory responses in Alzheimer's disease (AD). The apolipoprotein E (APOE) ε4 allele, the major genetic susceptibility gene for AD, might contribute to this process by modulating both tau pathology and inflammatory cascades in the brain.nnMETHODS: We used data from the Translational Biomarkers of Alzheimer's Disease (TRIAD) cohort (n = 137) to investigate the association between YKL-40, a marker of reactive astrogliosis, and tau burden measured with PET imaging, while also exploring the involvement of APOE ε4 carriership. Statistical analyses included correlation and regression models controlling for age and sex.nnRESULTS: Here we show that tau pathology is positively associated with YKL-40 levels, reflecting regional patterns of astrocyte activity in the brain. Furthermore, this association is more widespread in individuals carrying the APOE ε4 allele, suggesting a genotype-specific modulation of the glial neuroinflammatory response.nnCONCLUSIONS: Our findings demonstrate a link between tau accumulation and astrocyte-mediated neuroinflammation in AD and highlight the modulatory role of APOE ε4 in this process. Taken together, our findings help inform the multifaceted role of tau-associated neuroinflammation in the progression of AD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40982226,

title = {High brain network dynamics mediate audiovisual integration deficits and cognitive impairment in Alzheimer's disease},

author = {Jieying Li and Yang Yi and Xin Gao and Yanna Ren and Lin Gan and Ting Zou and Xiaohong Qin and Arui Tan and Xinxuan Yang and Fugui Jiang and Xuemei Liu and Haiyan Gao and Yiting Wang and Etienne Aumont and Jun Xiao and Bo Zhou and Wei Liao and Huafu Chen and Wei Zhang and Maxime Montembeault and Pedro Rosa-Neto and Rong Li},

doi = {10.1177/13872877251376717},

issn = {1875-8908},

year  = {2025},

date = {2025-11-01},

journal = {J Alzheimers Dis},

volume = {108},

number = {1},

pages = {397--410},

abstract = {BackgroundAudiovisual integration deficits are frequent in patients with Alzheimer's disease (AD). In addition, patients with AD have altered functional brain networks, such as those supporting auditory and visual processing. However, the mechanisms driving this association remain unclear.ObjectiveTo investigate whether dynamic functional network disruptions underlie audiovisual integration and cognitive deficits in AD.MethodsSeventy-nine participants (41 AD, 38 controls) completed audiovisual stimuli tasks. A multilayer modularity algorithm was utilized to assess the resting-state fMRI-based brain dynamics of the primary sensory and higher-order functional networks. Mediation analysis was conducted to test our hypothesis.ResultsAD patients showed delayed response time and reduced peak benefit of audiovisual integration. Dynamic switching rates of primary sensory and higher-order networks were significantly increased in AD, particularly in the dynamic integration between the default mode network (DMN) and visual network (VN). The peak benefit of audiovisual integration negatively correlated with DMN-VN dynamic integration and positively with Mini-Mental State Examination, Montreal Cognitive Assessment, and Auditory Verbal Learning Test delayed scores. Notably, excessive integration between the DMN and VN mediated the relationship between audiovisual integration deficits and cognitive impairment in patients with AD.ConclusionsThese findings suggest that audiovisual integration impairment may disturb the dynamic integration between the DMN and VN, contributing to cognitive impairment in AD. The neural mechanisms underlying audiovisual integration deficit and cognitive decline might help with early diagnosis and intervention for AD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41131662,

title = {Burden of psychiatric disease inversely correlates with Alzheimer's age at onset},

author = {Emily Eijansantos and Isabel E Allen and Jessica de Leon and Stephanie Grasso and Nicole Rogers and Rian Bogley and Andrew Paramo and Alexander J Ehrenberg and Maxime Montembeault and Virginia Sturm and Salvatore Spina and Lea T Grinberg and William W Seeley and Katherine P Rankin and Joel H Kramer and Howard J Rosen and Gil D Rabinovici and Maria Luisa Gorno-Tempini and Bruce L Miller and David C Perry and Zachary A Miller},

doi = {10.1002/alz.70677},

issn = {1552-5279},

year  = {2025},

date = {2025-10-01},

journal = {Alzheimers Dement},

volume = {21},

number = {10},

pages = {e70677},

abstract = {INTRODUCTION: Depression is regarded as a risk factor for Alzheimer's disease (AD). Associations between AD and other psychiatric disorders are less clear.nnMETHODS: We screened 1,500 AD UCSF Memory and Aging Center patients for prevalence of psychiatric disorders and compared results to 8,267 NACC AD participants.nnRESULTS: AD with depression, anxiety, or post-traumatic stress disorder were significantly younger at age at onset than AD without (p < 0.001; p < 0.001; p < 0.05). Comorbidity of depression, anxiety and PTSD led to further decreases in AD age at onset. Within the NACC cohort, we further demonstrated an inverse relationship between the severity of depression and anxiety symptoms and AD age at onset.nnDISCUSSION: Depression, anxiety, and post-traumatic stress disorder are inversely associated with AD age at onset. Age at onset further decreases with increasing number of psychiatric conditions and increasing severity of symptoms, suggesting that overall burden of psychiatric disease is highly relevant to AD.nnHIGHLIGHTS: Retrospective chart review revealed that in patients with AD, those who also had depression, anxiety, or post-traumatic stress disorder were significantly younger at age at onset than those without. Increasing burden of psychiatric disease, both in severity of psychiatric symptoms and number of comorbid psychiatric conditions, produced serial decreases in the age at onset of AD. In patients with AD, those with depression were more likely to have autoimmune disease, and those with anxiety were more likely to have a history of seizures.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41145530,

title = {Equivalence of the FCSRT and RAVLT to detect medial Temporal lobe atrophy and tauopathy},

author = {Etienne Aumont and Kelly Amiel and Delphine Oliva Lopez and Jaime Fernandez Arias and Maxime Montembeault and Gleb Bezgin and Brandon J Hall and Lydia Trudel and Tevy Chan and Nesrine Rahmouni and Jenna Stevenson and Stijn Servaes and Arthur C Macedo and Seyyed Ali Hosseini and Paolo Vitali and Nina Margherita Poltronetti and Jesse Klostranec and Joseph Therriault and Andréa L Benedet and Nicholas J Ashton and Henrik Zetterberg and Kaj Blennow and Thomas K Karikari and Gallen Triana-Baltzer and Hartmuth C Kolb and Serge Gauthier and Yasser Iturria-Medina and Pedro Rosa-Neto},

doi = {10.1038/s41598-025-21260-7},

issn = {2045-2322},

year  = {2025},

date = {2025-10-01},

journal = {Sci Rep},

volume = {15},

number = {1},

pages = {37425},

abstract = {In AD research, word-learning tests are often used interchangeably despite using distinct learning protocols. This study verified the equivalence of the Rey Auditory Learning Test (RAVLT) and Free and Cued Selective Reminding Test (FCSRT) when investigating medial temporal lobe (MTL) changes and AD-related tau pathology. We obtained the FCSRT and RAVLT immediate and delayed free recalls from 286 participants aged 51+. We segmented MTL regions to obtain the volume and tau-PET signal using the [F]MK-6240 tracer. Tau-PET Braak stages and plasma p-tau, p-tau and p-tau quantifications were also acquired. Using partial correlations, we compared FCSRT to RAVLT as well as their ability to detect the cognitive status the AD biomarker results. FCSRT and RAVLT were strongly correlated to one another (R > 0.779), with similar differentiation of cognitively impaired and cognitively unimpaired individuals (AUC > 0.810). Both predicted MTL volume, MTL tau-PET accumulation, plasma p-tau and Braak stages similarly, with no significant effect size differences. For all tests, a subtle memory impairment was found at tau-PET Braak stage III, while more robust impairments were found at stage IV onward. Despite their differences, both the RAVLT and FCSRT are equivalent at detecting AD-related pathology and symptoms, suggesting that, in these contexts, they may be used interchangeably. However, these results should be interpreted with care since the sample is not representative of a global population.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41020412,

title = {The PREVENT-AD cohort: Accelerating Alzheimer's disease research and treatment in Canada and beyond},

author = {Sylvia Villeneuve and Judes Poirier and John C S Breitner and Jennifer Tremblay-Mercier and Jordana Remz and Jean-Michel Raoult and Yara Yakoub and Jonathan Gallego-Rudolf and Ting Qiu and Alfonso Fajardo Valdez and Bery Mohammediyan and Mohammadali Javanray and Amelie Metz and Safa Sanami and Valentin Ourry and Alfie Wearn and Alexandre Pastor-Bernier and Manon Edde and Julie Gonneaud and Cherie Strikwerda-Brown and Christine L Tardif and Claudine J Gauthier and Maxime Descoteaux and Mahsa Dadar and Étienne Vachon-Presseau and Andrée-Ann Baril and Simon Ducharme and Maxime Montembeault and Maiya R Geddes and Jean-Paul Soucy and Natasha Rajah and Robert Laforce and Christian Bocti and Christos Davatzikos and Lune Bellec and Pedro Rosa-Neto and Sylvain Baillet and Alan C Evans and D Louis Collins and M Mallar Chakravarty and Kaj Blennow and Henrik Zetterberg and R Nathan Spreng and Alexa Pichet Binette and },

doi = {10.1002/alz.70653},

issn = {1552-5279},

year  = {2025},

date = {2025-10-01},

journal = {Alzheimers Dement},

volume = {21},

number = {10},

pages = {e70653},

abstract = {The PResymptomatic EValuation of Experimental or Novel Treatments for Alzheimer's Disease (PREVENT-AD) is an investigator-driven study that was created in 2011 and enrolled cognitively normal older adults with a family history of sporadic AD. Participants are deeply phenotyped and have now been followed annually for more than 12 years (median follow-up 8.0 years, SD 3.1). Multimodal magnetic resonance imaging (MRI), genetic, neurosensory, clinical, cerebrospinal fluid, and cognitive data collected until 2017 on 348 participants who agreed to open sharing with the neuroscience community were already available. We now share a new release including 6 years of additional follow-up cognitive data, and additional MRI follow-ups, clinical progression, new longitudinal behavioral and lifestyle measures (questionnaires, actigraphy), longitudinal AD plasma biomarkers, amyloid-beta and tau positron emission tomography (PET), magnetoencephalography, as well as neuroimaging analytic measures from all MRI modalities. We describe the PREVENT-AD study, the data shared with the global research community, as well as the model we created to sustain longitudinal follow-ups while also allowing new innovative data collection. HIGHLIGHTS: The PResymptomatic EValuation of Experimental or Novel Treatments for Alzheimer's Disease (PREVENT-AD) is a single-site longitudinal study that started in 2011 with annual follow-up data collection on individuals at risk of Alzheimer's disease who were all cognitively normal at enrolment. All 387 participants were enrolled between 2011 and 2017 and 306 (79%) of these participants were still in the study as of December 2023. While the PREVENT-AD dataset was not originally planned to be shared with the global research community, 348 participants retrospectively consented for their data to be shared with researchers worldwide. The first release of data was in 2019. We now share a second release that includes 6 years of additional follow-up visits, information on clinical progression and novel cognitive, behavioral, genetic, plasma and neuroimaging (amyloid and tau positron emission tomography [PET], magnetoencephalography [MEG], and new magnetic resonance imaging [MRI] sequences) data. It also includes analytic outputs for neuroimaging modalities.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40346617,

title = {Plasma GFAP for populational enrichment of clinical trials in preclinical Alzheimer's disease},

author = {Bruna Bellaver and Guilherme Povala and Pamela C L Ferreira and Guilherme Bauer-Negrini and Firoza Z Lussier and Douglas T Leffa and João Pedro Ferrari-Souza and Matheus S Rodrigues and Livia Amaral and Markley S Oliveira and Carolina Soares and Andreia Rocha and Pampa Saha and Nesrine Rahmouni and Arthur Macedo and Cécile Tissot and Joseph Therriault and Stijn Servaes and Jesse Klostranec and Maxime Montembeault and Andréa L Benedet and Nicholas J Ashton and Rebecca Langhough Koscik and Tobey J Betthauser and Brad T Christian and Rachael Wilson and Gallen Triana-Baltzer and Paolo Vitali and Serge Gauthier and Henrik Zetterberg and Kaj Blennow and Thomas K Karikari and Dana Tudorascu and Eduardo R Zimmer and Sterling Johnson and Pedro Rosa-Neto and Tharick A Pascoal},

doi = {10.1002/alz.70209},

issn = {1552-5279},

year  = {2025},

date = {2025-05-01},

journal = {Alzheimers Dement},

volume = {21},

number = {5},

pages = {e70209},

abstract = {INTRODUCTION: Cognitively unimpaired (CU) amyloid beta (Aβ)+ individuals with elevated plasma glial fibrillary acidic protein (GFAP) have an increased risk of Alzheimer's disease (AD)-related progression. We tested the utility of plasma GFAP for population enrichment CU populations in clinical trials.nnMETHODS: We estimated longitudinal progression, effect size, and costs of hypothetical clinical trials designed to test an estimated 25% drug effect on reducing tau positron emission tomography (PET) accumulation in the medial temporal lobe (MTL) and temporal neocortical region (NEO-T).nnRESULTS: CU GFAP+/Aβ+ individuals present an increased annual rate of change and effect size in tau PET and tau PET compared to the other groups. An enrichment strategy selecting CU GFAP+/Aβ+ individuals would require a smaller sample size (≈ 57% reduction) and fewer Aβ PET scans (≈ 74% reduction) than trials enriched with Aβ PET alone, reducing total clinical trial costs by up to 64%.nnDISCUSSION: Our results suggest that clinical trials focusing on preclinical AD recruiting Aβ+ individuals with elevated GFAP levels would improve cost effectiveness.nnHIGHLIGHTS: Cognitively unimpaired (CU) glial fibrillary acidic protein (GFAP)+/amyloid beta (Aβ)+ shows increased changes in tau positron emission tomography (PET) . CU GFAP+/Aβ+ enriched clinical trials require a reduced sample size compared to Aβ+ only. CU GFAP+/Aβ+ enrichment reduces Aβ PET scans required and costs. CU GFAP+/Aβ+ enrichment allows the selection of individuals at early stages of the Alzheimer's disease continuum.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40209131,

title = {Automated Speech Analysis to Differentiate Frontal and Right Anterior Temporal Lobe Atrophy in Frontotemporal Dementia},

author = {Jet M J Vonk and Brittany T Morin and Janhavi Pillai and David Rosado Rolon and Rian Bogley and David Paul Baquirin and Zoe Ezzes and Boon Lead Tee and Jessica de Leon and Lisa Wauters and Sladjana Lukic and Maxime Montembeault and Kyan Younes and Zachary Adam Miller and Adolfo M García and Maria Luisa Mandelli and Bruce L Miller and Howard J Rosen and Katherine P Rankin and Virginia Sturm and Maria Luisa Gorno-Tempini},

doi = {10.1212/WNL.0000000000213556},

issn = {1526-632X},

year  = {2025},

date = {2025-05-01},

journal = {Neurology},

volume = {104},

number = {9},

pages = {e213556},

abstract = {BACKGROUND AND OBJECTIVES: Frontotemporal dementia (FTD) includes behavioral-variant FTD (bvFTD) with predominant frontal atrophy and semantic behavioral-variant FTD (sbvFTD) with predominant right anterior temporal lobe (rATL) atrophy. These variants present diagnostic challenges because of overlapping symptoms and neuroanatomy. Accurate differentiation is crucial for clinical trial inclusion targeting TDP-43 proteinopathies. This study investigated whether automated speech analysis can distinguish between FTD-related rATL and frontal atrophy, potentially offering a noninvasive diagnostic tool.nnMETHODS: This cross-sectional study used data from the University of California, San Francisco Memory and Aging Center. Using stepwise logistic regression and receiver-operating characteristic curve analysis, we analyzed 16 linguistic and acoustic features that were extracted automatically from audio-recorded picture description tasks. Voxel-based morphometry was used to investigate brain-behavior relationships.nnRESULTS: We evaluated 62 participants: 16 with FTD-related predominant frontal atrophy, 24 with predominant rATL atrophy, and 22 healthy controls (mean age 68.3 years, SD = 9.2; 53.2% female). Logistic regression identified 3 features (content units, lexical frequency, and familiarity) differentiating the overall FTD group from controls (area under the curve [AUC] = 0.973), adjusted for age. Within the FTD group, 5 features (adpositions/total words ratio, arousal, syllable pause duration, restarts, and words containing "thing") differentiated frontal from rATL atrophy (AUC = 0.943). Neuroimaging analyses showed that semantic features (lexical frequency, content units, and "thing" words) were linked to bilateral inferior temporal lobe structures, speech and lexical features (syllable pause duration, and adpositions/total words ratio) to bilateral inferior frontal gyri, and socioemotional features (arousal) to areas known to mediate social cognition including the right insula and bilateral anterior temporal structures. As a composite score, this set of 5 features was uniquely associated with rATL atrophy.nnDISCUSSION: Automated speech analysis demonstrated high accuracy in differentiating FTD subtypes and provided insights into the neural basis of language impairments. Automated speech analysis could enhance early diagnosis and monitoring of FTD, offering a scalable, noninvasive alternative to traditional methods, particularly in resource-limited settings. Future research should focus on further clinical validation with other neuroimaging or fluid biomarkers and longitudinal cognitive data, as well as external validation in larger and more diverse populations.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39972340,

title = {The impact of kidney function on Alzheimer's disease blood biomarkers: implications for predicting amyloid-β positivity},

author = {Burak Arslan and Wagner S Brum and Ilaria Pola and Joseph Therriault and Nesrine Rahmouni and Jenna Stevenson and Stijn Servaes and Kübra Tan and Paolo Vitali and Maxime Montembeault and Jesse Klostranec and Arthur C Macedo and Cecile Tissot and Serge Gauthier and Juan Lantero-Rodriguez and Eduardo R Zimmer and Kaj Blennow and Henrik Zetterberg and Pedro Rosa-Neto and Andrea L Benedet and Nicholas J Ashton},

doi = {10.1186/s13195-025-01692-z},

issn = {1758-9193},

year  = {2025},

date = {2025-02-01},

journal = {Alzheimers Res Ther},

volume = {17},

number = {1},

pages = {48},

abstract = {BACKGROUND: Impaired kidney function has a potential confounding effect on blood biomarker levels, including biomarkers for Alzheimer's disease (AD). Given the imminent use of certain blood biomarkers in the routine diagnostic work-up of patients with suspected AD, knowledge on the potential impact of comorbidities on the utility of blood biomarkers is important. We aimed to evaluate the association between kidney function, assessed through estimated glomerular filtration rate (eGFR) calculated from plasma creatinine and AD blood biomarkers, as well as their influence over predicting Aβ-positivity.nnMETHODS: We included 242 participants from the Translational Biomarkers in Aging and Dementia (TRIAD) cohort, comprising cognitively unimpaired individuals (CU; n = 124), mild cognitive impairment (MCI; n = 58), AD dementia (n = 34), and non-AD dementia (n = 26) patients all characterized by [F] AZD-4694. Plasma samples were analyzed for Aβ42, Aβ40, glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), tau phosphorylated at threonine 181 (p-tau181), 217 (p-tau217), 231 (p-tau231) and N-terminal containing tau fragments (NTA-tau) using Simoa technology. Kidney function was assessed by eGFR in mL/min/1.73 m, based on plasma creatinine levels, age, and sex. Participants were also stratified according to their eGFR-indexed stages of chronic kidney disease (CKD). We evaluated the association between eGFR and blood biomarker levels with linear models and assessed whether eGFR provided added predictive value to determine Aβ-positivity with logistic regression models.nnRESULTS: Biomarker concentrations were highest in individuals with CKD stage 3, followed by stages 2 and 1, but differences were only significant for NfL, Aβ42, and Aβ40 (not Aβ42/Aβ40). All investigated biomarkers showed significant associations with eGFR except plasma NTA-tau, with stronger relationships observed for Aβ40 and NfL. However, after adjusting for either age, sex or Aβ-PET SUVr, the association with eGFR was no longer significant for all biomarkers except Aβ40, Aβ42, NfL, and GFAP. When evaluating whether accounting for kidney function could lead to improved prediction of Aβ-positivity, we observed no improvements in model fit (Akaike Information Criterion, AIC) or in discriminative performance (AUC) by adding eGFR to a base model including each plasma biomarker, age, and sex. While covariates like age and sex improved model fit, eGFR contributed minimally, and there were no significant differences in clinical discrimination based on AUC values.nnCONCLUSIONS: We found that kidney function seems to be associated with AD blood biomarker concentrations. However, these associations did not remain significant after adjusting for age and sex, except for Aβ40, Aβ42, NfL, and GFAP. While covariates such as age and sex improved prediction of Aβ-positivity, including eGFR in the models did not lead to improved prediction for any biomarker. Our findings indicate that renal function, within the normal to mild impairment range, does not seem to have a clinically relevant impact when using highly accurate blood biomarkers, such as p-tau217, in a biomarker-supported diagnosis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}