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Offert par Mila et le Forum des politiques publiques, ce programme est conçu pour outiller les décideur·euse·s et les responsables des politiques publiques à naviguer efficacement à travers les opportunités et les risques liés à l'IA. La prochaine cohorte se tiendra en anglais les 5 et 6 novembre 2026 à Ottawa.
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Lecteur Multimédia
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OBJECTIVES: Prefrontal regions are implicated in explore-exploit decision-making during foraging. Older adults often show an exploitation bi… (voir plus)as, and this age period is also marked by deteriorating prefrontal myelination. To investigate whether these phenomena are linked, we examined whether lower magnetization transfer saturation (MTsat), a myelin-sensitive quantitative MRI (qMRI) measure, in these regions predicts greater exploitation bias during foraging, and whether cortical microstructure is a better predictor of bias than macrostructure (i.e., cortical thickness). METHODS: Cognitively healthy older adults with familial risk of Alzheimer's disease (AD) (N=118, 60-88 years) completed a foraging task indexing explore-exploit decision-making. qMRI was used to derive MTsat values for the frontopolar cortex (FPC), medial orbitofrontal cortex (OFC), rostral middle frontal gyrus (rMFG), dorsal anterior cingulate cortex (dACC), as well as the locus coeruleus (LC), a core subcortical region strongly implicated in explore-exploit decision-making. Secondary analyses examined associations between available AD risk markers and foraging. RESULTS: Lower MTsat in the FPC, OFC, rMFG, and LC was associated with an exploitation bias, with LC and FPC emerging as the strongest predictors. No relationship was observed for the dACC. MTsat remained a significant predictor of foraging after controlling for cortical thickness. Observed associations were largely unrelated to AD risk markers. DISCUSSION: Individual differences in cortical microstructural integrity within a well-defined explore-exploit circuit are associated with an exploitative decision-making bias in older adults. These findings highlight the value of qMRI microstructural integrity markers, beyond standard macrostructural assays, in characterizing the neural correlates of exploitation biases in later life.
2026-07-22
Journals of Gerontology Series B: Psychological Sciences and Social Sciences (publié)
Importance: Among individuals with high levels of amyloid-β (Aβ), women exhibit higher insoluble tau burden and accumulation than age-matc… (voir plus)hed men. It remains unclear whether this sex difference is influenced by soluble phosphorylated tau (p-tau), a biomarker that changes early in Alzheimer disease. Objective: To investigate whether sex and aggregated Aβ synergistically predict plasma phosphorylated tau 217 (p-tau217) levels and whether levels of p-tau217 predict cross-sectional and longitudinal tau aggregation in a sex-specific manner (as measured by positron emission tomography [PET]). Design, Setting, and Participants: This longitudinal study analyzed data between September 7, 2024, and October 29, 2025, from 1 clinical trial cohort and 4 observational study cohorts including men and women without cognitive impairment who had undergone multiple assessments via tau PET (18F-flortaucipir or 18F-MK-6240) and plasma p-tau217 assay at baseline. Cognitive performance was measured with the Preclinical Alzheimer Cognitive Composite. Data on cognitive performance were available from 3 of the 5 cohorts for a mean of 4.6 years (SD, 3.1 years). Across the 5 cohorts, the mean follow-up for tau PET was 3.6 years (SD, 1.7 years). Exposures: Self-reported sex (male or female), tau PET, and p-tau217 assay. Main Outcomes and Measures: The primary analyses used linear and mixed-effects models to assess baseline and longitudinal sex × p-tau217 interactions for 9 tau PET regions. The secondary analyses assessed sex × p-tau217 interactions for cognitive change using the Preclinical Alzheimer Cognitive Composite. Results: Across the 5 cohorts, there were a total of 1292 participants (63.6% women; mean age, 70.6 [SD, 6.4] years) with tau PET assessments. Compared with men, women had significantly higher baseline p-tau217 levels at higher aggregated Aβ Centiloid levels (β, -0.21 [95% CI, -0.37 to -0.05], P = .009; highest interaction was found in the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease/Longitudinal Evaluation of Amyloid Risk and Neurodegeneration [A4/LEARN] cohort). The sex × p-tau217 interactions at baseline were significant for 1 tau PET region in the Harvard Aging Brain Study (HABS) cohort, for 2 tau PET regions in the A4/LEARN cohort, for 6 tau PET regions in the Wisconsin Registry of Alzheimer's Prevention (WRAP) cohort, and for 4 tau PET regions in the Presymptomatic Evaluation of Experimental or Novel Treatments for Alzheimer's Disease (PREVENT-AD) cohort. Longitudinal interactions were significant for 4 tau PET regions in the A4/LEARN cohort, for 5 tau PET regions in both the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort and the WRAP cohort, and for 2 PET regions in both the HABS cohort and the PREVENT-AD cohort. Compared with men, women displayed greater tau deposition and accumulation at higher p-tau217 levels. Use of a secondary model showed women with higher p-tau217 levels also exhibited faster rates of cognitive decline relative to men in the both the WRAP cohort and the ADNI cohort. Conclusion and Relevance: These findings add to growing evidence that women have a differential tau response to Aβ that may emerge at the point of p-tau secretion. These findings have implications for the therapeutics and diagnostics of preclinical Alzheimer disease.
Hippocampal atrophy, typically measured using volumetry, is a hallmark feature of both normal aging and Alzheimer’s disease (AD). However,… (voir plus) the earliest stages of atrophy manifest as microstructural changes in tissue composition rather than macroscopic volume loss. We conducted longitudinal in vivo mapping of hippocampal microstructure in healthy aging and incipient AD, highlighting demyelination, iron deposition, and changes in water content as markers of age and AD risk. A combination of macrostructural and microstructural measures provides a more comprehensive picture of brain health and disease, unlocking unique insights into the pathological state of brain tissue and the impact of AD at a point where therapeutic rescue of the tissue is most likely to be efficacious.
2025-10-26
Proceedings of the National Academy of Sciences (publié)
The Brain Imaging Data Structure (BIDS) is a community-driven standard for the organization of data and metadata from a growing range of neu… (voir plus)roscience modalities. This paper is meant as a history of how the standard has developed and grown over time. We outline the principles behind the project, the mechanisms by which it has been extended, and some of the challenges being addressed as it evolves. We also discuss the lessons learned through the project, with the aim of enabling researchers in other domains to learn from the success of BIDS.