Staging amyloid beta (Aβ) burden along a continuous spectrum provides clinically relevant information. Conventional phosphorylated tau (p‐tau)217 reliably identifies amyloid positron emission tomography (PET) positivity, but its ability to capture the full Aβ continuum is limited. Recently developed brain‐derived (BD) p‐tau217 assays enrich for central nervous system tau species and may improve specificity.
Lydia Trudel, J. Therriault, Arthur C. Macedo et al.· Alzheimer's & Dementia· 0 citations
Summary Background Reduced [18F]Fluorodeoxyglucose ([18F]FDG)-PET uptake is a core imaging feature of Alzheimer's disease (AD). While tau load correlates with this metabolic signature, it remains unclear whether the spatial extent of tauopathy (SEOT) more accurately explains brain glucose hypometabolic patterns. Here, we compared SEOT versus tau load to determine their ability to predict brain hypometabolic signatures in AD. Methods We performed a cross-sectional study of amyloid-β positive participants from ADNI (n = 150) and an atypical AD subset from the McGill University Research Centre for Studies in Ageing (MCSA; n = 44). Participants underwent [18F]AV1451 or [18F]MK6240 tau-PET and [18F]FDG-PET. Tau load was indexed with regional SUVR, and SEOT with the proportion of abnormal voxels. Linear regressions related temporal and whole-cortex tau-PET load or SEOT to [18F]FDG-PET. We also compared the accuracy of tau-PET metrics for identifying AD-like hypometabolism. Spearman correlations assessed SEOT/tau load-FDG associations at regional and network levels. Partial Least Squares (PLS) regression investigated whether distributed tau load and SEOT predicted [18F]FDG-PET signatures. Structural equation modelling and hierarchical linear models assessed associations between tau metrics and cognition dependent and independent of [18F]FDG-PET. Findings Whole-cortex SEOT best predicted decreased signal in the [18F]FDG-PET AD-meta-ROI. SEOT also performed better in classifying AD-related brain hypometabolism. Across regions and networks, SEOT performed similarly or better than tau load in predicting metabolic dysfunction. Voxelwise analyses suggested complementary predictive value of SEOT and tau load, each capturing slightly distinct spatial associations with [18F]FDG-PET. PLS demonstrated partially non-redundant contributions from tau load and SEOT. Cortical SEOT showed the strongest predictive value for cognition. Interpretation SEOT provides complementary, independent, and often stronger predictive value than tau load for brain metabolism, particularly for network-level dysfunction. SEOT may improve diagnostic characterisation and prediction of cognitive impairment beyond [18F]FDG-PET. Funding TRIAD is supported by the Weston Brain Institute, Canadian Institutes of Health Research, Canadian Consortium of Neurodegeneration and Aging, Brain Canada Foundation, the Fonds de Recherche du Québec – Santé, and the Colin J Adair Charitable Foundation. ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and the Canadian Institutes of Health Research.
Arthur C. Macedo, Lydia Trudel, S. A. Hosseini et al.· EBioMedicine· 0 citations
In low- and middle-income countries, Alzheimer’s disease (AD) constitutes a growing public health burden. However, AD biomarkers research remains underrepresented in African populations. This study assesses core biomarkers of AD and their relevance in the African context as potential aid in clinical diagnosis. Nigerian older adults from VALIANT cohort (n = 967) underwent biomarker quantification in plasma (p-tau217, GFAP, NfL, Aβ42 and Aβ40) employing both the Single Molecule Assay (Simoa, Quanterix) and Nucleic acid-Linked Immuno-Sandwich Assay (NULISA, Alamar). Biomarkers were associated with disease severity in clinical-diagnostic and clinical-biological groups, with stepwise increases of p-tau217, NfL and GFAP from cognitively unimpaired to dementia (p < 0.05). Results were consistent across platforms. Comparison between sexes showed higher biomarker levels in male participants across diagnostic groups. A significant effect of apoE-E4 proteotype on p-tau217 levels, after adjusting for age and sex was identified. These findings support the application of plasma AD biomarkers in the African context and the relevance of further AD biomarker research in diverse populations.
T. Akinyemi, I. Pola, K. Tan et al.· npj Dementia· 0 citations
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 (n = 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.
Felix-Etienne Colpron-Larin, É. Aumont, Samantha Schwartz et al.· Applied neuropsychology. Adu...· 0 citations
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.
M. S. Oliveira-Junior, M. Rodrigues, Livia Amaral et al.· Neurology· 0 citations
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