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  • 1
    Online Resource
    Online Resource
    Clinical relevance of brain atrophy subtypes categorization in memory clinics
    Wiley ; 2021
    In:  Alzheimer's & Dementia Vol. 17, No. 4 ( 2021-04), p. 641-652
    Details
    In: Alzheimer's & Dementia, Wiley, Vol. 17, No. 4 ( 2021-04), p. 641-652
    Abstract: The clinical relevance of brain atrophy subtypes categorization in non‐demented persons without a priori knowledge regarding their amyloid status or clinical presentation is unknown. Methods A total of 2083 outpatients with either subjective cognitive complaint or mild cognitive impairment at study entry were followed during 4 years (MEMENTO cohort). Atrophy subtypes were defined using baseline magnetic resonance imaging (MRI) and previously described algorithms. Results Typical/diffuse atrophy was associated with faster cognitive decline and the highest risk of developing dementia and Alzheimer's disease (AD) over time, both in the whole analytic sample and in amyloid‐positive participants. Hippocampal‐sparing and limbic‐predominant atrophy were also associated with incident dementia, with faster cognitive decline in the limbic predominant atrophy group. Lewy body dementia was more frequent in the hippocampal‐sparing and minimal/no atrophy groups. Discussion Atrophy subtypes categorization predicted different subsequent patterns of cognitive decline and rates of conversion to distinct etiologies of dementia in persons attending memory clinics.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    URL: Article
    DOI: 10.1002/alz.v17.4
    DOI: 10.1002/alz.12231
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2201940-6
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  • 2
    Online Resource
    Online Resource
    Validity and Performance of Blood Biomarkers for Alzheimer Disease to Predict Dementia Risk in a Large Clinic-Based Cohort
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Neurology Vol. 100, No. 5 ( 2023-01-31), p. e473-e484
    Details
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 100, No. 5 ( 2023-01-31), p. e473-e484
    Abstract: Blood biomarkers for Alzheimer disease (AD) have consistently proven to be associated with CSF or PET biomarkers and effectively discriminate AD from other neurodegenerative diseases. Our aim was to test their utility in clinical practice, from a multicentric unselected prospective cohort where patients presented with a large spectrum of cognitive deficits or complaints. Methods The MEMENTO cohort enrolled 2,323 outpatients with subjective cognitive complaint (SCC) or mild cognitive impairment (MCI) consulting in 26 French memory clinics. Participants had neuropsychological assessments, MRI, and blood sampling at baseline. CSF sampling and amyloid PET were optional. Baseline blood Aβ42/40 ratio, total tau, p181-tau, and neurofilament light chain (NfL) were measured using a Simoa HD-X analyzer. An expert committee validated incident dementia cases during a 5-year follow-up period. Results Overall, 2,277 individuals had at least 1 baseline blood biomarker available (n = 357 for CSF subsample, n = 649 for PET subsample), among whom 257 were diagnosed with clinical AD/mixed dementia during follow-up. All blood biomarkers but total tau were mildly correlated with their equivalence in the CSF (r = 0.33 to 0.46, p 〈 0.0001) and were associated with amyloid-PET status ( p 〈 0.0001). Blood p181-tau was the best blood biomarker to identify amyloid-PET positivity (area under the curve = 0.74 [95% CI = 0.69; 0.79]). Higher blood and CSF p181-tau and NfL concentrations were associated with accelerated time to AD dementia onset with similar incidence rates, whereas blood Aβ42/40 was less efficient than CSF Aβ42/40. Blood p181-tau alone was the best blood predictor of 5-year AD/mixed dementia risk (c-index = 0.73 [95% CI = 0.69; 0.77] ); its accuracy was higher in patients with clinical dementia rating (CDR) = 0 (c-index = 0.83 [95% CI = 0.69; 0.97]) than in patients with CDR = 0.5 (c-index = 0.70 [95% CI = 0.66; 0.74] ). A “clinical” reference model (combining demographics and neuropsychological assessment) predicted AD/mixed dementia risk with a c-index = 0.88 [95% CI = 0.86–0.91] and performance increased to 0.90 [95% CI = 0.88; 0.92] when adding blood p181-tau + Aβ42/40. A “research” reference model (clinical model + apolipoprotein E genotype and AD signature on MRI) had a c-index = 0.91 [95% CI = 0.89–0.93] increasing to 0.92 [95% CI = 0.90; 0.93] when adding blood p181-tau + Aβ42/40. Chronic kidney disease and vascular comorbidities did not affect predictive performances. Discussion In a clinic-based cohort of patients with SCC or MCI, blood biomarkers may be good hallmarks of underlying pathology but add little to 5-year dementia risk prediction models including traditional predictors.
    Type of Medium: Online Resource
    ISSN: 0028-3878 , 1526-632X
    URL: Article
    DOI: 10.1212/WNL.0000000000201479
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
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  • 3
    Online Resource
    Online Resource
    Diabetes Mellitus and Cognition : Pathway Analysis in the MEMENTO Cohort
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Neurology Vol. 97, No. 8 ( 2021-08-24), p. e836-e848
    Details
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 97, No. 8 ( 2021-08-24), p. e836-e848
    Abstract: To assess the role of biomarkers of Alzheimer disease (AD), neurodegeneration, and small vessel disease (SVD) as mediators in the association between diabetes mellitus and cognition. Methods The study sample was derived from MEMENTO, a cohort of French adults recruited in memory clinics and screened for either isolated subjective cognitive complaints or mild cognitive impairment. Diabetes was defined based on blood glucose assessment, use of antidiabetic agent, or self-report. We used structural equation modeling to assess whether latent variables of AD pathology (PET mean amyloid uptake, Aβ 42 /Aβ 40 ratio, and CSF phosphorylated tau), SVD (white matter hyperintensities volume and visual grading), and neurodegeneration (mean cortical thickness, brain parenchymal fraction, hippocampal volume, and mean fluorodeoxyglucose uptake) mediate the association between diabetes and a latent variable of cognition (5 neuropsychological tests), adjusting for potential confounders. Results There were 254 (11.1%) participants with diabetes among 2,288 participants (median age 71.6 years; 61.8% women). The association between diabetes and lower cognition was significantly mediated by higher neurodegeneration (standardized indirect effect: −0.061, 95% confidence interval: −0.089, −0.032), but not mediated by SVD and AD markers. Results were similar when considering latent variables of memory or executive functioning. Conclusion In a large clinical cohort in the elderly, diabetes is associated with lower cognition through neurodegeneration, independently of SVD and AD biomarkers.
    Type of Medium: Online Resource
    ISSN: 0028-3878 , 1526-632X
    URL: Article
    DOI: 10.1212/WNL.0000000000012440
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
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