ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2022
Contribution of Alzheimer's biomarkers and risk factors to cognitive impairment and decline across the Alzheimer's disease continuum.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 42 citations in OpenAlex.
- A randomized, open-label clinical trial in mild cognitive impairment with EGb 761 examining blood markers of inflammation and oxidative stress.Scientific reports · 2023Trial
- Modelling the temporal evolution of plasma p-tau217, amyloid PET, tau PET and cognition.Brain : a journal of neurology · 2026Article
- Orthogonal Contributions of Genetic, Clinical, and Social Determinants of Health Risk Burdens on Alzheimer's Disease Pathophysiology.medRxiv : the preprint server for health sciences · 2026Article
- Inflammation profiles in Alzheimer's disease relate to cognition and neurodegeneration.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Reproducibility-driven discovery and systematic benchmarking reveal a robust cerebrospinal fluid proteomic signature in Alzheimer's disease.medRxiv : the preprint server for health sciences · 2026Article
- Additive Effects of White Matter Hyperintensity and APOE ε4 Status on Risk of Incident Dementia in Two Large Longitudinal Cohorts.Annals of neurology · 2026Article
- Systems biology of Alzheimer's Disease: a scoping review of key pathways and mechanisms.Molecular neurodegeneration · 2026Article
- DNA methylation signature of cognitive reserve moderates CSF tau pathology in prodromal Alzheimer's disease.Research square · 2026Article
- Functional autonomy, comorbidities and cognitive decline: a mediation analysis in neurocognitive disorders.Frontiers in aging neuroscience · 2026Article
- Cross-sectional associations between lifecourse dementia risk factors, plasma neurodegenerative biomarkers, and cognition in older adults in India.Journal of Alzheimer's disease : JAD · 2026Article
- Measurement Error and Methodologic Issues in Analyses of the Proportion of Variance Explained in Cognition.Neuropsychology review · 2025Review
- Cross-sectional associations between lifecourse dementia risk factors, plasma neurodegenerative biomarkers, and cognition in older adults in India.medRxiv : the preprint server for health sciences · 2025Article
- Associations between blood-based neurodegenerative biomarkers and cognitive functioning and decline in India.Journal of Alzheimer's disease : JAD · 2025Article
- Amyloid PET in Sporadic Early- Versus Late-Onset Alzheimer's Disease: Comparison of the LEADS and ADNI Cohorts.Annals of neurology · 2025Article
- Ante-mortem cognitive trajectories associated with Aβ and tau biomarker profiles in older adults with cerebrovascular disease: a longitudinal cohort study.Alzheimer's research & therapy · 2025Article
- Longitudinal tau aggregation, atrophy, and cognitive decline in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Multimodal and longitudinal characterization of distinct tau and atrophy clusters in Alzheimer's disease spectrum.Scientific reports · 2025Article
- A cerebrospinal fluid synaptic protein biomarker for prediction of cognitive resilience versus decline in Alzheimer's disease.Nature medicine · 2025Article
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Corrections and comments
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Authors and funding
13 authors at 7 institutions in 1 country.
Funding
Abstract
introductionAmyloid beta (Aβ), tau, and neurodegeneration jointly with the Alzheimer's disease (AD) risk factors affect the severity of clinical symptoms and disease progression.
methodsWithin 248 Aβ-positive elderly with and without cognitive impairment and dementia, partial least squares structural equation pathway modeling was used to assess the direct and indirect effects of imaging biomarkers (global Aβ-positron emission tomography [PET] uptake, regional tau-PET uptake, and regional magnetic resonance imaging-based atrophy) and risk-factors (age, sex, education, apolipoprotein E [APOE], and white-matter lesions) on cross-sectional cognitive impairment and longitudinal cognitive decline.
resultsSixteen percent of variance in cross-sectional cognitive impairment was accounted for by Aβ, 46% to 47% by tau, and 25% to 29% by atrophy, although 53% to 58% of total variance in cognitive impairment was explained by incorporating mediated and direct effects of AD risk factors. The Aβ-tau-atrophy pathway accounted for 50% to 56% of variance in longitudinal cognitive decline while Aβ, tau, and atrophy independently explained 16%, 46% to 47%, and 25% to 29% of the variance, respectively. DISCUSSION: These findings emphasize that treatments that remove Aβ and completely stop downstream effects on tau and neurodegeneration would only be partially effective in slowing of cognitive decline or reversing cognitive impairment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.