ArticleJournal of Alzheimer's disease : JAD2023
The Spectrum of Alzheimer-Type Pathology in Cognitively Normal Individuals.
Article in Journal of Alzheimer's disease : JAD, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 16 citations in OpenAlex.
- Neocortical tau burden determines the degree of cognitive impairment in individuals with Braak stage V neurofibrillary degeneration.Acta neuropathologica · 2026Article
- Neuronal subtype governs amyloid structure, cellular response, and cognitive outcome in genetically targeted APP mouse models.Molecular neurodegeneration · 2026Article
- Longitudinal assessment of cognitive decline and resilience in high-level Alzheimer disease neuropathologic change.Alzheimer's research & therapy · 2025Article
- Monocyte inflammation and resilience to Alzheimer's disease: novel genetic risk genes identified by transcriptome-wide association study.Translational psychiatry · 2025Article
- Primary age-related tauopathy.Acta neuropathologica · 2025Review
- Amyloid-Beta Pathology and Cognitive Performance in Centenarians.JAMA neurology · 2025Article
- Unraveling the clinical-pathological correlations of subjects with isolated and mixed neurodegenerative processes in the National Alzheimer's Coordinating Center dataset.Journal of neuropathology and experimental neurology · 2025Article
- Disentangling and quantifying the relative cognitive impact of concurrent mixed neurodegenerative pathologies.Acta neuropathologica · 2024Article
- Unraveling Alzheimer's disease: insights from single-cell sequencing and spatial transcriptomic.Frontiers in neurology · 2024Review
- Cognitive symptoms progress with limbic-predominant age-related TDP-43 encephalopathy stage and co-occurrence with Alzheimer disease.Journal of neuropathology and experimental neurology · 2023Article
- The Role of Insulin-like Growth Factor I in Mechanisms of Resilience and Vulnerability to Sporadic Alzheimer's Disease.International journal of molecular sciences · 2023Review
- The relationship between hippocampal amyloid beta burden and spatial distribution of neurofibrillary degeneration.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Article
- Cognitive resistance to and resilience against multiple comorbid neurodegenerative pathologies and the impact of APOE status.Journal of neuropathology and experimental neurology · 2023Article
- Cognitive and Neuropsychological Profiles in Alzheimer's Disease and Primary Age-Related Tauopathy and the Influence of Comorbid Neuropathologies.Journal of Alzheimer's disease : JAD · 2023Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundThe strongest risk factor for the development of Alzheimer's disease (AD) is age. The progression of Braak stage and Thal phase with age has been demonstrated. However, prior studies did not include cognitive status.
objectiveWe set out to define normative values for Alzheimer-type pathologic changes in individuals without cognitive decline, and then define levels that would qualify them to be resistant to or resilient against these changes.
methodsUtilizing neuropathology data obtained from the National Alzheimer's Coordinating Center (NACC), we demonstrate the age-related progression of Alzheimer-type pathologic changes in cognitively normal individuals (CDR = 0, n = 542). With plots generated from these data, we establish standard lines that may be utilized to measure the extent to which an individual's Alzheimer-type pathology varies from the estimated normal range of pathology.
resultsAlthough Braak stage and Thal phase progressively increase with age in cognitively normal individuals, the Consortium to Establish a Registry for Alzheimer's Disease neuritic plaque score and Alzheimer's disease neuropathologic change remain at low levels.
conclusionThese findings suggest that an increasing burden of neuritic plaques is a strong predictor of cognitive decline, whereas, neurofibrillary degeneration and amyloid-β (diffuse) plaque deposition, both to some degree, are normal pathologic changes of aging that occur in almost all individuals regardless of cognitive status. Furthermore, we have defined the amount of neuropathologic change in cognitively normal individuals that would qualify them to be "resilient" against the pathology (significantly above the normative values for age, but still cognitively normal) or "resistant" to the development of pathology (significantly below the normative values for age).
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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.