ArticleAnnals of neurology2018
Person-specific contribution of neuropathologies to cognitive loss in old age.
Article in Annals of neurology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 298 papers, 4 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
298 citing papers in PubMed, 4 syntheses or guidelines pooled it, 503 citations in OpenAlex.
- Intensive Blood Pressure Lowering for Intracerebral Hemorrhage: A Systematic Review and Updated Meta-analysis of Randomized Controlled Trials.Neurocritical care · 2025Pooled it
- Neuropsychological differential diagnosis of Alzheimer's disease and vascular dementia: a systematic review with meta-regressions.Frontiers in aging neuroscience · 2023Pooled it
- Cerebral Microbleeds, Cerebral Amyloid Angiopathy, and Their Relationships to Quantitative Markers of Neurodegeneration.Neurology · 2022Pooled it
- Brain microRNAs are associated with variation in cognitive trajectory in advanced age.Translational psychiatry · 2022Pooled it
- Vascular brain injury modifies the relationship between sleep duration, cognition, and white matter hyperintensity burden in the Alzheimer's disease continuum.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Modelling the temporal evolution of plasma p-tau217, amyloid PET, tau PET and cognition.Brain : a journal of neurology · 2026Article
- The YTHDF proteins modulate Alzheimer's disease-associated brain gene signatures.Molecular neurodegeneration · 2026Article
- Urban-rural differences in health behaviors and cognition: Two Taiwanese older cohorts.Journal of the Chinese Medical Association : JCMA · 2026Article
- Multi-region brain transcriptomes uncover two subtypes of aging individuals with differences in Alzheimer risk and the impact ofiScience · 2026Article
- Associations of Alzheimer Disease and Related Dementia Neuropathologies With Timely Diagnosis of Dementia in Healthcare Settings.Neurology · 2026Article
- Why large-scale randomized trials of live-attenuated shingles vaccination for dementia prevention are urgently needed.Nature medicine · 2026Article
- Effects of concurrent neuropathologies with Alzheimer disease neuropathologic change on cognitive decline: Minimal impact of vascular brain injury compared with other combinations.Journal of neuropathology and experimental neurology · 2026Article
- Predicting Autopsy-Confirmed Neuropathology across Clinical, Neuroimaging, and CSF Biomarkers using Machine Learning.bioRxiv : the preprint server for biology · 2026Article
- Proteome-wide association study of cortical proteins that may provide resilience for late-life disability.The journals of gerontology. Series A, Biological sciences and medical sciences · 2026Article
- Brain endothelial cell-derived extracellular vesicles (c-BEEVs) as a promising biomarker for brain vascular pathology and cognitive decline.Nature aging · 2026Article
- How does type 2 diabetes modify the risk of Alzheimer's disease?Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Plasma proteomic signatures of preclinical Alzheimer's disease in clinically unimpaired older adults.Molecular neurodegeneration · 2026Article
- Biological classification of memory clinic patients.Brain : a journal of neurology · 2026Article
- Associations between structural brain alterations and dysfunction across cognitive domains in cerebral small vessel disease: A systematic review and meta-analysis.Neuroimage. Reports · 2026Review
- MarkVCID2 Consortium for Clinical Validation of Biomarkers of Cerebral Small Vessel Disease: Validation Framework and Baseline Characteristics.Annals of neurology · 2026Article
238 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
objectiveMixed neuropathologies are the most common cause of dementia at the population level, but how different neuropathologies contribute to cognitive decline at the individual level remains unknown. We quantified the contribution of 9 neuropathologies to cognitive loss at an individual level.
methodsParticipants (n = 1,079) came from 2 longitudinal clinical-pathologic studies of aging. All completed 2 + cognitive evaluations (maximum = 22), died, and underwent neuropathologic examinations to identify Alzheimer disease (AD), other neurodegenerative diseases, and vascular pathologies. Linear mixed models examined associations of neuropathologies with cognitive decline and estimated the proportion of cognitive loss accounted for by each neuropathology at a person-specific level.
resultsNeuropathology was ubiquitous, with 94% of participants having 1+, 78% having 2+, 58% having 3+, and 35% having 4+. AD was most frequent (65%) but rarely occurred in isolation (9%). Remarkably, >230 different neuropathologic combinations were observed, each of which occurred in <6% of the cohort. The relative contributions of specific neuropathologies to cognitive loss varied widely across individuals. Although AD accounted for an average of about 50% of the observed cognitive loss, the proportion accounted for at the individual level ranged widely from 22% to 100%. Lewy bodies and hippocampal sclerosis also had potent effects, but again their impacts varied at the person-specific level.
interpretationThere is much greater heterogeneity in the comorbidity and cognitive impact of age-related neuropathologies than currently appreciated, suggesting an urgent need for novel therapeutic approaches that embrace the complexity of disease to combat cognitive decline in old age. Ann Neurol 2018;83:74-83.
Indexed as
Identifiers
What OpenQuestion holds
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.