ArticleCurrent Alzheimer research2014
Cognitive changes preceding clinical symptom onset of mild cognitive impairment and relationship to ApoE genotype.
Article in Current Alzheimer research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 papers, 2 of them syntheses that pooled it.
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Who cites it
126 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Multi-ancestry genome-wide meta-analysis of 56,241 individuals identifies known and novel cross-population and ancestry-specific associations as novel risk loci for Alzheimer's disease.Genome biology · 2025Pooled it
- Association between apolipoprotein E gene polymorphism and mild cognitive impairment: a meta-analysis.Clinical interventions in aging · 2017Pooled it
- INTREPAD: A randomized trial of naproxen to slow progress of presymptomatic Alzheimer disease.Neurology · 2019Trial
- The countdown paradox: time-varying analysis of biomarker-clock age and symptom onset.medRxiv : the preprint server for health sciences · 2026Article
- Genetic architecture of the limbic white matter microstructure in aging and Alzheimer's Disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- APOE ε4 and amyloid status moderate the associations between sleep, physical activity, and tau-PET burden in cognitively unimpaired older adults.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Five-year change in brain metabolism across the spectrum of cognitive impairment in older adults: a quantitative MRI study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Coupled cross-sectional and longitudinal non-negative matrix factorization reveals dominant brain aging trajectories in 48,949 individuals.Nature communications · 2026Article
- Plasma biomarker trajectories across Alzheimer's clinical onset: a 17-year prospective study.Alzheimer's research & therapy · 2026Article
- Association Between Longitudinal Rate of Change in CSF Biomarkers and Subsequent Tau PET Burden in Early Braak Stages.Neurology · 2026Article
- Genetic modifiers of APOE-ε4-associated cognitive decline.Nature communications · 2026Article
- Tau burden across Braak stages is associated with regionally specific amyloid accumulation.Brain communications · 2026Article
- Longitudinal associations of rest-activity rhythms with executive function, plasma biomarkers, and clinical outcomes in older adults.Frontiers in aging neuroscience · 2026Article
- Modeling the age-specific incidence of mild cognitive impairment incorporating the time-varying relationship of Alzheimer's disease biomarkers over 28 years.Journal of Alzheimer's disease : JAD · 2026Article
- Associations of cerebrospinal fluid measures of synaptic function with white matter microstructure and cognition in older adults.Frontiers in aging neuroscience · 2026Article
- Probabilistic clustering using shared latent variable model for assessing Alzheimer's disease biomarkers.Biostatistics (Oxford, England) · 2025Article
- Cognitive resilience in preclinical Alzheimer's disease: Higher NPTX2 and VGF levels are associated with reduced cognitive decline.Neurobiology of aging · 2025Article
- Associations of adverse childhood experiences, inflammation, and cognition in older Black adults.Psychoneuroendocrinology · 2025Article
- Cognitive profiles among dementia-free older adults and their associations with neuroimaging markers.Brain imaging and behavior · 2025Article
- Tau PET Burden Is Associated With Hippocampal Microstructure and Episodic Memory in Amyloid Positive Older Adults.Hippocampus · 2025Article
66 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors.
Funding
Abstract
backgroundThis study had two goals (1) to evaluate changes in neuropsychological performance among cognitively normal individuals that might precede the onset of clinical symptoms, and (2) to examine the impact of Apolipoprotein E (ApoE) genotype on these changes.
methodsLongitudinal neuropsychological, clinical assessments and consensus diagnoses were completed prospectively in 268 cognitively normal individuals. The mean duration of follow-up was 9.2 years (+/- 3.3). 208 participants remained normal and 60 developed cognitive decline, consistent with a diagnosis of MCI or dementia. Cox regression analyses were completed, for both baseline scores and rate of change in scores, in relation to time to onset of clinical symptoms. Analyses were completed both with and without ApoE-4 status included. Interactions with ApoE-4 status were also examined.
resultsLower baseline test scores, as well as greater rate of change in test scores, were associated with time to onset of clinical symptoms (p<0.001). The mean time from baseline to onset of clinical symptoms was 6.15 (+/- 3.4) years. The presence of an ApoE-4 allele doubled the risk of progression. The rate of change in two of the test scores was significantly different in ApoE-4 carriers vs. non-carriers.
conclusionsCognitive performance declines prior to the onset of clinical symptoms that are a harbinger of a diagnosis of MCI. Cognitive changes in normal individuals who will subsequently decline may be observed at least 6.5 years prior to symptom onset. In addition, the risk of decline is doubled among individuals with an ApoE-4 allele.
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