ArticlePloS one2012
Rates of decline in Alzheimer disease decrease with age.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 3 of them syntheses that pooled it.
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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
61 citing papers in PubMed, 3 syntheses or guidelines pooled it, 102 citations in OpenAlex.
- A Meta-Analysis of the Relationship between Stroke and Alzheimer's Disease: Therapeutic and Prognostic Implications.Kidney & blood pressure research · 2025Pooled it
- CSF tau and the CSF tau/ABeta ratio for the diagnosis of Alzheimer's disease dementia and other dementias in people with mild cognitive impairment (MCI).The Cochrane database of systematic reviews · 2017Pooled it
- A Systematic Review of Longitudinal Studies Which Measure Alzheimer's Disease Biomarkers.Journal of Alzheimer's disease : JAD · 2017Pooled it
- Assessment of Efficacy and Safety of Zagotenemab: Results From PERISCOPE-ALZ, a Phase 2 Study in Early Symptomatic Alzheimer Disease.Neurology · 2024Trial
- Hippocampal grey matter changes across scales in Alzheimer's Disease.bioRxiv : the preprint server for biology · 2025Article
- Global trends in prevalence, disability adjusted life years, and risk factors for early onset dementia from 1990 to 2021.Scientific reports · 2025Article
- Association of Brain and Ventricular Boundary Shift Integral Measurements with CSF Biomarkers: A Case-Control Study.Current Alzheimer research · 2025Article
- The Compensation Effect of Mortality: A Global Analysis of Human Populations.Ageing and longevity research · 2025Article
- Compensation effect of mortality is a challenge to substantial lifespan extension of humans.Biogerontology · 2024Article
- Exploring Patterns of Human Mortality and Aging: A Reliability Theory Viewpoint.Biochemistry. Biokhimiia · 2024Review
- Does modulation of tau hyperphosphorylation represent a reasonable therapeutic strategy for Alzheimer's disease? From preclinical studies to the clinical trials.Molecular psychiatry · 2023Review
- Mapping cerebral atrophic trajectory from amnestic mild cognitive impairment to Alzheimer's disease.Cerebral cortex (New York, N.Y. : 1991) · 2023Article
- Longitudinal hippocampal atrophy in hippocampal sclerosis of aging.Aging brain · 2023Article
- Longitudinal Patterns of Brain Changes in a Community Sample in Relation to Aging and Cognitive Status.Journal of Alzheimer's disease : JAD · 2023Article
- Early-onset Alzheimer's disease shows a distinct neuropsychological profile and more aggressive trajectories of cognitive decline than late-onset.Annals of clinical and translational neurology · 2022Article
- Long-Term Multi-Sensory Gamma Stimulation of Dementia Patients: A Case Series Report.International journal of environmental research and public health · 2022Article
- Bridging patterns of neurocognitive aging across the older adult lifespan.Neuroscience and biobehavioral reviews · 2022Review
- Cross-Sectional and Longitudinal Hippocampal Atrophy, Not Cortical Thinning, Occurs in Amyloid-Negative, p-Tau-Positive, Older Adults With Non-Amyloid Pathology and Mild Cognitive Impairment.Frontiers in neuroimaging · 2022Article
- Heterogeneity in Alzheimer's Disease Diagnosis and Progression Rates: Implications for Therapeutic Trials.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Review
- Identifying individuals with Alzheimer's disease-like brains based on structural imaging in the Human Connectome Project Aging cohort.Human brain mapping · 2021Article
1 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
5 authors at 1 institution in 1 country.
Funding
Abstract
Age is the strongest risk factor for sporadic Alzheimer disease (AD), yet the effects of age on rates of clinical decline and brain atrophy in AD have been largely unexplored. Here, we examined longitudinal rates of change as a function of baseline age for measures of clinical decline and structural MRI-based regional brain atrophy, in cohorts of AD, mild cognitive impairment (MCI), and cognitively healthy (HC) individuals aged 65 to 90 years (total n = 723). The effect of age was modeled using mixed effects linear regression. There was pronounced reduction in rates of clinical decline and atrophy with age for AD and MCI individuals, whereas HCs showed increased rates of clinical decline and atrophy with age. This resulted in convergence in rates of change for HCs and patients with advancing age for several measures. Baseline cerebrospinal fluid densities of AD-relevant proteins, Aβ(1-42), tau, and phospho-tau(181p) (ptau), showed a similar pattern of convergence with advanced age across cohorts, particularly for ptau. In contrast, baseline clinical measures did not differ by age, indicating uniformity of clinical severity at baseline. These results imply that the phenotypic expression of AD is relatively mild in individuals older than approximately 85 years, and this may affect the ability to distinguish AD from normal aging in the very old. Our findings show that inclusion of older individuals in clinical trials will substantially reduce the power to detect disease-modifying therapeutic effects, leading to dramatic increases in required clinical trial sample sizes with age of study sample.
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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.