ArticleNeuroImage2018
Both hyper- and hypo-activation to cognitive challenge are associated with increased beta-amyloid deposition in healthy aging: A nonlinear effect.
Article in NeuroImage, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 2 of them syntheses that pooled it.
What it found
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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
32 citing papers in PubMed, 2 syntheses or guidelines pooled it, 49 citations in OpenAlex.
- Task-based fMRI brain activation in mild cognitive impairment and Alzheimer's disease: an ALE meta-analysis.GeroScience · 2026Pooled it
- Translation of task-evoked negative BOLD response into aging and Alzheimer's disease: a systematic review of the current literature.Journal of translational medicine · 2025Pooled it
- Brain Structure-Function Association as a Compensatory Factor in Cognitive Aging.bioRxiv : the preprint server for biology · 2026Article
- Association of functional brain alterations with β-amyloid, tau, and cognitive decline in Alzheimer's disease.Alzheimer's research & therapy · 2026Article
- Pre-plaque glutamatergic hyperexcitability, mitochondrial dysfunction, and dendritic remodeling in the hippocampus of one-month-old 5xFAD mice.Frontiers in aging neuroscience · 2026Article
- Distinct patterns of spontaneous brain activity in mild cognitive impairment patients stratified by cerebrospinal fluid biomarkers.Frontiers in aging neuroscience · 2026Article
- Amyloid-beta relates to default and attention network connectivity during working memory retrieval.Brain communications · 2026Article
- Multimodal neuroimaging insights into the neurobiology of healthy aging across the lifespan.European journal of nuclear medicine and molecular imaging · 2025Article
- Synergistic association of Aβ and tau pathology with cortical neurophysiology and cognitive decline in asymptomatic older adults.Nature neuroscience · 2024Article
- Age differences in BOLD modulation to task difficulty as a function of amyloid burden.Cerebral cortex (New York, N.Y. : 1991) · 2024Article
- Biophysical models applied to dementia patients reveal links between geographical origin, gender, disease duration, and loss of neural inhibition.Alzheimer's research & therapy · 2024Article
- Lost in space(s): Multimodal neuroimaging of disorientation along the Alzheimer's disease continuum.Human brain mapping · 2024Article
- Cerebral hyperactivation across the Alzheimer's disease pathological cascade.Brain communications · 2024Review
- Connectome-based modelling of neurodegenerative diseases: towards precision medicine and mechanistic insight.Nature reviews. Neuroscience · 2023Review
- Familial Alzheimer's disease-associated PSEN1 mutations affect neurodevelopment through increased Notch signaling.Stem cell reports · 2023Article
- Nonlinear changes in delayed functional network topology in Alzheimer's disease: relationship with amyloid and tau pathology.Alzheimer's research & therapy · 2023Article
- Review of Technological Challenges in Personalised Medicine and Early Diagnosis of Neurodegenerative Disorders.International journal of molecular sciences · 2023Review
- Past and future episodic detail retrieval is reduced among clinically normal older adults at higher genetic risk for late-onset Alzheimer's disease.Neuropsychology · 2023Article
- Novelty-Related fMRI Responses of Precuneus and Medial Temporal Regions in Individuals at Risk for Alzheimer Disease.Neurology · 2022Article
- Neuroimaging Modalities in Alzheimer's Disease: Diagnosis and Clinical Features.International journal of molecular sciences · 2022Review
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
Beta-amyloid (Aβ) positive individuals hyper-activate brain regions compared to those not at-risk; however, hyperactivation is then thought to diminish as Alzheimer's disease symptomatology begins, evidencing eventual hypoactivation. It remains unclear when in the disease staging this transition occurs. We hypothesized that differential levels of amyloid burden would be associated with both increased and decreased activation (i.e., a quadratic trajectory) in cognitively-normal adults. Participants (N = 62; aged 51-94) underwent an fMRI spatial distance-judgment task and Amyvid-PET scanning. Voxelwise regression modeled age, linear-Aβ, and quadratic-Aβ as predictors of BOLD activation to difficult spatial distance-judgments. A significant quadratic-Aβ effect on BOLD response explained differential activation in bilateral angular/temporal and medial prefrontal cortices, such that individuals with slightly elevated Aβ burden exhibited hyperactivation whereas even higher Aβ burden was then associated with hypoactivation. Importantly, in high-Aβ individuals, Aβ load moderated the effect of BOLD activation on behavioral task performance, where in lower-elevation, greater deactivation was associated with better accuracy, but in higher-elevation, greater deactivation was associated with poorer accuracy during the task. This study reveals a dose-response, quadratic relationship between increasing Aβ burden and alterations in BOLD activation to cognitive challenge in cognitively-normal individuals that suggests 1) the shift from hyper-to hypo-activation may begin early in disease staging, 2) depends, in part, on degree of Aβ burden, and 3) tracks cognitive performance.
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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.