Observational studyJournal of the American Geriatrics Society2015
Apolipoprotein E, carbon dioxide vasoreactivity, and cognition in older adults: effect of hypertension.
Observational study in Journal of the American Geriatrics Society, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis 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
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- The role of APOE ε4 in modulating the relationship between non-genetic risk factors and dementia: a system review and meta-analysis.Journal of neurology · 2025Pooled it
- APOE gene-dependent BOLD responses to a breath-hold across the adult lifespan.NeuroImage. Clinical · 2019Trial
- Longitudinal effects of cerebrovascular reactivity and cerebral pulsatility in cognitively intact older adults with APOE4: links with cognition.GeroScience · 2026Article
- Cortical layer multi-parameter analysis of neurovascular impairments in AD/ADRD rodent model with in vivo optical imaging.Translational neurodegeneration · 2025Article
- Neurovascular Decoupling Is Associated With Lobar Intracerebral Hemorrhages and White Matter Hyperintensities.Journal of the American Heart Association · 2025Observational
- Vascular Function and Ion Channels in Alzheimer's Disease.Microcirculation (New York, N.Y. : 1994) · 2024Review
- Lower neurovascular coupling response despite higher cerebral blood flow at rest in apolipoprotein ɛ4 positive adults.PloS one · 2024Article
- Machine learning based on the EEG and structural MRI can predict different stages of vascular cognitive impairment.Frontiers in aging neuroscience · 2024Article
- Inverse Association of APOE ε4 and Glaucoma Modified by Systemic Hypertension: The Canadian Longitudinal Study on Aging.Investigative ophthalmology & visual science · 2022Article
- An In Vitro Model of the Blood-Brain Barrier to Study Alzheimer's Disease: The Role of β-Amyloid and Its Influence on PBMC Infiltration.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Regulation of cerebral blood flow in humans: physiology and clinical implications of autoregulation.Physiological reviews · 2021Review
- Pathobiolgy and Management of Alzheimer's Disease.Chonnam medical journal · 2021Review
- Study Protocol: The Heart and Brain Study.Frontiers in physiology · 2021Article
- Cognitive and neuroimaging markers for preclinical vascular cognitive impairment.Cerebral circulation - cognition and behavior · 2021Review
- The Utility of Cerebrovascular Reactivity MRI in Brain Rehabilitation: A Mechanistic Perspective.Frontiers in physiology · 2021Review
- Cerebrovascular reactivity in cerebral amyloid angiopathy, Alzheimer disease, and mild cognitive impairment.Neurology · 2020Article
- Targeting Apolipoprotein E for Alzheimer's Disease: An Industry Perspective.International journal of molecular sciences · 2019Review
- The Contribution of Genetic Factors to Cognitive Impairment and Dementia: Apolipoprotein E Gene, Gene Interactions, and Polygenic Risk.International journal of molecular sciences · 2019Review
- Vascular dysfunction-The disregarded partner of Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2019Article
- Blood-Brain Barrier: From Physiology to Disease and Back.Physiological reviews · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 3 institutions in 1 country.
Funding
Abstract
objectivesTo investigate the associations between the apolipoprotein E (APOE) ε4 allele, carbon dioxide (CO2 ) vasoreactivity, and cognitive performance and to explore the effect of CO2 vasoreactivity and hypertension on the associations between APOE and cognition.
designObservational.
settingCommunity.
participantsOlder adults (N = 625) enrolled in the Maintenance of Balance, Independent Living, Intellect and Zest in the Elderly of Boston Study. MEASUREMENTS: Change in cerebral blood flow velocity in response to CO2 challenge (CO2 ), measured using transcranial Doppler ultrasonography, Trail-Making Test Part B - A (TMT), Hopkins Verbal Learning Test delayed recall (HVLT).
resultsAPOE-ε4 was associated with lower CO2 vasoreactivity (P = .009) and poorer performance on the TMT (P < .001) and HVLT (P < .001). Having hypertension and APOE-ε4 was associated with worse cognitive and CO2 vasoreactivity measures than having neither or either alone (P < .001 for TMT and HVLT, P = .01 for CO2 vasoreactivity). The association between APOE-ε4 and cognition was only significant if it was present concurrent with low CO2 vasoreactivity, defined as below the median of the sample (APOE by CO2 vasoreactivity interaction: P = .04 for TMT, P = .04 for HVLT). In hypertension, the association between APOE-ε4 and executive function was also only significant in participants with lower CO2 vasoreactivity (P = .005 for APOE by CO2 vasoreactivity).
conclusionIndividuals at risk of Alzheimer's disease (AD) because they have APOE-ε4 may have lower CO2 vasoreactivity, which in turn may be contributing to the observed lower cognitive performance associated with this allele. The cognitive effect of APOE-ε4 is magnified in hypertension and low CO2 vasoreactivity. This study offers evidence that APOE-ε4 may be associated with microvascular brain injury even in the absence of clinical AD.
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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.