Apolipoprotein E, Carbon Dioxide Vasoreactivity, and Cognition in Older Adults: Effect of Hypertension
Open accessAbstract
Objectives: To investigate the associations between the apolipoprotein E ( APOE ) ε 4 allele, carbon dioxide ( CO 2 ) vasoreactivity, and cognitive performance and to explore the effect of CO 2 vasoreactivity and hypertension on the associations between APOE and cognition. Design: Observational. Setting: Community. Participants: Older 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 CO 2 challenge ( CO 2 ), measured using transcranial Doppler ultrasonography, Trail‐Making Test Part B – A ( TMT ), Hopkins Verbal Learning Test delayed recall ( HVLT ). Results: APOE ‐ ε 4 was associated with lower CO 2 vasoreactivity ( P = .009) and poorer performance on the TMT ( P < .001) and HVLT ( P < .001). Having hypertension and APOE ‐ ε 4 was associated with worse cognitive and CO 2 vasoreactivity measures than having neither or either alone ( P < .001 for TMT and HVLT , P = .01 for CO 2 vasoreactivity). The association between APOE ‐ ε 4 and cognition was only significant if it was present concurrent with low CO 2 vasoreactivity, defined as below the median of the sample ( APOE by CO 2 vasoreactivity interaction: P = .04 for TMT , P = .04 for HVLT ). In hypertension, the association between APOE ‐ ε 4 and executive function was also only significant in participants with lower CO 2 vasoreactivity ( P = .005 for APOE by CO 2 vasoreactivity). Conclusion: Individuals at risk of Alzheimer's disease ( AD ) because they have APOE ‐ ε 4 may have lower CO 2 vasoreactivity, which in turn may be contributing to the observed lower cognitive performance associated with this allele. The cognitive effect of APOE ‐ ε 4 is magnified in hypertension and low CO 2 vasoreactivity. This study offers evidence that APOE ‐ ε 4 may be associated with microvascular brain injury even in the absence of clinical AD .
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- Authors
- Hajjar, I., Sorond, F., & Lipsitz, L. A.
- Affiliations
- Emory University (US)
- Brigham and Women's Hospital (US)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Hajjar, Ihab
- Venue
- Journal of the American Geriatrics Society
- Publisher
- Wiley
- Published
- 2015-02
- Volume
- 63
- Issue
- 2
- Pages
- 276-281
- ISSN
- 0002-8614 (ISSN-L)
- 1532-5415
- PMC
- PMC4375955
- OpenAlex
- W2079778822
- Cited by
- 37
- References
- 7
- Citations by year
- 2025: 4 · 2024: 3 · 2022: 2 · 2021: 6 · 2020: 5 · 2019: 5 · 2018: 4 · 2017: 4 · 2016: 2 · 2015: 2
- FWCI
- 3.25
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of the American Geriatrics Society (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (AG030057, AG042127, AG004390, AG025037)
- National Institutes of Health (AG030967, NS085002)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- APOE ε4, cerebral blood flow velocity, hypertension, cognitive performance, executive function, Alzheimer's disease risk, older adults, Trail Making Test, verbal learning
- MeSH terms
- Age Factors, Aged, Aged, 80 and over, Blood Flow Velocity, Carbon Dioxide, Cerebrovascular Circulation, Cognition, Female, Genotype, Humans, Hypertension, Male, Prospective Studies, Pulmonary Gas Exchange, Tidal Volume, Apolipoprotein E4
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