Apolipoprotein E, Carbon Dioxide Vasoreactivity, and Cognition in Older Adults: Effect of Hypertension

• Type of Material: Article
• Authors: Ihab Hajjar, Emory University; Farzaneh Sorond, Harvard University; Lewis A. Lipsitz, Harvard University
• Language: English
• Date: 2015-02-01
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.
• Final Published Version (URL): http://dx.doi.org/10.1111/jgs.13235
• Title of Journal or Parent Work: Journal of the American Geriatrics Society
• ISSN: 0002-8614
• Volume: 63
• Issue: 2
• Start Page: 276
• End Page: 281
• Grant/Funding Information: FAS was supported by AG030967 and NS085002 from the National Institutes of Health.; IH was supported by Grants AG030057 and AG042127 from the National Institute on Aging.; MOBILIZE Boston was funded by a grant from the National Institute on Aging to LAL (AG004390 and AG025037).
• Keywords: IMPACT; CEREBRAL VASOREACTIVITY; apolipoprotein E; CO2 vasoreactivity; CEREBROVASCULAR REACTIVITY; IMPAIRMENT; INTEGRITY; BLOOD-PRESSURE; ALZHEIMERS-DISEASE; Gerontology; hypertension; E EPSILON-4 ALLELE; cognition; Science & Technology; Geriatrics & Gerontology; Life Sciences & Biomedicine; MANNER; TRANSCRANIAL DOPPLER
• Research Categories: Psychology, Cognitive

Abstract

Objectives To 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. 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 CO2 challenge (CO2), measured using transcranial Doppler ultrasonography, Trail-Making Test Part B - A (TMT), Hopkins Verbal Learning Test delayed recall (HVLT). Results APOE-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). Conclusion Individuals 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.