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Apolipoprotein E, carbon dioxide vasoreactivity, and cognition in older adults: effect of hypertension.

ABSTRACT: To investigate the associations between the apolipoprotein E (APOE) ?4 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.Observational.Community.Older adults (N = 625) enrolled in the Maintenance of Balance, Independent Living, Intellect and Zest in the Elderly of Boston Study.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).APOE-?4 was associated with lower CO2 vasoreactivity (P = .009) and poorer performance on the TMT (P < .001) and HVLT (P < .001). Having hypertension and APOE-?4 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-?4 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-?4 and executive function was also only significant in participants with lower CO2 vasoreactivity (P = .005 for APOE by CO2 vasoreactivity).Individuals at risk of Alzheimer's disease (AD) because they have APOE-?4 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-?4 is magnified in hypertension and low CO2 vasoreactivity. This study offers evidence that APOE-?4 may be associated with microvascular brain injury even in the absence of clinical AD.

SUBMITTER: Hajjar I

PROVIDER: S-EPMC4375955 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Apolipoprotein E, carbon dioxide vasoreactivity, and cognition in older adults: effect of hypertension.

Hajjar Ihab I Sorond Farzaneh F Lipsitz Lewis A LA

Journal of the American Geriatrics Society 20150201 2

<h4>Objectives</h4>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.<h4>Design</h4>Observational.<h4>Setting</h4>Community.<h4>Participants</h4>Older adults (N = 625) enrolled in the Maintenance of Balance, Independent Living, Intellect and Zest in the Elderly of Boston Study.<h4>Measurements< ...[more]

PMID: 25688603

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Project description:ImportanceSex differences are established in associations between apolipoprotein E (APOE) ε4 and cognitive impairment in Alzheimer disease (AD). However, it is unclear whether sex-specific cognitive consequences of APOE are consistent across races and extend to the APOE ε2 allele.ObjectiveTo investigate whether sex and race modify APOE ε4 and ε2 associations with cognition.Design, setting, and participantsThis genetic association study included longitudinal cognitive data from 4 AD and cognitive aging cohorts. Participants were older than 60 years and self-identified as non-Hispanic White or non-Hispanic Black (hereafter, White and Black). Data were previously collected across multiple US locations from 1994 to 2018. Secondary analyses began December 2021 and ended September 2022.Main outcomes and measuresHarmonized composite scores for memory, executive function, and language were generated using psychometric approaches. Linear regression assessed interactions between APOE ε4 or APOE ε2 and sex on baseline cognitive scores, while linear mixed-effect models assessed interactions on cognitive trajectories. The intersectional effect of race was modeled using an APOE × sex × race interaction term, assessing whether APOE × sex interactions differed by race. Models were adjusted for age at baseline and corrected for multiple comparisons.ResultsOf 32 427 participants who met inclusion criteria, there were 19 007 females (59%), 4453 Black individuals (14%), and 27 974 White individuals (86%); the mean (SD) age at baseline was 74 years (7.9). At baseline, 6048 individuals (19%) had AD, 4398 (14%) were APOE ε2 carriers, and 12 538 (38%) were APOE ε4 carriers. Participants missing APOE status were excluded (n = 9266). For APOE ε4, a robust sex interaction was observed on baseline memory (β = -0.071, SE = 0.014; P = 9.6 × 10-7), whereby the APOE ε4 negative effect was stronger in females compared with males and did not significantly differ among races. Contrastingly, despite the large sample size, no APOE ε2 × sex interactions on cognition were observed among all participants. When testing for intersectional effects of sex, APOE ε2, and race, an interaction was revealed on baseline executive function among individuals who were cognitively unimpaired (β = -0.165, SE = 0.066; P = .01), whereby the APOE ε2 protective effect was female-specific among White individuals but male-specific among Black individuals.Conclusions and relevanceIn this study, while race did not modify sex differences in APOE ε4, the APOE ε2 protective effect could vary by race and sex. Although female sex enhanced ε4-associated risk, there was no comparable sex difference in ε2, suggesting biological pathways underlying ε4-associated risk are distinct from ε2 and likely intersect with age-related changes in sex biology.

Dataset Information

Apolipoprotein E, carbon dioxide vasoreactivity, and cognition in older adults: effect of hypertension.

Publications

Apolipoprotein E, carbon dioxide vasoreactivity, and cognition in older adults: effect of hypertension.

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