Influence of Hypertension on Longitudinal Changes in Brain Glucose Metabolism Was Modified by the APOE4 Allele Among Cognitively Normal Older Individuals

Abstract

Objective: To examine whether the influence of hypertension (HTN) status on longitudinal changes in brain glucose metabolism was modified by the apolipoprotein 4 (APOE4) status among older people with normal cognition. Methods: In this study, we included 217 older individuals with normal cognition from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. Participants were divided into the HTN and no HTN groups based on self-reported medical history. Brain glucose metabolism was assessed by 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET). Linear mixed model was fitted to examine the association between the HTN × APOE4 interaction and longitudinal changes in brain glucose metabolism after controlling for several covariates. Results: In the present study, we found that the association between HTN status and longitudinal changes in brain glucose metabolism varied as a function of the APOE4 status, such that the HTN/APOE4+ group showed a steeper decline in FDG SUVR than all other groups (No HTN/APOE4-, HTN/APOE4-, and No HTN/APOE4+). Nevertheless, there was no significant difference in the rate of decline in FDG SUVR among other groups (No HTN/APOE4-, HTN/APOE4-, and No HTN/APOE4+). Conclusion: The APOE4 genotype interacted with hypertension status to affect longitudinal changes in brain glucose metabolism among older individual with normal cognition, such that the HTN/APOE4+ group showed a steeper decline in FDG SUVR than other groups.

Using the Alzheimer's Disease Neuroimaging Initiative to improve early detection, diagnosis, and treatment of Alzheimer's disease

“…In CU elders, hypertensive APOE ε4 carriers had a steeper decrease in glucose metabolism than hypertensive non-carriers, carriers with normal blood pressure, or non-carriers with normal blood pressure suggesting that the APOE ε4 allele acts to exacerbate the effect of hypertension on glucose metabolism. 88 Overall, these studies provide further evidence for the detrimental effect of vascular risk factors on neurodegeneration and decline. Cerebrovascular disease may exert its effect directly, via Aβ or tau deposition, or by a combination of pathways, and its effect may be exacerbated by the APOE ε4 allele (Figure 6).…”

“…( 1) Cardiovascular risk factors are associated with markers of neurodegeneration and cognitive decline. 87,88,90,203 (2)…”

“…Cerebrovascular events can be directly caused by a lack of blood flow to the brain due cardiovascular disease 86 . Smoking, 87 hypertension, 88 body mass index (BMI), 89 and overall cardiovascular risk 90 were associated with impaired glucose metabolism, neurodegeneration or cognitive decline (Table S1). Cognitive decline in ADNI participants with Type 2 diabetes mellitus was mediated by baseline cortical thickness 91 .…”

“…The APOE ε4 allele may interact synergistically with vascular disease. In CU elders, hypertensive APOE ε4 carriers had a steeper decrease in glucose metabolism than hypertensive non‐carriers, carriers with normal blood pressure, or non‐carriers with normal blood pressure suggesting that the APOE ε4 allele acts to exacerbate the effect of hypertension on glucose metabolism 88 …”

“…Cerebrovascular impacts in AD supported by recent ADNI studies. (1) Cardiovascular risk factors are associated with markers of neurodegeneration and cognitive decline 87,88,90,203 . (2) The apolipoprotein E ( APOE ) ε4 allele may increase WMHs via induction of CAA 102 .…”