Effect of plasma lipids, hypertension and APOE genotype on cognitive decline

Abstract

We examined the combined effect of plasma lipids/hypertension and apolipoprotein E (APOE) genotype on cognitive function in elderly individuals. Plasma concentrations of high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride (TG), total cholesterol (TC), APOE, and history of hypertension were evaluated in 622 community-dwelling individuals aged 65 years and older. We investigated the associations between plasma lipids/hypertension and cognitive function in apolipoprotein E4 allele (APOE4) carrier (E4+) and APOE4 noncarrier (E4-) groups using 3-year longitudinal data. At baseline and 3 years later, cognitive scores were correlated with plasma APOE levels in both E4- and E4+, and HDL level in E4-. The combination of hypertension and E4+, but not E4-, was associated with a significant deterioration in cognitive function during the 3-year follow-up. Our findings suggest that an interaction between APOE and HDL is facilitated by APOE4, and is possibly linked with a protective effect on cognitive decline in later life. The findings also indicate a synergistic effect of an APOE4 allele and hypertension on the acceleration of cognitive decline.

Meta-Analysis of Peripheral Blood Apolipoprotein E Levels in Alzheimer’s Disease

“…Lower ApoE levels appear to be an additional risk factor in AD independently of ε4. In line with this notion, Fumihiko Yasuno et al found that lower plasma ApoE concentration had lower cognitive scores in both ε4- and ε4+ groups in elderly individuals of 3-year follow-up [36]. Of course, we found no significant association between lower ApoE levels and AD in ε3/ε4 carriers.…”

Screening Younger Individuals in a Primary Care Setting Flags Putative Dementia Cases and Correlates Gastrointestinal Diseases with Poor Cognitive Performance

“…Individuals carrying the ε4 allele have an increased risk of developing AD [51]; in contrast, the ε2 allele is protective [52,53,54]. The same correlation exists for the pcb-Cohort.…”

Risk Factors for β-Amyloid Deposition in Healthy Aging

“…A significant body of work has documented the deleterious effects of hypertension and other vascular risk factors on both normal and abnormal cognitive and brain aging, 23,34 as well as its interaction with various genetic risk factors for cognitive decline beyond APOE . 24–26,35–37 This literature highlights the complex nature of vascular and genetic effects on neurocognitive aging and suggests the synergistic effect of vascular compromise and genetic risk results in increased susceptibility to both the accumulation of neural insults and associated cognitive decline with aging. Understanding the time course, mechanism, and for whom the aging process becomes pathological is an open question in need of further study.…”

“…15–18 Midlife elevations in blood pressure have been shown to predict diagnosis of dementia later in the life span, and hypertension in even healthy adults has been associated with poorer cognitive performance, 19 increased rate of brain shrinkage, 20 degraded white matter connectivity, 21 and greater regional brain iron concentration 22 compared with adults with normal blood pressure. 23 Additionally, older adults with an APOE ε4 allele and cardiovascular disease may be at greater risk for cognitive decline than those without such factors, 24,25 although high levels of atherosclerosis have been linked with increased cognitive decline independent of APOE genotype. 26 Thus, genetic and vascular risk factors may work in synergy to bring about the neuropathological changes that lead to cognitive decline.…”