"The ε2-allele also seems to play a protective role against CVD (Bennet et al., 2007; Gerdes et al., 2000; Kolovou et al., 2002), though the evidence is probably weaker than for negative effect of the ε4-allele (Drenos and Kirkwood, 2010). In addition, previous large population-based longitudinal studies, i.e., the Rotterdam study (Slooter et al., 2001) and the Danish 1905 birth cohort (Lindahl-Jacobsen et al., 2013) reported no favorable effect of ε2-allele on mortality in the elderly, despite protecting against cognitive decline in the oldest old (≥93 years) (Lindahl-Jacobsen et al., 2013). Besides the rationale for postulating the ApoE as a candidate to influence EL, a major strength of our study was the clear definition we used for the criterion of EL (with all cases being centenarians). "
[Show abstract][Hide abstract] ABSTRACT: The ApoE gene is associated with the risk of Alzheimer or cardiovascular disease but its influence on exceptional longevity (EL) is uncertain. Our primary purpose was to determine, using a case-control design, if the ApoE gene is associated with EL. We compared ApoE allele/genotype frequencies among the following cohorts: cases (centenarians, most with 1 + major disease condition; n = 163, 100-111y) and healthy controls (n = 1039, 20-85y) from Spain; disease-free cases (centenarians; n = 79, 100-104y) and healthy controls (n = 597, age 27-81y) from Italy; and cases (centenarians and semi-supercentenarians, most with 1 + major disease condition; n = 729, 100-116) and healthy controls (n = 498, 23-59y) from Japan. Our main findings were two-fold. First, the ε4-allele was negatively associated with EL in the three cohorts, with the following odds ratio (OR) values (adjusted by sex) been found: 0.55 (95% confidence interval (CI): 0.33, 0.94), P = 0.030 (Spain); 0.41 (95%CI: 0.18, 0.99), P = 0.05 (Italy); and 0.35 (95%CI: 0.26, 0.57), P < 0.001 (Japan). Second, although no association was found in the Spanish cohort (OR = 1.42 (95%CI: 0.89, 2.26), P = 0.145), the ε2-allele was positively associated with EL in the Italian (OR = 2.14 (95%CI: 1.18, 3.45), P = 0.01) and Japanese subjects (OR = 1.81 (95%CI: 1.25, 2.63), P = 0.002). Notwithstanding the limitations of case-control designs, our data suggest that the ApoE might be a candidate to influence EL. The ε4-allele appears to decrease the likelihood of reaching EL among individuals of different ethnic/geographic origins. An additional, novel finding of our study was that the ε2-allele might favor EL, at least in the Italian and Japanese cohorts.
"was observed for those subjects with the ε2 allele (Rosvall et al. 2009), although this protective effect was not found by other studies (Koivisto et al. 2000; Slooter et al. 2001; Fillenbaum et al. 2003). At present, it seems that significant differences in APOE-related mortality may be suggested, but the different study design and follow-up periods of these population-based studies may explain the different results (Panza et al. 2009 "
[Show abstract][Hide abstract] ABSTRACT: The most common apolipoprotein E (APOE) allelic variation is implicated in many age-related diseases and human longevity with controversial findings. We investigated the effect of APOE gene polymorphism on all-cause mortality in elderly patients taking into consideration the functional disability, cognitive impairment, malnutrition, and the occurrence of common age-related diseases. APOE genotypes were determined in 2,124 geriatric hospitalized patients (46.5% men and 53.5% women; mean age, 78.2 +/- 7.1 years; range, 65-100 years). At hospital admission, all patients underwent a comprehensive geriatric assessment to evaluate functional disability, cognitive status, nutritional status, and comorbidity. The main and secondary diagnoses at hospital discharge were also recorded. Mortality status was evaluated in all patients after a maximum follow-up of 5 years (range, from 1.26 to 5.23 years; median, 2.86 years). During the study period, 671 patients died (32.0%). At hospital admission, these patients showed a significant higher prevalence of cardiovascular diseases (56.3% vs 53.4%; p = 0.007), neoplasias (32.3% vs 13.7%; p < 0.001), and lower prevalence of neurodegenerative diseases (17.7% vs 20.7%; p < 0.001) than survived patients. Moreover, they also showed an higher prevalence of disability (52.0% vs 25.6%; p < 0.001), cognitive impairment (31.0% vs 18.8%; p < 0.001), and malnutrition (74.0% vs 46.1%; p < 0.001) than survived patients. In the overall study population, the APOE epsilon2 allele was significantly associated to neurodegenerative diseases (odds ratio = 0.59; 95% confidence interval (CI), 0.37-0.94). No significant association between the APOE polymorphism and disability, malnutrition, co-morbidity status, and with all-cause mortality was observed. In patients with cardiovascular diseases, however, a decreased risk of all-cause mortality was found in the epsilon2 allele carriers (hazard ratio = 0.56; 95% CI, 0.36-0.88). In this population, APOE allele variants might play a role on cardiovascular disease-related mortality.
Age 09/2010; 32(3):411-20. DOI:10.1007/s11357-010-9144-x · 3.45 Impact Factor
"Six reports have provided longitudinal data concerning APOE and mortality, with inconsistent findings. Three studies could not identify an association (Koivisto et al., 2000; Frisoni et al., 2001; Slooter et al., 2001), and three studies found an association between APOE and mortality (Corder et al., 1996; Tilvis et al., 1998; Hayden et al., 2005). The inconsistent results may be explained by limited sample-sizes, different lengths of follow-up and different age distributions of the studied samples . "
[Show abstract][Hide abstract] ABSTRACT: Allele-frequency comparisons between younger and older populations suggest an effect of apolipoprotein E gene (APOE) on mortality, not consistently confirmed by longitudinal data. Our aim was to assess the effect of APOE on survival taking into account the possible contribution of Alzheimer's disease, other dementias, ischemic heart- and cerebrovascular disease (IHCD). In a community-based longitudinal study, the Kungsholmen Project, 75+ year-old individuals (n=1094) were examined, and followed for 18 years. An increased mortality-risk of 22% in those with the epsilon4 allele was detected; whereas a 28% decreased mortality-risk was detected in those with the epsilon2 allele compared to those with the epsilon3epsilon3 genotype. IHCD adjustment did not change the mortality-risk in those with the epsilon4 allele or the epsilon2 allele. Dementia accounted for the majority of the increased mortality-risk associated with the epsilon4 allele, but the protective effect of the epsilon2 allele remained. Both effects of the epsilon4 allele and the epsilon2 allele were strongly modified by gender. A 49% elevated risk for death in men was related to the epsilon4 allele, and a 36% decreased mortality-risk was found in women with the epsilon2 allele. These findings suggest different roles for the APOE alleles in survival by gender in old age.
Neurobiology of aging 02/2008; 30(10):1545-51. DOI:10.1016/j.neurobiolaging.2007.12.003 · 5.01 Impact Factor
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