Clinical chemistry and laboratory medicine: CCLM / FESCC
Apolipoprotein (apo) E is an important circulating and tissue protein involved in cholesterol homeostasis and many other functions. The common polymorphism in the coding region of the gene, four polymorphisms in the promoter region, other additional single nucleotide polymorphisms, as well as several apo E variants have been identified. The common coding polymorphism strongly influences the lipid metabolism and the circulating concentration of apo E itself.
Paraoxonase 1 (PON1) has been suggested as a plausible candidate gene for human longevity due to its modulation of cardiovascular disease risk, by preventing oxidation of atherogenic low-density lipoprotein. The role of the PON1 192 Q/R polymorphism has been analyzed for association with survival at old age in several populations, albeit with controversial results. To reconcile the conflicting evidence, we performed a large association study with two samples of 2357 Germans and 1025 French, respectively.
It is often claimed that genes affecting health in old age, such as cardiovascular and Alzheimer diseases, are beyond the reach of natural selection. We show in a simulation study based on known genetic (apolipoprotein E) and non-genetic risk factors (gender, diet, smoking, alcohol, exercise) that, because there is a statistical distribution of ages at which these genes exert their influence on morbidity and mortality, the effects of selection are in fact non-negligible.
Apolipoprotein-?4 (APOE-?4) is a major genetic risk factor for cognitive decline, Alzheimer's disease (AD) and early mortality. An accelerated rate of biological aging could contribute to this increased risk. Here, we determined whether APOE-?4 status impacts leukocyte telomere length (TL) and the rate of cellular senescence in healthy mid-life women and, further, whether hormone replacement therapy (HT) modifies this association. Post-menopausal women (N?=?63, Mean age?=?57.7), all HT users for at least one year, were enrolled in a randomized longitudinal study.
Translational Research: The Journal of Laboratory and Clinical Medicine
Alzheimer's disease (AD) is a large and growing public health problem. It is characterized by the accumulation of amyloid ? peptides and abnormally phosphorylated tau proteins that are associated with cognitive decline and dementia. Much has been learned about the genomics of AD from linkage analyses and, more recently, genome-wide association studies. Several but not all aspects of the genomic landscape are involved in amyloid ? metabolism. The moderate concordance of disease among twins suggests other factors, potentially epigenomic factors, are related to AD.
BACKGROUND: Numerous studies have linked dementia to the subsequent deterioration of oral health. Few investigators, however, have examined oral disease as a potential risk factor in the development of dementia. The authors conducted a study to investigate a potential association between a history of oral disease and the development of dementia. METHODS: Longitudinal dental records supplemented data collected from 10 annual cognitive assessments of 144 Milwaukee participants in the Nun Study, a longitudinal study of aging and Alzheimer disease, who were 75 to 98 years old.
CONTEXT: The herbal product Ginkgo biloba is taken frequently with the intention of improving cognitive health in aging. However, evidence from adequately powered clinical trials is lacking regarding its effect on long-term cognitive functioning. OBJECTIVE: To determine whether G. biloba slows the rates of global or domain-specific cognitive decline in older adults.
OBJECTIVES: Both apolipoprotein E (ApoE) ε-4 allele(s) and elevated trait neuroticism, the tendency to experience distress, are associated with cognitive function among older adults. We predicted that neuroticism moderates the association between ApoE and cognitive function and also explored whether other personality dimensions (openness to experience, agreeableness, extraversion, and conscientiousness) affect the association between ApoE status and cognitive function.
The American Journal of Geriatric Psychiatry: Official Journal of the American Association for Geriatric Psychiatry
OBJECTIVES: We tested the hypothesis that neuroticism moderates the association between APOE (apolipoprotein E) genotype and two major outcomes, cognitive function and Alzheimer disease. We also explored whether other personality dimensions (extraversion, openness to experience, agreeableness, and conscientiousness) moderate the associations of APOE with these outcomes. DESIGN: Primary analyses of existing randomized clinical trial data. SAMPLE: Six-hundred two older adults (mean age of 78 years at baseline).