دانلود مقاله ISI انگلیسی شماره 30863
عنوان فارسی مقاله

تاثیر ژن بیماری آلزایمر بر زوال شناختی: مطالعه گروهی

کد مقاله سال انتشار مقاله انگلیسی ترجمه فارسی تعداد کلمات
30863 2014 6 صفحه PDF سفارش دهید 4580 کلمه
خرید مقاله
پس از پرداخت، فوراً می توانید مقاله را دانلود فرمایید.
عنوان انگلیسی
Influence of Alzheimer's disease genes on cognitive decline: the Guangzhou Biobank Cohort Study
منبع

Publisher : Elsevier - Science Direct (الزویر - ساینس دایرکت)

Journal : Neurobiology of Aging, Volume 35, Issue 10, October 2014, Pages 2422.e3–2422.e8

کلمات کلیدی
- ' - زوال شناختی - بیماری آلزایمر - اثر مشترک
پیش نمایش مقاله
پیش نمایش مقاله تاثیر ژن بیماری آلزایمر بر زوال شناختی: مطالعه گروهی

چکیده انگلیسی

Cognitive decline is a reduction in cognitive ability usually associated with aging, and those with more extreme cognitive decline either have or are at risk of progressing to mild cognitive impairment and dementia including Alzheimer's disease (AD). We hypothesized that genetic variants predisposing to AD should be predictive of cognitive decline in elderly individuals. We selected 1325 subjects with extreme cognitive decline and 1083 well-matched control subjects from the Guangzhou Biobank Cohort Study in which more than 30,000 southern Chinese older people have been recruited and followed up. Thirty single-nucleotide polymorphisms in 29 AD-associated genes were genotyped. No statistically significant allelic associations with cognitive decline were found by individual variant analysis. At the level of genotypic association, we confirmed that the APOE ε4 homozygote significantly accelerated cognitive decline and found that carriers of the ACE rs1800764_C allele were more likely to show cognitive decline than noncarriers, particularly in those without college education. However, these effects do not survive after multiple testing corrections, and together they only explain 1.7% of the phenotypic variance in cognitive score change. This study suggests that AD risk variants and/or genes are not powerful predictors of cognitive decline in our Chinese sample.

مقدمه انگلیسی

Clinical dementia is becoming more prevalent because of changing demographics, particularly in developing countries like China with a rapidly aging population (Ferri et al., 2005). For those subjects with a clinical diagnosis of dementia in Hong Kong, Alzheimer's disease (AD) was the most common likely cause (73.5%), whereas 22.4% had vascular dementia, and 3.9% had dementia with symptoms of Parkinson's disease (Lam et al., 2008). AD usually begins with subtle and poorly recognized failure of memory and slowly becomes more severe and eventually incapacitating. Generally reflected by increasing difficulties with memory or speed of information processing, cognitive decline deterioration in cognitive function is usually associated with aging. The appearance of significant cognitive decline predicts the progression to mild cognitive impairment and then dementia (including AD), if not already at one of these stages (Cherbuin et al., 2009 and Dik et al., 2000). Because cognitive decline is often a prodromal symptom of AD, understanding of AD would uncover potential reasons for cognitive decline or vice versa (Daviglus et al., 2010). Though twin studies showed cognition performance or cognitive decline is highly heritable (Lee et al., 2010), even the APOE locus is not consistently associated with cognitive decline across different samples or populations ( Devore et al., 2009, Dik et al., 2000 and Lee et al., 2003). Therefore, more genes are expected to be found to explain the phenotypic variance of this complex trait, although this will require very large studies. Genetic risk factors from genome wide association studies (GWAS) as well as large systematic reviews for AD can serve to select candidate genes for cognitive decline ( Bertram et al., 2007 and Sleegers et al., 2010). Genetic variants from CLU, CR1, PICALM, and BIN1 genes have been repeatedly reported to be associated with AD ( Bertram et al., 2008, Harold et al., 2009, Hu et al., 2011b, Kamboh et al., 2012 and Lambert et al., 2009), and some of them are reported to be also involved in the trajectories of cognitive function ( Sweet et al., 2012). These newly found AD genes are clustered in biological pathways (amyloid pathway, lipid metabolism pathway, chaperone, and chronic inflammatory pathway) which play an important role in the development of late-onset AD ( Sleegers et al., 2010) and probably also in disease progression from cognitive decline. Most studies investigating the effect of AD genes on cognitive decline or performance have been conducted in Caucasian populations ( Barral et al., 2012, Hu et al., 2011a and Sweet et al., 2012); therefore, there is a need to evaluate AD genes for cognitive decline in Asian subjects. Initiated in 2003, the Guangzhou Biobank Cohort Study (GBCS) has recruited more than 30,000 southern Chinese older people and collected multidimensional data, including demographic, epidemiologic, and biochemical variables, with both an initial and follow-up assessment separated by around 3 years (Jiang et al., 2006). Several cross-sectional studies have been done for cognitive measurement and environmental factors (Au Yeung et al., 2010, Heys et al., 2010 and Xu et al., 2011). Here, we aimed to examine the impact of 30 known genetic risk variants (within 29 genes) for AD on cognitive decline. Meanwhile, potential genetic risk factors were co-investigated with risk factors (sex, age, education level, and neurologic disease status) previously demonstrated to be associated with decline (Xu et al., 2014) to evaluate their independent effects and genetic by environment interactions.

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