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Genetic risk for neurodegenerative disorders, and its overlap with cognitive ability and physical function.

ABSTRACT: Neurodegenerative disorders are associated with impaired cognitive function and worse physical health outcomes. This study aims to test whether polygenic risk for Alzheimer's disease, Amyotrophic Lateral Sclerosis (ALS), or frontotemporal dementia (FTD) is associated with cognitive function and physical health in the UK Biobank, a cohort of healthy individuals. Group-based analyses were then performed to compare the top and bottom 10% for the three neurodegenerative polygenic risk scores; these groups were compared on the cognitive and physical health variables. Higher polygenic risk for AD, ALS, and FTD was associated with lower cognitive performance. Higher polygenic risk for FTD was also associated with increased forced expiratory volume in 1s and peak expiratory flow. A significant group difference was observed on the symbol digit substitution task between individuals with high polygenic risk for FTD and high polygenic risk for ALS. The results suggest some overlap between polygenic risk for neurodegenerative disorders, cognitive function and physical health.

SUBMITTER: Hagenaars SP

PROVIDER: S-EPMC5983413 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Genetic risk for neurodegenerative disorders, and its overlap with cognitive ability and physical function.

Hagenaars Saskia P SP Radaković Ratko R Crockford Christopher C Fawns-Ritchie Chloe C Harris Sarah E SE Gale Catharine R CR Deary Ian J IJ

PloS one 20180601 6

Neurodegenerative disorders are associated with impaired cognitive function and worse physical health outcomes. This study aims to test whether polygenic risk for Alzheimer's disease, Amyotrophic Lateral Sclerosis (ALS), or frontotemporal dementia (FTD) is associated with cognitive function and physical health in the UK Biobank, a cohort of healthy individuals. Group-based analyses were then performed to compare the top and bottom 10% for the three neurodegenerative polygenic risk scores; these ...[more]

PMID: 29856801

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Project description:BACKGROUND:Optimization of vascular risk factor control is emerging as an alternative approach to improve cognitive outcomes in Alzheimer's disease, although its efficacy is still under debate. We aimed to investigate the contribution of vascular risk factors on Alzheimer's biomarkers and conversion rate to dementia in subjects with mild cognitive impairment (MCI) with low cerebral small vessel disease burden. METHODS:Two hundred ninety-five newly diagnosed MCI subjects were enrolled from March 2005 to May 2017 for a cross-sectional assessment of vascular risk factors and Alzheimer's plasma and imaging biomarkers, followed by a cognitive outcome assessment 24?months after enrollment. The association between vascular risk factors and Alzheimer's biomarkers were tested using multivariable linear regression models adjusted with age, gender, education, and APOE ?4 allele. The association between vascular risk factors and conversion to dementia was tested using multivariable logistic regression models adjusted with age, gender, education, and baseline Mini-Mental State Examination (MMSE) score. RESULTS:At baseline, higher low-density lipoprotein (LDL) cholesterol level was associated with more advanced plasma biomarkers, including A?42/A?40 ratio (P?=?0.012) and tau level (P?=?0.001). A history of hypertension was associated with more advanced white matter hyperintensity (P?=?0.011), while statin therapy for dyslipidemia was associated with less advanced white matter hyperintensity (P?=?0.002). At 24?months, individual vascular risk factor was not significantly associated with cognitive outcome. By contrast, statin therapy for dyslipidemia was associated with reduced conversion to dementia (adjusted OR?=?0.191, 95% CI?=?0.062~0.586, P?=?0.004). CONCLUSIONS:For MCI subjects, dyslipidemia may contribute to AD-related neurodegeneration while hypertension may contribute to vascular pathology. The association between statin therapy for dyslipidemia and reduced conversion to dementia supports further interventional study to evaluate the potential beneficial effect of statin in MCI subjects.

Project description:Cognitive impairment has been described in elderly subjects with high normal concentrations of serum uric acid. However, it remains unclear if gout confers an increased poorer cognition than those in individuals with asymptomatic hyperuricemia. The present study aimed at evaluating cognitive function in patients suffering from gout in an elderly male population, and further investigating the genetic contributions to the risk of cognitive function.This study examined the cognitive function as assessed by Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) in 205 male gout patients and 204 controls. The genetic basis of these cognitive measures was evaluated by genome-wide association study (GWAS) data in 102 male gout patients. Furthermore, 7 loci associated with cognition in GWAS were studied for correlation with gout in 1179 male gout patients and 1848 healthy male controls.Compared with controls, gout patients had significantly lower MoCA scores [22.78 ± 3.01 vs 23.42 ± 2.95, P = .023, adjusted by age, body mass index (BMI), education, and emotional disorder]. GWAS revealed 7 single-nucleotide polymorphisms (SNPs) associations with MoCA test at a level of conventional genome-wide significance (P < 9.6 × 10). The most significant association was observed between rs12895072 and rs12434554 within the KTN1 gene (Padjusted = 4.2 × 10, Padjusted = 4.7 × 10) at 14q22. The next best signal was in RELN gene (rs155333, Padjusted = 1.3 × 10) at 7q22, while the other variants at rs17458357 (Padjusted = 3.98 × 10), rs2572683 (Padjusted = 8.9 × 10), rs12555895 (Padjusted = 2.6 × 10), and rs3764030 (Padjusted = 9.4 × 10) were also statistically significant. The 7 SNPs were not associated with gout in further analysis (all P > .05).Elderly male subjects with gout exhibit accelerated decline in cognition performance. Several neurodegenerative disorders risk loci were identified for genetic contributors to cognitive performance in our Chinese elderly male gout population. Larger prospective studies of the cognitive performance and genetic analysis in gout subjects are recommended.

Dataset Information

Genetic risk for neurodegenerative disorders, and its overlap with cognitive ability and physical function.

Publications

Genetic risk for neurodegenerative disorders, and its overlap with cognitive ability and physical function.

Similar Datasets

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