Association of the LRP1 gene and cognitive performance with amnestic mild cognitive impairment in elderly Chinese

ABSTRACTBackground: The genetic region coding for low-density lipoprotein receptor-related protein1 (LRP1) is considered an intriguing susceptibility locus for Alzheimer's disease (AD). Amnestic mild cognitive impairment (aMCI) is characterized by episodic memory impairment and represents the prodromal stage of AD. Our aim in this study is to investigate the relationship between LRP1 genetic variation and aMCI, and the influence of LRP1 on cognitive performance.Methods: We performed a case-control association study analyzing five polymorphisms in LRP1 gene by TaqMan Assays-on-Demand SNP Genotyping. All samples were derived from Chinese subjects (109 cases, 104 healthy controls) and assessed using multi-dimension neuropsychological instruments.Results: We identified haplotypes within the region containing the LRP1 gene. Of these, haplotype TAA (T: rs1800194; A: rs11837145; A: rs10876967) was significantly associated with aMCI, being over-represented in aMCI versus healthy controls. Haplotype TAA was associated with poor performance on episodic memory in all subjects.Conclusions: This study confirms the association between genetic variants in LRP1 and aMCI. Moreover, we have identified a relationship between LRP1 genetic variation and specific aspects of neurocognitive function. Our convergent results suggest that LRP1 plays an important role in cognitive function and possibly in the pathogenesis of aMCI.

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Joint effects of gray matter atrophy and altered functional connectivity on cognitive deficits in amnestic mild cognitive impairment patients

Psychological Medicine ◽

10.1017/s0033291714002876 ◽

2014 ◽

Vol 45 (9) ◽

pp. 1799-1810 ◽

Cited By ~ 14

Author(s):

C. Xie ◽

F. Bai ◽

B. Yuan ◽

H. Yu ◽

Y. Shi ◽

...

Keyword(s):

Regression Analysis ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Functional Connectivity ◽

Episodic Memory ◽

Cognitive Performance ◽

Gray Matter ◽

Cognitive Deficits ◽

Amnestic Mild Cognitive Impairment ◽

Multivariate Linear Regression Analysis

BackgroundGray matter (GM) atrophy and disrupted intrinsic functional connectivity (IFC) are often present in patients with amnestic mild cognitive impairment (aMCI), which shows high risk of developing into Alzheimer's disease. Little is known, however, about the relationship between GM atrophy and altered IFC, and whether they are related to cognitive decline.MethodA total of 30 aMCI and 26 cognitively normal (CN) subjects were recruited for this study. Optimized voxel-based morphometric and resting-state functional connectivity magnetic resonance imaging approaches were performed to measure the GM volumes (GMVs) and atrophy-related IFC, respectively. Multivariate linear regression analysis was used to examine the effects of GM atrophy and IFC on cognitive performance across subjects, after controlling for the effects of age, education, gender and group.ResultsCompared with CN subjects, aMCI subjects showed significantly reduced GMVs and decreased IFC in the frontal-parietal and medial temporal lobe systems. Multivariate regression analysis further demonstrated that the GMVs and decreased IFC simultaneously affected the cognitive function. Specifically, GMVs were positively correlated with cognitive performances, including global cognition and episodic memory, and showed a strong trend in correlation between GMVs and non-episodic memory, whilst IFC was positively correlated with the above three cognitive measures, across all subjects. In addition, significant correlation was found between GMVs and altered IFC strength across all subjects.ConclusionsOur findings demonstrated that GMVs and IFC jointly contribute to cognitive performance, and combining quantitative information about GMVs and the strength of functional connectivity may serve as an indicator of cognitive deficits in non-demented elderly.

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