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The Relationship between Hypoxia Related Factors and Cognitive Impairment

Author: ZouYan
Tutor: LvYang
School: Chongqing Medical University
Course: Geriatrics
Keywords: vascular risk factors hypertension coronary heart disease cerebrovascular disease mild cognitive impairmentHypoxia up-regulated mitochondrial movement regulator Alzheimer’s disease APP/PS1double transgenic mouse mitochondria
CLC: R749.2
Type: Master's thesis
Year: 2013
Downloads: 43
Quote: 0
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Abstract


Part one: The relationship between vascular risk factorsand mild cognitive impairmentBackground/Aims: Increasing evidence has demonstrated thatvascular risk factors (VRFs) contribute to cognitive impairment in the agedpopulation. Prevention and administration of VRFs can be a vital strategyfor delaying the onset and the progression of cognitive impairment. Theaim of the present study was to determine the impact of VRFs on cognitivefunction of the aged from Chongqing, Southwest China. Methods: A totalof597subjects (≥60years) from hospital and community population wereenrolled in the cross-sectional study. Cognitive function was assessed withMini-Mental State Examination (MMSE) and Clinical Dementia Rating(CDR). Hypertension, coronary heart disease (CHD) and cerebrovasculardisease (CVD) were screened. Blood pressure (SBP, DBP) and blood lipid(TG, TC, LDL, HDL) from all subjects were measured. Logistic regressionanalysis was used to look for dominating VRFs impacting the progression of MCI. Then we investigated the relationship between varieties of vasculardiseases and MCI. Results:457subjects (76.5%) showed normal cognitivefunction (NC) and140subjects (23.5%) showed mild cognitive impairment(MCI). After adjusting for age，sex and education, logistic regressionanalysis demonstrated that hypertension, CVD, SBP, DBP, TC, HDL andLDL were independently associated with MCI; however, CHD and TGwere not associated with MCI. Importantly, vascular diseases significantlycontributed to cognitive impairment compared with no vascular disease(p<0.05); however, there were no significant differences among varieties ofvascular diseases (p>0.05). Conclusion: VRFs including hypertension,CVD, SBP, DBP, TC, HDL and LDL are independent risk factors of MCI.Higher SBP and lower DBP, higher LDL, TC and lower HDL contribute tothe risk of MCI. However, varieties of vascular diseases were notassociated with the risk degree of MCI. Part two: The relationship between HUMMR andAlzheimer’s diseaseBackground/Aims: It has been demonstrated that mitochondrialdysfunction is associated with Alzheimer’s disease (AD); meanwhile,hypoxia up-regulated mitochondrial movement regulator (HUMMR) playsan important role on regulating mitochondrial function. The present studyaimed to confirm the association between HUMMR and mitochondrialfunction in AD. Methods: We detected the expression of HUMMR intranscriptional and translational levels in the cortex and hippocampus ofAPP/PS1double transgenic mice using real time quantitative RT-PCR andwestern blotting. Age-and gender-matched wild-type (WT) littermates (12months, six male and four female) were used as controls. Mitochondrialmorphology was observed in the hippocampus and cortex of APP/PS1double transgenic mice using transmission electron microscopy. Results:Damages of mitochondrial morphology in the hippocampus and cortex ofAPP/PS1double transgenic mice were found, including swelling andcavitations. Our analysis showed that the expression of HUMMR had nostatistical differences between APP/PS1double transgenic mice and WTlittermates (P>0.05). These results showed that there was no associationbetween HUMMR and mitochondrial dysfunction in APP/PS1transgenic mice. Conclusion: These results indicate that HUMMR may not play a keyrole on mitochondrial dysfunction in the APP/PS1double transgenic mouseof AD.

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