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The contribution of vascular risk factors in neurodegenerative disorders: from mild cognitive impairment to Alzheimer's disease.

ABSTRACT: 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.

SUBMITTER: Cheng YW

PROVIDER: S-EPMC7401210 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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The contribution of vascular risk factors in neurodegenerative disorders: from mild cognitive impairment to Alzheimer's disease.

Cheng Yu-Wen YW Chiu Ming-Jang MJ Chen Ya-Fang YF Cheng Ting-Wen TW Lai Ya-Mei YM Chen Ta-Fu TF

Alzheimer's research & therapy 20200804 1

<h4>Background</h4>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.<h4>Methods</h4>Two hundred ninety-five newly diagnosed MCI subjects were enrol ...[more]

PMID: 32753051

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Project description:PURPOSE:Evaluate and compare the retinal microvasculature in the superficial capillary plexus (SCP) in Alzheimer's disease (AD), mild cognitive impairment (MCI), and cognitively intact controls using OCT angiography. OCT parameters were also compared. DESIGN:Cross-sectional study. PARTICIPANTS:Seventy eyes from 39 AD participants, 72 eyes from 37 MCI participants, and 254 eyes from 133 control participants were enrolled. METHODS:Participants were imaged using Zeiss Cirrus HD-5000 with AngioPlex (Carl Zeiss Meditec, Dublin, CA) and underwent cognitive evaluation with Mini-Mental State Examination. MAIN OUTCOME MEASURES:Vessel density (VD) and perfusion density (PD) in the SCP within the Early Treatment Diabetic Retinopathy Study 6-mm circle, 3-mm circle, and 3-mm ring were compared between groups. Foveal avascular zone (FAZ) area, central subfield thickness (CST), macular ganglion cell-inner plexiform layer (GC-IPL) thickness, and peripapillary retinal nerve fiber layer (RNFL) thickness were also compared. RESULTS:Alzheimer's participants showed significantly decreased SCP VD and PD in the 3-mm ring (P = 0.001 and P = 0.002, respectively) and 3-mm circle (P = 0.003 and P = 0.004, respectively) and decreased SCP VD in the 6-mm circle (P = 0.047) compared with MCI and significantly decreased SCP VD and PD in the 3-mm ring (P = 0.008 and P = 0.004, respectively) and 3-mm circle (P = 0.015 and P = 0.009, respectively) and SCP PD in the 6-mm circle (P = 0.033) when compared with cognitively intact controls. There was no difference in SCP VD or PD between MCI and controls (P > 0.05). FAZ area and CST did not differ significantly between groups (P > 0.05). Alzheimer's participants showed significantly decreased GC-IPL thickness over the inferior (P = 0.032) and inferonasal (P = 0.025) sectors compared with MCI and significantly decreased GC-IPL thickness over the entire (P = 0.012), superonasal (P = 0.041), inferior (P = 0.004), and inferonasal (P = 0.006) sectors compared to controls. MCI participants showed significantly decreased temporal RNFL thickness (P = 0.04) compared with controls. CONCLUSIONS:Alzheimer's participants showed significantly reduced macular VD, PD, and GC-IPL thickness compared with MCI and controls. Changes in the retinal microvasculature may mirror small vessel cerebrovascular changes in AD.

Dataset Information

The contribution of vascular risk factors in neurodegenerative disorders: from mild cognitive impairment to Alzheimer's disease.

Publications

The contribution of vascular risk factors in neurodegenerative disorders: from mild cognitive impairment to Alzheimer's disease.

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