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Cerebrovascular medin is associated with Alzheimer's disease and vascular dementia.

ABSTRACT: Introduction:Medin, an aging-associated amyloidogenic protein, induces cerebrovascular dysfunction and inflammation. We investigated the relationship between cerebrovascular medin and Alzheimer's disease (AD) and vascular dementia (VaD). Methods:Cerebral arteriole medin was quantified from 91 brain donors with no dementia (ND), AD, VaD, or combined AD and VaD. Correlation analyses evaluated the relationship between arteriole medin, and plaques, tangles, or white matter lesions (WML). Receiver operating characteristic and regression analyses assessed whether medin is predictive of AD or VaD versus other cerebrovascular pathologies (circle of Willis [CoW] atherosclerosis and cerebral amyloid angiopathy [CAA]). Results:Arteriole medin was higher in those with AD, VaD, or combined AD/VaD versus ND (P < .05), and correlated with tangle, plaque, and WML, but not CAA or CoW atherosclerosis. Among cerebrovascular pathologies, medin was the strongest predictor of AD diagnosis, whereas CoW atherosclerosis and arteriole medin were predictors of VaD. Discussion:Cerebral arteriole medin is associated with and could be a potential novel risk factor or biomarker for AD and VaD.

SUBMITTER: Migrino RQ

PROVIDER: S-EPMC7447901 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Cerebrovascular medin is associated with Alzheimer's disease and vascular dementia.

Migrino Raymond Q RQ Karamanova Nina N Truran Seth S Serrano Geidy E GE Davies Hannah A HA Madine Jillian J Beach Thomas G TG

Alzheimer's & dementia (Amsterdam, Netherlands) 20200825 1

<h4>Introduction</h4>Medin, an aging-associated amyloidogenic protein, induces cerebrovascular dysfunction and inflammation. We investigated the relationship between cerebrovascular medin and Alzheimer's disease (AD) and vascular dementia (VaD).<h4>Methods</h4>Cerebral arteriole medin was quantified from 91 brain donors with no dementia (ND), AD, VaD, or combined AD and VaD. Correlation analyses evaluated the relationship between arteriole medin, and plaques, tangles, or white matter lesions (WM ...[more]

PMID: 32875054

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Project description:Vascular dementia (VaD) accounts for 15-20% of all dementia cases. It is a syndrome of acquired cognitive impairment with a complex pathophysiological basis. A novel herbal formulation (Sailuotong; SLT) consisting of Panax ginseng C.A Mey, Ginkgo biloba L and Crocus sativus L extracts was developed to treat VaD. Preclinical animal studies found significant improvements in memory and in pathogenic biochemical parameters. Appropriate safety of SLT was shown in acute and chronic toxicity studies, and early clinical trials of SLT demonstrated enhancements in cognition in VaD patients. A fully powered study with a long intervention period is needed to confirm the efficacy and safety of this novel intervention. A rigorous phase III clinical trial was developed with the aim of recruiting 238 patients diagnosed with mild to moderate probable VaD, or VaD mixed with Alzheimer's disease (where cerebrovascular disease is the clinical dominant contributor to dementia, abbreviated as CVD+AD). Using a permuted block strategy, participants will be randomly allocated to receive SLT (120 mg bd) or placebo capsules for an intervention period of 52 weeks and will be followed-up for an additional 13 weeks. The primary outcome measures are the Vascular Dementia Assessment Scale-cognitive subscale and Alzheimer's Disease Cooperative Study-Activities of Daily Living scale. Secondary outcome measures include the Clinician's Interview Based Impression of Change-Plus, CLOX, EXIT-25, Neuropsychiatric Inventory-Clinician rating scale, and Dementia Quality of Life questionnaire. Safety is assessed through adverse event reports and liver, renal, and coagulation studies. Primary and secondary outcome measures will be compared between treatment and placebo groups, using intention to treat and per protocol analyses. We hypothesise that a 52-week treatment of SLT will be clinically effective and well tolerated in participants with VaD or AD+CVD. This project will provide vital efficacy and safety data for this novel treatment approach to VaD.

Project description:BACKGROUND:Physical activity might reduce the risk of developing dementia. However, it is still unclear whether the protective effect differs depending on the subtype of dementia. We aimed to investigate if midlife physical activity affects the development of vascular dementia (VaD) and Alzheimer's disease (AD) differently in two large study populations with different designs. METHODS:Using a prospective observational design, we studied whether long-distance skiers of the Swedish Vasaloppet (n = 197,685) exhibited reduced incidence of VaD or AD compared to matched individuals from the general population (n = 197,684) during 21 years of follow-up (median 10, interquartile range (IQR) 5-15 years). Next, we studied the association between self-reported physical activity, stated twice 5 years apart, and incident VaD and AD in 20,639 participants in the Swedish population-based Malmo Diet and Cancer Study during 18 years of follow-up (median 15, IQR 14-17 years). Finally, we used a mouse model of AD and studied brain levels of amyloid-β, synaptic proteins, and cognitive function following 6 months of voluntary wheel running. RESULTS:Vasaloppet skiers (median age 36.0 years [IQR 29.0-46.0], 38% women) had lower incidence of all-cause dementia (adjusted hazard ratio (HR) 0.63, 95% CI 0.52-0.75) and VaD (adjusted HR 0.49, 95% CI 0.33-0.73), but not AD, compared to non-skiers. Further, faster skiers exhibited a reduced incidence of VaD (adjusted HR 0.38, 95% CI 0.16-0.95), but not AD or all-cause dementia compared to slower skiers. In the Malmo Diet and Cancer Study (median age 57.5 years [IQR 51.0-63.8], 60% women), higher physical activity was associated with reduced incidence of VaD (adjusted HR 0.65, 95% CI 0.49-0.87), but not AD nor all-cause dementia. These findings were also independent of APOE-ε4 genotype. In AD mice, voluntary running did not improve memory, amyloid-β, or synaptic proteins. CONCLUSIONS:Our results indicate that physical activity in midlife is associated with lower incidence of VaD. Using three different study designs, we found no significant association between physical activity and subsequent development of AD.

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Cerebrovascular medin is associated with Alzheimer's disease and vascular dementia.

Publications

Cerebrovascular medin is associated with Alzheimer's disease and vascular dementia.

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