Vascular Risk Factors and Cardiovascular Outcomes in the Alzheimer's Disease Neuroimaging Initiative
Vascular disease and medical factors are associated with cognitive decline and cardiovascular events. We examined the association between vascular risk factors and events in the Alzheimer's Disease Neuroimaging Initiative cohort.
The association between vascular risk factors and cardiovascular events in a cohort of 810 participants, including 400 with mild cognitive impairment, 184 with Alzheimer's, and 226 controls was investigated using a longitudinal hazard model.
There were 31 events including 11 strokes, 7 myocardial infarctions, 5 revascularizations, and 8 deaths during an average follow-up of 31 months. Longitudinal cardiovascular event rates were low and similar between diagnostic groups.
All baseline vascular risk factors that were expected to be associated with longitudinal cardiovascular events were, or were trending toward, associating with cardiovascular events except atrial fibrillation, depression, and apolipoprotein E genotype. Despite differences in baseline vascular risk factors, longitudinal cardiovascular event rates were similar between diagnostic groups.
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ABSTRACT: beta-Amyloid (A beta) is deposited in neurons and vascular cells of the brain and is characterized as a pathologic feature of Alzheimer's disease (AD). Recently studies have reported that there is an association between cardiovascular risk factors and AD, however the mechanism of this association is still uncertain. In this study we observed A beta had an effect on cardiovascular cells. We represent as a major discovery that A beta(25-35) had toxicity on isolated rat cardiac myocytes by impacting the cytoskeleton assembly and causing ER stress, ultimately contributing to the apoptosis of the myocytes. Importantly, the activation of ER stress and subsequent cellular dysfunction and apoptosis by A beta(25-35) was regulated by the MAPK pathway, which could be prevented by inhibition of p38 via pharmacological inhibitors. It was noteworthy that A beta(25-35) played a critical role in cardiac myocytes, suggesting that Alzheimer's disease (AD) had a relation with the heart and understanding of these associations in future will help search for effective treatment strategies.
Molecules 08/2014; 19(8):12242-12257. DOI:10.3390/molecules190812242 · 2.42 Impact Factor
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ABSTRACT: The Alzheimer's Disease Neuroimaging Initiative (ADNI) is an ongoing, longitudinal, multicenter study designed to develop clinical, imaging, genetic, and biochemical biomarkers for the early detection and tracking of Alzheimer's disease (AD). The initial study, ADNI-1, enrolled 400 subjects with early mild cognitive impairment (MCI), 200 with early AD, and 200 cognitively normal elderly controls. ADNI-1 was extended by a 2-year Grand Opportunities grant in 2009 and by a competitive renewal, ADNI-2, which enrolled an additional 550 participants and will run until 2015. This article reviews all papers published since the inception of the initiative and summarizes the results to the end of 2013. The major accomplishments of ADNI have been as follows: (1) the development of standardized methods for clinical tests, magnetic resonance imaging (MRI), positron emission tomography (PET), and cerebrospinal fluid (CSF) biomarkers in a multicenter setting; (2) elucidation of the patterns and rates of change of imaging and CSF biomarker measurements in control subjects, MCI patients, and AD patients. CSF biomarkers are largely consistent with disease trajectories predicted by β-amyloid cascade (Hardy, J Alzheimer's Dis 2006;9(Suppl 3):151-3) and tau-mediated neurodegeneration hypotheses for AD, whereas brain atrophy and hypometabolism levels show predicted patterns but exhibit differing rates of change depending on region and disease severity; (3) the assessment of alternative methods of diagnostic categorization. Currently, the best classifiers select and combine optimum features from multiple modalities, including MRI, [18F]-fluorodeoxyglucose-PET, amyloid PET, CSF biomarkers, and clinical tests; (4) the development of blood biomarkers for AD as potentially noninvasive and low-cost alternatives to CSF biomarkers for AD diagnosis and the assessment of α-syn as an additional biomarker; (5) the development of methods for the early detection of AD. CSF biomarkers, β-amyloid 42 and tau, as well as amyloid PET may reflect the earliest steps in AD pathology in mildly symptomatic or even nonsymptomatic subjects and are leading candidates for the detection of AD in its preclinical stages; (6) the improvement of clinical trial efficiency through the identification of subjects most likely to undergo imminent future clinical decline and the use of more sensitive outcome measures to reduce sample sizes. Multimodal methods incorporating APOE status and longitudinal MRI proved most highly predictive of future decline. Refinements of clinical tests used as outcome measures such as clinical dementia rating-sum of boxes further reduced sample sizes; (7) the pioneering of genome-wide association studies that leverage quantitative imaging and biomarker phenotypes, including longitudinal data, to confirm recently identified loci, CR1, CLU, and PICALM and to identify novel AD risk loci; (8) worldwide impact through the establishment of ADNI-like programs in Japan, Australia, Argentina, Taiwan, China, Korea, Europe, and Italy; (9) understanding the biology and pathobiology of normal aging, MCI, and AD through integration of ADNI biomarker and clinical data to stimulate research that will resolve controversies about competing hypotheses on the etiopathogenesis of AD, thereby advancing efforts to find disease-modifying drugs for AD; and (10) the establishment of infrastructure to allow sharing of all raw and processed data without embargo to interested scientific investigators throughout the world.
Alzheimer's & dementia: the journal of the Alzheimer's Association 06/2015; 11(6):e1-e120. DOI:10.1016/j.jalz.2014.11.001 · 12.41 Impact Factor
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