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      Lipoprotein-associated Phospholipase A2 Is Associated with Risk of Mild Cognitive Impairment in Chinese Patients with Type 2 Diabetes

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          Abstract

          Type 2 diabetes mellitus (T2DM) is a low-grade chronic inflammatory diseases, which have been implicated in the pathogenesis of cognitive decline. We aim to evaluate associations between inflammatory markers and the risk of mild cognitive impairment (MCI) in T2DM. This study of 140 diabetic patients involved 71 with MCI and 69 controls. Clinical parameters, neuropsychological tests, high sensitivity C reactive protein (hsCRP), interleukin-6 (IL-6), lipoprotein-associated Phospholipase A2 (Lp-PLA2) mass and activity were measured. The results showed significantly higher plasma hsCRP, IL-6, Lp-PLA2 mass and activity in MCI group compared to controls. In T2DM with MCI, the Montreal Cognitive Assessment (MoCA) score was positively correlated with education level and high-density lipoprotein cholesterol (HDL-c), but inversely correlated with age, glycosylated hemoglobin, intima-media thickness (IMT), hsCRP, IL-6, and Lp-PLA2 mass and activity. Correlation analysis showed that both plasma Lp-PLA2 mass and activity were positively correlated with total cholesterol, low-density lipoprotein cholesterol, and IMT but negatively associated with MoCA score. Multivariable logistic regression analysis indicated higher hsCRP, Lp-PLA2 mass, Lp-PLA2 activity, and lower HDL-c to be independent risk factors increasing the possibility of MCI in T2DM. In conclusion, plasma Lp-PLA2 and hsCRP were found to be associated with the risk of MCI among T2DM patients.

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          Brain infarction and the clinical expression of Alzheimer disease. The Nun Study.

          To determine the relationship of brain infarction to the clinical expression of Alzheimer disease (AD). Cognitive function and the prevalence of dementia were determined for participants in the Nun Study who later died. At autopsy, lacunar and larger brain infarcts were identified, and senile plaques and neurofibrillary tangles in the neocortex were quantitated. Participants with abundant senile plaques and some neurofibrillary tangles in the neocortex were classified as having met the neuropathologic criteria for AD. Convents in the Midwestern, Eastern, and Southern United States. A total of 102 college-educated women aged 76 to 100 years. Cognitive function assessed by standard tests and dementia and AD assessed by clinical and neuropathologic criteria. Among 61 participants who met the neuropathologic criteria for AD, those with brain infarcts had poorer cognitive function and a higher prevalence of dementia than those without infarcts. Participants with lacunar infarcts in the basal ganglia, thalamus, or deep white matter had an especially high prevalence of dementia, compared with those without infarcts (the odds ratio [OR] for dementia was 20.7, 95% confidence interval [95% CI], 1.5-288.0). Fewer neuropathologic lesions of AD appeared to result in dementia in those with lacunar infarcts in the basal ganglia, thalamus, or deep white matter than in those without infarcts. In contrast, among 41 participants who did not meet the neuropathologic criteria for AD, brain infarcts were only weakly associated with poor cognitive function and dementia. Among all 102 participants, atherosclerosis of the circle of Willis was strongly associated with lacunar and large brain infarcts. These findings suggest that cerebrovascular disease may play an important role in determining the presence and severity of the clinical symptoms of AD.
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            Mild cognitive impairment (MCI) in medical practice: a critical review of the concept and new diagnostic procedure. Report of the MCI Working Group of the European Consortium on Alzheimer's Disease.

            Mild cognitive impairment (MCI) was proposed as a nosological entity referring to elderly people with mild cognitive deficit but no dementia. MCI is a heterogeneous clinical entity with multiple sources of heterogeneity. The concept of MCI was reviewed and a diagnostic procedure with three different stages was proposed by the European Consortium on Alzheimer's Disease Working Group on MCI. Firstly, MCI should correspond to cognitive complaints coming from the patients or their families; the reporting of a relative decline in cognitive functioning during the past year by a patient or informant; cognitive disorders as evidenced by clinical evaluation; absence of major repercussions on daily life; and absence of dementia. These criteria, similar to those defined during an international workshop in Stockholm, make it possible to identify an MCI syndrome, which is the first stage of the diagnostic procedure. Secondly, subtypes of MCI had to be recognised. Finally, the aetiopathogenic subtype could be identified. Identifying patients at a high risk for progression to dementia and establishing more specific and adapted therapeutic strategies at an early stage, together with more structured overall management, is made possible by the diagnostic procedure proposed.
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              Early inflammation and dementia: a 25-year follow-up of the Honolulu-Asia Aging Study.

              Inflammatory responses are associated with cardiovascular disease and may be associated with dementing disease. We evaluated the long-term prospective association between dementia and high-sensitivity C-reactive protein, a nonspecific marker of inflammation. Data are from the cohort of Japanese American men who were seen in the second examination of the Honolulu Heart Program (1968-1970) and subsequently were reexamined 25 years later for dementia in the Honolulu-Asia Aging Study (1991-1996). In a random subsample of 1,050 Honolulu-Asia Aging Study cases and noncases, high-sensitivity C-reactive protein concentrations were measured from serum taken at the second examination; dementia was assessed in a clinical examination that included neuroimaging and neuropsychological testing and was evaluated using international criteria. Compared with men in the lowest quartile (<0.34mg/L) of high-sensitivity C-reactive protein, men in the upper three quartiles had a 3-fold significantly increased risk for all dementias combined, Alzheimer's disease, and vascular dementia. For vascular dementia, the risk increased with increasing quartile. These relations were independent of cardiovascular risk factors and disease. These data support the view that inflammatory markers may reflect not only peripheral disease, but also cerebral disease mechanisms related to dementia, and that these processes are measurable long before clinical symptoms appear.
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                Author and article information

                Contributors
                gyjwsh@163.com
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                26 September 2017
                26 September 2017
                2017
                : 7
                : 12311
                Affiliations
                [1 ]GRID grid.452290.8, Department of Endocrinology, , The Affiliated ZhongDa Hospital of Southeast University, ; Nanjing, China
                [2 ]ISNI 0000 0004 1761 0489, GRID grid.263826.b, Medical school of Southeast University, ; Nanjing, China
                [3 ]GRID grid.470060.5, Department of Endocrinology, , Yixing People’s Hospital, ; Yixing, China
                [4 ]Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
                [5 ]GRID grid.440298.3, Department of Endocrinology, , Wuxi No.2 People’s Hospital, ; Wuxi, China
                Article
                12515
                10.1038/s41598-017-12515-z
                5615059
                28951620
                a4e00d02-d387-43b0-b904-3b58258874b4
                © The Author(s) 2017

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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                : 5 September 2016
                : 12 September 2017
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