Association between platelet function and recurrent ischemic vascular events after TIA and minor stroke
.

Platelet activation and aggregation play an important role in the pathological and physiological processes of recurrent ischemic vascular events in stroke patients. The purpose of this study is to determine the association between platelet function measured in the acute period and recurrent ischemic vascular events in patients with transient ischemic attack (TIA) or minor stroke. A total of 417 patients who were within the 24-hour period of clopidogrel-aspirin therapy after onset of a minor stroke or high-risk transient ischemic attack according to the Clopidogrel in High-risk patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial were included in this study. The platelet aggregation ratio was detected using a method of continuous platelet counting; patients underwent CYP2C19 genotyping, and the baseline data were recorded. The patients underwent a 6-month follow-up period during which the recurrent ischemic vascular events were observed. Logistic regression analysis was performed to obtain the risk factors for recurrent ischemic vascular events. The number of patients with recurrent ischemic events who had an arachidonic acid-induced maximum platelet aggregation ratio (MAR-AA) (aspirin 100 mg) (31.85 ± 12.86 vs. 26.71 ± 12.44, p = 0.007) and adenosine diphosphate-induced maximum platelet aggregation ratio (MAR-ADP) after the administration of 75 mg clopidogrel for 12 ± 2 days (65.82 ± 10.72 vs. 53.10 ± 12.98, p < 0.001) was significantly higher compared with the no ischemic vascular event group. Multivariate logistic regression analyses showed that being a carrier of the CYP2C19 loss-of-function (LOF) allele (OR = 2.308, 95% CI: 1.087 ~ 4.901, p = 0.029) as well as the MAR-AA (aspirin 100 mg) (OR = 1.028, 95% CI: 1.006  ~  1.052, p = 0.014) and MAR-ADP after the administration of 75 mg clopidogrel (OR = 1.067, 95% CI: 1.037 ~ 1.095, p < 0.001) were risk factors for ischemic vascular events. The MAR-ADP after the administration of 75 mg clopidogrel was significantly higher in patients who were carriers of the CYP2C19 (LOF) allele compared with non-carriers (57.53 ± 13.32 vs. 50.86 ± 12.55, p < 0.001), and no significant differences between the CYP2C19 LOF allele carriers and non-carriers in the MAR-ADP were detected after the administration of 300 mg clopidogrel (37.18 ± 11.36 vs. 35.86 ± 12.49, p = 0.264). Being a carrier of the CYP2C19 LOF allele has a significant influence on clopidogrel response. Platelet function is closely related to recurrent ischemic vascular events in acute minor stroke or TIA patients.
.

The effect of creatine and coenzyme q10 combination therapy on mild cognitive impairment in Parkinson's disease.

BACKGROUND: To investigate the effect of creatine and coenzyme Q10 (CoQ10) combination therapy on mild cognitive impairment (MCI) in Parkinson's disease (PD; PD-MCI) and its influences on plasma phospholipid (PL) levels in PD-MCI. METHODS: The demographic data of 75 PD-MCI patients who enrolled in this collaborative PD study were collected. These patients were evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS) III and the Montreal Cognitive Assessment (MoCA). These 75 PD-MCI patients were randomly treated with creatine monohydrate 5 g b.i.d. and CoQ10 100 mg t.i.d. orally or placebo. MoCA evaluation and PL level measurements were performed after 12 and 18 months of treatment. RESULTS: After 12 and 18 months of treatment, the differences in the MoCA scores of the combination therapy and control groups were statistically significant (p < 0.05 at 12 months and p < 0.01 at 18 months), and the plasma PL levels of the combination therapy group were significantly lower than those of the control group (p < 0.01 at 12 months and p < 0.001 at 18 months). CONCLUSIONS: Combination therapy with creatine and CoQ10 could delay the decline of cognitive function in PD-MCI patients and could lower their plasma PL levels; therefore, this combination therapy may have a neuroprotective function.

Cerebral Microbleeds Are Associated With Mild Cognitive Impairment in Patients With Hypertension.

BACKGROUND: Cerebral microbleeds (CMBs) are hypothesized downstream markers of brain damage caused by vascular and amyloid pathologic mechanisms. The aim of this study was to determine whether CMB count and location are associated with an increased risk for mild cognitive impairment (MCI) in patients with essential hypertension without a history of transient ischemic attack or stroke. METHODS AND RESULTS: In this cross-sectional study, patients were prospectively enrolled from consecutive outpatients with essential hypertension 50 years and older at 3 centers in northern China. Generalized linear Poisson models were used to determine the association between the number and location of CMBs and MCI in patients with hypertension. The association of microbleeds with different cognitive domains was estimated using linear mixed models. The presence, number, and distribution of CMBs were greater in patients with hypertension who had MCI (P<0.001). The presence of any CMBs, strictly lobar CMBs, and deep or infratentorial CMBs were all related to MCI after adjusting for age, sex, education, cardiovascular risk factors, body mass index, intima-media thickness, the presence of silent lacunar infarctions, white matter lesion grade, and brain atrophy. Furthermore, the presence of multiple microbleeds (≥5) was associated with lower Montreal Cognitive Assessment total scores and worse performance on specific domains of cognitive tests, such as global cognitive function, information processing speed, and motor speed. CONCLUSIONS: This study suggests that the presence of and a greater number of cerebral CMBs independently correlate with MCI in patients with essential hypertension without a history of transient ischemic attack or stroke.

Plasma Phospholipids are Associated with Mild Cognitive Impairment in Type 2 Diabetic Patients.

BACKGROUND: Phospholipids and their metabolisms are closely allied to nosogenesis and aggravation of Type 2 diabetes mellitus and cognitive impairment. The aim of this study is to characterize the plasma levels of phospholipids in type 2 diabetes patients and type 2 diabetes patients with mild cognitive impairment (MCI), and to identify potential biomarkers of type 2 diabetes patients with MCI. METHODS: In this cross-sectional study, a total of 374 type 2 diabetes patients were prospectively enrolled. There were 103 patients with MCI and 271 patients without MCI. Plasma levels of lysophosphatidic acid (LPA) and phospholipids with solubility similar to that of LPA (PSS-LPA) were assayed. RESULTS: Plasma LPA and PSS-LPA levels were significantly higher in patients with MCI than those without MCI (P = 0.007, P ＜ 0.001). A logistic regression analysis indicates that elevated plasma PSSLPA was associated with increased risk of MCI in type 2 diabetic patients, with an OR of 1.87 (1.04- 3.47) after additional adjustment for hyperlipidemia, hypertension, High-sensitivity C-reactive protein, hemoglobin A1c, Intima-media thickness, ankle brachial index, and brachial-ankle pulse wave velocity. In type 2 diabetic patients with MCI, there were negative correlations between plasma LPA, PSS-LPA and the MoCA scores (r =﹣0.322, P < 0.01; r =﹣0.349, P < 0.001). Furthermore, plasma PSS-LPA exhibited a fair diagnostic value for MCI, with an area under the curve of 0.86. CONCLUSION: The level of plasma PSS-LPA may be an important biomarker for diagnosis of MCI.

Repetitive transcranial magnetic stimulation improves cognitive function of Alzheimer's disease patients.

Repetitive transcranial magnetic stimulation (rTMS) acts as a kind of widely-applied and non-invasive method in the intervention of some neurological disorders. This prospective, randomized, double-blind, placebo-controlled trial investigates the effect of rTMS on 30 cases of Alzheimer's disease (AD) participants, who were classified into mild and moderate groups. Neuropsychological tests were carried out using the AD Assessment Scale-cognitive subscale (ADAS-cog), Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and World Health Organization University of California-Los Angeles, Auditory Verbal Learning Test (WHO-UCLA AVLT) before, immediately after, and 6 weeks after the intervention. In this work, data from 30 AD patients revealed that there was no obvious interaction effect of time-by-group. The ADAS-cog, MMSE and WHO-UCLA AVLT score in the rTMS group was significantly improved compared with baselines at 6 weeks after treatment (all p<0.05). Meanwhile, MoCA scores were also obviously ameliorated in the mild AD patients with rTMS. Besides, subgroup analysis showed that the effect of rTMS on the memory and language of mild AD patients was superior to those of moderate AD patients. In conclusion, our findings suggested that repetitive transcranial magnetic stimulation improves cognitive function, memory and language level of AD patients, especially in the mild stage of AD. Thus, rTMS can be recommended as a promising adjuvant therapy combined with cholinesterase inhibitors at the mild stage of AD patients.