Randomized controlled trial comparing impact on platelet reactivity of twice-daily with once-daily aspirin in people with Type 2 diabetes.

AIMS: Reduced aspirin efficacy has been demonstrated in people with Type 2 diabetes. Because increased platelet reactivity and/or turnover are postulated mechanisms, we examined whether higher and/or more frequent aspirin dosing might reduce platelet reactivity more effectively. METHODS: Participants with Type 2 diabetes (n = 24) but without known cardiovascular disease were randomized in a three-way crossover design to 2-week treatment periods with aspirin 100 mg once daily, 200 mg once daily or 100 mg twice daily. The primary outcome was platelet reactivity, assessed using the VerifyNow(™) ASA method. Relationships between platelet reactivity and aspirin dosing were examined using generalized linear mixed models with random subject effects. RESULTS: Platelet reactivity decreased from baseline with all doses of aspirin. Modelled platelet reactivity was more effectively reduced with aspirin 100 mg twice daily vs. 100 mg once daily, but not vs. 200 mg once daily. Aspirin 200 mg once daily did not differ from 100 mg once daily. Aspirin 100 mg twice daily was also more effective than once daily as measured by collagen/epinephrine-stimulated platelet aggregation and urinary thromboxane levels, with a similar trend measured by serum thromboxane levels. No episodes of bleeding occurred. CONCLUSIONS: In Type 2 diabetes, aspirin 100 mg twice daily reduced platelet reactivity more effectively than 100 mg once daily, and numerically more than 200 mg once daily. Clinical outcome trials evaluating primary cardiovascular disease prevention with aspirin in Type 2 diabetes may need to consider using a more frequent dosing schedule.

Cerebral subcortical small vessel disease and its relation to cognition in elderly subjects: a pathological study in the Oxford Project to Investigate Memory and Ageing (OPTIMA) cohort.

BACKGROUND: Subcortical small vessel disease (SVD) is known to contribute to vascular cognitive impairment and vascular dementia, but understanding about the extent of its influence is limited because there is a lack of consensus about how this pathology should be assessed. METHODS: In this study we have made use of a simple, novel, image-matching scoring system to assess the extent of SVD in a group of 70 cases from the prospectively assessed Oxford Project to Investigate Memory and Ageing (OPTIMA) cohort. These cases were found at autopsy to have cerebrovascular disease and no other pathology except Braak stage 4 or less tau pathology, and insufficient amyloid plaque pathology to meet Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria for the diagnosis of Alzheimer's disease. Pathology scores for SVD were correlated with cognitive scores [Mini-Mental State Examination (MMSE) and cognitive section of the Cambridge Examination for Mental Disorders in the Elderly (CAMDEX) (CAMCOG)] at the last clinical assessment before death. RESULTS: The severity of SVD pathology was inversely related to cognitive score before death (P < 0.008 for MMSE and P < 0.024 for CAMCOG). Thirty-one per cent and 33% of cases were rated as demented by MMSE or CAMCOG respectively. The degree of dementia was generally mild. Age did not influence severity of SVD. CONCLUSIONS: An image-based scoring system for SVD in a group of 70 elderly subjects enabled the severity of SVD pathology to be assessed with results that showed a significant correlation between SVD pathology severity and cognitive impairment.

APOE alleles predict the rate of cognitive decline in Alzheimer disease: a nonlinear model.

BACKGROUND: The APOE genotype predicts the age at onset of Alzheimer disease (AD) and neuropathologic progression. However, studies relating APOE alleles to the rate of cognitive decline have been inconclusive. This may stem from their use of linear statistical analyses. OBJECTIVE: To model relations of APOE alleles to the rate of cognitive decline in AD, nonlinearly. METHODS: Serial measures of cognitive ability were obtained using the cognitive scale of the Cambridge Examination for Mental Disorders of the Elderly in 218 patients with AD. The relations of these serial scores to APOE alleles were tested using nonlinear and linear mixed-effects models. RESULTS: In the non-linear model, possession of an APOE epsilon4 allele related to earlier and faster cognitive decline, but possession of an APOE epsilon2 related to slower decline. Patients homozygous for APOE epsilon4 showed faster cognitive decline than heterozygotes. The linear model was less sensitive and did not detect differences between APOE epsilon4 homo- and heterozygotes. CONCLUSIONS: APOE genotype strongly predicts the rate of cognitive decline in Alzheimer disease. The decline shows a dose-response relation with the APOE epsilon4 allele, but the APOE epsilon2 allele is protective. The nonlinear model yielded larger estimates of the maximal rate of decline than the linear.