Effects of aspirin on dementia and cognitive function in diabetic patients: the ASCEND trial.
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ABSTRACT: Aims
Aspirin is widely used in cardiovascular disease prevention but is also associated with an increased risk of bleeding. The net effect of aspirin on dementia and cognitive impairment is uncertain.Methods and results
In the ASCEND trial, 15 480 people from the UK with diabetes and no history of cardiovascular disease were randomized to aspirin 100 mg daily or matching placebo for a mean of 7.4 years. The 15 427 ASCEND participants with no recorded dementia prior to baseline were included in this cognitive study with a primary pre-specified outcome of 'broad dementia', comprising dementia, cognitive impairment, or confusion. This was ascertained through participant, carer, or general practitioner report or hospital admission diagnosis, by 31 March 2019 (∼2 years beyond the scheduled treatment period). The broad dementia outcome occurred in a similar percentage of participants in the aspirin group and placebo group: 548 participants (7.1%) vs. 598 (7.8%), rate ratio 0.91 [95% confidence interval (CI), 0.81-1.02]. Thus, the CI excluded proportional hazards of >2% and proportional benefits of >19%.Conclusion
Aspirin does not have a large proportional effect on the risk of dementia. Trials or meta-analyses with larger total numbers of incident dementia cases to increase statistical power are needed to assess whether any modest proportional 10-15% benefits of 5-7 years of aspirin use on dementia exist.Clinical trial registration
Current Controlled Trials number, ISRCTN60635500; ClinicalTrials.gov number: NCT00135226.
SUBMITTER: Parish S
PROVIDER: S-EPMC9242621 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo determine the effect of low-dose aspirin vs placebo on incident all-cause dementia, incident Alzheimer disease (AD), mild cognitive impairment (MCI), and cognitive decline in older individuals.MethodsAspirin in Reducing Events in the Elderly (ASPREE) was a double-blind, placebo-controlled trial of low-dose aspirin. In the United States and Australia, community-dwelling individuals aged ≥70 years (US minorities ≥65 years) and free of cardiovascular disease, physical disability, and diagnosed dementia were enrolled. Participants were randomized 1:1-100 mg daily aspirin or placebo. The Modified Mini-Mental State Examination, Hopkins Verbal Learning Test-Revised, Symbol Digit Modalities Test, and Controlled Oral Word Association Test assessed cognition at baseline and over follow-up. Additional cognitive testing was performed in participants with suspected dementia ("trigger") based on within-study assessments or clinical history. Dementia was adjudicated according to DSM-IV criteria. National Institute on Aging-Alzheimer's Association criteria were used for AD and MCI subclassification.ResultsA total of 19,114 participants were followed over a median 4.7 years and 964 triggered further dementia assessments. There were 575 adjudicated dementia cases, and 41% were classified as clinically probable AD. There was no substantial difference in the risk of all dementia triggers (hazard ratio [HR], 1.03; 95% confidence interval [CI], 0.91-1.17), probable AD (HR, 0.96; 95% CI, 0.74-1.24), or MCI (HR, 1.12; 95% CI, 0.92-1.37) between aspirin and placebo. Cognitive change over time was similar in the aspirin and placebo groups.ConclusionsThere was no evidence that aspirin was effective in reducing risk of dementia, MCI, or cognitive decline. Follow-up of these outcomes after initial exposure is ongoing.Classification of evidenceThis study provides Class II evidence that for healthy older individuals, low-dose aspirin does not significantly reduce the incidence of dementia, probable AD, MCI, or cognitive decline.Clinicaltrialsgov identifierNCT01038583.
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Project description:Although physical exercise has been suggested to influence cognitive function, previous exercise studies show inconsistent results in people with dementia.To investigate effects of exercise on cognitive function in people with dementia.The Umeå Dementia and Exercise (UMDEX) study, a cluster-randomized controlled trial, was set in 16 nursing homes in Umeå, Sweden. One hundred-and-forty-one women and 45 men with dementia; mean age of 85 y and mean Mini-Mental State Examination (MMSE) score of 15, were randomized to a High-Intensity Functional Exercise program or a seated attention control activity. Blinded assessors measured global cognitive function using the MMSE and the Alzheimer's disease Assessment Scale - Cognitive subscale (ADAS-Cog), and executive function using Verbal fluency (VF) at baseline and 4 months (directly after intervention completion), and MMSE and VF at 7 months.Linear mixed models showed no between-group effects in mean difference from baseline (95% confidence intervals, CI) at 4 months in MMSE (-0.27; 95% CI -1.4 to 0.87, p?=?0.644), ADAS-Cog (-1.04, 95% CI -4 to 1.92, p?=?0.491), or VF (-0.53, 95% CI -1.42 to 0.35, p?=?0.241) or at 7 months in MMSE (-1.15, 95% CI -2.32 to 0.03, p?=?0.056) or VF (-0.18, 95% CI -1.09 to 0.74, p?=?0.707).A 4-month, high-intensity functional exercise program had no superior effects on global cognition or executive function in people with dementia living in nursing homes when compared with an attention control activity.
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Project description:Major Depressive Disorder (MDD) is highly prevalent in patients with End Stage Renal Disease (ESRD) treated with maintenance hemodialysis (HD). Despite the high prevalence and robust data demonstrating an independent association between depression and poor clinical and patient-reported outcomes, MDD is under-treated when identified in such patients. This may in part be due to the paucity of evidence confirming the safety and efficacy of treatments for depression in this population. It is also unclear whether HD patients are interested in receiving treatment for depression. ASCEND (Clinical Trials Identifier Number NCT02358343), A Trial of Sertraline vs. Cognitive Behavioral Therapy (CBT) for End-stage Renal Disease Patients with Depression, was designed as a multi-center, 12-week, open-label, randomized, controlled trial of prevalent HD patients with comorbid MDD or dysthymia. It will compare (1) a single Engagement Interview vs. a control visit for the probability of initiating treatment for comorbid depression in up to 400 patients; and (2) individual chair-side CBT vs. flexible-dose treatment with a selective serotonin reuptake inhibitor, sertraline, for improvement of depressive symptoms in 180 of the up to 400 patients. The evolution of depressive symptoms will also be examined in a prospective longitudinal cohort of 90 HD patients who choose not to be treated for depression. We discuss the rationale and design of ASCEND, the first large-scale randomized controlled trial evaluating efficacy of non-pharmacologic vs. pharmacologic treatment of depression in HD patients for patient-centered outcomes.
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Project description:Aspirin modestly influences cardiovascular events in patients with type 2 diabetes mellitus (T2DM), but the reason is unclear. The aim of the study was to determine whether in T2DM patients aspirin enhances platelet isoprostanes, which are eicosanoids with proaggregating properties derived from arachidonic acid oxidation by platelet NOX2, the catalytic subunit of reduced NAD phosphate oxidase. A cross-sectional study was performed comparing T2DM patients, treated (n = 50) or not treated (n = 50) with 100 mg/day aspirin, with 100 nondiabetic patients, matched for age, sex, atherosclerosis risk factors, and aspirin treatment. A short-term (7 days) treatment with 100 mg/day aspirin also was performed in 36 aspirin-free diabetic and nondiabetic patients. Higher platelet recruitment, platelet isoprostane, and NOX2 activation was found in diabetic versus nondiabetic patients and in aspirin-treated diabetic patients versus nontreated patients (P < 0.001). Platelet thromboxane (Tx) A(2) (P < 0.001) was inhibited in all aspirin-treated patients. In the interventional study, aspirin similarly inhibited platelet TxA(2) in diabetic and nondiabetic patients (P < 0.001). Platelet recruitment, isoprostane levels, and NOX2 activation showed a parallel increase in diabetic patients (P < 0.001) and no changes in nondiabetic patients. These findings suggest that in aspirin-treated diabetic patients, oxidative stress-mediated platelet isoprostane overproduction is associated with enhanced platelet recruitment, an effect that mitigates aspirin-mediated TxA(2) inhibition.
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Project description:Endothelial dysfunction is intimately related to the development of various cardiovascular diseases, including hypertension, and is often used as a target for pharmacological treatment. The scope of this review is to assess effects of aspirin on endothelial function and their clinical implication in arterial hypertension.Emerging data indicate the role of platelets in the development of vascular inflammation due to the release of proinflammatory mediators, for example, triggered largely by thromboxane. Vascular inflammation further promotes oxidative stress, diminished synthesis of vasodilators, proaggregatory and procoagulant state. These changes translate into vasoconstriction, impaired circulation and thrombotic complications. Aspirin inhibits thromboxane synthesis, abolishes platelets activation and acetylates enzymes switching them to the synthesis of anti-inflammatory substances. Aspirin pleiotropic effects have not been fully elucidated yet. In secondary prevention studies, the decrease in cardiovascular events with aspirin outweighs bleeding risks, but this is not the case in primary prevention settings. Ongoing trials will provide more evidence on whether to expand the use of aspirin or stay within current recommendations.
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Project description:To determine the interrelationships between baseline Mini-Mental State Examination (MMSE) score and risk of overall dementia, post-recurrent stroke dementia, and dementia without recurrent stroke among patients with a history of stroke.Prospective cohort study among participants enrolled in the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) for whom baseline MMSE score was available. Baseline MMSE score was divided into 4 categories: 30, 29-27, 26-24, and <24. Participants were followed for incident dementia and recurrent stroke. Logistic regression models were used to examine the association between MMSE score and dementia.Of the 6080 participants included in this analysis, 2493 had an MMSE score of 30, 1768 had a score of 29-28, 1369 had a score of 26-24, and 450 had a score of <24. Average follow-up time was 3.8 years. There were 407 cases of dementia, 106 of which were preceded by a recurrent stroke. The risk of overall dementia increased with decreasing MMSE score. However, the impact of MMSE score on the risk of dementia without recurrent stroke was much stronger than the impact of MMSE score on the risk of post-recurrent stroke dementia. For those with MMSE score <24, the risk of dementia without recurrent stroke was 47.89 (95% confidence interval, 28.57-80.26), whereas the risk of post-recurrent stroke dementia was only 7.17 (95% confidence interval, 3.70-13.89). Higher MMSE scores were even less strongly associated with the risk of post-recurrent stroke dementia.Patients with stroke with low MMSE scores are at high risk of dementia over time, even in the absence of a recurrent stroke, and should therefore be followed closely for further cognitive decline.
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Project description:Background: The recent COVID-19 pandemic is not only a major healthcare problem in itself, but also poses enormous social challenges. Though nursing homes increasingly receive attention, the majority of people with cognitive decline and dementia live at home. We aimed to explore the psychosocial effects of corona measures in memory clinic (pre-)dementia patients and their caregivers. Methods: Between April 28th and July 13th 2020, n = 389 patients of Alzheimer center Amsterdam [n = 121 symptomatic (age = 69 ± 6, 33%F, MMSE = 23 ± 5), n = 268 cognitively normal (age = 66 ± 8, 40% F, MMSE = 29 ± 1)] completed a survey on psychosocial effects of the corona measures. Questions related to social isolation, worries for faster cognitive decline, behavioral problems and discontinuation of care. In addition, n = 147 caregivers of symptomatic patients completed a similar survey with additional questions on caregiver burden. Results: Social isolation was experienced by n = 42 (35%) symptomatic and n = 67 (25%) cognitively normal patients and two third of patients [n = 129 (66%); n = 58 (75%) symptomatic, n = 71 (61%) cognitively normal] reported that care was discontinued. Worries for faster cognitive decline were existed in symptomatic patients [n = 44 (44%)] and caregivers [n = 73 (53%)], but were also reported by a subgroup of cognitively normal patients [n = 27 (14%)]. Both patients [n = 56 (46%) symptomatic, n = 102 (38%) cognitively normal] and caregivers [n = 72 (48%)] reported an increase in psychological symptoms. More than three quarter of caregivers [n = 111(76%)] reported an increase in patients' behavioral problems. A higher caregiver burden was experienced by n = 69 (56%) of caregivers and n = 43 (29%) of them reported that a need for more support. Discontinuation of care (OR = 3.3 [1.3-7.9]), psychological (OR = 4.0 [1.6-9.9]) and behavioral problems (OR = 3.0 [1.0-9.0]) strongly related to experiencing a higher caregiver burden. Lastly, social isolation (OR = 3.2 [1.2-8.1]) and psychological symptoms (OR = 8.1 [2.8-23.7]) were red flags for worries for faster cognitive decline. Conclusion: Not only symptomatic patients, but also cognitively normal patients express worries for faster cognitive decline and psychological symptoms. Moreover, we identified patients who are at risk of adverse outcomes of the corona measures, i.e., discontinued care, social isolation, psychological and behavioral problems. This underlines the need for health care professionals to provide ways to warrant the continuation of care and support (informal) networks surrounding patients and caregivers to mitigate the higher risk of negative psychosocial effects.
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