Aspirin and Risk of Dementia in Patients with Late-Onset Depression: A Population-Based Cohort Study

Abstract

Background. Late onset depression (LOD) often occurs in the context of vascular disease and may be associated with risk of dementia. Aspirin is widely used to reduce the risk of cardiovascular disease and stroke. However, its role in patients with LOD and risk of dementia remains inconclusive. Materials and Methods. A population-based study was conducted using data from National Health Insurance of Taiwan during 1996–2009. Patients fulfil diagnostic criteria for LOD with or without subsequent dementia (incident dementia) and among whom users of aspirin (75 mg daily for at least 6 months) were identified. The time-dependent Cox proportional hazards model was applied for multivariate analyses. Propensity scores with the one-to-one nearest-neighbor matching model were used to select matching patients. Cumulative incidence of incident dementia after diagnosis of LOD was calculated by Kaplan–Meier Method. Results. A total of 6028 (13.4%) and 40,411 (86.6%) patients were defined as, with and without diagnosis of LOD, among whom 2,424 (41.9%) were aspirin users. Patients with LOD had more comorbidities such as cardiovascular diseases, diabetes, and hypertension comparing to those without LOD. Among patients with LOD, aspirin users had lower incidence of subsequent incident dementia than non-users (Hazard Ratio = 0.734, 95% CI 0.641–0.841, p<0.001). After matching aspirin users with non-users by propensity scores-matching method, the cumulative incidence of incident dementia was significantly lower in aspirin users of LOD patients (p=0.022). Conclusions. Aspirin may be associated with a lower risk of incident dementia in patients with LOD. This beneficial effect of aspirin in LOD patients needs validation in prospective clinical trials and our results should be interpreted with caution.

Aspirin Use on Incident Dementia and Mild Cognitive Decline: A Systematic Review and Meta-Analysis

“…Twelve included studies were cohort studies (Zandi and Breitner, 2001 ; Jonker et al, 2003 ; Kang and Grodstein, 2003 ; Nilsson et al, 2003 ; Cornelius et al, 2004 ; Arvanitakis et al, 2008 ; Szekely et al, 2008 ; Kern et al, 2012 ; Kelley et al, 2015 ; Chang et al, 2016 ; Wichmann et al, 2016 ; Yang et al, 2020 ) and three RCTs (Kang et al, 2007 ; Matsumoto et al, 2020 ; Ryan et al, 2020 ). Studies were conducted in the US (Zandi and Breitner, 2001 ; Kang and Grodstein, 2003 ; Kang et al, 2007 ; Arvanitakis et al, 2008 ; Szekely et al, 2008 ; Kelley et al, 2015 ; Wichmann et al, 2016 ), Europe (Jonker et al, 2003 ; Nilsson et al, 2003 ; Cornelius et al, 2004 ; Kern et al, 2012 ), and Asia (Chang et al, 2016 ; Matsumoto et al, 2020 ; Yang et al, 2020 ). However, only one RCT (Ryan et al, 2020 ) included both American and Australian data.…”

“…However, only one RCT (Ryan et al, 2020 ) included both American and Australian data. Two of the studies were from Taiwan (Chang et al, 2016 ; Yang et al, 2020 ) and extracted their data from the National Health Insurance Research Database, but the investigators used different study populations and separate cohorts.…”

“…Twelve cohort studies (10 prospective studies and two retrospective studies) investigated the association between aspirin use and the risk of dementia or MCI (Zandi and Breitner, 2001 ; Jonker et al, 2003 ; Kang and Grodstein, 2003 ; Nilsson et al, 2003 ; Cornelius et al, 2004 ; Arvanitakis et al, 2008 ; Szekely et al, 2008 ; Kern et al, 2012 ; Kelley et al, 2015 ; Chang et al, 2016 ; Wichmann et al, 2016 ; Yang et al, 2020 ). Overall, when adjusted for confounders, aspirin use showed no significant decreased risk of developing dementia or MCI (the pooled RR = 0.97; 95% CI = 0.85–1.11; = 65%) ( Figure 2 ).…”

Long-term low-dose acetylsalicylic use shows protective potential for the development of both vascular dementia and Alzheimer’s disease in patients with coronary heart disease but not in other individuals from the general population: results from two large cohort studies

“…Among the four studies on all-cause dementia, three reported statistically significant results and only the study of Kern et al, 39 which was underpowered (n=41 cases), showed no statistical differences between LDASA users and non-users regarding the 5-year risk of dementia. None of the 4 individual studies is comparable to our study populations from the UK Biobank and ESTHER (general population, age ≥55) because they included either only women, 39 twins aged 80 years or older, 41 patients with late-onset depression 42 or type 2 diabetes patients. 40…”

“…7 Overall, a meta-analysis of 8 studies indicated that the use of any dose of ASA did not significantly decrease the risk of developing dementia (pooled relative risk (RR) [95% CI]: 0.94 [0.77 to 1.16]. However, when the authors restricted the meta-analysis to 4 studies with LDASA exposure and the outcome all-cause dementia 39-42 and 2 studies with LDASA exposure and the outcome AD, 40 41 LDASA use showed a protective effect against all-cause dementia (pooled RR [95% CI]: 0.82 [0.71 to 0.96]) and AD (pooled RR [95% CI]: 0.54 [0.33 to 0.89]). Among the four studies on all-cause dementia, three reported statistically significant results and only the study of Kern et al, 39 which was underpowered (n=41 cases), showed no statistical differences between LDASA users and non-users regarding the 5-year risk of dementia.…”