Aspirin Use, Depression, and Cognitive Impairment in Later Life: The Health in Men Study

To the Editor: Treatment with low dosages of aspirin reduces the risk of recurrent strokes or other serious vascular events by approximately 13%.1 Because cerebrovascular disease seems to play a central role in the clinical expression of depression and dementia in later life,2,3 aspirin use could conceivably contribute to prevent these disorders. The present study was designed to determine whether exposure to aspirin treatment decreases the prevalence of depression and cognitive impairment. The present analyses involved 5,556 men aged 69 to 87 living in Australia.4 Between 2001 and 2004, they completed a two-stage assessment that included the evaluation of mood by self-rating (15-item Geriatric Depression Scale, GDS-15) and a face-to-face ascertainment of cognitive function (Mini-Mental State Examination, MMSE). In total, 5,273 participants completed the assessment of depression and 3,679 of cognitive function. Information on exposure to aspirin was collected at this assessment as well as 5 years earlier. The presence of cardiovascular diseases or risk factors was investigated by asking men whether they had “ever been told by a doctor” that they had hypertension, diabetes mellitus, high cholesterol, high lipids, or angina pectoris or had a heart attack or stroke (yes/no). Participants were also asked whether they were taking tablets for the treatment of hypertension, diabetes mellitus, or high lipids or cholesterol (yes/no). Men who answered yes to any of these questions were classified as having cardiovascular disease. Finally, administrative medical information was obtained from the Western Australian Data Linkage System (WADLS) during the 10 years before assessment at the Health In Men Study (HIMS) to calculate the Charlson Comorbidity Index.5 Men who had used aspirin in the past but were not at the time of assessment had greater odds of displaying clinically significant symptoms of depression than never users (Table 1), even after the analyses were adjusted for the possible effect of confounding (odds ratio=1.41, 95% confidence interval (CI)=1.00–1.99; z=1.98, P=.047). The number of medical contacts with health services between the first and the second assessment was also determined according to WADLS. The average number of contacts was 2.6, 4.5, 3.2, and 3.8 for men in each of the following aspirin intake groups: (1) past, no, current, no; (2) past, yes, current, no; (3) past, no, current, yes; (4) past, yes, current, yes. Men in Group 2 had more contacts with the health services than men in Groups 1 (Mann–Whitney test z=8.54, P<.001) and 3 (Mann–Whitney test z=2.52, P=.01). The results of the current study show that the use of aspirin is not associated with lower odds of depression or cognitive impairment in older men and indicate that participants who discontinued the use of aspirin between the two assessments had greater odds of depression than nonusers. These men also had more frequent contact with health services, a finding that is consistent with the possibility that aspirin use was discontinued because of medical complications that occurred between assessments. Because cardiovascular diseases are associated with prevalent and incident depression,6 the link between aspirin use and depression could be due to confounding (i.e., cardiovascular disease leading to depression and use of aspirin), although the analyses suggest that this is unlikely. One possibility is that men who stopped using aspirin might have been frailer, which may have contributed to a larger number of hospital admissions, depression, and discontinuation of treatment with aspirin to avoid further complications. A second possibility is that aspirin use led to greater morbidity (e.g., medical complications due to bleeding), which in turn could have contributed to greater depression and the resulting discontinuation of treatment. Recently published data from the Rotterdam Scan Study showed that older adults who used aspirin were 2.7 (95% CI=1.4–5.0) times as likely to show lobar microbleeds on magnetic resonance imaging as nonusers.7 In addition, results from the Aspirin in Alzheimer's Disease Trial revealed that daily treatment for 3 years with 75 mg of aspirin had no effect on the mood, cognition, or functional capacity of patients with Alzheimer's disease but increased the relative risk (RR) of serious bleeding (RR=4.4, 95% CI=1.5–12.8).8 These findings suggest that treatment with aspirin in later life may increase rather than decrease the risk of small cerebrovascular lesions, which in turn could contribute to increasing the incidence of depression and cognitive impairment. At this point, it is unclear whether other antiplatelet agents might reduce the prevalence of depression and cognitive impairment, but similarities between those drugs and aspirin suggest that they are unlikely to be a viable and helpful alternative. The investigators thank HIMS participants and research staff. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Support was provided by National Health and Medical Research Council of Australia Project Grants 279408, 379600, and 403963 to Jamrozik, Hankey, Flicker, and Almeida and the MBF Foundation Project Grant DS 080608 to Almeida. Author Contributions: Almeida had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Almeida. Acquisition of data: Almeida, Jamrozik, Hankey, and Flicker. Alfonso performed all analyses. Almeida provided advice in relation to the analyses of the data and interpretation of the results. Drafting of the manuscript: Almeida and Alfonso. Critical revision of the manuscript for important intellectual content: Almeida, Alfonso, Jamrozik, Hankey, and Flicker. Sponsor's Role: The sponsors had no role in the design or conduct of the study; collection, management, analysis, or interpretation of the data; or preparation, review, or approval of the manuscript.