The Story of Aspirin is not over yet! These are some of the new possible uses.
- Prevention of eclampsia and retarded foetal growth
- Prevention of cataract
- Prevention of colo-rectal cancer
- Reduction of cognitive decline, senility and dementia
Some of these possible uses arise from the anti-thrombotic action of aspirin, but others do not. Thus, possible benefit in pre-eclampsia and in retarded foetal growth, are likely to be due to a reduced risk of placental infarction. Granted these effects are controversial, but certain limitations in the CLASP trial, which was thought to have settled this issue negatively, have become apparent. (60)
Then there is an observed negative association between regular aspirin taking and the development of cataract. (61) If real, this may be due to the inhibition of an enzyme within the eye tissues.
A marked negative association between regular aspirin taking and colo-rectal cancer in three cohort studies (62-4) is of particular interest. If true, this almost certainly has nothing to do with any anti-thrombotic effect and it has been suggested that aspirin may enhance the apoptosis mechanism in early cancer. This will be a most difficult association to test, but a multi-centred RCT is being set up in cases of familial polyposis.
A possible beneficial effect of low-dose aspirin which, if true, is of enormous public health benefit, is a possible reduction in cognitive decline and dementia. This seems to be a most reasonable expectation through the anti-thrombotic effect of aspirin, though an anti-inflammatory effect of aspirin may be additional.
Clearly numerous factors are involved in cognitive decline, and as yet few of these are understood. The most obvious cause is, of course, a stroke. Geriatricians and neurologists however now accept that a less dramatic, and often unrecognised process of small repeated infarcts can contribute to cognitive decline in the elderly. This has become known as ‘vascular dementia’ or, ‘multi-infarct dementia’, and the fact that aspirin reduces the risk of stroke makes a reduction of cognitive decline, through the prevention of mult-infarct lesions by aspirin, a most reasonable expectation.
The quantitative contribution of multi-infarct lesions to the overall cognitive decline of the elderly is not known, but the literature yields estimates which vary between about 15% and 50%.
There seem to have been only two intervention studies. Though these are seriously limited, both give encouragement. In one, aspirin was given in a non-placebo controlled trial to half of a group of 70 elderly patients who were judged to be at high-risk of multi-infarct dementia. One year later, and in subsequent examinations, the subjects who had received aspirin scored significantly higher in cognitive tests than those who had not received aspirin. (65)
Better evidence comes from another randomised, placebo-controlled intervention study in 400 patients who had been judged to be at high risk of cardiovascular disease. (66) These had been on aspirin, warfarin, both or neither for five years. The results are encouraging, especially for aspirin.
The possibility that aspirin might be of benefit in Alzheimer’s disease has been raised in the Baltimore Longitudinal Study of Ageing. (67) Amongst subjects with two or more years use of aspirin, the relative risk of Alzheimer’s disease was 0.4 (95% CI 0.2 to 0.8). The authors draw the tentative conclusion that aspirin may reduce the inflammatory process in Alzheimer’s disease. A study of 50 elderly twins (68), led to a similar tentative conclusion.
If this is true, then questions naturally arise as to the dose of aspirin needed to achieve an anti-inflammatory effect, and an effect from the low-doses recommended for anti-thrombosis are likely to be dismissed. Nevertheless, based on a matched case-control prospective comparison in the Physicians Health Study, (69) Hennekens group detected a positive linear relationship between the beneficial effect of only 325 mg aspirin on alternate days, and a marker of inflammation at base-line, C-reactive protein.
The possible benefit of low-dose aspirin on cognitive decline is one of the most important questions yet to be answered. If confirmed, the benefits to patients and carers, and savings to health services could be almost incalculable.