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Dementia

Acquiring reliable randomised evidence of the effects of cardiovascular interventions on cognitive decline is a priority. Many studies have shown that higher levels of vascular risk factors in midlife, and cardiovascular disease and diabetes are associated with future risk of dementia and cognitive decline. Hence, one important way that interventions that reduce vascular risk factors may prevent dementia is by preventing cerebrovascular and other vascular events. 

However, randomised clinical trials to prevent cardiovascular disease that have included cognitive assessment have failed to demonstrate compelling benefits for cognitive function. Despite evidence that the interventions prevent non-fatal vascular events, the absolute differences in the percentage of patients who experience such events during a trial may have been insufficient for plausible benefits on cognition to be detected.

To understand whether reports of non-significant results exclude worthwhile benefit, researchers from CTSU conducted a secondary analysis of the HPS, SEARCH and THRIVE randomised clinical trials including 45,029 participants undergoing cognitive assessment and estimated the association of the avoidance of vascular events with differences in cognitive function, expressed as years of cognitive aging – the years of aging over which such a difference would normally occur.

The results, published in JAMA Network Open, showed that incident stroke was associated with seven years of cognitive aging; and 'mini-stroke' (transient ischemic attack or TIA), myocardial infarction, heart failure and new onset diabetes were associated with one to two years of cognitive aging.

Applying this in HPS, (in which allocation to statin for five years successfully reduced the incidence of cardiovascular events) the researchers found that the avoidance of non-fatal stroke or TIA in 2% of surviving participants and of non-fatal cardiac events in 2.4% of such participants yielded an expected reduction in cognitive aging of 0.15 years. However, the study was only powered to detect a difference in cognitive aging of at least one year.

Lead author, Professor Sarah Parish said ‘Non-significant findings, even from large trials, should not be taken as good evidence of a lack of worthwhile benefit on cognitive function of prolonged use of cardio-protective therapies’. She added ‘New ways to assess decline in cognitive function more precisely that can be used in large-scale randomised trials may allow direct evidence of the benefits of cardiovascular interventions to emerge’.