Statins and cognitive impairment

“Statins 'halve' the risk of dementia” is the headline in_ The Independent_ . Findings from a study in “1,674 elderly Mexican-Americans….who had conditions that typically lead to dementia, including diabetes, obesity, high blood pressure and high cholesterol” found that people who took statins reduced by half their risk of developing dementia over a period of five to seven years, the newspaper says.

Contrary to the reports, this study looked at the risk of developing either cognitive impairment or dementia, not just dementia. The authors note that previous studies have not all found that statins reduce the risk of cognitive impairment. This fact, and the limitations of this study, mean that these results alone do not provide strong enough evidence to suggest that we should all be taking statins to ward off cognitive decline. Statins, as with all drugs, carry the risk of side effects, and these need to be balanced against their benefits. In people with high cholesterol, the main aim of taking statins remains to reduce their risk of cardiovascular events.

Where did the story come from?

Dr Caryn Cramer and colleagues from the University of Michigan carried out this research. The study was funded by the National Institute on Aging. Dr Cramer was employed by the Pfizer Corporation during the time this study was carried out. Pfizer did not play any role in funding, performing or analysing the study. It was published in the peer-reviewed medical journal Neurology .

What kind of scientific study was this?

This was a prospective cohort study called the Sacramento Area Latino Study on Aging (SALSA), which looked at the relationship between lifestyle and cardiovascular factors, and the risk of cognitive and physical decline.

In 1998, the researchers enrolled 1,789 Latinos (mostly Mexican-American) aged 60 and over, living in the Sacramento area of California. At the start of the study, participants were interviewed in their homes and asked about their lifestyle, any medical diagnoses and any depressive symptoms. They also provided a blood sample and mouth swab for DNA extraction. Researchers also asked questions about the participants’ statin use at the start of the study and every year after that. This was checked by looking in the participants’ medicine cabinets. Participants also reported their statin use every six months by telephone.

The participants completed standard cognitive tests at the start of the study, and then again every 12 to 15 months. Those scoring below a certain threshold on these tests, or those who had declined by a pre-specified amount, were referred for further testing. Based on all the information collected, diagnoses of dementia were made by a multidisciplinary team of specialists, using standard criteria (DSM-IV and NINCDS-ADRDA criteria).

Only the 1,674 participants who did not have dementia or cognitive impairment at the start of the study were included in the analyses for this study. The researchers looked at who developed cognitive impairment (below the threshold for dementia) or dementia over the follow-up period, using verified diagnostic criteria. They compared the risk of developing dementia or cognitive impairment among those who took statins and those who did not. The researchers adjusted their analyses for factors which might affect the risk of developing cognitive impairment, such as genetic factors (presence of an APOE ε4 allele), smoking, educational level and having diabetes or previous stroke at the start of the study.

What were the results of the study?

Participants were followed-up for five years, and in this period 130 people (about 8%) developed dementia or cognitive impairment below the threshold for dementia. Just over a quarter of participants (27%) took statins at some point during the study.

Among those who took statins, about 6% developed cognitive impairment or dementia, compared with about 8% in the participants who did not take statins. After adjusting their analyses for potential confounding factors, the researchers found that this represented a reduction in risk of developing cognitive impairment or dementia by almost half (44%) compared with those who did not take statins.

What interpretations did the researchers draw from these results?

The researchers concluded that their results add to the pool of evidence suggesting that statins can improve cognitive outcomes.

What does the NHS Knowledge Service make of this study?

There are some issues which need to be considered when interpreting this study:

As the use of statins was not randomly assigned. There may be differences between statin users and non-users, which may account for the differences seen. The researchers did take into account known risk factors for cognitive decline and known differences between the groups in their analyses, which increases confidence in their results, but there may still be unknown or unmeasured confounding factors that are partly responsible for the results.
Studies looking at the relationship between statins and cognitive impairment have not had consistent findings, with the randomised studies tending not to find an association between statin use and cognitive impairment, while the observational studies (like this study) mostly finding a link. Although a randomised controlled trial would be the best way to determine whether statin use reduces risk of cognitive impairment, the authors suggest that the existing randomised studies had issues that limit the reliability of their findings. For example, dementia and cognitive decline were not their primary (main) outcomes.
The authors report that studies have found that statins may not be prescribed to people with signs of dementia, and this could bias the results if this were the case in this sample. The exclusion of those with cognitive impairment or dementia at the start of this study aimed to avoid this potential bias. However, it is possible that some mild cognitive impairment may not have been identified by the regular tests carried out on participants, but may have been detected by the participant’s physician, leading to non-prescription of statins.
Statins would only be prescribed to people with high cholesterol. It is not possible to determine from this study whether statins would reduce the risk of cognitive impairment or dementia in people who did not have raised cholesterol.
Loss to follow-up differed between the groups, with 7% of statin users and 18% of nonusers lost. This may bias the results if those lost to follow-up differed from those who were retained in the study.
The absolute numbers of people who developed cognitive impairment or dementia during follow-up were relatively small - only 6% of those who used statins and 8% of those who did not.
This study only included Latinos, therefore the results may not be able to be generalised to other ethnic groups. It also included only people aged over 60, and the results may not apply to a younger population.

Statins, as with all drugs, carry the risk of side effects, and these need to be balanced against their benefits. In people with high cholesterol who are prescribed a statin to reduce their risk of cardiovascular events, this potential improvement in cognitive function may be an added bonus. This study by itself does not provide strong enough evidence to suggest that we should all be taking statins to ward off cognitive decline.

Sir Muir Gray adds...

What is needed is a systematic review of all the evidence; one swallow does not a summer make.