Chicago, IL - A large, longitudinal study suggests that statin use does not lower the risk of Alzheimer's disease (AD), nor does it appear to reduce cerebral infarction or classic AD brain pathology, including the burden of amyloid and tangles [1].

The study results, which run contrary to some cross-sectional data, are consistent with findings of other longitudinal studies. In addition, this current study is the first to examine the link between statin use and incident AD, cognitive decline, and pathologic changes in the brain in the same cohort.

"In this longitudinal, clinical-pathologic study, statins were not associated with a lower risk of Alzheimer's disease, less cognitive decline, or less AD brain pathology at the time of death. These findings, which are consistent across clinical and pathological measures of Alzheimer's disease, give additional confidence in these results," study investigator Dr Zoe Arvanitakis (Rush University Medical Center, Chicago, IL) noted.

The study is published online January 16, 2008 in Neurology.

Typically, said Arvanitakis, it is a much greater challenge to get negative studies, such as this one, published. However, she added, negative research that goes unpublished may place doctors and patients in peril.

"If we don't get these [null] studies out there the medical community, our patients may be led down the wrong path. We have to take a clear and balanced approach to the evidence to ensure the research is moving in the right direction and ultimately leads to the best patient care," she said.

According to Arvanitakis, the results of basic-research studies, as well as cross-sectional data, have left an impression among some patients and the medical community that statins have a protective effect against AD. Currently, she added, statins are among the most widely prescribed agents in the US.

"At this time, treating physicians should continue to refrain from prescribing statins for prevention of AD. I know there's a lot of talk about using statins for AD and, understandably, patients want to do everything possible to decrease their likelihood of developing this devastating illness. But at this point the evidence is just not there to support it," she said.

To determine whether statins are associated with a lower risk of AD, slower rate of cognitive decline, and decreased AD pathology, investigators used data from the Religious Orders Study, an ongoing prospective clinical-pathologic study of dementia.

At study outset, the 929 participants had a median age of 75 years and were free of dementia.

With an average 12-year follow-up, study subjects underwent annual clinical evaluations to assess statin use and cognitive status, which was based on 19 neuropsychological tests. In addition, subjects agreed to brain autopsy at the time of death.

Of 929 study subjects, 119 were statin users at baseline and 810 were not. Among statin users, 67 were taking an agent with more lipophilic properties and 52 subjects were taking drugs with less lipophilic properties.

During the follow-up period, 191 individuals developed AD, 16 of whom were baseline statin users. After adjustment for age, sex, and education, baseline statin use was not associated with AD risk.

Furthermore, the authors report, AD risk remained unchanged when the presence of vascular disease or vascular risk factors were considered.

In addition, statin use was not linked to the level of or change in cognitive function, and the type of statin (less lipophilic vs more lipophilic) also did not influence cognition.

It is interesting to note, said Arvanitakis, that some research has suggested that less lipophilic statins, which do not cross the blood-brain barrier easily, may be more beneficial in curtailing AD pathology than agents with more lipophilic properties, which are able to penetrate the brain.

Such findings may suggest that it is statins' anti-inflammatory effects and ability to reduce oxidative stress, in addition to their cholesterol-lowering effects, that may play a role in reducing AD risk.

A total of 262 individuals—47 statin users and 215 nonusers—underwent brain autopsy at time of death. Researchers found statin use at any time during the study had no influence on the classic AD pathology or cerebral infarction.

"We were somewhat surprised that statins were not associated with fewer strokes or less cerebral infarction pathology," she said.

More research to replicate the current study's findings in a community-based population will help determine their generalizability. Arvanitakis said she and her colleagues would be able to conduct such a study in a cohort of more than 1100 community-dwelling older persons in the Chicago area.

Reference

Arvanitakis Z, Schneider JA, Wilson RS, et al. Statins, incident Alzheimer disease, change in cognitive function, and neuropathology. Neurology 2008: DOI:10.1212/01.wnl.0000288181.00826.63