Kivipelto and associates point out that community-based preventive studies in the field of cardiovascular disease began more than 20 years ago and have been continuously modified to focus on areas evidencing potential. To establish epidemiologic evidence of preventive effect they note, “one needs to do the right thing and do enough of it.”3
Kivipelto and colleagues further argue against a fatalistic view of the inevitability of AD onset. Claiming that there are indications of a number of modifiable risk factors they declare, “aetiological treatment may belong to the future, but prevention is now.”3
In a critical view of the evidence for the potential of statins to modify onset and development of AD, Rockwood4 points out that initial expectations were based on cross-sectional observational reports, the results of which were not subsequently supported by 2 large clinical trials with cognitive add-on studies. Although these studies were not originally designed to evaluate statin effect, epidemiologic data from the Canadian Study of Health and Aging also presented a mixed picture, he notes.
“The first reports appear to have overestimated the extent of protection,” Rockwood comments, “so that unless there are important effects achievable with specific statins, more than a modest role for statins preventing AD seems unlikely.”4
A mixed case for statin mechanisms
Several observations have suggested that the cholesterol-lowering action of the statins might be protective and/or therapeutic in AD. In their review, Wolozin and coauthors5 cite that, as an example, the determination that the apoE4 allele of the cholesterol transporter apoE4 is a major risk factor for late-onset AD. A closely following supportive epidemiologic finding is that the risk of AD appears to increase in persons with heart disease.6 Wolozin and colleagues5 also note cell biology studies that found that the processing of amyloid precursor protein (APP) and production of ß-amyloid (Aß)—a component of the amyloid plaques in AD—are strongly modulated by cholesterol.
In contrast, Höglund and colleagues7 point out that more recent epidemiologic studies have not associated lowered cholesterol levels with slowing cognitive decline; both animal8 and clinical9 studies have had negative findings, they note.
“The intake of cholesterol and other lipids has also been found to be inconsistent when related to the risk of developing dementia,” these authors observe.7
Other actions of the statins may be neuroprotective, note Sparks and colleagues,10 including lipid-independent pleiotropic effects that interfere with Aß production and accumulation. In their review, separate from the ADCLT report, they also note in vitro studies with glioma cells in which pravastatin(Drug information on pravastatin) (Pravachol) reduced interleuken-6 and free radical inflammatory mediators.