Posted by Dementia is a progressive and irreversible deterioration in cognition that has a significant impact on the person’s activities of daily living and quality of life. Currently, there is no curative treatment for dementia, and the treatments used in clinical practice have limited therapeutic reach. This review starts with a discussion of apolipoprotein E4 (apoE4) and its role in the pathogenesis of dementia. The molecular involvement of statins is discussed and why they are no longer clinically indicated in mild cognitive impairment or mild to moderate dementia. The 11 studies outlined show that although statins have neuroprotective actions owing to their anti-inflammatory properties, this neuroprotective effect is to a certain extent negated by the involvement of other variables, such as apoA, Lp(a) and vascular risk factors such as high blood glucose.
ApoE4 oligodendroglia treated with cyclodextrin evidenced reduced cholesterol staining (P = 0.0092) as well as a reduction in the accumulation of other lipid compounds, such as triglycerides. A further 6-week treatment with cyclodextrin also improved myelination (P = 0.0274). Cyclodextrin also improved learning and executive function in old APOE4 mice when treated for a further 8 weeks.
The studies regarding the effects of statins and cyclodextrins on apoE4, present evidence in support of and against their neuroprotective effects in cognitive impairment. Although the studies on cyclodextrins have all been on animals, they provide a strong background for a potential research hypothesis for future clinical trials in the treatment of dementia.
Jamali Q, Oraegbunam C. Neuroprotective effects of statins and cyclodextrins: review and potential role in dementia treatment. BJPsych Advances. 2025;31(5):258-266. https://doi.org/10.1192/bja.2025.10112