Hostname: page-component-65f69f4695-s8crj Total loading time: 0 Render date: 2025-06-27T21:58:12.973Z Has data issue: false hasContentIssue false
  • English
  • Français

Neuroprotective effects of statins and cyclodextrins: review and potential role in dementia treatment

Published online by Cambridge University Press:  24 June 2025

Qutub Jamali Open the ORCID record for Qutub Jamali [Opens in a new window]  and
Chukwuma Oraegbunam Open the ORCID record for Chukwuma Oraegbunam [Opens in a new window]
Qutub Jamali*
Affiliation:
A specialist liaison psychiatrist who has been working in neuropsychiatry for the past 10 years. His research interests include evidence-based literature reviews that can be practically implemented in clinical practice.
Chukwuma Oraegbunam
Affiliation:
A Consultant older adult psychiatrist for over 5 years, with research interests in old age psychiatry, neuropsychiatry and psychopharmacology.
*
Correspondence Qutub Jamali. Email: qutubkhan@rediffmail.com
Get access Rights & Permissions [Opens in a new window]

Summary

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. We begin this descriptive review with a discussion of apolipoprotein E4 (apoE4) and its role in the pathogenesis of dementia. We consider the molecular involvement of statins and why they are no longer clinically indicated in mild cognitive impairment or mild to moderate dementia. We then explore the evidence regarding the effects of statins and cyclodextrins on apoE4, presenting 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.

Keywords

Dementia/neurodegenerative diseasestatincyclodextrinapolipoproteinneuroprotective effect

Information

Type
Article
Information
BJPsych Advances , First View , pp. 1 - 9
Check for updates
Copyright
© The Author(s), 2025. Published by Cambridge University Press on behalf of Royal College of Psychiatrists

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

Footnotes

*

A version of this article appears online as the following preprint: Jamali Q (2024) Neuroprotective effects of statins and cyclodextrin: a review and the way forward. Advance, July 16.

References

Agarwal, T, Manandhar, S, Famurewa, AC, et al (2024) Oxyresveratrol-β-cyclodextrin mitigates streptozotocin-induced Alzheimer’s model cognitive impairment, histone deacetylase activity in rats: in silico & in vivo studies. Scientific Reports, 14: 9897.CrossRefGoogle ScholarPubMed
Bhatia, M, Howard, SC, Clark, TG, et al (2006) Apolipoproteins as predictors of ischaemic stroke in patients with a previous transient ischaemic attack. Cerebrovascular Diseases, 21: 323–8.CrossRefGoogle ScholarPubMed
Blanchard, JW, Akay, LA, Davila-Velderrain, J, et al (2022) APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes. Nature, 611: 769–79.CrossRefGoogle ScholarPubMed
Cai, C, Wen, Z, Li, L (2021) The relationship between ApoE gene polymorphism and the efficacy of statins controlling hyperlipidemia. American Journal of Translational Research, 13: 6772–7.Google ScholarPubMed
Climent, E, Benaiges, D, Pedro-Botet, J (2021) Hydrophilic or lipophilic statins? Frontiers in Cardiovascular Medicine, 8: 687585.CrossRefGoogle ScholarPubMed
Dassati, S, Waldner, A, Schweigreiter, R (2014) Apolipoprotein D takes center stage in the stress response of the aging and degenerative brain. Neurobiology of Aging, 35: 1632–42.CrossRefGoogle ScholarPubMed
Davis, AA, Inman, CE, Wargel, ZM, et al (2020) APOE genotype regulates pathology and disease progression in synucleinopathy. Science Translational Medicine, 12: eaay3069.CrossRefGoogle ScholarPubMed
De Giorgi, R, Rizzo Pesci, N, Rosso, G, et al (2023) The pharmacological bases for repurposing statins in depression: a review of mechanistic studies. Translational Psychiatry, 13: 253.CrossRefGoogle ScholarPubMed
Dickson, DW, Heckman, MG, Murray, ME, et al (2018) APOE ε4 is associated with severity of Lewy body pathology independent of Alzheimer pathology. Neurology, 91: e1182–95.CrossRefGoogle ScholarPubMed
Duong, MT, Nasrallah, IM, Wolk, DA, et al (2021) Cholesterol, atherosclerosis, and APOE in vascular contributions to cognitive impairment and dementia (VCID): potential mechanisms and therapy. Frontiers in Aging Neuroscience, 13: 647990.CrossRefGoogle ScholarPubMed
El-Lebedy, D, Raslan, HM, Mohammed, AM (2016) Apolipoprotein E gene polymorphism and risk of type 2 diabetes and cardiovascular disease. Cardiovascular Diabetology, 15: 12.CrossRefGoogle ScholarPubMed
Gentreau, M, Rukh, G, Miguet, M, et al (2024) The effects of statins on cognitive performance are mediated by low-density lipoprotein, C-reactive protein and blood glucose concentrations. Journals of Gerontology: Series A, Biological Sciences and Medical Sciences, 78: 1964–72.Google Scholar
Huang, Y, Weisgraber, KH, Mucke, L, et al (2004) Apolipoprotein E: diversity of cellular origins, structural and biophysical properties, and effects in Alzheimer’s disease. Journal of Molecular Neuroscience, 23: 189–204.CrossRefGoogle ScholarPubMed
Jamali, Q, Adeyemo, S, Abdelgawad, A, et al (2023a) Identification of cognitive impairment in cardiovascular rehabilitation: a pilot cross-sectional study. BJPsych Open, 9(suppl 1): S40–1.CrossRefGoogle Scholar
Jamali, Q, Akinfala, A, Upendram, A (2023b) Identification of biomarkers for vascular dementia: a literature review. BJPsych Advances 30: 89–96.CrossRefGoogle Scholar
Lin, JH, Walter, P, Yen, TSB (2008) Endoplasmic reticulum stress in disease pathogenesis. Annual Review of Pathology, 3: 399–425.CrossRefGoogle ScholarPubMed
Mahjoubin-Tehran, M, Kovanen, PT, Xu, S, et al (2020) Cyclodextrins: potential therapeutics against atherosclerosis. Pharmacology & Therapeutics, 214: 107620.CrossRefGoogle ScholarPubMed
Marcum, ZA, Vande Griend, JP, Linnebur, SA (2012) FDA drug safety communications: a narrative review and clinical considerations for older adults. American Journal of Geriatric Pharmacotherapy, 10: 264–71.CrossRefGoogle ScholarPubMed
McGuinness, B, Barrett, SL, Craig, D, et al (2010) Attention deficits in Alzheimer’s disease and vascular dementia. Journal of Neurology, Neurosurgery, and Psychiatry, 81: 157–9.CrossRefGoogle ScholarPubMed
McQueen, MJ, Hawken, S, Wang, X, et al (2008) Lipids, lipoproteins, and apolipoproteins as risk markers of myocardial infarction in 52 countries (the INTERHEART study): a case-control study. Lancet, 372: 224–33.CrossRefGoogle ScholarPubMed
Mendis, S (2024) Apolipoproteins (last updated 21 Oct 2024). Patient (Apolipoproteins) (http://patient.info/doctor/apolipoproteins).Google Scholar
Okubo, M, Toromanovic, A, Ebara, T, et al (2015) Apolipoprotein C-II Tuzla: a novel large deletion in APOC2 caused by Alu-Alu homologous recombination in an infant with apolipoprotein C-II deficiency. Clinica Chimica Acta, 438: 148–53.CrossRefGoogle Scholar
Olmastroni, E, Molari, G, De Beni, N, et al (2023) Statin use and risk of dementia or Alzheimer’s disease: a systematic review and meta-analysis of observational studies. European Journal of Preventive Cardiology, 29: 804–4.CrossRefGoogle Scholar
National Institute for Health and Care Excellence (2018) Dementia: Assessment, Management and Support for People Living with Dementia and Their Carers (NICE Guideline 97). Methods, Evidence and Recommendations. NICE.Google Scholar
Pankratz, N, Byder, L, Halter, C, et al (2006) Presence of an APOE4 allele results in significantly earlier onset of Parkinson’s disease and a higher risk with dementia. Movement Disorders: Official Journal of the Movement Disorder Society, 21: 45–9.CrossRefGoogle Scholar
Poly, TN, Islam, MM, Walther, BA, et al (2019) Association between use of statin and risk of dementia: a meta-analysis of observational studies. Neuroepidemiology, 54: 214–26.CrossRefGoogle ScholarPubMed
Raulin, A, Doss, SV, Trottier, ZA, et al (2022) ApoE in Alzheimer’s disease: pathophysiology and therapeutic strategies. Molecular Neurodegeneration, 17: 72.CrossRefGoogle ScholarPubMed
Ren, Q, Katherine Teng, T, Tse, Y, et al (2024) Statins and risks of dementia among patients with heart failure: a population-based retrospective cohort study in Hong Kong. Lancet Regional Health – Western Pacific, 44: 101006.CrossRefGoogle ScholarPubMed
Saher, G, Quintes, S, Nave, K (2011) Cholesterol: a novel regulatory role in myelin formation. Neuroscientist, 17: 79–93.CrossRefGoogle ScholarPubMed
Schultz, BG, Patten, DK, Berlau, DJ (2018) The role of statins in both cognitive impairment and protection against dementia: a tale of two mechanisms. Translational Neurodegeneration, 7: 5.CrossRefGoogle ScholarPubMed
US Food and Drug Administration (2012) FDA Drug Safety Communication: Important Safety Label Changes to Cholesterol-Lowering Statin Drugs. FDA.Google Scholar
Wagstaff, LR, Mitton, MW, Arvik, BM, et al (2003) Statin-associated memory loss: analysis of 60 case reports and review of the literature. Pharmacotherapy, 23: 871–80.CrossRefGoogle ScholarPubMed
Wang, W, Li, X (2024) Cognitive function in dyslipidemia patients: exploring the impact of statins. Frontiers in Neurology, 15: 1436010.CrossRefGoogle ScholarPubMed
Wong, KH, Xie, Y, Huang, X, et al (2020) Delivering crocetin across the blood-brain barrier by using γ-cyclodextrin to treat Alzheimer’s disease. Scientific Reports, 10: 3654.CrossRefGoogle ScholarPubMed
Xu, Q, Bernardo, A, Walker, D, et al (2006) Profile and regulation of apolipoprotein E (ApoE) expression in the CNS in mice with targeting of green fluorescent protein gene to the ApoE locus. The Journal of Neuroscience, 26: 4985–94.CrossRefGoogle Scholar
Yalcin, A, Soddu, E, Turunc, BE, et al (2016) Neuroprotective effects of engineered polymeric nasal microspheres containing hydroxypropyl-β-cyclodextrin on β-amyloid (1-42)-induced toxicity. Journal of Pharmaceutical Sciences, 105: 2372–80.CrossRefGoogle ScholarPubMed
Yao, J, Ho, D, Calingasan, NY, et al (2012) Neuroprotection by cyclodextrin in cell and mouse models of Alzheimer disease. Journal of Experimental Medicine, 209: 2501–13.CrossRefGoogle ScholarPubMed
Ye, Z, Deng, J, Wu, X, et al (2025) Association of statins use and genetic susceptibility with incidence of Alzheimer’s disease. Journal of Prevention of Alzheimer’s Disease, 12: 100025.CrossRefGoogle ScholarPubMed
Zhu, L, Fang, Y, Gao, B, et al (2022) Effect of an increase in Lp(a) following statin therapy on cardiovascular prognosis in secondary prevention population of coronary artery disease. BMC Cardiovascular Disorders, 22: 474.CrossRefGoogle Scholar
Submit a response

eLetters

No eLetters have been published for this article.