title: Possible modification of Alzheimer's disease by statins in midlife: interactions with genetic and non-genetic risk factors.
abstract: The benefits of statins, commonly prescribed for hypercholesterolemia, in treating Alzheimer's disease (AD) have not yet been fully established. A recent randomized clinical trial did not show any therapeutic effects of two statins on cognitive function in AD. Interestingly, however, the results of the Rotterdam study, one of the largest prospective cohort studies, showed reduced risk of AD in statin users. Based on the current understanding of statin actions and AD pathogenesis, it is still worth exploring whether statins can prevent AD when administered decades before the onset of AD or from midlife. This review discusses the possible beneficial effects of statins, drawn from previous clinical observations, pathogenic mechanisms, which include β-amyloid (Aβ) and tau metabolism, genetic and non-genetic risk factors (apolipoprotein E, cholesterol, sex, hypertension, and diabetes), and other clinical features (vascular dysfunction and oxidative and inflammatory stress) of AD. These findings suggest that administration of statins in midlife might prevent AD in late life by modifying genetic and non-genetic risk factors for AD. It should be clarified whether statins inhibit Aβ accumulation, tau pathological features, and brain atrophy in humans. To answer this question, a randomized controlled study using amyloid positron emission tomography (PET), tau-PET, and magnetic resonance imaging would be useful. This clinical evaluation could help us to overcome this devastating disease.
authors.affiliation: Department of Clinical Gene Therapy, Graduate School of Medicine, Osaka University Suita, Japan ; Department of Geriatric Medicine, Graduate School of Medicine, Osaka University Suita, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Shinohara
authors.affiliation: Department of Clinical Gene Therapy, Graduate School of Medicine, Osaka University Suita, Japan ; Department of Geriatric Medicine, Graduate School of Medicine, Osaka University Suita, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Sato
authors.affiliation: Division of Vascular Medicine and Epigenetics, Department of Child Development, United Graduate School of Child Development, Osaka University Office for University-Industry Collaboration Suita, Japan.
authors.forename: Munehisa
authors.initials: M
authors.lastname: Shimamura
authors.affiliation: Division of Vascular Medicine and Epigenetics, Department of Child Development, United Graduate School of Child Development, Osaka University Office for University-Industry Collaboration Suita, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Kurinami
authors.affiliation: Department of Biomedical Statistics, Graduate School of Medicine, Osaka University Suita, Japan.
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Hamasaki
authors.affiliation: Department of Clinical Gene Therapy, Graduate School of Medicine, Osaka University Suita, Japan.
authors.forename: Amarnath
authors.initials: A
authors.lastname: Chatterjee
authors.affiliation: Department of Geriatric Medicine, Graduate School of Medicine, Osaka University Suita, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Rakugi
authors.affiliation: Department of Clinical Gene Therapy, Graduate School of Medicine, Osaka University Suita, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Morishita
keywords: Abeta; Alzheimer’s disease; isoprenoids; prevention; statin