Treatment of agitation in people with Alzheimer's dementia: Rationale for the clinical investigation of AVP-923 (dextromethorphan/quinidine)

Background: Dementia and glaucoma have been hypothesized to be connected, through common risk factors or common mechanisms. Our aim was to evaluate the longitudinal relationship between open-angle glaucoma (OAG) and incident dementia.Methods: The 3C Bordeaux-Alienor study is a population-based cohort of 812 participants aged 72 years and over, followed-up three years. An eye examination was performed and OAG was classified according to optic nerve damage and visual field loss. Incident dementia was actively screened and confirmed by a neurologist. Results: A total of 41 participants developed a dementia over the three-year followup. Future incident dementia cases had more often a diagnosis of OAG (in 17.5% vs 4.5% for non-demented, p1⁄40.003). After adjustment for age, gender, education, family history of glaucoma, vascular comorbidities, and apolipoprotein e4, OAG participants had a nearly four-time increased risk of developing dementia over the three years of follow-up (OR1⁄43.8, 95%CI 1.5-10.1, p1⁄40.006). An increased risk of dementia was also evidenced for two markers of optic nerve degeneration (vertical cup:disc ratio and minimal rim:disc ratio) whereas no association was found between ocular hypertension and incident dementia. Conclusions: If this association between OAG and dementia is confirmed, direct and non-invasive quantification of the amount of retinal ganglion cell axonal loss might represent a useful biomarker of cerebral axonal loss in the future. It may also offer new breakthroughs in the understanding of the pathophysiological mechanisms underlying both diseases.