Open-angle glaucoma and Alzheimer's disease: a population-based 30-year follow-up study.

Abstract

Open-angle glaucoma (OAG) and Alzheimer's disease (AD) are two age-related neurodegenerative disorders of significant public health importance. Similarities between the two disorders have raised the question of whether they share common risk factors or if one condition has an influence on the other. This study was undertaken to examine the relationship between OAG and AD in a cohort of people 65–74 years of age. In 1984–1986, a population survey was conducted in the municipality of Tierp, in south-central Sweden. Of the eligible number of 838 residents, 760 underwent a detailed eye examination (Ekström 1996). One individual joined the cohort after being examined in 1993. Thus, this part of the cohort comprised 761 subjects. To expand the sample size, 968 patients were recruited by means of glaucoma case records established at the Eye Department in Tierp in 1978–2007. With the exception of visual field testing, they underwent an eye examination that was identical to that of the population survey. Of the total number of 1,729 people, 118 were defined as ineligible for the study. At least 2 years of follow-up was required before new cases of dementia were accepted. Consequently, data for 68 participants who reached an endpoint within 2 years were removed. Ten individuals did not want to take part in the study. The remaining 1533 constituted the study cohort. The research was approved by the Regional Ethical Review Board of Uppsala University. Follow-up started after the baseline examination and ended on 31 December 2015. Medical records were reviewed to identify subjects diagnosed with dementia. If the word dementia was found anywhere in the text, pertinent parts of the records were copied and de-identified. A geriatrician (LK) that was not cognizant of the baseline data approved the diagnoses. For this study, ‘pure AD’ was combined with ‘mixed’ and ‘unspecified dementia’ into a single category. To qualify for a diagnosis of OAG, a reproducible visual field defect was a prerequisite. Follow-up time was calculated from the baseline to the date of the dementia diagnosis, death, migration out of Uppsala County or the end of the study, whichever occurred first. Cox proportional hazard models were developed to assess the effect of OAG on the risk of developing AD. By the end of the study, 326 cases of dementia had been identified, 281 of whom had AD, mixed dementia or unspecified dementia. Of the 281 cases, 51 had definite OAG in either eye at baseline. Cox models included age, gender, participating in the population survey, smoking habits, diabetes mellitus, systemic hypertension, ischaemic heart disease and OAG. The ultimate model is presented in Table 1. Higher age and ischaemic heart disease were the only predictors found to be associated with AD. However, there was evidence of interaction between age and gender. Spanning 30 years, this study on a defined population is the longest follow-up study on OAG and the risk of developing AD yet to be reported. Contrary to a recent publication (Lin et al. 2014), OAG was found not to be a risk factor. Two main hypotheses have been proposed to explain the connection between OAG and AD. The first hypothesis includes a common neurodegenerative process involving activation of enzymatic caspases and the production of neurotoxic amyloid β (McKinnon 2003). The second hypothesis implicates optic nerve damage as a consequence of an abnormally high-pressure difference across the lamina cribrosa in AD (Wostyn et al. 2009). It is beyond the scope of this report to discuss which of these hypotheses, if any, is most plausible. However, our findings do not corroborate an association between the two disorders.