Retinal Vein Occlusion Could Serve as Age-Dependent Risk Factor for Dementia

Jakob Grauslund, DMSci, PhD, MD
Credit: University of Southern Denmark

An analysis of data from a prospective nationwide cohort study of more than 2.2 million older adults suggests retinal vein occlusion could serve as an age-dependent marker of incident dementia risk.

Leveraging data from Danish national health registers, adjusted analyses of data from more than 2 decades suggest those with a diagnosis of retinal vein occlusion were at increased risk of all-cause dementia, but this risk was not apparent among those with retinal vein occlusion after 75 years of age.¹

“This study establishes that individuals with a [retinal vein occlusion] debut before 75 years of age have an independently increased risk of incident all-cause dementia. Individuals older than 75 years when diagnosed with a [retinal vein occlusion] are at lower risk of all-cause dementia, but this should be interpreted with care," wrote investigators.¹

As the population In the US and globally continues to age, the impact on health systems is becoming more and more apparent. The impact of strides made in the earlier portions of the 21st century have shown promise in the form of reduced dementia rates. However, a greater understanding of risk factors could stand to have a significant benefit on individual and population-level health.^2,3

With this in mind, a team led by Jakob Grassland, DMSci, PhD, MD, of the University of Southern Denmark, sought to assess whether or not retinal vein occlusion could serve as an age-dependent risk factor for dementia in older adults, citing previous work suggesting an association with increased risk not fully explained by shared risk factors.¹

The primary outcome of interest for the study was all-cause dementia. Investigators noted this included Alzheimer disease and vascular dementia as well as mixed and unspecified dementia defined by diagnostic codes. Investigators used vascular dementia and Alzheimer disease as isolated endpoints for secondary outcomes. Investigators sought to estimate the hazard ratio (HR) for retinal vein occlusion using Cox regression analysis.¹

Investigators included all Danish citizens aged older than 65 years beginning on January 1, 1998 and through December 31, 2020, which were the sampling start and end of inclusion dates, respectively. For the purpose of analysis, follow-up occurred through December 31, 2022.¹

Overall, 2,205,152 people were identified for inclusion in the study. Of these, 19,669 received a diagnosis of retinal vein occlusion during the study period. Relative to those who did not, patients with retinal vein occlusion were more likely to be older at inclusion (P=.008, k-sample test), to have cardiovascular diseases (P=.004, χ2 test), COPD (P <.001), obstructive sleep apnea (P=.035), chronic kidney disease (P <.001), dyslipidemia (P <.001), arterial hypertension (P <.001), diabetes (P <.001), glaucoma (P <.001), to be divorced/widowed, and never married (P=.005).¹

Upon analysis, results suggested those who received a diagnosis of retinal vein occlusion younger than 75 years of age had an increased risk of all-cause dementia (aHR, 1.09; 95% Confidence Interval [CI], 1.01–1.18). In contrast, those older than 75 years of age receiving a diagnosis of retinal vein occlusion had a reduced risk of all-cause dementia (aHR, 0.92; 95% CI, 0.86-0.98).¹

A similar trend was observed in the secondary analysis for Alzheimer disease, with those diagnosed with retinal vein occlusion younger than 75 years of age (aHR, 1.10; 95% CI, 0.98-1.23) appeared to be at increased risk while their counterparts receiving a diagnosis after 75 years of age (aHR, 0.95; 95% CI, 0.85-1.05) having a reduced risk. In contrast, increased risk was observed in both age groups when assessing risk of vascular dementia as an isolated endpoint.¹

“[Retinal vein occlusion] is not independently associated with [Alzheimer disease] or [vascular dementia], but the exposed individuals have a higher incidence, indicating the need for risk factor assessment and treatment in patients seen at hospitals with a [retinal vein occlusion],” investigators added.¹

References:

1. Clausen AR, Stokholm L, Frederiksen KH, et al. Retinal vein occlusion as an age-dependent marker of incident dementia in a long-term Danish national cohort [published online ahead of print, 2023 Oct 24]. Acta Ophthalmol. 2023;10.1111/aos.15797. doi:10.1111/aos.15797
2. Cheng X, Yang Y, Schwebel DC, et al. Population ageing and mortality during 1990-2017: A global decomposition analysis. PLoS Med. 2020;17(6):e1003138. Published 2020 Jun 8. doi:10.1371/journal.pmed.1003138
3. Hudomiet P, Hurd MD, Rohwedder S. Trends in inequalities in the prevalence of dementia in the United States. Proc Natl Acad Sci U S A. 2022;119(46):e2212205119. doi:10.1073/pnas.2212205119