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Comorbid Ophthalmic, Systemic Conditions Linked With Higher Risk of Dementia


People with both ophthalmic and systemic conditions were found to be at higher risk of dementia compared with those with only 1 such condition. Some ophthalmic conditions—age-related macular degeneration, cataract, and diabetes-related eye disease—also increased risk on their own.

Incidence of dementia is significantly higher in patients with ophthalmic and systemic diseases, with risk increasing for those with both conditions, according to study findings published this week in the British Journal of Ophthalmology.

In considering modifiable risk factors for the prevention of dementia, a disease with no effective treatment to stop its progression, several systemic conditions have been identified to increase risk, including obesity, depression, hypertension, diabetes, heart disease, and stroke.

Moreover, vision impairment has been indicated as one of the first manifestations of the development of dementia, in which loss of visual input potentially leads to reduced activation in central sensory pathways and subsequently increased risk of cognitive load and brain structure damage.

“Ophthalmic and systemic conditions are frequently clustered in pairs, as they are all heavily age-related conditions,” noted researchers. “Therefore, an increased risk of dementia associated with ophthalmic conditions may be due to their positive associations with systemic conditions such as obesity and cardiovascular disorders.”

Seeking to explore the independent and interactive associations of both ophthalmic and systemic conditions with dementia, researchers conducted a prospective cohort study of 12,364 adults aged 55 to 73 years registered in the UK Biobank. Participants were assessed at baseline, between 2006 and 2010, and were followed up until 2021, with incident dementia identified using hospital inpatient, death records, and self-reported data.

Ophthalmic conditions examined in the study included age-related macular degeneration (AMD), cataract, glaucoma, and diabetes-related eye disease (DRED; diabetic retinopathy, diabetic AMD, diabetes-related cataract, and diabetes-related glaucoma).

Evaluated systemic conditions consisted of stroke, high blood pressure, diabetes, and heart disease (heart attack and angina). Depression was also assessed as a nonophthalmic condition in the analysis.

Across the 1,263,513 person-years of follow-up, 2304 cases of incident dementia were identified in the study cohort. After adjusting for covariates such as dietary intake and lifestyle, results showed significant associations between all-cause dementia and all assessed ophthalmic conditions at baseline except for glaucoma:

  • AMD (multivariable-adjusted HR, 1.26; 95% CI, 1.05-1.52)
  • Cataract (multivariable-adjusted HR, 1.11; 95% CI, 1.00-1.24)
  • DRED (multivariable-adjusted HR, 1.61; 95% CI, 1.30-2.00)

Furthermore, diabetes, heart disease, stroke, and depression at baseline were all associated with an increased risk of dementia.

In regards to comorbid ophthalmic and systemic conditions, participants with cataract and a systemic condition were 1.19 to 2.29 times more likely to develop dementia, whereas people with DRED and a systemic condition were 1.50 to 3.24 times more likely to develop dementia, all compared with those without both corresponding conditions.

AMD with any systemic condition as a comorbidity was associated with an increased risk of dementia, with AMD and diabetes associated with the highest risk for incident dementia (HR, 2.73; 95% CI, 1.79-4.17).

Diabetes, hypertension, heart disease, depression, and stroke newly identified during follow-up were indicated to mediate the association between cataract and incident dementia, as well as the association between DRED and incident dementia.


Shang X, Zhu Z, Huang Y, et al. Associations of ophthalmic and systemic conditions with incident dementia in the UK Biobank. Br J Ophthalmol. Published online September 13, 2021. doi:10.1136/bjophthalmol-2021-319508

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