Combination Ocular, Systemic Conditions Increase Dementia Risk

Senile Macular Degeneration
Age Related Macular Degeneration, Also Called Senile Macular Degeneration. Photograph Of The Back Of Eye. (Photo By BSIP/UIG Via Getty Images)
Patients with diabetes had an increased dementia risk if they also had diabetic retinopathy, compared with those without it.

The presence of age-related macular degeneration (AMD), cataract, or diabetes-related eye disease (DRED) with a systemic condition such as heart disease or diabetes is associated with an increased risk of incident dementia, according to research results published in the British Journal of Ophthalmology. 

Researchers reviewed data from the UK Biobank study to evaluate the independent and interactive associations between ophthalmic and systemic conditions with incident dementia. These data were also evaluated to determine if the clustering of these conditions was associated with an increased dementia risk. 

Ophthalmic conditions were defined based on clinical review; systemic conditions were defined based on self-reported data or patient interviews. Investigators determined incident dementia diagnosis via hospital inpatient records, death records, and self-reported data. 

A total of 502,505 participants were assessed at baseline. After exclusion criteria were applied, a total of 112,364 adults (54% women; mean age, 62.4±4.1 years) remained. Patients with incident dementia were more likely to be older men with APOE4 vs those without incident dementia

Within a total of 1,263,513 person-years of follow-up, (median follow-up, 11.0 years; IQR 10.7-11.7 years), a total of 2304 new cases of incident all-cause dementia, 945 new cases of Alzheimer disease, and 513 new cases of vascular dementia were identifier. 

Within the group of participants who had ophthalmic conditions at baseline, patients with AMD developed all-cause dementia at a rate of 2.94 cases per 1000 person-years, vs 1.78 per 1000 person-years among those without age-related macular degeneration (multivariable adjusted hazard ratio [HR], 1.26; 95% CI, 1.05-1.52). The multivariable adjusted HR of dementia associated with cataract was 1.11 (95% CI, 1.00-1.24), while the multivariable adjusted HR associated with DRED was 1.61 (95% CI, 1.30-2.00). 

Glaucoma was associated with an elevated risk of vascular dementia, but not Alzheimer disease (HR, 1.48 and 0.89, respectively), nor was it associated with all-cause dementia after adjusting for confounders (HR, 1.07). 

The presence of stroke only, heart disease only, hypertension only, and depression only at baseline were all independently associated with an increased risk of dementia. The combination of AMD plus any systemic condition as a comorbidity was associated with an increased dementia risk, which was larger than the risk associated with AMD only or a systemic condition only. 

AMD and diabetes were associated with the highest incident dementia risk (HR, 2.73; 95% CI, 1.79-4.17), followed by AMD and obesity (HR, 1.88; 95% CI, 1.35-2.63). 

Cataract only was not independently associated with an increased incident dementia risk, however cataract with comorbid stroke, heart disease, hypertension, diabetes, depression, or any systemic condition was associated with an increased dementia risk. 

Among ophthalmic conditions, DRED only was associated with the largest incident dementia risk. Those with DRED plus a systemic comorbid condition were between 1.50 and 3.24 times more likely to develop dementia compared with those without DRED and the corresponding comorbidity. 

Glaucoma only was not significantly correlated with incident all-cause dementia, unless it co-occurred with stroke, heart disease, diabetes, hypertension, or depression. 

The association between cataract and incident dementia explained by diabetes, hypertension, heart disease, depression, and stroke was 9.2%, 7.1%, 9.1%, 12%, and 22.4%, respectively; this association was fully mediated by the combination of these significant mediators (65.4%; 95% CI, 5.3%-98.5%). 

Patients with diabetic retinopathy had an increased dementia risk compared with those without among patients with diabetes at baseline (HR, 1.65; 95% CI, 1.25-2.16). When those who developed dementia within the first 5 years of follow-up were excluded, multivariable-adjusted HRs for dementia and AMD, cataract, DRED, and glaucoma were 1.28, 1.13, 1.65, and 1.09, respectively. HRs for dementia associated with 1 and ≥2 ophthalmic conditions were 1.11 and 1.55, respectively. 

Study limitations include the self-report nature of ophthalmic conditions, the potential miscapture of some dementia cases, the timeline of documented dementia development before eye diseases due to the nature of the prodromal dementia period, and the lack of generalizability to patients outside of the UK Biobank cohort. 

The researchers found AMD, cataract, and DRED “associated with an increased risk of dementia, [and] individuals with both ophthalmic and systemic conditions are at a higher risk of dementia compared with those with an ophthalmic or systemic condition only,” the study says.


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