Alzheimer disease (AD), all-cause dementia, and vascular dementia are all more likely to occur in in patients with diabetes mellitus 2 (DM2) than without — and the risks for all-cause and vascular dementia continue to rise from onset of diabetic retinopathy (DR) through proliferative DR (PDR), indicates a study posted in the American Journal of Ophthalmology.

Researchers used the TriNetX database to gather a cohort of 769,930 individuals who were 65 years of age or older and had no macular edema.

They were divided into 4 groups: 447,054 healthy control individuals; 208,640 with DM2 but no DR; 29,188 presenting with nonproliferative diabetic retinopathy (NPDR); and 14,034 with proliferative diabetic retinopathy (PDR). Diagnostic eye exam or imaging took place between 2010 and 2020. Primary measures were dementia incidence and risks.

Routine ophthalmologic screening in patients with DM may provide an opportunity for early identification of individuals at higher risk of cognitive decline.

Compared with control individuals, all following hazard ratios (HRs) proved statistically significant:

DM2 but no DR reached HR 1.262 for all-cause dementia, 1.117 for AD, and 1.384 vascular dementia (VaD)

NPDR 1.405 all-cause dementia, 1.233 for AD, and 1.917 VaD

PDR 1.583 all-cause dementia, 1.175 for AD, and 2.077 VaD

Next, in reference to DM2 without DR, only all-cause and VaD proved significant:

NPDR scored HR of 1.113 for all-cause dementia, and 1.322 VaD

PDR 1.202 all-cause dementia, and 1.504 VaD

Further, Kaplan-Meier analysis revealed shorter time to all-cause or VaD in those with NPDR or PDR vs type 2 diabetes alone. Finally, compared with NPDR, PDR showed HR 1.121 for all-cause dementia (P =.0003), and 1.177 in VaD (P =.0126).

A notably higher risk for Alzheimer disease emerged only when looking at diabetes vs no diabetes. In contrast, two prior articles with smaller samples than the present investigation found higher AD risk in those with DR.

The literature indicates Alzheimer disease arises from processes that are not solely vascular. Previous studies report ocular vessel damage found in DR could parallel the level of systemic vascular injury. These small vessel pathways particularly relate to VaD.

“Routine ophthalmologic screening in patients with DM may provide an opportunity for early identification of individuals at higher risk of cognitive decline,” according to the investigators.

This research may be limited by potentially different coding approaches, and lack of data on education and economic level. Most centers are US-based. Also, the study followed patients only to 6.7 years.

Disclosures: One investigator has disclosed affiliations in the pharmaceutical, investment research, and biotech industries. Please see the original reference for complete disclosures.