June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Diabetic retinopathy and dementia link is more than microvascular disease and poor glycemic control mechanisms
Author Affiliations & Notes
  • Cecilia S Lee
    Department of Ophthalmology, University of Washington, Seattle, Washington, United States
  • Yu-Ru Su
    Kaiser Permanente Washington Health Research Institute, Seattle, Washington, United States
  • Chloe Krakauer
    Department of Biostatistics, University of Washington, Seattle, Washington, United States
  • Rod Walker
    Kaiser Permanente Washington Health Research Institute, Seattle, Washington, United States
  • Aaron Y Lee
    Department of Ophthalmology, University of Washington, Seattle, Washington, United States
  • Ann O’Hare
    Division of Nephrology, VA Puget Sound Health Care System, Seattle, Washington, United States
  • Eric B. Larson
    Kaiser Permanente Washington Health Research Institute, Seattle, Washington, United States
  • Paul K. Crane
    Department of Medicine, University of Washington, Seattle, Washington, United States
  • Footnotes
    Commercial Relationships   Cecilia Lee, None; Yu-Ru Su, None; Chloe Krakauer, None; Rod Walker, None; Aaron Lee, Carl Zeiss Meditec (F), Genentech (C), Novartis (F), NVIDIA (F), Santen (F), Topcon (R), US Food and Drug Administration (E), Verana Health (C); Ann O’Hare, None; Eric Larson, UpToDate (royalties) (I); Paul Crane, None
  • Footnotes
    Support  NIH/NIA R01AG060942 (Cecilia S. Lee); Latham Vision Innovation Award, and an unrestricted grant from Research to Prevent Blindness (Cecilia S. Lee and Aaron Y. Lee); NIH/NIP50 AG05136 and NIH/NIA U01AG006781 (Paul K. Crane and Eric B. Larson)
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 1171. doi:
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      Cecilia S Lee, Yu-Ru Su, Chloe Krakauer, Rod Walker, Aaron Y Lee, Ann O’Hare, Eric B. Larson, Paul K. Crane; Diabetic retinopathy and dementia link is more than microvascular disease and poor glycemic control mechanisms. Invest. Ophthalmol. Vis. Sci. 2021;62(8):1171.

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Abstract

Purpose : To evaluate the relationship between eye diseases-diabetic retinopathy (DR), age-related macular degeneration (AMD), and glaucoma-and the development of Alzheimer’s disease and related dementia (ADRD) and the extent to which these might be explained by poor glycemic control and retinal microvascular disease burden.

Methods : The Adult Changes in Thought (ACT) is a 25-year-old ongoing longitudinal study of dementia-free adults aged >65 followed for the development of ADRD. Among participants with diabetes, we used information from the electronic health record and ACT study visits to ascertain time-varying exposures of DR, AMD, and/or glaucoma at study entry or during follow-up and how established these conditions were (onset <5 vs ≥5 yrs ago). Using estimated glomerular filtration (eGFR) as a marker for retinal microvascular disease burden, we also computed time-varying estimates of mean level, trajectory, and variability of eGFR, as well as mean blood glucose (BG), using fasting/random glucose and HbA1C. We fit Cox models to estimate the relationship between each eye disease and risk of ADRD after adjusting for eGFR, BG, sex, education, >1APOE ε4, race, and smoking. The potential modifying effect of BG and eGFR were assessed by changes in the magnitude of each association from adjusted models.

Results : Over 3342.4 person-years of follow-up among 526 ACT participants with diabetes, 131(25%) developed dementia including 98 (19%) who developed AD. A total of 85,439 eGFR and 72,960 GB measures were available for analysis. DR was associated with the development of both AD and dementia (the association was similar in magnitude to APOE ε4). (Figure) The hazard ratios (HR) for established DR vs. no DR and established AMD vs. no AMD changed very little after adjustment for eGFR and BG (from 1.65 [p=0.04] to 1.67 [p=0.03] for DR), (from 1.66 [p=0.07] to 1.74 [p=0.045]). There was no association between glaucoma and either outcome.

Conclusions : An association between diabetic retinopathy and the development of Alzheimer’s and dementia in people with diabetes did not appear to be explained by markers of glycemic control and microvascular disease.

This is a 2021 ARVO Annual Meeting abstract.

 

Figure. Forest plots for estimated HRs (95% CIs) of Alzheimer’s and dementia with/without glucose/eGFR adjustments; reference groups “no eye diseases”. Dotted lines: p >0.05.

Figure. Forest plots for estimated HRs (95% CIs) of Alzheimer’s and dementia with/without glucose/eGFR adjustments; reference groups “no eye diseases”. Dotted lines: p >0.05.

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