Characterization of cognitive decline in long-duration type 1 diabetes by cognitive, neuroimaging and pathological examinations

Hetal S. Shah; Matthew N. DeSalvo; Anastasia Haidar; Surya Vishva Teja Jangolla; Marc Gregory Yu; Rebecca S. Roque; Amanda Hayes; John Gauthier; Nolan Ziemniak; Elizabeth Viebranz; I-Hsien Wu; Kyoungmin Park; Ward Fickweiler; Tanvi J. Chokshi; Tashrif Billah; Lipeng Ning; Atif Adam; Jennifer K. Sun; Lloyd Paul Aiello; Yogesh Rathi; Mel B. Feany; George L. King

doi:10.1172/jci.insight.180226

Characterization of cognitive decline in long-duration type 1 diabetes by cognitive, neuroimaging and pathological examinations

Hetal S. Shah,¹ Matthew N. DeSalvo,² Anastasia Haidar,³ Surya Vishva Teja Jangolla,¹ Marc Gregory Yu,¹ Rebecca S. Roque,¹ Amanda Hayes,¹ John Gauthier,¹ Nolan Ziemniak,¹ Elizabeth Viebranz,¹ I-Hsien Wu,¹ Kyoungmin Park,¹ Ward Fickweiler,¹ Tanvi J. Chokshi,¹ Tashrif Billah,³ Lipeng Ning,³ Atif Adam,¹ Jennifer K. Sun,¹ Lloyd Paul Aiello,¹ Yogesh Rathi,² Mel B. Feany,⁴ and George L. King¹

Published January 30, 2025 - More info

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Abstract

BACKGROUND. We aimed to characterize factors associated with the under-studied complication of cognitive decline in aging people with long-duration type 1 diabetes (T1D).

METHODS. Joslin “Medalists” (n = 222; T1D ≥ 50 years) underwent cognitive testing. Medalists (n = 52) and age-matched non-diabetic controls (n = 20) underwent neuro- and retinal imaging. Brain pathology (n = 26) was examined. Relationships amongst clinical, cognitive and neuroimaging parameters were evaluated.

RESULTS. Compared to controls, Medalists had worse psychomotor function and recall, which associated with female gender, lower visual acuity, reduced physical activity, longer diabetes duration and higher inflammatory cytokines. On neuroimaging, compared to controls, Medalists had significantly lower total and regional brain volumes, equivalent to 9 years of accelerated aging, but small vessel disease markers did not differ. Reduced brain volumes associated with female sex, reduced psychomotor function, worse visual acuity, longer diabetes duration and higher inflammation, but not with glycemic control. Worse cognitive function, lower brain volumes, and diabetic retinopathy correlated with thinning of the outer retinal nuclear layer. Worse baseline visual acuity associated with declining psychomotor function in longitudinal analysis. Brain volume mediated the association between visual acuity and psychomotor function by 57%. Brain pathologies showed decreased volumes, but predominantly mild vascular or Alzheimer’s-related pathology.

CONCLUSION. This first comprehensive study of cognitive function, neuroimaging and pathology in aging T1D individuals demonstrated that cognitive decline was related to parenchymal rather than neurovascular abnormalities, unlike type 2 diabetes, suggestive of accelerated aging in T1D. Improving visual acuity could perhaps be an important preventive measure against cognitive decline in people with T1D.

Characterization of cognitive decline in long-duration type 1 diabetes by cognitive, neuroimaging and pathological examinations

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Characterization of cognitive decline in long-duration type 1 diabetes by cognitive, neuroimaging and pathological examinations

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