1268-P: P-tau217 and Cognitive Function in Long-Duration Type 1 Diabetes

Introduction and Objective: People with diabetes have an increased risk of dementia. Plasma Phosphorylated Tau 217 (pTau217), a novel marker of Alzheimer’s disease (AD), hasn’t been examined in type 1 diabetes (T1D). Joslin Medalists (mean age 71 and T1D ≥50 years) had previously shown worse cognitive function compared to age-matched non-diabetic people (NDM). Thus, we examined the associations of pTau217 with cognitive function in Medalists. Methods: Plasma pTau217 (S-Plex, Meso Scale Discovery) was assayed in 164 Medalists who had undergone cognitive testing for psychomotor function (Grooved Pegboard), immediate and delayed recall (RAVLT), executive function (Delis Kaplan), and working memory (Wechsler). Poor cognitive function was defined as 1.5 SD deviation from means of NDM group. High pTau217 was defined using ≥7.3 pg/ml as the optimal cutoff-point for AD risk published previously. Associations between pTau217 and cognitive function were tested cross-sectionally in stepwise logistic regression models adjusted by age, sex, education, T1D duration, HbA1c, lipids, eGFR, and advanced glycation end-products (AGEs: carboxymethyl- and carboxyethyl-lysine). Results: Higher pTau217 associated with male sex, older age, longer diabetes duration, worse lipids and renal function, higher IL1β and AGEs, but not with HbA1c or continuous glucose monitoring metrics including hypoglycemia. Odds of having pTau217 ≥7.3 pg/ml were higher (p<0.05) among those with poor immediate (OR=3.8) and delayed (OR=2.7) recall. There was no association with other cognitive domains. Within people with poor cognitive function, a significant proportion (61%) had low pTau217 <7.3 pg/ml. Conclusion: Among older individuals with long-duration T1D, higher plasma pTau217 associated with poor recall, though AD risk may not explain a significant proportion of Medalists having poor cognitive function. Further studies are needed to examine if pTau217 associates with AD markers on PET scans or brain pathology in these individuals. Disclosure H. Shah: None. S. Jangolla: None. E.R. Viebranz: None. J. Gauthier: None. I. Wu: None. V. Bhagat: None. K. Park: None. M. Yu: None. A. Adam: None. G.L. King: None. Funding The Beatson Foundation; NIH/NIDDK (3P30DK036836-34S1)