Nrf2-Mediated Neuroprotection Against Recurrent Hypoglycemia Is Insufficient to Prevent Cognitive Impairment in a Rodent Model of Type 1 Diabetes

Objective: To assess associations between cognitive impairment and longitudinal changes in retinal microvasculature, over 18 years, in adults with type 1 diabetes. Research design and methods: Participants of the Pittsburgh Epidemiology of Diabetes Complications Study received ≥3 fundus photographs between baseline (1986–1988) and time of cognitive assessment (2010–2015: N = 119; 52% male; mean age and type 1 diabetes duration 43 and 34 years, respectively). Central retinal arteriolar equivalent and central retinal venular equivalent were estimated via computer-based methods; overall magnitude and speed of narrowing were quantified as cumulative average and slope, respectively. Median regression models estimated associations of central retinal arteriolar equivalent and central retinal venular equivalent measures with cognitive impairment status, adjusted for type 1 diabetes duration. Interactions with HbA1c, proliferative retinopathy and white matter hyperintensities were assessed. Results: Compared with participants without cognitive impairment, those with clinically relevant cognitive impairment experienced 1.8% greater and 31.1% faster central retinal arteriolar equivalent narrowing during prior years (t = −2.93, p = 0.004 and t = −3.97, p < 0.0001, respectively). Interactions with HbA1c, proliferative retinopathy and white matter hyperintensities were not significant. No associations were found between central retinal arteriolar equivalent at baseline, at time of cognitive testing, or any central retinal venular equivalent measures, and cognitive impairment. Conclusion: Long-term arterial retinal changes could indicate type 1 diabetes–related cognitive impairment. Studies examining longitudinal central retinal arteriolar equivalent changes as early biomarkers of cognitive impairment risk are warranted.

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Abstract P268: Greater Cognitive Impairment Among Older Adults With Type 1 Diabetes as Compared to Non-diabetic Controls: Results From the Study of Longevity in Diabetes (SOLID)

Circulation ◽

10.1161/circ.141.suppl_1.p268 ◽

2020 ◽

Vol 141 (Suppl_1) ◽

Author(s):

Mary E Lacy ◽

Paola Gilsanz ◽

Chloe Eng ◽

Michal S Beeri ◽

Andrew J Karter ◽

...

Keyword(s):

Older Adults ◽

Type 1 Diabetes ◽

Cognitive Impairment ◽

Executive Function ◽

Cognitive Function ◽

Episodic Memory ◽

Regression Models ◽

Cognitive Test ◽

Race Ethnicity

Introduction: Studies have shown poorer cognitive function in children and adolescents with type 1 diabetes (T1D) as compared to non-diabetic peers. However, little is known about cognitive function in older adults with T1D. Hypothesis: We hypothesized that older adults with T1D and type 2 diabetes (T2D) would have greater cognitive impairment than age, sex, race/ethnicity, and education-matched controls without diabetes. Methods: We compared baseline cognitive impairment among older adults (aged ≥60) from the Study of Longevity in Diabetes (SOLID) with T1D (n=771), T2D (=234) and no diabetes (n=253). Cognitive tests assessed three cognitive domains identified via factor analysis (language, executive function, episodic memory). All cognitive test scores were standardized and cognitive impairment was defined as 1.5 SD below the mean. In logistic regression models adjusted for age, sex, education, and race/ethnicity, we examined the association between diabetes status (T1D, T2D or no diabetes) and cognition on each cognitive domain and on global cognition (average of scores on the 3 domains). Results: In adjusted regression models, compared to older adults without diabetes, those with T1D were more likely to have impaired cognitive function on the language (OR=2.13, 95% CI: 1.08, 4.17) and executive function domains (OR=2.66, 95% CI: 1.36, 5.22). No significant differences in global cognitive impairment or impairment on the episodic memory domain were observed for T1D and no significant differences on any domain were observed for T2D. Conclusions: Our findings suggest that older adults with T1D have greater cognitive impairment than their peers without diabetes; findings were specific to the language and executive function domains, with episodic memory being unaffected. No increase in cognitive impairment was observed for older adults with T2D. Additional research is needed to understand the causes and potentially modifiable factors associated with impaired cognition among older adults with T1D.

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