Adults with type 1 diabetes (T1D) are at increased risk for cognitive impairment, accelerated brain aging, and Alzheimer's disease and related dementias (ADRD). It is well-established that T1D is associated with small but meaningful deficits in cognitive performance across the lifespan,1., 2., 3. with increasing recognition that age-related cognitive decline is accelerated. Older adults with T1D accumulate risk factors for cognitive dysfunction and decline across the lifespan, including micro and macrovascular disease,4,5 chronic hyperglycemia,2,6., 7., 8. and severe hypoglycemia.9,10 Clinically meaningful mild cognitive impairment (MCI) is present in nearly a third of middle-aged adults2 and almost half of older adults with T1D.1 Further, there is evidence of neuroimaging abnormalities11., 12., 13., 14., 15., 16., 17., 18., 19., 20. and elevated Alzheimer's disease (AD) biomarkers measured by cerebrospinal fluid levels, including B-amyloid 42, phosphorylated Tau and soluble form of low-density lipoprotein receptor-related protein 112 by middle-age. Importantly, elevated relative risk for ADRD based on medical record system data is present by age 30–39 in adults with T1D, particularly for vascular dementia.21

Glycemic factors are important mediators of adverse cognitive outcomes in T1D, with long-term exposure to elevated blood glucose being associated with increased cognitive decline8 and ADRD risk.22 Additionally, exposure to severe hypoglycemia23,24 and continuous glucose monitoring (CGM) metrics24 have also been linked to MCI and ADRD in T1D. In particular, mean glucose at night was higher in those with cognitive impairment than those without, while CGM nocturnal % time below 60 mg/dL was associated with decreased odds of cognitive impairment.24 Glycemic factors, such as poorer glycemic control and longer exposure to higher HbA1c, are increasingly recognized as contributing to ADRD risk in the general population and individuals with type 2 diabetes (T2D) have an increased risk of cognitive decline and ADRD.21,25., 26., 27., 28., 29., 30. Despite these findings, longitudinal data on cognitive aging, MCI and ADRD with T1D are still relatively scarce.31., 32., 33. One notable exception to this is the DCCT/EDIC study which recently reported findings from 32-years of follow-up. While minimal cognitive decline was observed at the midlife assessment, more substantial decline, particularly in the psychomotor and mental efficiency domain, was apparent as the cohort moved into older adulthood (mean age 59; range 43–75). However, there was an 18-year gap between cognitive assessments in the EDIC study, and several questions remain, including the pace of cognitive decline and whether the DCCT/EDIC cohort is generalizable to the broader older adult population with T1D given stringent initial trial selection criteria. In addition, while cognitive decline was noted over time in the EDIC cohort, the clinical significance of this decline is not clear given the low proportion of participants who met criteria for cognitive impairment using the Montreal Cognitive Assessment (i.e., 5.5 % of the EDIC sample had a MoCA score < 21/30).

Characterizing cognitive change and clinically significant cognitive impairment over relatively short time periods in older adults with T1D is essential to guiding clinical care of this population as they age. The aims of this study were to 1) identify factors associated with cognitive performance and clinically significant cognitive impairment and 2) characterize change in cognition and impairment status in a sample of older adults with T1D who underwent longitudinal cognitive assessment using the NIH Toolbox Cognition Battery over 52 weeks.