Utility of the NIH Toolbox Cognition Battery in middle to older aged adults with longstanding type 1 diabetes: The DCCT/EDIC study

Abstract

Objective: Adults with type 1 diabetes (T1D) face an increased risk for cognitive decline and dementia. Diabetes-related and vascular risk factors have been linked to cognitive decline using detailed neuropsychological testing; however, it is unclear if cognitive screening batteries can detect cognitive changes associated with aging in T1D. Method: 1,049 participants with T1D (median age 59 years; range 43–74) from the Diabetes Control and Complications Trial (DCCT), and the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study, completed the NIH Toolbox Cognition Battery (NIHTB-C) and Montreal Cognitive Assessment (MoCA). Neuropsychological assessments, depression, glycated hemoglobin levels (HbA1c), severe hypoglycemia, T1D complications, and vascular risk factors were assessed repeatedly over 32 years to determine associations with current NIHTB-C performance. Available cognitive data was clinically adjudicated to determine cognitive impairment status. Results: NIHTB-C scores had moderate associations (r = 0.36–0.53) with concurrently administered neuropsychological tests. In multivariate models, prior severe hypoglycemic episodes, depression symptoms, nephropathy, lower BMI, and higher HbA1c and LDL cholesterol were associated with poorer NIHTB-C Fluid Cognition Composite scores. The NIHTB-C adequately detected adjudicated cognitive impairment (Area Under the Curve = 0.86; optimal cut score ≤90). The MoCA performed similarly (Area Under the Curve = 0.83; optimal cut score ≤25). Conclusions: The NIHTB-C is sensitive to the cognitive effects of diabetes-related and vascular risk factors, correlated with neuropsychological testing, and accurately detects adjudicated cognitive impairment. These data support its use as a screening test in middle to older aged adults with T1D to determine if referral for detailed neuropsychological assessment is needed.

Keywords:

• Type 1 diabetes
• NIH toolbox
• cognition
• aging
• validation

Authors’ contributions

NC, VRT, and CMR designed the analyses and wrote the manuscript. BHB, LMF, GML, RAG, SH, KF, AMJ wrote portions of the manuscript, reviewed, and edited the manuscript. VRT and BHB conducted the statistical analyses and prepared the tables and figures.

Industry support

Industry contributors have had no role in the DCCT/EDIC study but have provided free or discounted supplies or equipment to support participants’ adherence to the study: Abbott Diabetes Care (Alameda, CA), Animas (Westchester, PA), Bayer Diabetes Care (North America Headquarters, Tarrytown, NY), Becton, Dickinson and Company (Franklin Lakes, NJ), Eli Lilly (Indianapolis, IN), Extend Nutrition (St. Louis, MO), Insulet Corporation (Bedford, MA), Lifescan (Milpitas, CA), Medtronic Diabetes (Minneapolis, MN), Nipro Home Diagnostics (Ft. Lauderdale, FL), Nova Diabetes Care (Billerica, MA), Omron (Shelton, CT), Perrigo Diabetes Care (Allegan, MI), Roche Diabetes Care (Indianapolis, IN), and Sanofi-Aventis (Bridgewater, NJ).

Trial registration

clinicaltrials.gov NCT00360815 and NCT00360893

Guarantor statement

AMJ, CMR, and BHB are the guarantors of this work and, as such, had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. AMJ had final responsibility for the decision to submit for publication.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Data collected for the DCCT/EDIC study through June 30th, 2017 are available to the public through the NIDDK Central Repository (https://repository.niddk.nih.gov/studies/edic/). Data collected in the current cycle (July 2017–June 2022) will be available within two years after the end of the funding cycle.

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

The DCCT/EDIC has been supported by cooperative agreement grants [1982–1993, 2012–2017, 2017–2022], and contracts [1982–2012] with the Division of Diabetes Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Disease [current grant numbers U01 DK094176 and U01 DK094157], and through support by the National Eye Institute, the National Institute of Neurologic Disorders and Stroke, the General Clinical Research Centers Program (1993–2007), and Clinical Translational Science Center Program (2006–present), Bethesda, Maryland, USA. The funding source had no role in the study design, collection, analysis, interpretation of the data, or in the writing of the report.