Joshua I Barzilay1, Alokananda Ghosh2, Rodica Pop Busui3, Andrew Ahmann4, Ashok Balasubramanyam5, Mary Ann Banerji6, Robert M Cohen7, Jennifer Green8, Faramarz Ismail-Beigi9, Catherine L Martin3, Elizabeth Seaquist10, José A Luchsinger11. 1. Division of Endocrinology, Kaiser Permanente of Georgia and the Division of Endocrinology, Emory University School of Medicine, Atlanta, GA, United States of America. Electronic address: joshua.barzilay@kp.org. 2. The Biostatistics Center, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Rockville, MD, United States of America. 3. Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, United States of America. 4. Division of Endocrinology, Diabetes & Clinical Nutrition, Oregon Health & Science University, Portland, OR, United States of America. 5. Division of Diabetes, Endocrinology and Metabolism, Baylor College of Medicine, Houston, TX, United States of America. 6. State University of New York Downstate Medical Center, Kings County Hospital, Brooklyn, NY, United States of America. 7. Division of, Endocrinology, Diabetes, and Metabolism, University of Cincinnati College of Medicine and Cincinnati VA Medical Center, Cincinnati, OH, United States of America. 8. Department of Medicine, Division of Endocrinology, Duke University Medical Center, Durham, NC, United States of America. 9. Division of Endocrinology, Case Western Reserve University and Cleveland VA Medical Center, Cleveland, OH, United States of America. 10. Division of Diabetes and Endocrinology, Department of Medicine, University of Minnesota, Minneapolis, MN, United States of America. 11. Columbia University Irving Medical Center, Department of Medicine, New York, NY, United States of America; Columbia University Irving Medical Center, Department of Epidemiology, New York, NY, United States of America.
Abstract
BACKGROUND: Studies examining whether measures of cognition are related to the presence of diabetic peripheral neuropathy (DPN) and/or cardiovascular autonomic neuropathy (CAN) are lacking, as are data regarding factors potentially explaining such associations. METHODS: Participants were from the Glycemia Reduction Approaches in Diabetes Study (GRADE) that examined 5047 middle-aged people with type 2 diabetes of <10 years of known duration. Verbal learning and immediate and delayed recall (memory) were assessed with the Spanish English Verbal Learning Test; frontal executive function and processing speed with the Digit Symbol Substitution Test; and ability to concentrate and organize data with word and animal fluency tests. DPN was assessed with the Michigan Neuropathy Screening Instrument and CAN by indices of heart rate variability (standard deviation of normal beat to beat variation [SDNN] and root mean square of successive differences [RMSSD]). RESULTS: DPN was significantly inversely related to measures of immediate recall and processing speed. The percent of cognitive variation explained by DPN was small. Tests of CAN had an inconsistent or absent association with measures of cognition. Higher waist circumference and urine albumin creatinine (UACR) levels were the strongest correlates in the relationship between DPN and cognitive impairment. CONCLUSION: DPN, but not CAN, was cross-sectionally associated with lower performance in measures of cognition in people with type 2 diabetes of <10 years of known duration. Greater waist circumference and UACR were important variables in this association. The mechanisms underlying the cross-sectional association of DPN with cognitive impairment are unknown. Clinicaltrials.gov: NCT01794143.
BACKGROUND: Studies examining whether measures of cognition are related to the presence of diabetic peripheral neuropathy (DPN) and/or cardiovascular autonomic neuropathy (CAN) are lacking, as are data regarding factors potentially explaining such associations. METHODS: Participants were from the Glycemia Reduction Approaches in Diabetes Study (GRADE) that examined 5047 middle-aged people with type 2 diabetes of <10 years of known duration. Verbal learning and immediate and delayed recall (memory) were assessed with the Spanish English Verbal Learning Test; frontal executive function and processing speed with the Digit Symbol Substitution Test; and ability to concentrate and organize data with word and animal fluency tests. DPN was assessed with the Michigan Neuropathy Screening Instrument and CAN by indices of heart rate variability (standard deviation of normal beat to beat variation [SDNN] and root mean square of successive differences [RMSSD]). RESULTS: DPN was significantly inversely related to measures of immediate recall and processing speed. The percent of cognitive variation explained by DPN was small. Tests of CAN had an inconsistent or absent association with measures of cognition. Higher waist circumference and urine albumin creatinine (UACR) levels were the strongest correlates in the relationship between DPN and cognitive impairment. CONCLUSION: DPN, but not CAN, was cross-sectionally associated with lower performance in measures of cognition in people with type 2 diabetes of <10 years of known duration. Greater waist circumference and UACR were important variables in this association. The mechanisms underlying the cross-sectional association of DPN with cognitive impairment are unknown. Clinicaltrials.gov: NCT01794143.
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