The cross-sectional association of cognition with diabetic peripheral and autonomic neuropathy-The GRADE study

J Diabetes Complications. 2021 Dec;35(12):108047. doi: 10.1016/j.jdiacomp.2021.108047. Epub 2021 Sep 15.


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. NCT01794143.

Keywords: Cardiovascular autonomic neuropathy; Cognitive tests; Diabetes; Diabetic peripheral neuropathy.

Publication types

  • Clinical Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Autonomic Nervous System Diseases / etiology
  • Cardiovascular Diseases / complications
  • Cognition
  • Cognition Disorders* / diagnosis
  • Cognition Disorders* / etiology
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2* / complications
  • Diabetic Neuropathies* / complications
  • Female
  • Humans
  • Male
  • Middle Aged
  • Peripheral Nervous System Diseases / etiology

Associated data