GAD65 as a potential marker for cognitive performance in an adult population with prediabetes

Diabetes mellitus (DM) is a well-known risk factor for cognitive dysfunction in aged populations. However, there are inconsistent reports about impaired fasting glucose or prediabetes as an independent risk factor for cognitive function. Glutamic acid decarboxylase 65 (GAD65) is the key enzyme responsible for γ-aminobutyric acid synthesis in the central nervous system. Antibodies against GAD65 (GAD65Abs) are not only detected in approximately 80% of early-onset type 1 DM, but also linked to several neurological disorders.

This study aims to investigate the association between GAD65Ab titer levels and cognitive performance. In addition, we assessed the effect of GAD65Ab on cognitive function in adults with normal fasting glucose, prediabetes and DM.

A total of 328 subjects aged 49.10 ± 5.72 years were enrolled from the Third Health and Nutrition Examination Survey dataset. Cognitive performance was assessed by three computerized neurobehavioral tests, including the serial digit learning test, simple reaction time test (SRTT) and symbol-digit substitution test (SDST).

Subjects with higher GAD65Ab titers had significantly poorer cognitive function in the SRTT and SDST (P < 0.05). Additionally, GAD65Ab was associated with cognitive decline in non-diabetic adults after adjusting for a number of relevant variables (P < 0.05 in both SRTT and SDST).

These results indicate that GAD65Ab may be a potential marker for cognitive impairment in non-diabetic adults.