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Association of Brain-Derived Neurotrophic Factor With Cognitive Function

An Investigation of Sex Differences in Patients With Type 2 Diabetes

Zhen, Yan-Feng MD, PhD; Liu, Xing-Yu MD; Li, Yu-Kai MD; Fang, Hui MD; Cassidy, Ryan M. MD; Zhang, Xiang Yang MD, PhD

doi: 10.1097/PSY.0000000000000709

Objective Although a reduction in brain-derived neurotrophic factor (BDNF) has been implicated as a cause of cognitive impairment in type 2 diabetes mellitus (T2DM), the role of sex in moderating this effect has not been explored.

Methods We compared the difference in serum BDNF and performance on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) between 96 men and 134 women with T2DM. We compared this with the difference in serum BDNF and performance in the control group (104 men, 144 women).

Results Patients with T2DM performed worse on most RBANS indices (η2 = 0.372, all p < .05); within T2DM patients, men performed worse than women on the delayed memory score (74.1 (12.1) versus 79.9 (11.5), p = .002) and on the total score (71.4 (11.5) versus 76.5 (10.8), p = .025). Serum BDNF was lower in patients with T2DM versus controls (7.5 (2.7) ng/ml versus 11.5 (2.7) ng/ml, p < .001), and in men compared with women (6.9 (2.4) versus 7.9 (2.8), p = .024). Serum BDNF levels positively correlated with delayed memory score in patients with T2DM (β = 0.19, p = .007). However, this association was only observed in women, not in men (pinteraction = 0.04). Among healthy controls, no sex differences were noted in either RBANS or BDNF levels (η2 = 0.04, Cohen's d < 0.163, all p > .05).

Conclusions Our results show sex differences in poorer cognitive performance, lower BDNF concentration, and their relationship in T2DM patients, suggesting that female sex may be a protective factor for cognitive decline in T2DM patients. However, the findings should be regarded as preliminary because of the cross-sectional design and chronicity of the diabetes.

From the Departments of Endocrinology (Zhen, Li, Fang) and Neurosurgery (Liu), Tangshan Gongren Hospital, Tangshan, China; the Department of Psychiatry and Behavioral Sciences (Cassidy), The University of Texas Health Science Center at Houston, Texas; and CAS Key Laboratory of Mental Health (Zhang), Institute of Psychology, Chinese Academy of Sciences, Beijing, China.

Address correspondence to Hui Fang, MD, Department of Endocrinology, Tangshan Gongren Hospital, No. 27, Wenhua Rd, Lubei District, Tangshan City, Hebei Province, China. E-mail:; Xiang Yang Zhang, MD, PhD, CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, 16 Lincui Rd, Chaoyang District, Beijing 100101, China. E-mail:

Zhen and Liu have contributed equally to this study, and they should be regarded as joint first authors.

Received for publication July 12, 2018; revision received March 31, 2019.

Online date: May 13, 2019

Copyright © 2019 by American Psychosomatic Society
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