TY - JOUR
T1 - Cognitive dysfunction associated with anti-glutamic acid decarboxylase autoimmunity
T2 - A case-control study
AU - Takagi, Masahito
AU - Ishigaki, Yasushi
AU - Uno, Kenji
AU - Sawada, Shojiro
AU - Imai, Junta
AU - Kaneko, Keizo
AU - Hasegawa, Yutaka
AU - Yamada, Tetsuya
AU - Tokita, Ai
AU - Iseki, Kazumi
AU - Kanno, Shigenori
AU - Nishio, Yoshiyuki
AU - Katagiri, Hideki
AU - Mori, Etsuro
N1 - Funding Information:
This study was partially supported by the Global COE Program (Basic & Translational Research Center for Global Brains Science), MEXT, and Health, Labour Science Research Grants (Research on Dementia) from Ministry of Health, labour and Welfare, Japan. The authors thank Dr. Shunji Mugikura and Professor Shoki Takahashi for performing the MRI data acquisition and Dr. Hiroshi Yamasaki for helpful advice. We also acknowledge the great support and encouragement of Professor Yoshitomo Oka.
PY - 2013/7/9
Y1 - 2013/7/9
N2 - Background: Glutamic acid decarboxylase (GAD) is the rate-limiting enzyme in the synthesis of γ-aminobutyric acid (GABA). Anti-GAD antibodies (GADA) are associated with the progression of stiff person syndrome and other neurological diseases, as well as the immune-mediated (type 1) diabetes. GABA is one of the most widely distributed neurotransmitters, but the non-motor symptoms of GADA-positive patients are not well understood. Diabetes is increasingly recognized as a risk factor for dementia; however, the relationship between diabetes and dementia is controversial.The objective of this study was to assess cognitive function in patients with GADA-positive diabetes using subjects with GADA-negative type 2 diabetes as controls.Methods: Twenty-one patients with GADA-positive diabetes (mean age 52.5 ± 12.3 years, mean duration 7.7 ± 6.6 years) and 19 control subjects with GADA-negative type 2 diabetes (mean age 53.4 ± 8.9 years, mean duration 12.5 ± 6.7) were included in the study. The subjects underwent extensive neuropsychological testing and brain MRI.Results: The neuropsychological test scores were lower in the GADA-positive group than the control group (GADA-negative). Twelve subjects (57%) in the GADA group and 4 subjects (21%) in the control group had low performances (p = 0.027). No statistically significant differences were found between the GADA and control groups regarding demographics, diabetic severity cardiovascular risks, cerebral T2 hyperintensities, white matter volume and gray matter volume.Conclusions: Our study showed that GADA-positive diabetic patients have an increased risk of cognitive decline compared to patients with type 2 diabetes of comparable diabetic severity. It also showed that GADA may be associated with isolated cognitive decline in the absence of other neurological complications.
AB - Background: Glutamic acid decarboxylase (GAD) is the rate-limiting enzyme in the synthesis of γ-aminobutyric acid (GABA). Anti-GAD antibodies (GADA) are associated with the progression of stiff person syndrome and other neurological diseases, as well as the immune-mediated (type 1) diabetes. GABA is one of the most widely distributed neurotransmitters, but the non-motor symptoms of GADA-positive patients are not well understood. Diabetes is increasingly recognized as a risk factor for dementia; however, the relationship between diabetes and dementia is controversial.The objective of this study was to assess cognitive function in patients with GADA-positive diabetes using subjects with GADA-negative type 2 diabetes as controls.Methods: Twenty-one patients with GADA-positive diabetes (mean age 52.5 ± 12.3 years, mean duration 7.7 ± 6.6 years) and 19 control subjects with GADA-negative type 2 diabetes (mean age 53.4 ± 8.9 years, mean duration 12.5 ± 6.7) were included in the study. The subjects underwent extensive neuropsychological testing and brain MRI.Results: The neuropsychological test scores were lower in the GADA-positive group than the control group (GADA-negative). Twelve subjects (57%) in the GADA group and 4 subjects (21%) in the control group had low performances (p = 0.027). No statistically significant differences were found between the GADA and control groups regarding demographics, diabetic severity cardiovascular risks, cerebral T2 hyperintensities, white matter volume and gray matter volume.Conclusions: Our study showed that GADA-positive diabetic patients have an increased risk of cognitive decline compared to patients with type 2 diabetes of comparable diabetic severity. It also showed that GADA may be associated with isolated cognitive decline in the absence of other neurological complications.
KW - Anti-glutamic acid decarboxylase antibodies
KW - Cognitive impairment
KW - Diabetes mellitus
KW - GABAergic neural system
KW - Stiff-person syndrome
KW - Voxel-based morphometry
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U2 - 10.1186/1471-2377-13-76
DO - 10.1186/1471-2377-13-76
M3 - Article
C2 - 23835051
AN - SCOPUS:84880016724
VL - 13
JO - BMC Neurology
JF - BMC Neurology
SN - 1471-2377
M1 - 76
ER -
