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 - Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
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 -