title: Cognitive dysfunction associated with anti-glutamic acid decarboxylase autoimmunity: a case-control study.
abstract: 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.
authors.affiliation: Department of Behavioral Neurology and Cognitive Neuroscience, Tohoku University Graduate School of Medicine, Sendai, Japan. mastakagi@med.tohoku.ac.jp
authors.forename: Masahito
authors.initials: M
authors.lastname: Takagi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ishigaki
authors.forename: Kenji
authors.initials: K
authors.lastname: Uno
authors.forename: Shojiro
authors.initials: S
authors.lastname: Sawada
authors.forename: Junta
authors.initials: J
authors.lastname: Imai
authors.forename: Keizo
authors.initials: K
authors.lastname: Kaneko
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yamada
authors.forename: Ai
authors.initials: A
authors.lastname: Tokita
authors.forename: Kazumi
authors.initials: K
authors.lastname: Iseki
authors.forename: Shigenori
authors.initials: S
authors.lastname: Kanno
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Nishio
authors.forename: Hideki
authors.initials: H
authors.lastname: Katagiri
authors.forename: Etsuro
authors.initials: E
authors.lastname: Mori
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000704:Analysis of Variance; D000906:Antibodies / Q000378:metabolism*; D015551:Autoimmunity / Q000502:physiology*; D001921:Brain / Q000473:pathology; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000276:immunology* / Q000503:physiopathology*; D048909:Diabetes Complications / Q000503:physiopathology; D003920:Diabetes Mellitus / Q000276:immunology; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006801:Humans; D056784:Leukoencephalopathies; D008279:Magnetic Resonance Imaging; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009460:Neurologic Examination; D009483:Neuropsychological Tests
chemical_list: D000906:Antibodies; D005968:Glutamate Decarboxylase