title: Diabetes mellitus is independently associated with more severe cognitive impairment in Parkinson disease.
abstract: BACKGROUND
  There is increasing interest in interactions between metabolic syndromes and neurodegeneration. Diabetes mellitus (DM) contributes to cognitive impairment in the elderly but its effect in Parkinson disease (PD) is not well studied.
  
  
  OBJECTIVE
  To investigate effects of comorbid DM on cognition in PD independent from PD-specific primary neurodegenerations.
  
  
  METHODS
  Cross-sectional study. Patients with PD (n = 148); age 65.6 ± 7.4 years, Hoehn and Yahr stage 2.4 ± 0.6, with (n = 15) and without (n = 133) comorbid type II DM, underwent [(11)C]methyl-4-piperidinyl propionate (PMP) acetylcholinesterase (AChE) PET imaging to assess cortical cholinergic denervation, [(11)C]dihydrotetrabenazine (DTBZ) PET imaging to assess nigrostriatal denervation, and neuropsychological assessments. A global cognitive Z-score was calculated based on normative data. Analysis of covariance was performed to determine cognitive differences between subjects with and without DM while controlling for nigrostriatal denervation, cortical cholinergic denervation, levodopa equivalent dose and education covariates.
  
  
  RESULTS
  There were no significant differences in age, gender, Hoehn and Yahr stage or duration of disease between diabetic and non-diabetic PD subjects. There was a non-significant trend toward lower years of education in the diabetic PD subjects compared with non-diabetic PD subjects. PD diabetics had significantly lower mean (±SD) global cognitive Z-scores (-0.98 ± 1.01) compared to the non-diabetics (-0.36 ± 0.91; F = 7.78, P = 0.006) when controlling for covariate effects of education, striatal dopaminergic denervation, and cortical cholinergic denervation (total model F = 8.39, P < 0.0001).
  
  
  CONCLUSIONS
  Diabetes mellitus is independently associated with more severe cognitive impairment in PD likely through mechanisms other than disease-specific neurodegenerations.
authors.affiliation: Department of Radiology, University of Michigan, Ann Arbor, MI, USA; Department of Neurology, University of Michigan, Ann Arbor, MI, USA; Neurology Service and GRECC, VAAAHS, Ann Arbor, MI, USA. Electronic address: nbohnen@umich.edu.
authors.forename: Nicolaas I
authors.initials: NI
authors.lastname: Bohnen
authors.affiliation: Department of Neurology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Vikas
authors.initials: V
authors.lastname: Kotagal
authors.affiliation: Department of Radiology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Martijn L T M
authors.initials: ML
authors.lastname: Müller
authors.affiliation: Department of Radiology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Koeppe
authors.affiliation: Department of Radiology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Peter J H
authors.initials: PJ
authors.lastname: Scott
authors.affiliation: Department of Neurology, University of Michigan, Ann Arbor, MI, USA; Neurology Service and GRECC, VAAAHS, Ann Arbor, MI, USA; Michigan Alzheimer Disease Center, Ann Arbor, MI, USA.
authors.forename: Roger L
authors.initials: RL
authors.lastname: Albin
authors.affiliation: Department of Radiology, University of Michigan, Ann Arbor, MI, USA; Department of Neurology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Kirk A
authors.initials: KA
authors.lastname: Frey
authors.affiliation: Department of Radiology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Myria
authors.initials: M
authors.lastname: Petrou
mesh_terms: D000368:Aged; D002087:Butyrates; D002247:Carbon Isotopes; D003072:Cognition Disorders / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000209:etiology*; D003430:Cross-Sectional Studies; D048909:Diabetes Complications / Q000150:complications* / Q000453:epidemiology; D003920:Diabetes Mellitus / Q000453:epidemiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D059906:Neuroimaging; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000150:complications* / Q000453:epidemiology; D010880:Piperidines; D049268:Positron-Emission Tomography; D012720:Severity of Illness Index; D013747:Tetrabenazine / Q000031:analogs & derivatives
chemical_list: D002087:Butyrates; D002247:Carbon Isotopes; D010880:Piperidines; C496589:methyl-4-piperidinyl n-butyrate; C032811:dihydrotetrabenazine; D013747:Tetrabenazine
keywords: Acetylcholine; Cognitive impairment; Diabetes mellitus; Dopamine; PET; Parkinson disease