title: Diabetes, Gray Matter Loss, and Cognition in the Setting of Parkinson Disease.
abstract: OBJECTIVE
  Parkinson disease (PD) is a progressive neurodegenerative disorder affecting motor and cognitive functions. Prior studies showed that patients with PD and diabetes (DM) demonstrate worse clinical outcomes compared to nondiabetic subjects with PD. Our study aimed at defining the relationship between DM, gray matter volume, and cognition in patients with PD.
  
  
  METHODS
  This study included 36 subjects with PD (12 with DM, 24 without DM, mean age = 66). Subjects underwent high-resolution T1-weighted brain magnetic resonance imaging, [(11)C]dihydrotetrabenazine positron emission tomography imaging to quantify nigrostriatal dopaminergic denervation, clinical, and cognitive assessments. Magnetic resonance images were postprocessed to determine total and lobar cortical gray matter volumes. Cognitive testing scores were converted to z-scores for specific cognitive domains and a composite global cognitive z-score based on normative data computed. Analysis of covariance, accounting for effects of age, gender, intracranial volume, and striatal [(11)C]dihydrotetrabenazine binding, was used to test the relationship between DM and gray matter volumes.
  
  
  RESULTS
  Impact of DM on total gray matter volume was significant (P = 0.02). Post hoc analyses of lobar cortical gray matter volumes revealed that DM was more selectively associated with lower gray matter volumes in the frontal regions (P = 0.01). Cognitive post hoc analyses showed that interaction of total gray matter volume and DM status was significantly associated with composite (P = 0.007), executive (P = 0.02), and visuospatial domain cognitive z-scores (P = 0.005). These associations were also significant for the frontal cortical gray matter.
  
  
  CONCLUSIONS
  DM may exacerbate brain atrophy and cognitive functions in PD with greater vulnerability in the frontal lobes. Given the high prevalence of DM in the elderly, delineating its effects on patient outcomes in the PD population is of importance.
authors.affiliation: Department of Radiology, University of Michigan, Ann Arbor, Michigan; Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: mpetrou@umich.edu.
authors.forename: M
authors.initials: M
authors.lastname: Petrou
authors.affiliation: Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: C
authors.initials: C
authors.lastname: Davatzikos
authors.affiliation: Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: M
authors.initials: M
authors.lastname: Hsieh
authors.affiliation: Department of Radiology, University of Michigan, Ann Arbor, Michigan; Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland; Veterans Administration Healthcare System, Ann Arbor, Michigan.
authors.forename: B R
authors.initials: BR
authors.lastname: Foerster
authors.affiliation: Veterans Administration Healthcare System, Ann Arbor, Michigan; Department of Neurology, University of Michigan, Ann Arbor, Michigan; Univerity of Michigan Morris K. Udall Center for Excellence in Parkinson's Disease Research, Ann Arbor, Michigan.
authors.forename: R L
authors.initials: RL
authors.lastname: Albin
authors.affiliation: Department of Neurology, University of Michigan, Ann Arbor, Michigan.
authors.forename: V
authors.initials: V
authors.lastname: Kotagal
authors.affiliation: Department of Radiology, University of Michigan, Ann Arbor, Michigan; Univerity of Michigan Morris K. Udall Center for Excellence in Parkinson's Disease Research, Ann Arbor, Michigan.
authors.forename: M L
authors.initials: ML
authors.lastname: Müller
authors.affiliation: Department of Radiology, University of Michigan, Ann Arbor, Michigan; Univerity of Michigan Morris K. Udall Center for Excellence in Parkinson's Disease Research, Ann Arbor, Michigan.
authors.forename: R A
authors.initials: RA
authors.lastname: Koeppe
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
authors.forename: W H
authors.initials: WH
authors.lastname: Herman
authors.affiliation: Department of Radiology, University of Michigan, Ann Arbor, Michigan; Department of Neurology, University of Michigan, Ann Arbor, Michigan.
authors.forename: K A
authors.initials: KA
authors.lastname: Frey
authors.affiliation: Department of Radiology, University of Michigan, Ann Arbor, Michigan; Veterans Administration Healthcare System, Ann Arbor, Michigan; Department of Neurology, University of Michigan, Ann Arbor, Michigan; Univerity of Michigan Morris K. Udall Center for Excellence in Parkinson's Disease Research, Ann Arbor, Michigan.
authors.forename: N I
authors.initials: NI
authors.lastname: Bohnen
mesh_terms: D000368:Aged; D001284:Atrophy; D001288:Attention / Q000502:physiology; D001479:Basal Ganglia / Q000000981:diagnostic imaging; D001927:Brain Diseases / Q000150:complications*; D002250:Carbon Radioisotopes; D016022:Case-Control Studies; D003071:Cognition / Q000502:physiology*; D003430:Cross-Sectional Studies; D048909:Diabetes Complications; D059290:Dopaminergic Neurons / Q000473:pathology; D056344:Executive Function / Q000502:physiology; D005260:Female; D005625:Frontal Lobe / Q000000981:diagnostic imaging; D066128:Gray Matter / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000000981:diagnostic imaging; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000150:complications*; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals; D013747:Tetrabenazine / Q000031:analogs & derivatives
chemical_list: D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; C032811:dihydrotetrabenazine; D013747:Tetrabenazine
keywords: MRI; PET; Parkinson disease; cognition; diabetes; gray matter