title: Age at onset influences neurodegenerative processes underlying PD with levodopa-induced dyskinesias.
abstract: OBJECTIVE
  Recently, we demonstrated that PD patients with levodopa-induced dyskinesias are characterized by neuroanatomical and functional changes involving the prefrontal cortex. When compared with non-dyskinetic PD patients, dyskinetic PD patients showed increased volume of the inferior frontal cortex and a dysfunctional imbalance between this region and the supplementary motor area during motor task. In the current study, we investigated the impact of age at onset of the disease on the neuroanatomical characteristics of dyskinetic patients, because it is well known that early-onset PD patients usually develop dyskinesias sooner with respect to late-onset PD.
  
  
  METHODS
  Whole-brain voxel-wise investigations of gray matter volume and cortical thickness were carried out in dyskinetic (n = 33), non-dyskinetic PD patients (n = 33) and in age-sex-matched healthy controls (n = 40). Neuroimaging analyses were performed separately according to the age at onset (early < 50 y > late).
  
  
  RESULTS
  Independent of age at onset, dyskinetic PD patients showed altered morphology in the inferior frontal cortex when compared with non-dyskinetic patients. Moreover, additional significant abnormalities emerged in the early- and late-onset PD patients when compared to controls. In fact, early-onset dyskinetic patients showed increased volume in a large cluster of the midbrain encompassing substantia nigra and red nucleus, whereas late-onset dyskinetic patients were characterized by abnormal gray matter increase in the supplementary motor area.
  
  
  CONCLUSIONS
  Our findings demonstrate different patterns of brain abnormalities in patients with LID according to age at onset, highlighting the role of the nigral pathology in early-onset and of the cortical pathology in late-onset patients with PD.
authors.affiliation: Neuroimaging Research Unit, Institute of Neurological Sciences, National Research Council, Germaneto, CZ, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cerasa
authors.forename: Maria
authors.initials: M
authors.lastname: Salsone
authors.forename: Maurizio
authors.initials: M
authors.lastname: Morelli
authors.forename: Pierfrancesco
authors.initials: P
authors.lastname: Pugliese
authors.forename: Gennarina
authors.initials: G
authors.lastname: Arabia
authors.forename: Cecilia M
authors.initials: CM
authors.lastname: Gioia
authors.forename: Fabiana
authors.initials: F
authors.lastname: Novellino
authors.forename: Aldo
authors.initials: A
authors.lastname: Quattrone
mesh_terms: D017668:Age of Onset; D000368:Aged; D000978:Antiparkinson Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D002540:Cerebral Cortex / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology*; D005260:Female; D005625:Frontal Lobe / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007980:Levodopa / Q000009:adverse effects* / Q000627:therapeutic use*; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000209:etiology / Q000503:physiopathology*; D016011:Normal Distribution; D010300:Parkinson Disease / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology*; D013378:Substantia Nigra / Q000473:pathology
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa
keywords: Age at onset of disease; Inferior frontal cortex; Levodopa-induced dyskinesias; Parkinson's disease; Substantia nigra; Supplementary motor area