title: Neural correlates of anxiety symptoms in mild Parkinson's disease: A prospective longitudinal voxel-based morphometry study.
abstract: BACKGROUND
  Anxiety is prevalent in patients with Parkinson's disease (PD) and may affect patients' quality of life. Yet, little is known about the neural basis of anxiety in PD, and none have used a longitudinal design.
  
  
  METHODS
  73 patients with mild PD were recruited and followed up for 18months. A whole-brain analysis was first used to identify brain regions associated with anxiety symptoms, followed by a regional analysis focusing on a priori hypothesised regions at baseline. A multivariate generalized estimating equations analysis was then conducted to determine the longitudinal association between grey matter (GM) volumetric changes of these significant regions and changes of anxiety symptoms.
  
  
  RESULTS
  At baseline, anxiety symptom severity was associated with decreased GM volumes in the bilateral precuneus and anterior cingulate cortex (ACC). Over 18months, increased severity of anxiety symptoms was associated with decreased GM volume in the left precuneus and ACC, independent of age, gender, education, depressive symptom severity or use of psychiatric medication.
  
  
  CONCLUSIONS
  These results mainly implicate the precuneus and ACC in the pathogenesis of anxiety in PD. We speculate that these structural changes could reflect the disrupted default mode network due to PD pathology, contributing to spontaneous anxiety-related self-focused thoughts.
authors.affiliation: Duke-NUS Graduate Medical School, 8 College Road, 169857, Singapore.
authors.forename: Natalie
authors.initials: N
authors.lastname: Wee
authors.affiliation: Department of Neurology, National Neuroscience Institute, 11 Jalan Tan Tock Seng, 308433, Singapore.
authors.forename: Ming-Ching
authors.initials: MC
authors.lastname: Wen
authors.affiliation: Duke-NUS Graduate Medical School, 8 College Road, 169857, Singapore; Department of Neurology, National Neuroscience Institute, 11 Jalan Tan Tock Seng, 308433, Singapore.
authors.forename: Nagaendran
authors.initials: N
authors.lastname: Kandiah
authors.affiliation: Department of Neurology, National Neuroscience Institute, 11 Jalan Tan Tock Seng, 308433, Singapore.
authors.forename: Russell J
authors.initials: RJ
authors.lastname: Chander
authors.affiliation: Department of Neurology, National Neuroscience Institute, 11 Jalan Tan Tock Seng, 308433, Singapore.
authors.forename: Aloysius
authors.initials: A
authors.lastname: Ng
authors.affiliation: Duke-NUS Graduate Medical School, 8 College Road, 169857, Singapore; Department of Neurology, National Neuroscience Institute, 11 Jalan Tan Tock Seng, 308433, Singapore.
authors.forename: Wing Lok
authors.initials: WL
authors.lastname: Au
authors.affiliation: Duke-NUS Graduate Medical School, 8 College Road, 169857, Singapore; Department of Neurology, National Neuroscience Institute, 11 Jalan Tan Tock Seng, 308433, Singapore. Electronic address: louis.tan.c.s.@singhealth.com.sg.
authors.forename: Louis C S
authors.initials: LC
authors.lastname: Tan
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use; D001007:Anxiety / Q000000981:diagnostic imaging* / Q000188:drug therapy; D001921:Brain / Q000000981:diagnostic imaging*; D005260:Female; D005500:Follow-Up Studies; D066128:Gray Matter / Q000000981:diagnostic imaging; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D009929:Organ Size; D010300:Parkinson Disease / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000523:psychology*; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D011619:Psychotropic Drugs / Q000627:therapeutic use; D012720:Severity of Illness Index
chemical_list: D000978:Antiparkinson Agents; D011619:Psychotropic Drugs
keywords: Anxiety; Longitudinal; Parkinson's disease; Precuneus; Voxel-based morphometry