title: Olfactory impairment predicts cognitive decline in early Parkinson's disease.
abstract: OBJECTIVE
  To evaluate the association between baseline olfaction and both cross-sectional and longitudinal cognitive assessments, motor symptoms, non-motor symptoms (NMS), and CSF biomarkers in early Parkinson's disease (PD).
  
  
  METHODS
  Parkinson's Progression Marker's Initiative (PPMI) participants underwent baseline olfactory testing with the University of Pennsylvania Smell Identification Test (UPSIT). Serial assessments included measures of motor symptoms, NMS, neuropsychological assessment, and CSF biomarkers. Up to three years follow-up data were included.
  
  
  RESULTS
  At baseline, worse olfaction (lowest tertile) was associated with more severe NMS, including anxiety and autonomic symptoms. Those in the lowest olfactory tertile were more likely to report cognitive impairment (37.4%) compared to those in the middle (24.4%) and highest olfactory tertiles (14.2%, p < 0.001). Aβ1-42 was significantly lower, and tau/Aβ1-42 ratio was higher in those with worse olfaction. In longitudinal analyses, lower UPSIT score was associated with greater decline in MoCA score (β = 0.02 [0.01, 0.03], p = 0.001) over time, as were composite measures of UPSIT score and either Aβ1-42 or tau/Aβ1-42 ratio. In a Cox proportional hazards model, a composite measure of olfaction and Aβ1-42 was a significant predictor of conversion from normal cognition to mild cognitive impairment (MCI; i.e., MoCA < 26), with subjects most impaired on both measures being 87% more likely to develop incident MCI (HR = 1.87 [1.16, 3.01], p = 0.01).
  
  
  CONCLUSIONS
  Worse baseline olfaction is associated with long-term cognitive decline. The addition of AD CSF biomarkers to olfactory testing may increase the likelihood of identifying those at highest risk for cognitive decline and progression to MCI.
authors.affiliation: Parkinson's Disease Research, Education, and Clinical Center (PADRECC), Philadelphia VA Medical Center, 3900 Woodland Ave, Philadelphia, PA 19104, USA.|Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA.
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Fullard
authors.affiliation: Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA.
authors.forename: Baochan
authors.initials: B
authors.lastname: Tran
authors.affiliation: Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, 423 Guardian Drive, Philadelphia, PA 19104, USA.
authors.forename: Sharon X
authors.initials: SX
authors.lastname: Xie
authors.affiliation: Department of Pathology & Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA.
authors.forename: Jon B
authors.initials: JB
authors.lastname: Toledo
authors.affiliation: Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA.
authors.forename: Christi
authors.initials: C
authors.lastname: Scordia
authors.affiliation: Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA.
authors.forename: Carly
authors.initials: C
authors.lastname: Linder
authors.affiliation: Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA.
authors.forename: Rachael
authors.initials: R
authors.lastname: Purri
authors.affiliation: Parkinson's Disease Research, Education, and Clinical Center (PADRECC), Philadelphia VA Medical Center, 3900 Woodland Ave, Philadelphia, PA 19104, USA.|Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA.|Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Weintraub
authors.affiliation: Parkinson's Disease Research, Education, and Clinical Center (PADRECC), Philadelphia VA Medical Center, 3900 Woodland Ave, Philadelphia, PA 19104, USA.|Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA.
authors.forename: John E
authors.initials: JE
authors.lastname: Duda
authors.affiliation: Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA.
authors.forename: Lama M
authors.initials: LM
authors.lastname: Chahine
authors.affiliation: Parkinson's Disease Research, Education, and Clinical Center (PADRECC), Philadelphia VA Medical Center, 3900 Woodland Ave, Philadelphia, PA 19104, USA.|Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA.
authors.forename: James F
authors.initials: JF
authors.lastname: Morley
mesh_terms: D000368:Aged; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000209:etiology*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D000857:Olfaction Disorders / Q000134:cerebrospinal fluid / Q000209:etiology*; D010300:Parkinson Disease / Q000134:cerebrospinal fluid / Q000150:complications*; D016016:Proportional Hazards Models; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D016875:tau Proteins
keywords: Cerebrospinal fluid; Mild cognitive impairment; Non-motor symptoms; Olfaction; Parkinson's disease