title: Decreased striatal dopamine transporter uptake in the non-fluent/agrammatic variant of primary progressive aphasia.
abstract: OBJECTIVE
  Patients with the non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA) may develop atypical parkinsonian syndromes. However, there is no current biomarker to assess which patients are at high risk of developing parkinsonism. 123I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane (123I-FP-CIT)-SPECT detects striatal dopamine dysfunction in vivo. The objective of the present study was to study whether non-fluent/agrammatic patients without parkinsonism at baseline present decreased striatal 123I-FP-CIT uptake.
  
  
  METHODS
  Visual and semi-quantitative assessments of the striatal 123I-FP-CIT uptake ratio were carried out in 15 patients with nfvPPA, eight patients with the logopenic variant of PPA (lvPPA) and 18 controls. To rule out progranulin mutations or underlying Alzheimer's disease (AD), serum progranulin levels and cerebrospinal fluid (CSF) biomarkers of AD (Aβ42 , total-tau, phosphorylated-tau181 ) were determined. A second 123I-FP-CIT-SPECT analysis in the biomarker-enriched groups was also carried out.
  
  
  RESULTS
  Patients with nfvPPA presented reduced striatal 123I-FP-CIT binding, especially in the left hemisphere (P = 0.002), compared with controls. All lvPPA patients had normal striatal 123I-FP-CIT uptake. 123I-FP-CIT striatal binding in nfvPPA patients with normal progranulin and CSF biomarker levels (nfvPPA/bio-) was also significantly reduced (P < 0.05) compared with lvPPA patients with positive AD biomarkers. Sixty-four per cent (9/14) of nfvPPA patients and 80% of nfvPPA/bio- patients (8/10) showed a diminished individual left striatal 123I-FP-CIT uptake ratio. On follow-up, seven nfvPPA/bio- patients developed parkinsonism (median 1.9 years; range 1.2-2.9), six of them with baseline reduced 123I-FP-CIT uptake.
  
  
  CONCLUSIONS
  Reduced striatal tracer uptake in nfvPPA patients prior to clinical parkinsonism can be detected by 123I-FP-CIT-SPECT, especially in those with nfvPPA/bio-, suggesting subclinical nigrostriatal degeneration. Decreased striatal 123I-FP-CIT binding might identify PPA patients at increased risk of developing atypical parkinsonian syndromes, probably related to tau-pathology.
authors.affiliation: Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Department, Hospital Clínic, Barcelona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Gil-Navarro
authors.forename: F
authors.initials: F
authors.lastname: Lomeña
authors.forename: A
authors.initials: A
authors.lastname: Cot
authors.forename: A
authors.initials: A
authors.lastname: Lladó
authors.forename: N
authors.initials: N
authors.lastname: Montagut
authors.forename: M
authors.initials: M
authors.lastname: Castellví
authors.forename: B
authors.initials: B
authors.lastname: Bosch
authors.forename: L
authors.initials: L
authors.lastname: Rami
authors.forename: A
authors.initials: A
authors.lastname: Antonell
authors.forename: M
authors.initials: M
authors.lastname: Balasa
authors.forename: J
authors.initials: J
authors.lastname: Pavia
authors.forename: A
authors.initials: A
authors.lastname: Iranzo
authors.forename: J L
authors.initials: JL
authors.lastname: Molinuevo
authors.forename: R
authors.initials: R
authors.lastname: Sánchez-Valle
mesh_terms: D000368:Aged; D015415:Biomarkers; D018450:Disease Progression; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017072:Neostriatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000378:metabolism*; D057178:Primary Progressive Nonfluent Aphasia / Q000000981:diagnostic imaging / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D014326:Tropanes
chemical_list: D015415:Biomarkers; D050483:Dopamine Plasma Membrane Transport Proteins; D014326:Tropanes; C087552:2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane
keywords: 123I-FP-CIT; Alzheimer's disease; frontotemporal dementia; parkinsonian disorders; primary progressive aphasia; primary progressive non-fluent aphasia