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Decreased striatal dopamine transporter uptake in the non-fluent/agrammatic variant of primary progressive aphasia

Authors

  • S. Gil-Navarro,

    1. Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Department, Hospital Clínic, Barcelona, Spain
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  • F. Lomeña,

    1. Nuclear Medicine Department, Hospital Clínic, Barcelona, Spain
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  • A. Cot,

    1. Biophysics and Bioengineering Unit, Universitat de Barcelona, Barcelona, Spain
    2. Biomateriales y Nanomedicina (CIBER-BBN), CIBER de Bioingeniería, Barcelona, Spain
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  • A. Lladó,

    1. Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Department, Hospital Clínic, Barcelona, Spain
    2. Institut d'Investigació Biomédica August Pi I Sunyer (IDIBAPS), Barcelona, Spain
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  • N. Montagut,

    1. Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Department, Hospital Clínic, Barcelona, Spain
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  • M. Castellví,

    1. Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Department, Hospital Clínic, Barcelona, Spain
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  • B. Bosch,

    1. Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Department, Hospital Clínic, Barcelona, Spain
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  • L. Rami,

    1. Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Department, Hospital Clínic, Barcelona, Spain
    2. Institut d'Investigació Biomédica August Pi I Sunyer (IDIBAPS), Barcelona, Spain
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  • A. Antonell,

    1. Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Department, Hospital Clínic, Barcelona, Spain
    2. Institut d'Investigació Biomédica August Pi I Sunyer (IDIBAPS), Barcelona, Spain
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  • M. Balasa,

    1. Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Department, Hospital Clínic, Barcelona, Spain
    2. Institut d'Investigació Biomédica August Pi I Sunyer (IDIBAPS), Barcelona, Spain
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  • J. Pavia,

    1. Nuclear Medicine Department, Hospital Clínic, Barcelona, Spain
    2. Biomateriales y Nanomedicina (CIBER-BBN), CIBER de Bioingeniería, Barcelona, Spain
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  • A. Iranzo,

    1. Institut d'Investigació Biomédica August Pi I Sunyer (IDIBAPS), Barcelona, Spain
    2. Neurology Department, Hospital Clínic, Barcelona, Spain
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  • J. L. Molinuevo,

    1. Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Department, Hospital Clínic, Barcelona, Spain
    2. Institut d'Investigació Biomédica August Pi I Sunyer (IDIBAPS), Barcelona, Spain
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  • R. Sánchez-Valle

    Corresponding author
    1. Institut d'Investigació Biomédica August Pi I Sunyer (IDIBAPS), Barcelona, Spain
    • Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Department, Hospital Clínic, Barcelona, Spain
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Correspondence: R. Sánchez-Valle, Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Department, Hospital Clínic de Barcelona, c/Villarroel 170, 08036, Barcelona, Spain (tel.: +34 932 275785; fax: +34 932 275783; e-mail: rsanchez@clinic.ub.es).

Abstract

Background and purpose

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.

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