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Decreased striatal dopamine transporter uptake in the non‐fluent/agrammatic variant of primary progressive aphasia
Author(s) -
GilNavarro S.,
Lomeña F.,
Cot A.,
Lladó A.,
Montagut N.,
Castellví M.,
Bosch B.,
Rami L.,
Antonell A.,
Balasa M.,
Pavia J.,
Iranzo A.,
Molinuevo J. L.,
SánchezValle R.
Publication year - 2013
Publication title -
european journal of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 124
eISSN - 1468-1331
pISSN - 1351-5101
DOI - 10.1111/ene.12196
Subject(s) - medicine , biomarker , parkinsonism , primary progressive aphasia , dopamine transporter , oncology , gastroenterology , pathology , dopamine , frontotemporal dementia , disease , dementia , dopaminergic , biology , biochemistry
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. 123 I‐2β‐carbomethoxy‐3β‐(4‐iodophenyl)‐N‐(3‐fluoropropyl)‐nortropane ( 123 I‐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 123 I‐FP‐CIT uptake. Methods Visual and semi‐quantitative assessments of the striatal 123 I‐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 (Aβ 42 , total‐tau, phosphorylated‐tau 181 ) were determined. A second 123 I‐FP‐CIT‐SPECT analysis in the biomarker‐enriched groups was also carried out. Results Patients with nfvPPA presented reduced striatal 123 I‐FP‐CIT binding, especially in the left hemisphere ( P = 0.002), compared with controls. All lvPPA patients had normal striatal 123 I‐FP‐CIT uptake. 123 I‐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 123 I‐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 123 I‐FP‐CIT uptake. Conclusions Reduced striatal tracer uptake in nfvPPA patients prior to clinical parkinsonism can be detected by 123 I‐FP‐CIT‐SPECT, especially in those with nfvPPA/bio‐, suggesting subclinical nigrostriatal degeneration. Decreased striatal 123 I‐FP‐CIT binding might identify PPA patients at increased risk of developing atypical parkinsonian syndromes, probably related to tau‐pathology.