Distinct brain perfusion pattern associated with CSF biomarkers profile in primary progressive aphasia
- Aurélie Kas1,2,
- Olga Uspenskaya3,
- Foudil Lamari4,
- Leonardo Cruz de Souza3,5,
- Marie-Odile Habert1,2,
- Bruno Dubois3,5,
- Marc Teichmann3,5,
- Marie Sarazin3,5
- 1Service de Médecine Nucléaire, AP-HP, Groupe hospitalier Pitié-Salpêtrière, Paris, France
- 2INSERM, UMR-S 678, Université Pierre et Marie Curie-Paris 6, Paris, France
- 3Alzheimer's Institute, AP-HP, Groupe hospitalier Pitié-Salpêtrière, Paris, France
- 4Department of Metabolic Biochemistry, AP-HP, Pitié-Salpêtrière Hospital, Paris, France
- 5CRICM, Université Pierre et Marie Curie-Paris 6, Pitié-Salpêtrière Hospital, Paris, France
- Correspondence toDr Marie Sarazin, Alzheimerb's Institute, AP-HP, Pitié-Salpêtrière Hospital, Paris, F-75013, France;
Contributors AK: study concept and design, analysis and interpretation of the imaging data and writing/revising the manuscript. OU: analysis and interpretation of the clinical imaging data and revising the manuscript. FL: analysis and interpretation of the CSF biomarkers and revising the manuscript. LCdS: acquisition, analysis and interpretation of the data, and revising the manuscript. M-OH: study concept and design, analysis and interpretation of imaging data, and revising the manuscript. BD: clinical diagnosis of the patients, analysis and interpretation of the data, and revising the manuscript. MT: clinical diagnosis of the patients, analysis and interpretation of the data, and revising the manuscript. MS: clinical diagnosis of the patients, study concept and design, analysis and interpretation of data, and writing/revising the manuscript. Statistical analyses were performed by OU and AK.
- Received 1 January 2012
- Revised 14 March 2012
- Accepted 16 April 2012
Objective A new classification of primary progressive aphasia (PPA) was recently proposed to differentiate between non-fluent aphasia (NF-PPA), semantic variant of PPA (S-PPA) and logopenic aphasia (LPA) by their phenotypic presentations. CSF biomarkers (BM) may differentiate PPA with atypical Alzheimer's disease (AD) that presents with LPA from PPA with frontotemporal lobe degeneration that presents with either NF-PPA or S-PPA. Single photon emission computed tomography (SPECT) was used to investigate brain hypoperfusion differences among PPA subtypes according to their CSF AD profiles.
Methods 34 PPA patients underwent lumbar puncture and brain perfusion SPECT. PPA patients were classified into two subgroups according to theAβ42:tau ratio: PPA BM positive (with an AD CSF profile) and PPA BM negative (not having an AD CSF profile). The biological classification was made while blind to the phenotypical presentation. The brain perfusion profiles of the PPA subgroups were compared with those of 24 healthy subjects.
Results PPA BM positive patients had left-side predominant hypoperfusion in the temporoparietal cortex that extended to the dorsolateral prefrontal cortex and perisylvian region while PPA BM negative patients had hypoperfusion that was predominant in the temporal poles (p<10−4 corrected).
Conclusion Distinct hypoperfusion patterns in PPA BM positive and PPA BM negative patients were observed, similar to those that have been described for S-PPA and LPA. These results support using CSF biomarkers to classify PPA.
See Editorial commentary, p 671
AK and OU contributed equally to this work.
Competing interests AK received speaker honoraria from GE Amersham Health. OU received research support from the European Federation of Neurological Societies. LCdS received speaker honoraria from Lundbeck Company, and research support from the France Alzheimer's Association and Fondation pour la Recherche Médicale. M-OH has consulted or received speaker honoraria from Bristol-Myers Squibb, GE Amersham Health and IBA. BD has consulted or served on advisory boards for Bristol-Myers Squibb, Roche, Elan, Eli Lilly, Eisai and Janssen. His institution has received grants from Novartis and Sanofi-Aventis. MS received speaker honoraria from EISAI, Pfizer, Lundbeck, Janssen and Novartis; she belongs to a scientific advisory board for EISAI Company and serves as an associate editor for La Lettre du Neurologue.
Ethics approval All the imaging and clinical data were generated during routine clinical workups in the neurology department. Consistent with French legislation, explicit informed consent was waived. However, the regulations on electronic filing were followed, and the patients were informed that their individual data could be used in clinical research.
Provenance and peer review Not commissioned; externally peer reviewed.