Varying Degrees of Temporoparietal Hypometabolism on FDG-PET Reveal Amyloid-Positive Logopenic Primary Progressive Aphasia is not a Homogeneous Clinical Entity

Article type: Research Article

Authors: Krishnan, Kamini^a | Machulda, Mary M.^{a; *} | Whitwell, Jennifer L.^c | Butts, Alissa M.^a | Duffy, Joseph R.^b | Strand, Edythe A.^b | Senjem, Matthew L.^{c; d} | Spychalla, Anthony J.^c | Jack Jr., Clifford R.^c | Lowe, Val J.^c | Josephs, Keith A.^b

Affiliations: [a] Department of Psychiatry and Psychology (Neuropsychology), Mayo Clinic, Rochester, MN, USA | [b] Department of Neurology, Mayo Clinic, Rochester, MN, USA | [c] Department of Radiology, Mayo Clinic, Rochester, MN, USA | [d] Department of Information Technology, Mayo Clinic, Rochester, MN, USA

Correspondence: [*] Correspondence to: Mary M. Machulda, PhD, AssociateProfessor of Psychology, Mayo Clinic, 200 1st St. S.W., Rochester, MN 55905, USA. Tel.: +1 507 266 5100; Fax: +1 507 284 4158; E-mail: [email protected].

Abstract: Background: The logopenic variant of primary progressive aphasia (lvPPA) manifests due to a breakdown of the language network with prominent hypometabolism of the left temporoparietal region. LvPPA is strongly associated with amyloid deposition, yet there is question as to whether it is a homogeneous clinical entity. Objective: This study investigated whether differences in temporoparietal metabolic patterns on 18F fludeoxyglucose positron emission tomography (FDG-PET) could elucidate brain regions preferentially affected in lvPPA. Method: We used differences in FDG-PET metabolic z-scores relative to controls for means of left lateral temporal, left inferior parietal, and left superior parietal regions to classify 53 amyloid-positive lvPPA patients into temporal, parietal, or temporoparietal predominate groups. Clinical features and FDG-PET regions of hypometabolism outside of the temporoparietal region were then compared across the three groups; the latter using statistical parametric mapping. Results: Of the 53 lvPPA patients, 15 were classified as temporal, 14 as temporoparietal, and 22 as parietal predominate. There were no significant differences between the groups on demographic measures, language evaluation, or apolipoprotein E genotype. Compared to the other two groups, individuals with the parietal predominate pattern had extensive hypometabolism in left frontal lobe and the precuneus. Furthermore, this group had greater behavioral dyscontrol and deficits in executive function, visuospatial skills, visual memory retention, working memory, and cognitive flexibility (Bonferronip < 0.05). Conclusions: This study demonstrates that there is clinical heterogeneity within amyloid-positive lvPPA. Patients with lvPPA with predominant parietal hypometabolism, unlike those with temporal or temporoparietal predominant hypometabolism, demonstrated widespread cognitive and behavioral changes.

Keywords: Amyloid-β, executive function, ¹⁸F fludeoxyglucose, positron emission tomography, primary progressiveaphasia, visuospatial deficit, working memory

DOI: 10.3233/JAD-160614

Journal: Journal of Alzheimer's Disease, vol. 55, no. 3, pp. 1019-1029, 2017