Aβ amyloid and glucose metabolism in three variants of primary progressive aphasia

Abstract

OBJECTIVE-Alzheimer's disease (AD) is found at autopsy in up to one-third of patients with primary progressive aphasia (PPA), but clinical features that predict AD pathology in PPA are not well defined. We studied the relationships between language presentation, Aβ amyloidosis and glucose metabolism in three variants of PPA using [ 11 C]PIB and [ 18 F]FDG-PET. METHODS-Patientsmeeting PPA criteria (N=15) were classified as logopenic aphasia (LPA), progressive non-fluent aphasia (PNFA) or semantic dementia (SD) based on language testing. [ 11 C] PIB distribution volume ratios were calculated using Logan graphical analysis (cerebellar reference).[ 18 F]FDG images were normalized to pons. Partial volume correction was applied.RESULTS-Elevated cortical PIB (by visual inspection) was more common in LPA (4/4 patients) than in PNFA (1/6) and SD (1/5) (p<0.02). In all PIB-positive cases, PIB uptake was diffuse and indistinguishable from the pattern in matched AD patients (N=10). FDG patterns were focal and varied by PPA subtype, with left temporoparietal hypometabolism in LPA, left frontal hypometabolism in PNFA, and left anterior temporal hypometabolism in SD. FDG patterns in PIBpositive PNFA and SD were similar to PIB-negative cases. Language regions showed asymmetric left hypometabolism in PPA (p<0.005) but not in AD.INTERPRETATION-LPA is associated with Aβ amyloidosis, suggesting that sub-classification of PPA based on language features can help predict the likelihood of underlying AD pathology. Language phenotype in PPA is closely related to metabolic changes that are focal and anatomically distinct between subtypes, but not to amyloid deposition patterns that are diffuse and similar to AD.

The logopenic/phonological variant of primary progressive aphasia

“…Furthermore, all US patients described in this article had cortical amyloid binding on PET scans using the Pittsburgh compound B tracer. 38 Taken together, all these findings suggest that AD could be the most frequent cause of LPA, whereas it may be less frequently responsible for the other PPA syndromes.…”

Frontotemporal Dementia: Implications for Understanding Alzheimer Disease

“…They include most cases of PNFA, 45% of cases of bvFTD and some cases of SD (Piguet et al 2011a). Most cases of LPA are characterized by focal Alzheimer disease pathology (Ab plaques and tau tangles), as are some cases of SD and PNFA (Mesulam et al 2008;Rabinovici et al 2008). Focal Alzheimer disease pathology accounts for 25% of autopsy cases of PPA.…”

Subject-specific Models for the Analysis of Pathological FDG PET Data

“…-a frontal region, comprising the inferior frontal gyrus, precentral gyrus and anterior insula, was defined as relevant for PNFA subjects [2,3]; -the anterior temporal region, comprising the hippocampus, amygdala and temporal pole, was defined as relevant for SD [3]; -the tempoparietal region, comprising the inferior parietal lobule, posterior middle and superior temporal gyri, was defined as relevant for LPA [3]; -finally, the occipital region, comprising the inferior, middle and superior occipital gyri, was defined as relevant for PCA [4]. Each hemisphere was analysed separately to account for left/right asymmetry.…”

“…FDG uptake reflects glucose consumption, which is reduced by synaptic dysfunction and neuronal degeneration [1]. Different neurodegenerative diseases affect different areas of the brain, and localising abnormalities is essential for differential diagnosis [2][3][4].…”