Amyloid and FDG-PET study of logopenic primary progressive aphasia: evidence for the existence of two subtypes

Abstract

The logopenic variant of primary progressive aphasia (lvPPA) has been associated with Alzheimer disease, although this relationship is still subject to debate. The purpose of this study is to determine the frequency of amyloid biomarkers in patients with lvPPA, and record any potential clinical or topographic differences between patients with and without amyloid deposits. We conducted cognitive examination and positron-emission tomography studies with fluorodeoxyglucose ((18)F) and florbetapir ((18)F) in a cohort of 16 patients diagnosed with lvPPA. We evaluated the prevalence of amyloid deposits as well as any clinical and metabolic differences between the groups with and without significant presence of amyloid deposits. Eleven patients (69 %) were considered amyloid-positive. The amyloid-positive group displayed less metabolic activity in the left temporoparietal region than the control group, while the amyloid-negative group showed lower metabolism in the left temporoparietal region extending to the anterior temporal and basal frontal regions. The percentage of change in patients with clinical and FDG-PET follow-up did not differ between the amyloid-positive and amyloid-negative subgroups. The frequency of amyloid-positive cases confirms that lvPPA is frequently associated with Alzheimer disease. Amyloid-negative patients show a different cerebral metabolic pattern. These findings show the relevance of using amyloid PET to study lvPPA, and also suggest that the logopenic variant may not be specific to Alzheimer disease in certain cases.

Rates of Amyloid Imaging Positivity in Patients With Primary Progressive Aphasia

“…The amyloid negative lvPPA case in our cohort showed more semantic impairment, and her pattern of left temporal atrophy was more anterior and left asymmetric than the amyloid positive lvPPA group. Recent studies have also reported a trend toward worse semantics 13 and greater left asymmetric anterior temporal atrophy and/or hypometabolism 11,12 in amyloid-negative lvPPA. According to current genetic and pathologic data, most amyloid negative lvPPA cases are associated with an autosomal dominant granulin mutation 11,39 or sporadic TDP-43–A pathology.…”

Primary progressive aphasia: a clinical approach

“…This explains the extensive phenotypic overlap of lvPPA with both later-stage typical Alzheimer’s disease and the posterior cortical atrophy variant, corroborated at post-mortem as well as on neuropsychological, CSF (raised phosphorylated tau levels, raised ratio of total tau to beta-amyloid 1-42 ) and amyloid-PET case series [35, 70–72]. On the other hand, cases of lvPPA lacking Alzheimer markers are consistently represented across series; the pathological substrates have not been clarified, but these may point to separable clinico-anatomical sub-syndromes [16, 68, 71–73].…”

Cholinergic depletion and basal forebrain volume in primary progressive aphasia

“…LV PPA can occur as an atypical variant of AD and 50–60% of cases show AD pathology (Matías-Guiu et al, 2015). Loss of the cholinergic systems integrity is among the earliest events in the pathogenesis of typical AD: several studies have shown reduced AChE activity in typical AD patients using [ 11 C]PMP-PET (Bohnen et al, 2005, Bohnen et al, 2003, Kuhl et al, 1999).…”