Is in vivo amyloid distribution asymmetric in primary progressive aphasia?

Abstract

We aimed to determine whether (18) F-florbetapir amyloid positron emission tomography imaging shows a clinically concordant, left-hemisphere-dominant pattern of deposition in primary progressive aphasia (PPA). Elevated cortical amyloid (Aβ(+) ) was found in 19 of 32 PPA patients. Hemispheric laterality of amyloid burden was compared between Aβ(+) PPA and an Aβ(+) amnestic dementia groups (n = 22). The parietal region showed significantly greater left lateralized amyloid uptake in the PPA group than the amnestic group (p < 0.007), consistent with the left lateralized pattern of neurodegeneration in PPA. These results suggest that the cortical distribution of amyloid may have a greater clinical concordance than previously reported.

Figure 1. Mean cortical SUVR values for PPA and amnestic participants by clinical subtype

Amyloid burden for individual participants based on the mean cortical cerebral-to-cerebellar standard uptake value ratio (global mask of anterior cingulate, posterior cingulate, precuneus, frontal, temporal, and parietal regions). Nineteen PPA and 22 DAT/MCI amnestic subjects were above the 1.10 threshold and showed elevated florbetapir burden. Abbreviations: Aβ+ = elevated amyloid, mean cortical SUVR ≥ 1.10; Aβ– = Amyloid below threshold, mean cortical SUVR < 1.10; PPA = primary progressive aphasia; PPA-G = agrammatic subtype of PPA; PPA-L = logopenic subtype of PPA; PPA-S = semantic subtype of PPA; PPA-U = unclassifiable subtype of PPA; DAT = dementia of the Alzheimer's type; MCI = mild cognitive impairment; SUVR = standard uptake value ratio; VOI = volume of interest.

Figure 2. Laterality of the florbetapir PET signal for PPA and amnestic individuals with elevated amyloid

(A) Laterality scores of each Aβ+ PPA (n = 19) and amnestic (n = 22) subject in each of six volumes of interest (VOI) and the mean SUVR, which is the average SUVR of the 6 VOIs. A positive laterality score indicates left > right asymmetry. * The parietal VOI showed significant differences between groups (PPA-Aβ+ mean laterality score = 0.146 ± 0.110; amnestic-Aβ+ group mean laterality score = – 0.001 ± 0.028). (B) An Aβ+ PPA patient (CDR = 0.5; MMSE = 28; mean cortical Aβ SUVR = 1.436) with an asymmetric left lateralized distribution of cortical amyloid in comparison to an amnestic DAT patient at similar stage of disease and amyloid load (CDR = 0.5; MMSE = 28; mean cortical Aβ SUVR = 1.437). Axial slices (radiological orientation) for visualization are provided (MNI-Talairach z = 5) and scaled at the same SUVR. The flame scale (1.1 to 2.0 SUVR) is provided, with warmer colors representing higher cerebral-to-cerebellar SUVR values. Abbreviations: PPA = primary progressive aphasia; PPA-L = logopenic subtype of PPA; PPA-G = agrammatic subtype of PPA; PPA-U = unclassifiable subtype of PPA; Aβ+ = elevated amyloid, mean cortical SUVR ≥ 1.10; L = Left hemisphere; R = right hemisphere; MMSE = mini-mental state examination; DAT = dementia of the Alzheimer's type; SUVR = standard uptake value ratio.