Longitudinal flortaucipir ([18F]AV-1451) PET uptake in semantic dementia

Abstract

To assess volume loss and flortaucipir uptake in patients with semantic dementia (SD) over time. Eight SD patients (3 female) underwent clinical evaluations, flortaucipir positron emission tomography, and brain magnetic resonance imaging at 2 visits. Voxel-level comparisons of magnetic resonance imaging gray and white matter volume loss and flortaucipir positron emission tomography uptake were performed in SPM12, comparing SD patients to controls at each visit. T-tests on difference images and paired t-tests of flortaucipir uptake were also performed. At the voxel level, SD patients showed asymmetric, bilateral gray volume loss in the temporal lobes, which, via visual inspection, extended posteriorly at follow-up. White matter loss and flortaucipir uptake were noted in SD patients in the left temporal lobe only, which appeared to extend posteriorly, without involvement of the right hemisphere at follow-up. Longitudinal analyses did not support significant changes in flortaucipir uptake between visits. The biological mechanisms of flortaucipir signal in suspected underlying TAR-DNA binding protein 43 pathology are unknown. A 1-year interval is not sufficient time to demonstrate significant longitudinal flortaucipir uptake changes in SD.

Keywords: MRI; PET; Primary progressive aphasia; Semantic dementia; Tau.

Figure 1.

Coronal views of gray matter loss (top), white matter loss (middle), and flortaucipir uptake (bottom) in semantic dementia patients, compared to age- and sex- matched controls (FWE_c, p < .05; details provided in Supplementary Table 1). Results shown in MCALT space.

Figure 2.

Plot of annualized change in cortical thicknesses by region and hemisphere. Each colored line represents an individual patient; values are connected to facilitate visualization. Dark underlaid black line represents the median change in the control cohort (solid line) or SD cohort (dashed line). Note: Broca = Broca’s area, ERC = entorhinal cortex, Fus = fusiform gyrus, Ins = insula, Orb Cort = orbitofrontal cortex, Pref Cort = prefrontal cortex, Temp Inf = inferior temporal gyrus, Temp Mid = middle temporal gyrus, and Temp Pole = temporal pole.

Figure 3.

Plot of annualized change in flortaucipir SUVR, with two-compartment partial volume-correction, by region and hemisphere. Each colored line represents an individual patient; values are connected to facilitate visualization. Patients are represented as the same color as in Figure 2. Dark underlaid black line represents the median change in the control cohort (solid line) or SD cohort (dashed line). Note: Amyg = Amygdala, Broca = Broca’s area, ERC = entorhinal cortex, Fus = fusiform gyrus, Ins = insula, Orb Cort = orbitofrontal cortex, Pref Cort = prefrontal cortex, Temp Inf = inferior temporal gyrus, Temp Mid = middle temporal gyrus, and Temp Pole = temporal pole.