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O3‐13‐03: THE RELATIONSHIP BETWEEN TAU PET AND OTHER AD BIOMARKERS IN AUTOSOMAL DOMINANT ALZHEIMER DISEASE
Author(s) -
Gordon Brian A.,
Blazey Tyler M.,
Christensen Jon,
Flores Shaney,
Dincer Aylin,
Keefe Sarah,
McDade Eric,
Wang Guoqiao,
Raichle Marcus E.,
Koeppe Bob,
Jack Clifford R.,
Morris John C.,
Bateman Randall J.,
Benzinger Tammie L.S.
Publication year - 2018
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2018.06.2845
Subject(s) - presenilin , precuneus , voxel , medicine , asymptomatic carrier , cohort , asymptomatic , clinical dementia rating , oncology , alzheimer's disease , disease , pathology , neuroscience , psychology , radiology , functional magnetic resonance imaging
2017). The aim of this study was to develop a simple, quantitative tau PET-based patient classification algorithm based on sequential lobar accumulation of flortaucipir signal. Methods: The EXPEDITION3 trial enrolled amyloid-positive patients with mild AD (MMSE 20-26). Flortaucipir images were acquired for a subset of participants at baseline, week 40 and week 80. We quantified tau burden in baseline scans from the placebo arm (N1⁄497), using average SUVR values in atlas-based lateral temporal, parietal and frontal lobes with respect to a white matter-based reference region (PERSI). Elevated tau burden in the temporal (T+), parietal (P+) and frontal (F+) lobes bilaterally was determined using a single positivity threshold. All possible lobar profiles were grouped into four stages 0-III (T-P-F-, T+PF-, T+/-P+Fand T+/-P+/-F+), reflecting the stereotypical patterns of tau spread inferred from neuropathological studies. A mixed effects repeated measures method was used to characterize changes in global weighted SUVR (MUBADA), cognition and structural MRI. Results:Lobar stages were strongly concordant with a global tau burden measured by MUBADA SUVR. On average, individuals belonging to more advanced lobar stages at baseline demonstrated numerically more rapid cognitive (MMSE, ADAS-Cog14 and iADRS) and neurodegenerative (whole brain and whole temporal lobe volumes) decline over 80 weeks follow-up. In these analyses, approximately 25-30% of the cases were classified to each of stages I-III, with a slightly lower proportion assigned to stage 0. If scans were staged using a more rigorous sequential classification (T-P-F-, T+P-F-, T+P+Fand T+P+F+), <5% scans remained unclassified. Conclusions: We propose a simple quantitative algorithm based on suprathreshold lobar flortaucipir SUVR values for AD staging in vivo. Specifically, a symptomatic, amyloid-positive AD population may potentially be further segmented into four flortaucipir-measured pathological stages characterized by an escalating risk of cognitive decline. Further validation of these findings using independent datasets is warranted.