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European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 6/2022

Open Access 01-05-2022 | Alzheimer's Disease | Original Article

Differential associations between neocortical tau pathology and blood flow with cognitive deficits in early-onset vs late-onset Alzheimer’s disease

Authors: Denise Visser, Sander C. J. Verfaillie, Emma E. Wolters, Emma M. Coomans, Tessa Timmers, Hayel Tuncel, Ronald Boellaard, Sandeep S. V. Golla, Albert D. Windhorst, Philip Scheltens, Wiesje M. van der Flier, Bart N. M. van Berckel, Rik Ossenkoppele

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 6/2022

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Abstract

Purpose

Early-onset Alzheimer’s disease (EOAD) and late-onset Alzheimer’s disease (LOAD) differ in neuropathological burden and type of cognitive deficits. Assessing tau pathology and relative cerebral blood flow (rCBF) measured with [18F]flortaucipir PET in relation to cognition may help explain these differences between EOAD and LOAD.

Methods

Seventy-nine amyloid-positive individuals with a clinical diagnosis of AD (EOAD: n = 35, age-at-PET = 59 ± 5, MMSE = 23 ± 4; LOAD: n = 44, age-at-PET = 71 ± 5, MMSE = 23 ± 4) underwent a 130-min dynamic [18F]flortaucipir PET scan and extensive neuropsychological assessment. We extracted binding potentials (BPND) and R1 (proxy of rCBF) from parametric images using receptor parametric mapping, in medial and lateral temporal, parietal, occipital, and frontal regions-of-interest and used nine neuropsychological tests covering memory, attention, language, and executive functioning. We first examined differences between EOAD and LOAD in BPND or R1 using ANOVA (region-of-interest analysis) and voxel-wise contrasts. Next, we performed linear regression models to test for potential interaction effects between age-at-onset and BPND/R1 on cognition.

Results

Both region-of-interest and voxel-wise contrasts showed higher [18F]flortaucipir BPND values across all neocortical regions in EOAD. By contrast, LOAD patients had lower R1 values (indicative of more reduced rCBF) in medial temporal regions. For both tau and flow in lateral temporal, and occipitoparietal regions, associations with cognitive impairment were stronger in EOAD than in LOAD (EOAD BPND − 0.76 ≤ stβ ≤  − 0.48 vs LOAD − 0.18 ≤ stβ ≤  − 0.02; EOAD R1 0.37 ≤ stβ ≤ 0.84 vs LOAD − 0.25 ≤ stβ ≤ 0.16).

Conclusions

Compared to LOAD, the degree of lateral temporal and occipitoparietal tau pathology and relative cerebral blood-flow is more strongly associated with cognition in EOAD.
Appendix
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Metadata
Title
Differential associations between neocortical tau pathology and blood flow with cognitive deficits in early-onset vs late-onset Alzheimer’s disease
Authors
Denise Visser
Sander C. J. Verfaillie
Emma E. Wolters
Emma M. Coomans
Tessa Timmers
Hayel Tuncel
Ronald Boellaard
Sandeep S. V. Golla
Albert D. Windhorst
Philip Scheltens
Wiesje M. van der Flier
Bart N. M. van Berckel
Rik Ossenkoppele
Publication date
01-05-2022
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 6/2022
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-021-05669-6

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