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

Visser, Denise ; Verfaillie, Sander C.J. ; Wolters, Emma E. ; Coomans, Emma M. ; Timmers, Tessa ; Tuncel, Hayel ; Boellaard, Ronald ; Golla, Sandeep S.V. ; Windhorst, Albert D. and Scheltens, Philip , et al. (2022) In European Journal of Nuclear Medicine and Molecular Imaging 49(6). p.1951-1963
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... (More)

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.

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Contribution to journal
publication status
published
subject
keywords
Alzheimer’s disease, Cerebral blood flow, Cognition, Early-onset, Tau pathology, [F]flortaucipir
in
European Journal of Nuclear Medicine and Molecular Imaging
volume
49
issue
6
pages
1951 - 1963
publisher
Springer
external identifiers
  • pmid:34997294
  • scopus:85122515377
ISSN
1619-7070
DOI
10.1007/s00259-021-05669-6
language
English
LU publication?
yes
id
e1f41840-1d6d-462e-b7ec-3c22859c48fc
date added to LUP
2022-02-08 14:48:28
date last changed
2024-04-18 06:03:06
@article{e1f41840-1d6d-462e-b7ec-3c22859c48fc,
  abstract     = {{<p>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 [<sup>18</sup>F]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 [<sup>18</sup>F]flortaucipir PET scan and extensive neuropsychological assessment. We extracted binding potentials (BP<sub>ND</sub>) and R<sub>1</sub> (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 BP<sub>ND</sub> or R<sub>1</sub> 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 BP<sub>ND</sub>/R<sub>1</sub> on cognition. Results: Both region-of-interest and voxel-wise contrasts showed higher [<sup>18</sup>F]flortaucipir BP<sub>ND</sub> values across all neocortical regions in EOAD. By contrast, LOAD patients had lower R<sub>1</sub> 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 BP<sub>ND</sub> − 0.76 ≤ stβ ≤ − 0.48 vs LOAD − 0.18 ≤ stβ ≤ − 0.02; EOAD R<sub>1</sub> 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.</p>}},
  author       = {{Visser, Denise and Verfaillie, Sander C.J. and Wolters, Emma E. and Coomans, Emma M. and Timmers, Tessa and Tuncel, Hayel and Boellaard, Ronald and Golla, Sandeep S.V. and Windhorst, Albert D. and Scheltens, Philip and van der Flier, Wiesje M. and van Berckel, Bart N.M. and Ossenkoppele, Rik}},
  issn         = {{1619-7070}},
  keywords     = {{Alzheimer’s disease; Cerebral blood flow; Cognition; Early-onset; Tau pathology; [F]flortaucipir}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{1951--1963}},
  publisher    = {{Springer}},
  series       = {{European Journal of Nuclear Medicine and Molecular Imaging}},
  title        = {{Differential associations between neocortical tau pathology and blood flow with cognitive deficits in early-onset vs late-onset Alzheimer’s disease}},
  url          = {{http://dx.doi.org/10.1007/s00259-021-05669-6}},
  doi          = {{10.1007/s00259-021-05669-6}},
  volume       = {{49}},
  year         = {{2022}},
}