Associations between quantitative [18F]flortaucipir tau PET and atrophy across the Alzheimer's disease spectrum

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Associations between quantitative [18F]flortaucipir tau PET and atrophy across the Alzheimer's disease spectrum. / Timmers, Tessa; Ossenkoppele, Rik; Wolters, Emma E.; Verfaillie, Sander C.J.; Visser, Denise; Golla, Sandeep S.V.; Barkhof, Frederik; Scheltens, Philip; Boellaard, Ronald; Van Der Flier, Wiesje M.; Van Berckel, Bart N.M.

I: Alzheimer's Research and Therapy, Vol. 11, Nr. 1, 60, 04.07.2019.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

Timmers, T, Ossenkoppele, R, Wolters, EE, Verfaillie, SCJ, Visser, D, Golla, SSV, Barkhof, F, Scheltens, P, Boellaard, R, Van Der Flier, WM & Van Berckel, BNM 2019, 'Associations between quantitative [18F]flortaucipir tau PET and atrophy across the Alzheimer's disease spectrum', Alzheimer's Research and Therapy, vol. 11, nr. 1, 60. https://doi.org/10.1186/s13195-019-0510-3

APA

CBE

Timmers T, Ossenkoppele R, Wolters EE, Verfaillie SCJ, Visser D, Golla SSV, Barkhof F, Scheltens P, Boellaard R, Van Der Flier WM, Van Berckel BNM. 2019. Associations between quantitative [18F]flortaucipir tau PET and atrophy across the Alzheimer's disease spectrum. Alzheimer's Research and Therapy. 11(1). https://doi.org/10.1186/s13195-019-0510-3

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Timmers, Tessa ; Ossenkoppele, Rik ; Wolters, Emma E. ; Verfaillie, Sander C.J. ; Visser, Denise ; Golla, Sandeep S.V. ; Barkhof, Frederik ; Scheltens, Philip ; Boellaard, Ronald ; Van Der Flier, Wiesje M. ; Van Berckel, Bart N.M. / Associations between quantitative [18F]flortaucipir tau PET and atrophy across the Alzheimer's disease spectrum. I: Alzheimer's Research and Therapy. 2019 ; Vol. 11, Nr. 1.

RIS

TY - JOUR

T1 - Associations between quantitative [18F]flortaucipir tau PET and atrophy across the Alzheimer's disease spectrum

AU - Timmers, Tessa

AU - Ossenkoppele, Rik

AU - Wolters, Emma E.

AU - Verfaillie, Sander C.J.

AU - Visser, Denise

AU - Golla, Sandeep S.V.

AU - Barkhof, Frederik

AU - Scheltens, Philip

AU - Boellaard, Ronald

AU - Van Der Flier, Wiesje M.

AU - Van Berckel, Bart N.M.

PY - 2019/7/4

Y1 - 2019/7/4

N2 - Background: Neuropathological studies have linked tau aggregates to neuronal loss. To describe the spatial distribution of neurofibrillary tangle pathology in post-mortem tissue, Braak staging has been used. The aim of this study was to examine in vivo associations between tau pathology, quantified with [18F]flortaucipir PET in regions corresponding to Braak stages, and atrophy across the Alzheimer's disease (AD) spectrum. Methods: We included 100 subjects, including 58 amyloid-β positive patients with mild cognitive impairment (MCI, n = 6) or AD dementia (n = 52) and 42 controls with subjective cognitive decline (36% amyloid-β positive). All subjects underwent a dynamic [18F]flortaucipir PET to generate non-displaceable binding potential (BPND) maps. We extracted average [18F]flortaucipir BPND entorhinal, Braak III-IV (limbic) and Braak V-VI (neocortical) regions of interest (ROIs). T1-weighted MRI was used to assess gray matter (GM) volumes. We performed linear regression analyses using [18F]flortaucipir BPND ROIs as independent and GM density (ROI or voxelwise) as dependent variable. Results: In MCI/AD subjects (age [mean ± SD] 65 ± 8 years, MMSE 23 ± 4), [18F]flortaucipir BPND was higher than in controls (age 65 ± 8, MMSE 29 ± 1) across all ROIs (entorhinal 0.06 ± 0.21 vs 0.46 ± 0.25 p < 0.001, Braak III-IV 0.11 ± 0.10 vs 0.46 ± 0.26, p < 0.001, Braak V-VI 0.07 ± 0.07 vs 0.38 ± 0.29, p < 0.001). In MCI/AD, greater [18F]flortaucipir BPND in entorhinal cortex was associated with lower GM density in medial temporal lobe (β - 0.40, p < 0.001). Greater [18F]flortaucipir BPND in ROI Braak III-IV and Braak V-VI was associated with smaller GM density in lateral and inferior temporal, parietal, occipital, and frontal lobes (range standardized βs - 0.30 to - 0.55, p < 0.01), but not in medial temporal lobe (β - 0.22, p 0.07). [18F]Flortaucipir BPND in ROI Braak I-II was not associated with GM density loss anywhere. When quantifying [18F]flortaucipir BPND across brain lobes, we observed both local and distant associations with GM atrophy. In controls, there were no significant associations between [18F]flortaucipir BPND and GM density (standardized βs ranging from - 0.24 to 0.02, all p > 0.05). Conclusions: In MCI/AD patients, [18F]flortaucipir binding in entorhinal, limbic, and neocortical regions was associated with cortical atrophy.

AB - Background: Neuropathological studies have linked tau aggregates to neuronal loss. To describe the spatial distribution of neurofibrillary tangle pathology in post-mortem tissue, Braak staging has been used. The aim of this study was to examine in vivo associations between tau pathology, quantified with [18F]flortaucipir PET in regions corresponding to Braak stages, and atrophy across the Alzheimer's disease (AD) spectrum. Methods: We included 100 subjects, including 58 amyloid-β positive patients with mild cognitive impairment (MCI, n = 6) or AD dementia (n = 52) and 42 controls with subjective cognitive decline (36% amyloid-β positive). All subjects underwent a dynamic [18F]flortaucipir PET to generate non-displaceable binding potential (BPND) maps. We extracted average [18F]flortaucipir BPND entorhinal, Braak III-IV (limbic) and Braak V-VI (neocortical) regions of interest (ROIs). T1-weighted MRI was used to assess gray matter (GM) volumes. We performed linear regression analyses using [18F]flortaucipir BPND ROIs as independent and GM density (ROI or voxelwise) as dependent variable. Results: In MCI/AD subjects (age [mean ± SD] 65 ± 8 years, MMSE 23 ± 4), [18F]flortaucipir BPND was higher than in controls (age 65 ± 8, MMSE 29 ± 1) across all ROIs (entorhinal 0.06 ± 0.21 vs 0.46 ± 0.25 p < 0.001, Braak III-IV 0.11 ± 0.10 vs 0.46 ± 0.26, p < 0.001, Braak V-VI 0.07 ± 0.07 vs 0.38 ± 0.29, p < 0.001). In MCI/AD, greater [18F]flortaucipir BPND in entorhinal cortex was associated with lower GM density in medial temporal lobe (β - 0.40, p < 0.001). Greater [18F]flortaucipir BPND in ROI Braak III-IV and Braak V-VI was associated with smaller GM density in lateral and inferior temporal, parietal, occipital, and frontal lobes (range standardized βs - 0.30 to - 0.55, p < 0.01), but not in medial temporal lobe (β - 0.22, p 0.07). [18F]Flortaucipir BPND in ROI Braak I-II was not associated with GM density loss anywhere. When quantifying [18F]flortaucipir BPND across brain lobes, we observed both local and distant associations with GM atrophy. In controls, there were no significant associations between [18F]flortaucipir BPND and GM density (standardized βs ranging from - 0.24 to 0.02, all p > 0.05). Conclusions: In MCI/AD patients, [18F]flortaucipir binding in entorhinal, limbic, and neocortical regions was associated with cortical atrophy.

KW - Alzheimer's disease

KW - Atrophy

KW - MCI (mild cognitive impairment)

KW - MRI

KW - PET

KW - Tau

UR - http://www.scopus.com/inward/record.url?scp=85068547893&partnerID=8YFLogxK

U2 - 10.1186/s13195-019-0510-3

DO - 10.1186/s13195-019-0510-3

M3 - Article

VL - 11

JO - Alzheimer's Research & Therapy

T2 - Alzheimer's Research & Therapy

JF - Alzheimer's Research & Therapy

SN - 1758-9193

IS - 1

M1 - 60

ER -