Grey zone amyloid burden affects memory function: the SCIENCe project

Purpose To determine thresholds for amyloid beta pathology and evaluate associations with longitudinal memory performance with the aim to identify a grey zone of early amyloid beta accumulation and investigate its clinical relevance. Methods We included 162 cognitively normal participants with subje...

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Published in:European journal of nuclear medicine and molecular imaging 2021-03, Vol.48 (3), p.747-756
Main Authors: Ebenau, J. L., Verfaillie, S. C. J., van den Bosch, K. A., Timmers, T., Wesselman, L. M. P., van Leeuwenstijn, M., Tuncel, H., Golla, S. V. S., Yaqub, M. M., Windhorst, A. D., Prins, N. D., Barkhof, F., Scheltens, P., van der Flier, W. M., van Berckel, B. N. M.
Format: Article
Language:English
Subjects:
Aged
Alzheimer Disease
Amyloid
Amyloid beta-Peptides
Aniline Compounds
Cardiology
Cognitive ability
Cognitive Dysfunction
Female
Humans
Imaging
Magnetic resonance imaging
Male
Medicine
Medicine & Public Health
Memory
Middle Aged
Neurology
Nuclear Medicine
Oncology
Original
Original Article
Orthopedics
Pathology
Positron emission
Positron-Emission Tomography
Quantiles
Quartiles
Radiology
Subgroups
Thresholds
Tomography
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cited_by cdi_FETCH-LOGICAL-c527t-b6eb30239e42777f99abe4259fcca862aa78beaabf5b87d41374cc4f1ba2619e3
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container_issue 3
container_start_page 747
container_title European journal of nuclear medicine and molecular imaging
container_volume 48
creator Ebenau, J. L.
Verfaillie, S. C. J.
van den Bosch, K. A.
Timmers, T.
Wesselman, L. M. P.
van Leeuwenstijn, M.
Tuncel, H.
Golla, S. V. S.
Yaqub, M. M.
Windhorst, A. D.
Prins, N. D.
Barkhof, F.
Scheltens, P.
van der Flier, W. M.
van Berckel, B. N. M.
description Purpose To determine thresholds for amyloid beta pathology and evaluate associations with longitudinal memory performance with the aim to identify a grey zone of early amyloid beta accumulation and investigate its clinical relevance. Methods We included 162 cognitively normal participants with subjective cognitive decline from the SCIENCe cohort (64 ± 8 years, 38% F, MMSE 29 ± 1). Each underwent a dynamic [ 18 F] florbetapir PET scan, a T1-weighted MRI scan and longitudinal memory assessments (RAVLT delayed recall, n  = 655 examinations). PET scans were visually assessed as amyloid positive/negative. Additionally, we calculated the mean binding potential (BP ND ) and standardized uptake value ratio (SUVr 50–70 ) for an a priori defined composite region of interest. We determined six amyloid positivity thresholds using various data-driven methods (resulting thresholds: BP ND 0.19/0.23/0.29; SUVr 1.28/1.34/1.43). We used Cohen’s kappa to analyse concordance between thresholds and visual assessment. Next, we used quantiles to divide the sample into two to five subgroups of equal numbers (median, tertiles, quartiles, quintiles), and operationalized a grey zone as the range between the thresholds (0.19–0.29 BP ND /1.28–1.43 SUVr). We used linear mixed models to determine associations between thresholds and memory slope. Results As determined by visual assessment, 24% of 162 individuals were amyloid positive. Concordance with visual assessment was comparable but slightly higher for BP ND thresholds (range kappa 0.65–0.70 versus 0.60–0.63). All thresholds predicted memory decline (range beta − 0.29 to − 0.21, all p  
doi_str_mv 10.1007/s00259-020-05012-5
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L. ; Verfaillie, S. C. J. ; van den Bosch, K. A. ; Timmers, T. ; Wesselman, L. M. P. ; van Leeuwenstijn, M. ; Tuncel, H. ; Golla, S. V. S. ; Yaqub, M. M. ; Windhorst, A. D. ; Prins, N. D. ; Barkhof, F. ; Scheltens, P. ; van der Flier, W. M. ; van Berckel, B. N. M.</creator><creatorcontrib>Ebenau, J. L. ; Verfaillie, S. C. J. ; van den Bosch, K. A. ; Timmers, T. ; Wesselman, L. M. P. ; van Leeuwenstijn, M. ; Tuncel, H. ; Golla, S. V. S. ; Yaqub, M. M. ; Windhorst, A. D. ; Prins, N. D. ; Barkhof, F. ; Scheltens, P. ; van der Flier, W. M. ; van Berckel, B. N. M.</creatorcontrib><description>Purpose To determine thresholds for amyloid beta pathology and evaluate associations with longitudinal memory performance with the aim to identify a grey zone of early amyloid beta accumulation and investigate its clinical relevance. Methods We included 162 cognitively normal participants with subjective cognitive decline from the SCIENCe cohort (64 ± 8 years, 38% F, MMSE 29 ± 1). Each underwent a dynamic [ 18 F] florbetapir PET scan, a T1-weighted MRI scan and longitudinal memory assessments (RAVLT delayed recall, n  = 655 examinations). PET scans were visually assessed as amyloid positive/negative. Additionally, we calculated the mean binding potential (BP ND ) and standardized uptake value ratio (SUVr 50–70 ) for an a priori defined composite region of interest. We determined six amyloid positivity thresholds using various data-driven methods (resulting thresholds: BP ND 0.19/0.23/0.29; SUVr 1.28/1.34/1.43). We used Cohen’s kappa to analyse concordance between thresholds and visual assessment. Next, we used quantiles to divide the sample into two to five subgroups of equal numbers (median, tertiles, quartiles, quintiles), and operationalized a grey zone as the range between the thresholds (0.19–0.29 BP ND /1.28–1.43 SUVr). We used linear mixed models to determine associations between thresholds and memory slope. Results As determined by visual assessment, 24% of 162 individuals were amyloid positive. Concordance with visual assessment was comparable but slightly higher for BP ND thresholds (range kappa 0.65–0.70 versus 0.60–0.63). All thresholds predicted memory decline (range beta − 0.29 to − 0.21, all p  &lt; 0.05). Analyses in subgroups showed memory slopes gradually became steeper with higher amyloid load (all p for trend &lt; 0.05). Participants with a low amyloid burden benefited from a practice effect (i.e. increase in memory), whilst high amyloid burden was associated with memory decline. Memory slopes of individuals in the grey zone were intermediate. Conclusion We provide evidence that not only high but also grey zone amyloid burden subtly impacts memory function. Therefore, in case a binary classification is required, we suggest using a relatively low threshold which includes grey zone amyloid pathology.</description><identifier>ISSN: 1619-7070</identifier><identifier>EISSN: 1619-7089</identifier><identifier>DOI: 10.1007/s00259-020-05012-5</identifier><identifier>PMID: 32888039</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Aged ; Alzheimer Disease ; Amyloid ; Amyloid beta-Peptides ; Aniline Compounds ; Cardiology ; Cognitive ability ; Cognitive Dysfunction ; Female ; Humans ; Imaging ; Magnetic resonance imaging ; Male ; Medicine ; Medicine &amp; Public Health ; Memory ; Middle Aged ; Neurology ; Nuclear Medicine ; Oncology ; Original ; Original Article ; Orthopedics ; Pathology ; Positron emission ; Positron-Emission Tomography ; Quantiles ; Quartiles ; Radiology ; Subgroups ; Thresholds ; Tomography</subject><ispartof>European journal of nuclear medicine and molecular imaging, 2021-03, Vol.48 (3), p.747-756</ispartof><rights>The Author(s) 2020</rights><rights>The Author(s) 2020. 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L.</creatorcontrib><creatorcontrib>Verfaillie, S. C. J.</creatorcontrib><creatorcontrib>van den Bosch, K. A.</creatorcontrib><creatorcontrib>Timmers, T.</creatorcontrib><creatorcontrib>Wesselman, L. M. P.</creatorcontrib><creatorcontrib>van Leeuwenstijn, M.</creatorcontrib><creatorcontrib>Tuncel, H.</creatorcontrib><creatorcontrib>Golla, S. V. S.</creatorcontrib><creatorcontrib>Yaqub, M. M.</creatorcontrib><creatorcontrib>Windhorst, A. D.</creatorcontrib><creatorcontrib>Prins, N. D.</creatorcontrib><creatorcontrib>Barkhof, F.</creatorcontrib><creatorcontrib>Scheltens, P.</creatorcontrib><creatorcontrib>van der Flier, W. M.</creatorcontrib><creatorcontrib>van Berckel, B. N. M.</creatorcontrib><title>Grey zone amyloid burden affects memory function: the SCIENCe project</title><title>European journal of nuclear medicine and molecular imaging</title><addtitle>Eur J Nucl Med Mol Imaging</addtitle><addtitle>Eur J Nucl Med Mol Imaging</addtitle><description>Purpose To determine thresholds for amyloid beta pathology and evaluate associations with longitudinal memory performance with the aim to identify a grey zone of early amyloid beta accumulation and investigate its clinical relevance. Methods We included 162 cognitively normal participants with subjective cognitive decline from the SCIENCe cohort (64 ± 8 years, 38% F, MMSE 29 ± 1). Each underwent a dynamic [ 18 F] florbetapir PET scan, a T1-weighted MRI scan and longitudinal memory assessments (RAVLT delayed recall, n  = 655 examinations). PET scans were visually assessed as amyloid positive/negative. Additionally, we calculated the mean binding potential (BP ND ) and standardized uptake value ratio (SUVr 50–70 ) for an a priori defined composite region of interest. We determined six amyloid positivity thresholds using various data-driven methods (resulting thresholds: BP ND 0.19/0.23/0.29; SUVr 1.28/1.34/1.43). We used Cohen’s kappa to analyse concordance between thresholds and visual assessment. Next, we used quantiles to divide the sample into two to five subgroups of equal numbers (median, tertiles, quartiles, quintiles), and operationalized a grey zone as the range between the thresholds (0.19–0.29 BP ND /1.28–1.43 SUVr). We used linear mixed models to determine associations between thresholds and memory slope. Results As determined by visual assessment, 24% of 162 individuals were amyloid positive. Concordance with visual assessment was comparable but slightly higher for BP ND thresholds (range kappa 0.65–0.70 versus 0.60–0.63). All thresholds predicted memory decline (range beta − 0.29 to − 0.21, all p  &lt; 0.05). Analyses in subgroups showed memory slopes gradually became steeper with higher amyloid load (all p for trend &lt; 0.05). Participants with a low amyloid burden benefited from a practice effect (i.e. increase in memory), whilst high amyloid burden was associated with memory decline. Memory slopes of individuals in the grey zone were intermediate. Conclusion We provide evidence that not only high but also grey zone amyloid burden subtly impacts memory function. 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L.</au><au>Verfaillie, S. C. J.</au><au>van den Bosch, K. A.</au><au>Timmers, T.</au><au>Wesselman, L. M. P.</au><au>van Leeuwenstijn, M.</au><au>Tuncel, H.</au><au>Golla, S. V. S.</au><au>Yaqub, M. M.</au><au>Windhorst, A. D.</au><au>Prins, N. D.</au><au>Barkhof, F.</au><au>Scheltens, P.</au><au>van der Flier, W. M.</au><au>van Berckel, B. N. M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Grey zone amyloid burden affects memory function: the SCIENCe project</atitle><jtitle>European journal of nuclear medicine and molecular imaging</jtitle><stitle>Eur J Nucl Med Mol Imaging</stitle><addtitle>Eur J Nucl Med Mol Imaging</addtitle><date>2021-03-01</date><risdate>2021</risdate><volume>48</volume><issue>3</issue><spage>747</spage><epage>756</epage><pages>747-756</pages><issn>1619-7070</issn><eissn>1619-7089</eissn><abstract>Purpose To determine thresholds for amyloid beta pathology and evaluate associations with longitudinal memory performance with the aim to identify a grey zone of early amyloid beta accumulation and investigate its clinical relevance. Methods We included 162 cognitively normal participants with subjective cognitive decline from the SCIENCe cohort (64 ± 8 years, 38% F, MMSE 29 ± 1). Each underwent a dynamic [ 18 F] florbetapir PET scan, a T1-weighted MRI scan and longitudinal memory assessments (RAVLT delayed recall, n  = 655 examinations). PET scans were visually assessed as amyloid positive/negative. Additionally, we calculated the mean binding potential (BP ND ) and standardized uptake value ratio (SUVr 50–70 ) for an a priori defined composite region of interest. We determined six amyloid positivity thresholds using various data-driven methods (resulting thresholds: BP ND 0.19/0.23/0.29; SUVr 1.28/1.34/1.43). We used Cohen’s kappa to analyse concordance between thresholds and visual assessment. Next, we used quantiles to divide the sample into two to five subgroups of equal numbers (median, tertiles, quartiles, quintiles), and operationalized a grey zone as the range between the thresholds (0.19–0.29 BP ND /1.28–1.43 SUVr). We used linear mixed models to determine associations between thresholds and memory slope. Results As determined by visual assessment, 24% of 162 individuals were amyloid positive. Concordance with visual assessment was comparable but slightly higher for BP ND thresholds (range kappa 0.65–0.70 versus 0.60–0.63). All thresholds predicted memory decline (range beta − 0.29 to − 0.21, all p  &lt; 0.05). Analyses in subgroups showed memory slopes gradually became steeper with higher amyloid load (all p for trend &lt; 0.05). Participants with a low amyloid burden benefited from a practice effect (i.e. increase in memory), whilst high amyloid burden was associated with memory decline. Memory slopes of individuals in the grey zone were intermediate. Conclusion We provide evidence that not only high but also grey zone amyloid burden subtly impacts memory function. Therefore, in case a binary classification is required, we suggest using a relatively low threshold which includes grey zone amyloid pathology.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>32888039</pmid><doi>10.1007/s00259-020-05012-5</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0001-5447-7224</orcidid><oa>free_for_read</oa></addata></record>
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ispartof European journal of nuclear medicine and molecular imaging, 2021-03, Vol.48 (3), p.747-756
issn 1619-7070
1619-7089
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8036199
source Springer Link
subjects Aged
Alzheimer Disease
Amyloid
Amyloid beta-Peptides
Aniline Compounds
Cardiology
Cognitive ability
Cognitive Dysfunction
Female
Humans
Imaging
Magnetic resonance imaging
Male
Medicine
Medicine & Public Health
Memory
Middle Aged
Neurology
Nuclear Medicine
Oncology
Original
Original Article
Orthopedics
Pathology
Positron emission
Positron-Emission Tomography
Quantiles
Quartiles
Radiology
Subgroups
Thresholds
Tomography
title Grey zone amyloid burden affects memory function: the SCIENCe project
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