Longitudinal changes in 18 F-Flutemetamol amyloid load in cognitively intact APOE4 carriers versus noncarriers: Methodological considerations.

Autor: Luckett ES; Laboratory for Cognitive Neurology, Department of Neurosciences, Leuven Brain Institute, KU Leuven, Leuven, Belgium; Alzheimer Research Centre KU Leuven, Leuven Brain Institute, Leuven, Belgium., Schaeverbeke J; Laboratory for Cognitive Neurology, Department of Neurosciences, Leuven Brain Institute, KU Leuven, Leuven, Belgium; Alzheimer Research Centre KU Leuven, Leuven Brain Institute, Leuven, Belgium., De Meyer S; Laboratory for Cognitive Neurology, Department of Neurosciences, Leuven Brain Institute, KU Leuven, Leuven, Belgium; Alzheimer Research Centre KU Leuven, Leuven Brain Institute, Leuven, Belgium; Laboratory for Molecular Neurobiomarker Research, KU Leuven, Leuven, Belgium., Adamczuk K; Clario, Newark, CA, USA., Van Laere K; Division of Nuclear Medicine, UZ Leuven, Leuven, Belgium; Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium., Dupont P; Laboratory for Cognitive Neurology, Department of Neurosciences, Leuven Brain Institute, KU Leuven, Leuven, Belgium; Alzheimer Research Centre KU Leuven, Leuven Brain Institute, Leuven, Belgium., Vandenberghe R; Laboratory for Cognitive Neurology, Department of Neurosciences, Leuven Brain Institute, KU Leuven, Leuven, Belgium; Alzheimer Research Centre KU Leuven, Leuven Brain Institute, Leuven, Belgium; Neurology Department, University Hospitals Leuven, Leuven, Belgium. Electronic address: rik.vandenberghe@uz.kuleuven.ac.be.
Jazyk: angličtina
Zdroj: NeuroImage. Clinical [Neuroimage Clin] 2023; Vol. 37, pp. 103321. Date of Electronic Publication: 2023 Jan 05.
DOI: 10.1016/j.nicl.2023.103321
Abstrakt: Purpose: Measuring longitudinal changes in amyloid load in the asymptomatic stage of Alzheimer's disease is of high relevance for clinical research and progress towards more efficacious, timely treatments. Apolipoprotein E ε4 (APOE4) has a well-established effect on the rate of amyloid accumulation. Here we investigated which region of interest and which reference region perform best at detecting the effect of APOE4 on longitudinal amyloid load in individuals participating in the Flemish Prevent Alzheimer's Disease Cohort KU Leuven (F-PACK).
Methods: Ninety cognitively intact F-PACK participants (baseline age: 68 (52-80) years, 46 males, 42 APOE4 carriers) received structural MRI and 18 F-Flutemetamol PET scans at baseline and follow-up (6.2 (3.4-10.9) year interval). Standardised uptake value ratios (SUVRs) and Centiloids (CLs) were calculated in a composite cortical volume of interest (SUVR comp /CL) and in the precuneus (SUVR prec ), and amyloid rate of change derived: (follow-up amyloid load - baseline amyloid load) / time interval (years). Four reference regions were used to derive amyloid load: whole cerebellum, cerebellar grey matter, eroded subcortical white matter, and pons.
Results: When using whole cerebellum or cerebellar grey matter as reference region, APOE4 carriers had a significantly higher SUVR comp amyloid rate of change than non-carriers (p corr  = 0.004, t = 3.40 (CI 0.005-0.018); p corr  = 0.036, t = 2.66 (CI 0.003-0.018), respectively). Significance was not observed for eroded subcortical white matter or pons (p corr  = 0.144, t = 2.13 (CI 0.0003-0.008); p corr  = 0.116, t = 2.22 (CI 0.005-0.010), respectively). When using CLs as the amyloid measurement, and whole cerebellum, APOE4 carriers had a higher amyloid rate of change than non-carriers (p corr  = 0.012, t = 3.05 (CI 0.499-2.359)). Significance was not observed for the other reference regions. No significance was observed with any of the reference regions and amyloid rate of change in the precuneus (SUVR prec ).
Conclusion: In this cognitively intact cohort, a composite neocortical volume of interest together with whole cerebellum or cerebellar grey matter as reference region are the methods of choice for detecting APOE4-dependent differences in amyloid rate of change.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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