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PET measurement of longitudinal amyloid load identifies the earliest stages of amyloid-beta accumulation during Alzheimer's disease progression in Down syndrome
- Source :
- NeuroImage, NeuroImage, Vol 228, Iss, Pp 117728-(2021)
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- Introduction Adults with Down syndrome (DS) are predisposed to Alzheimer's disease (AD) and reveal early amyloid beta (Aβ) pathology in the brain. Positron emission tomography (PET) provides an in vivo measure of Aβ throughout the AD continuum. Due to the high prevalence of AD in DS, there is need for longitudinal imaging studies of Aβ to better characterize the natural history of Aβ accumulation, which will aid in the staging of this population for clinical trials aimed at AD treatment and prevention. Methods Adults with DS (N = 79; Mean age (SD) = 42.7 (7.28) years) underwent longitudinal [C-11]Pittsburgh compound B (PiB) PET. Global Aβ burden was quantified using the amyloid load metric (AβL). Modeled PiB images were generated from the longitudinal AβL data to visualize which regions are most susceptible to Aβ accumulation in DS. AβL change was evaluated across Aβ(-), Aβ-converter, and Aβ(+) groups to assess longitudinal Aβ trajectories during different stages of AD-pathology progression. AβL change values were used to identify Aβ-accumulators within the Aβ(-) group prior to reaching the Aβ(+) threshold (previously reported as 20 AβL) which would have resulted in an Aβ-converter classification. With knowledge of trajectories of Aβ(-) accumulators, a new cutoff of Aβ(+) was derived to better identify subthreshold Aβ accumulation in DS. Estimated sample sizes necessary to detect a 25% reduction in annual Aβ change with 80% power (alpha 0.01) were determined for different groups of Aβ-status. Results Modeled PiB images revealed the striatum, parietal cortex and precuneus as the regions with earliest detected Aβ accumulation in DS. The Aβ(-) group had a mean AβL change of 0.38 (0.58) AβL/year, while the Aβ-converter and Aβ(+) groups had change of 2.26 (0.66) and 3.16 (1.34) AβL/year, respectively. Within the Aβ(-) group, Aβ-accumulators showed no significant difference in AβL change values when compared to Aβ-converter and Aβ(+) groups. An Aβ(+) cutoff for subthreshold Aβ accumulation was derived as 13.3 AβL. The estimated sample size necessary to detect a 25% reduction in Aβ was 79 for Aβ(-) accumulators and 59 for the Aβ-converter/Aβ(+) group in DS. Conclusion Longitudinal AβL changes were capable of distinguishing Aβ accumulators from non-accumulators in DS. Longitudinal imaging allowed for identification of subthreshold Aβ accumulation in DS during the earliest stages of AD-pathology progression. Detection of active Aβ deposition evidenced by subthreshold accumulation with longitudinal imaging can identify DS individuals at risk for AD development at an earlier stage.
- Subjects :
- Adult
Male
medicine.medical_specialty
Down syndrome
Amyloid
Amyloid beta
Cognitive Neuroscience
Population
Precuneus
Alpha (ethology)
Striatum
Article
050105 experimental psychology
lcsh:RC321-571
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Alzheimer Disease
Internal medicine
medicine
Humans
0501 psychology and cognitive sciences
Longitudinal Studies
education
lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
education.field_of_study
Amyloid beta-Peptides
biology
business.industry
05 social sciences
Brain
Alzheimer's disease
medicine.disease
Endocrinology
medicine.anatomical_structure
Neurology
chemistry
Amyloid PET
Positron-Emission Tomography
biology.protein
Longitudinal
Disease Progression
Female
Pittsburgh compound B
business
Alzheimer’s disease
Subthreshold amyloid
030217 neurology & neurosurgery
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- NeuroImage, NeuroImage, Vol 228, Iss, Pp 117728-(2021)
- Accession number :
- edsair.doi.dedup.....10b9819dc52a47dc4cc6d27c6bb3bb5b
- Full Text :
- https://doi.org/10.17863/cam.66484