title: Memory decline shows stronger associations with estimated spatial patterns of amyloid deposition progression than total amyloid burden.
abstract: The development of amyloid imaging compounds has allowed in vivo imaging of amyloid deposition. In this study, we examined the spatial patterns of amyloid deposition throughout the brain using Pittsburgh Compound Blue ((11)C-PiB) positron emission tomography data from the Baltimore Longitudinal Study of Aging. We used a new methodology that allowed us to approximate spatial patterns of the temporal progression of amyloid plaque deposition from cross-sectional data. Our results are consistent with patterns of progression known from autopsy studies, with frontal and precuneus regions affected early and occipital and sensorimotor cortices affected later in disease progression--here, disease progression means lower-to-higher total amyloid burden. Furthermore, we divided participants into subgroups based on longitudinal change in memory performance, and demonstrated significantly different spatial patterns of the estimated progression of amyloid deposition between these subgroups. Our results indicate that the spatial pattern of amyloid deposition is related to cognitive performance and may be more informative than a biomarker reflecting total amyloid burden, the use of which is the current practice. This finding has broad implications for our understanding of the relationship between cognitive decline/resilience and amyloid deposition, as well as for the use of amyloid imaging as a biomarker in research and clinical applications.
authors.affiliation: Center for Biomedical Image Computing and Analytics, Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: rachel.yotter@uphs.upenn.edu.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Yotter
authors.forename: Jimit
authors.initials: J
authors.lastname: Doshi
authors.forename: Vanessa
authors.initials: V
authors.lastname: Clark
authors.forename: Jitka
authors.initials: J
authors.lastname: Sojkova
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhou
authors.forename: Dean F
authors.initials: DF
authors.lastname: Wong
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.forename: Susan M
authors.initials: SM
authors.lastname: Resnick
authors.forename: Christos
authors.initials: C
authors.lastname: Davatzikos
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D058227:Amyloidogenic Proteins / Q000378:metabolism*; D000814:Aniline Compounds; D015415:Biomarkers / Q000378:metabolism; D002250:Carbon Radioisotopes; D002540:Cerebral Cortex / Q000000981:diagnostic imaging* / Q000378:metabolism*; D003072:Cognition Disorders / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000523:psychology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008568:Memory / Q000502:physiology*; D057054:Molecular Imaging / Q000379:methods*; D019275:Radiopharmaceuticals; D013844:Thiazoles; D014055:Tomography, Emission-Computed
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D058227:Amyloidogenic Proteins; D000814:Aniline Compounds; D015415:Biomarkers; D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; D013844:Thiazoles
keywords: Amyloid; CVLT; Cognition; PET; PiB