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 examine the spatial patterns of amyloid deposition throughout the brain using Pittsburgh Compound Blue (11C-PiB) PET data from the Baltimore Longitudinal Study of Aging. We used a new methodology that allows 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, 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.

Predicting Regional Pattern of Longitudinal β-Amyloid Accumulation by Baseline PET

“…A pseudotemporal analysis was initially reported by Braak and Braak, who studied progression of Ab deposition in cross-sectional data from postmortem brain tissue (22). Recently, a pseudotemporal analysis of PET images has been applied at the voxel level (18). Assuming that total amyloid burden would be a reasonable approximation of the disease severity, Yotter et al (18) estimated spatial patterns of the longitudinal Ab accumulation from cross-sectional image data.…”

“…The ADNI study was approved by institutional review boards of all participating centers, and written informed consent was obtained from all participants or authorized representatives. Considered were all patients with incipient and mild dementia due to AD, for whom structural MRI, baseline, and 2-y follow-up (FU) 18 F-florbetapir PET scans were available. Subjects with incipient AD were those diagnosed with late mild cognitive impairment at the time of baseline florbetapir scanning but who converted to dementia due to AD within 2 y of FU.…”

“…Specifically, subjects were ranked according to their SUVR in whole-brain GM (SUVR-GM), resulting in an across-subject waveform for each region (18). For a given region r, the SUVRs for n subjects can be expressed as: The assumption behind is that there is a spatial spread of amyloid deposition with disease progression.…”

Imaging Morphologic Substrates and Molecular Changes for Differential Diagnosis of Vascular Dementia

“…Whereas only small amounts of amyloid can be detected in the white matter in normal aging [34], accumulation is visible in the frontal and temporo-parietal cortex in AD and MCI. However, also in 20-30% of aged persons without relevant cognitive impairment an increased accumulation of amyloid can be detected [35], and the grade of amyloid deposition as detected by PET is not related to the severity of cognitive impairment [36]. That means that amyloid might be deposited in the brain eventually long before cognitive impairment is recognized.…”

Animal models of Alzheimer disease: historical pitfalls and a path forward

“…Expanded use of Pittsburgh Compound Blue positron emission tomography to detect and track amyloid deposition in the brain may enhance the search for viable biomarkers of AD. Recent research indicates that spatial distribution of amyloid deposits, rather than total amyloid burden, correlates well with cognitive decline (Yotter et al, 2013). Use of this in combination with cognitive outcome will allow researchers to more accurately track the progression of mild cognitive impairment to AD.…”