Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Nov;22(10):978-990.
doi: 10.1017/S1355617716000928.

Patterns of Cortical and Subcortical Amyloid Burden across Stages of Preclinical Alzheimer's Disease

Emily C Edmonds  1 , Katherine J Bangen  1 , Lisa Delano-Wood  1 , Daniel A Nation  2 , Ansgar J Furst  3 , David P Salmon  4 , Mark W Bondi  1 ; Alzheimer’s Disease Neuroimaging Initiative
Affiliations

Patterns of Cortical and Subcortical Amyloid Burden across Stages of Preclinical Alzheimer's Disease

Emily C Edmonds et al. J Int Neuropsychol Soc. 2016 Nov.

Abstract

Objectives: We examined florbetapir positron emission tomography (PET) amyloid scans across stages of preclinical Alzheimer's disease (AD) in cortical, allocortical, and subcortical regions. Stages were characterized using empirically defined methods.

Methods: A total of 312 cognitively normal Alzheimer's Disease Neuroimaging Initiative participants completed a neuropsychological assessment and florbetapir PET scan. Participants were classified into stages of preclinical AD using (1) a novel approach based on the number of abnormal biomarkers/cognitive markers each individual possessed, and (2) National Institute on Aging and the Alzheimer's Association (NIA-AA) criteria. Preclinical AD groups were compared to one another and to a mild cognitive impairment (MCI) sample on florbetapir standardized uptake value ratios (SUVRs) in cortical and allocortical/subcortical regions of interest (ROIs).

Results: Amyloid deposition increased across stages of preclinical AD in all cortical ROIs, with SUVRs in the later stages reaching levels seen in MCI. Several subcortical areas showed a pattern of results similar to the cortical regions; however, SUVRs in the hippocampus, pallidum, and thalamus largely did not differ across stages of preclinical AD.

Conclusions: Substantial amyloid accumulation in cortical areas has already occurred before one meets criteria for a clinical diagnosis. Potential explanations for the unexpected pattern of results in some allocortical/subcortical ROIs include lack of correspondence between (1) cerebrospinal fluid and florbetapir PET measures of amyloid, or between (2) subcortical florbetapir PET SUVRs and underlying neuropathology. Findings support the utility of our novel method for staging preclinical AD. By combining imaging biomarkers with detailed cognitive assessment to better characterize preclinical AD, we can advance our understanding of who is at risk for future progression. (JINS, 2016, 22, 978-990).

Keywords: Alzheimer disease; Beta-amyloid peptides; Biomarkers; Dementia; Florbetapir; Neuropsychology; Positron emission tomography.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Flowchart showing which participants from the overall ADNI database were included in the current study.
Fig. 2
Fig. 2
Mean regional and global florbetapir standard uptake ratio (SUVR) for cortical regions in preclinical AD stages (based on number of abnormal biomarkers) and MCI. Error bars denote standard error of the mean. Letters denote significant group differences: a = different than 0 Biomarkers; b = different than 1 Biomarker; c = different than 2 Biomarkers; d = different than 3 Biomarkers; e = different than MCI.
Fig. 3
Fig. 3
Mean standard uptake ratio (SUVR) for allocortical/subcortical regions in preclinical AD stages (based on number of abnormal biomarkers) and MCI. Error bars denote standard error of the mean. Letters denote significant group differences: a = different than 0 Biomarkers; b = different than 1 Biomarker; c = different than 2 Biomarkers; d = different than 3 Biomarkers; e = different than MCI.
Fig. 4
Fig. 4
Mean standard uptake ratio (SUVR) for (a) cortical and (b) subcortical regions when participants were classified based on NIA-AA criteria for preclinical AD. Error bars denote standard error of the mean. Letters denote significant group differences: a = different than Stage 0; b = different than Stage 1; c = different than Stage 2; d = different than Stage 3; e = different than SNAP; f = different than Unclassified; g = different than MCI.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Arriagada PV, Growdon JH, Hedley-Whyte ET, Hyman BT. Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer’s disease. Neurology. 1992;42:631–639. - PubMed
    1. Balasubramanian AB, Kawas CH, Peltz CB, Brookmeyer R, Corrada MM. Alzheimer disease pathology and longitudinal cognitive performance in the oldest-old with no dementia. Neurology. 2012;79(9):915–921. doi: 10.1212/WNL.0b013e318266fc77. - DOI - PMC - PubMed
    1. Bangen KJ, Clark AL, Werhane M, Edmonds E, Nation DA, Evangelista N, … Delano-Wood L. Cortical amyloid burden in empirically-derived MCI subtypes. Journal of Alzheimer’s Disease. 2016;52:849–861. - PMC - PubMed
    1. Bateman RJ, Xiong C, Benzinger TL, Fagan AM, Goate A, Fox NC, … Morris JC. Clinical and biomarker changes in dominantly inherited Alzheimer’s disease. New England Journal of Medicine. 2012;367(9):795–804. doi: 10.1056/NEJMoa1202753. - DOI - PMC - PubMed
    1. Beach TG, Thal DR, Zanette M, Smith A, Buckley C. Detection of striatal amyloid plaques with [18F] flutemetamol: Validation with postmortem histopathology. Journal of Alzheimer’s Disease. 2016;52:863–873. - PubMed

Publication types