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. 2017 May 23:9:1-9.
doi: 10.1016/j.dadm.2017.05.001. eCollection 2017.

Longitudinal changes in amyloid positron emission tomography and volumetric magnetic resonance imaging in the nondemented Down syndrome population

Patrick J Lao  1 , Ben L Handen  2 , Tobey J Betthauser  1 , Iulia Mihaila  1 , Sigan L Hartley  1 , Annie D Cohen  2 , Dana L Tudorascu  2 , Peter D Bulova  2 , Brian J Lopresti  2 , Rameshwari V Tumuluru  2 , Dhanabalan Murali  1 , Chester A Mathis  2 , Todd E Barnhart  1 , Charles K Stone  1 , Julie C Price  2 , Darlynne A Devenny  3 , Marsha R Mailick  1 , William E Klunk  2 , Sterling C Johnson  1 , Bradley T Christian  1
Affiliations

Longitudinal changes in amyloid positron emission tomography and volumetric magnetic resonance imaging in the nondemented Down syndrome population

Patrick J Lao et al. Alzheimers Dement (Amst). .

Abstract

Introduction: Down syndrome (DS) arises from a triplication of chromosome 21, causing overproduction of the amyloid precursor protein and predisposes individuals to early Alzheimer's disease (AD).

Methods: Fifty-two nondemented adults with DS underwent two cycles of carbon 11-labeled Pittsburgh compound B ([11C]PiB) and T1 weighted magnetic resonance imaging (MRI) scans 3.0 ± 0.6 years apart. Standard uptake value ratio (SUVR) images (50-70 minutes; cerebellar gray matter [GM]) and GM volumes were analyzed in standardized space (Montreal Neurological Institute space).

Results: 85% of PiB(-) subjects remained PiB(-), whereas 15% converted to PiB(+), predominantly in the striatum. None reverted from PiB(+) to PiB(-). Increases in SUVR were distributed globally, but there were no decreases in GM volume. The PiB positivity groups differed in the percent rate of change in SUVR [PiB(-): 0.5%/year, PiB converters: 4.9%/year, and PiB(+): 3.7%/year], but not in GM volume.

Discussion: Despite the characteristic striatum-first pattern, the global rate of amyloid accumulation differs by pre-existing amyloid burden and precedes atrophy or dementia in the DS population, similar to general AD progression.

Keywords: Alzheimer's disease; Amyloid PET; Down syndrome; Longitudinal; PiB.

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Figures

Fig. 1
Fig. 1
Average images of PiB SUVR at cycle 1 and cycle 2, as well as the difference image between cycles and parametric t-maps indicating clusters of significant differences between cycles (P < .001, >50 voxels). Abbreviations: PiB, Pittsburgh compound B; SUVR, standard uptake value ratio.
Fig. 2
Fig. 2
Longitudinal plots of mean PiB SUVR against age with the PiB positivity thresholds in each ROI shown as the dotted line. Each line represents a nondemented adult with DS. The PiB(−) group (N = 35) is shown in blue, the PiB converter group (N = 6) is shown in green, and the PiB(+) group (N = 11) is shown in red. Abbreviations: PiB, Pittsburgh compound B; ROI, region of interest; SUVR, standard uptake value ratio.
Fig. 3
Fig. 3
Longitudinal plots of mean GM volume against age. Each line represents a nondemented adult with DS. The PiB(−) group (N = 35) is shown in blue, the PiB converter group (N = 6) is shown in green, and the PiB(+) group (N = 11) is shown in red. Abbreviations: PiB, Pittsburgh compound B; SUVR, standard uptake value ratio.
See this image and copyright information in PMC

References

    1. Parker S.E., Mai C.T., Canfield M.A., Rickard R., Wang Y., Meyer R.E. Updated national birth prevalence estimates for selected birth defects in the United States, 2004–2006. Birth Defects Res A Clin Mol Teratol. 2010;88:1008–1016. - PubMed
    1. Oyama G., Cairns N.J., Shimada H., Oyama R., Titani K., Ihara Y. Down's syndrome: up-regulation of β-amyloid protein precursor and τ mRNAs and their defective coordination. J Neurochem. 1994;62:1062–1066. - PubMed
    1. Wisniewski K.E., Wisniewski H.M., Wen G.Y. Occurrence of neuropathological changes and dementia of Alzheimer's disease in Down's syndrome. Ann Neurol. 1985;17:278–282. - PubMed
    1. Mann D.M., Esiri M.M. The pattern of acquisition of plaques and tangles in the brains of patients under 50 years of age with Down's syndrome. J Neurol Sci. 1989;89:169–179. - PubMed
    1. Masters C.L., Simms G., Weinman N.A., Multhaup G., McDonald B.L., Beyreuther K. Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc Natl Acad Sci U S A. 1985;82:4245–4249. - PMC - PubMed