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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
Free PMC article

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). .
Free PMC article

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.
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