Investigation of white matter PiB uptake as a marker of white matter integrity

Burcu Zeydan, Christopher Schwarz, Val Lowe, Robert I. Reid, Scott A. Przybelski, Timothy G. Lesnick, Walter K Kremers, Matthew L. Senjem, Jeffrey L. Gunter, Hoon Ki Min, Prashanthi D Vemuri, David S Knopman, Ronald Carl Petersen, Clifford R Jr. Jack, Orhun H Kantarci, Kejal M Kantarci

Research output: Contribution to journalArticle

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Abstract

Objective: To investigate the associations of Pittsburgh compound-B (PiB) uptake in white matter hyperintensities (WMH) and normal appearing white matter (NAWM) with white matter (WM) integrity measured with DTI and cognitive function in cognitively unimpaired older adults. Methods: Cognitively unimpaired older adults from the population-based Mayo Clinic Study of Aging (n = 537, age 65–95) who underwent both PiB PET and DTI were included. The associations of WM PiB standard uptake value ratio (SUVr) with fractional anisotropy (FA) and mean diffusivity (MD) in the WMH and NAWM were tested after adjusting for age. The associations of PiB SUVr with cognitive function z-scores were tested after adjusting for age and global cortical PiB SUVr. Results: The WMH PiB SUVr was lower than NAWM PiB SUVr (P < 0.001). In the WMH, lower PiB SUVr correlated with lower FA (r = 0.21, P < 0.001), and higher MD (r = −0.31, P < 0.001). In the NAWM, lower PiB SUVr only correlated with higher MD (r = −0.10, P = 0.02). Both in the WMH and NAWM, lower PiB SUVr was associated with lower memory, language, and global cognitive function z-scores after adjusting for age and global cortical PiB SUVr. Interpretation: Reduced PiB uptake in the WMH is associated with a loss of WM integrity and cognitive function after accounting for the global cortical PiB uptake, suggesting that WM PiB uptake may be an early biomarker of WM integrity that precedes cognitive impairment in older adults. When using WM as a reference region in cross-sectional analysis of PiB SUVr, individual variability in WMH volume as well as age should be considered.

Original languageEnglish (US)
Pages (from-to)678-688
Number of pages11
JournalAnnals of Clinical and Translational Neurology
Volume6
Issue number4
DOIs
StatePublished - Apr 1 2019

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Cognition
White Matter
2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
Anisotropy
Language
Cross-Sectional Studies
Biomarkers
Population

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology

Cite this

Investigation of white matter PiB uptake as a marker of white matter integrity. / Zeydan, Burcu; Schwarz, Christopher; Lowe, Val; Reid, Robert I.; Przybelski, Scott A.; Lesnick, Timothy G.; Kremers, Walter K; Senjem, Matthew L.; Gunter, Jeffrey L.; Min, Hoon Ki; Vemuri, Prashanthi D; Knopman, David S; Petersen, Ronald Carl; Jack, Clifford R Jr.; Kantarci, Orhun H; Kantarci, Kejal M.

In: Annals of Clinical and Translational Neurology, Vol. 6, No. 4, 01.04.2019, p. 678-688.

Research output: Contribution to journalArticle

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abstract = "Objective: To investigate the associations of Pittsburgh compound-B (PiB) uptake in white matter hyperintensities (WMH) and normal appearing white matter (NAWM) with white matter (WM) integrity measured with DTI and cognitive function in cognitively unimpaired older adults. Methods: Cognitively unimpaired older adults from the population-based Mayo Clinic Study of Aging (n = 537, age 65–95) who underwent both PiB PET and DTI were included. The associations of WM PiB standard uptake value ratio (SUVr) with fractional anisotropy (FA) and mean diffusivity (MD) in the WMH and NAWM were tested after adjusting for age. The associations of PiB SUVr with cognitive function z-scores were tested after adjusting for age and global cortical PiB SUVr. Results: The WMH PiB SUVr was lower than NAWM PiB SUVr (P < 0.001). In the WMH, lower PiB SUVr correlated with lower FA (r = 0.21, P < 0.001), and higher MD (r = −0.31, P < 0.001). In the NAWM, lower PiB SUVr only correlated with higher MD (r = −0.10, P = 0.02). Both in the WMH and NAWM, lower PiB SUVr was associated with lower memory, language, and global cognitive function z-scores after adjusting for age and global cortical PiB SUVr. Interpretation: Reduced PiB uptake in the WMH is associated with a loss of WM integrity and cognitive function after accounting for the global cortical PiB uptake, suggesting that WM PiB uptake may be an early biomarker of WM integrity that precedes cognitive impairment in older adults. When using WM as a reference region in cross-sectional analysis of PiB SUVr, individual variability in WMH volume as well as age should be considered.",
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T1 - Investigation of white matter PiB uptake as a marker of white matter integrity

AU - Zeydan, Burcu

AU - Schwarz, Christopher

AU - Lowe, Val

AU - Reid, Robert I.

AU - Przybelski, Scott A.

AU - Lesnick, Timothy G.

AU - Kremers, Walter K

AU - Senjem, Matthew L.

AU - Gunter, Jeffrey L.

AU - Min, Hoon Ki

AU - Vemuri, Prashanthi D

AU - Knopman, David S

AU - Petersen, Ronald Carl

AU - Jack, Clifford R Jr.

AU - Kantarci, Orhun H

AU - Kantarci, Kejal M

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