Dataset Information

White Matter Reference Region in PET Studies of 11C-Pittsburgh Compound B Uptake: Effects of Age and Amyloid-? Deposition.

ABSTRACT: Amyloid-? (A?) deposition as seen on PET using an A?-binding agent is a critical diagnostic biomarker for Alzheimer disease (AD). Some reports suggest using white matter (WM) as a reference region for quantification of serial A? PET studies; however, nonspecific WM retention in A? PET in people with dementia or cognitively unimpaired (CU) has been widely reported and is poorly understood. Methods: To investigate the suitability of WM as a reference region and the factors affecting WM 11C-Pittsburgh compound B (11C-PiB) uptake variability, we conducted a retrospective study on 2 large datasets: a longitudinal study of participants (n = 577) who were CU, had mild cognitive impairment, or had dementia likely due to AD; and a cross-sectional study of single-scan PET imaging in CU subjects (n = 1,349). In the longitudinal study, annual changes in WM 11C-PiB uptake were assessed, and in the cross-sectional study, WM 11C-PiB uptake was assessed relative to subject age. Results: Overall, we found that WM 11C-PiB uptake showed age-related increases, which varied with the WM regions selected. Further, variable annual WM 11C-PiB uptake changes were seen with different gray matter (GM) 11C-PiB baseline uptake levels. Conclusion: WM binding increases with age and varies with GM 11C-PiB. These correlations should be considered when using WM for normalization in 11C-PiB PET studies. The cerebellar crus1+crus2 showed no increase with age and cerebellar GM+WM showed minimal increase, supporting their use as reference regions for cross-sectional studies comparing wide age spans. In longitudinal studies, the increase in WM uptake may be minimal in the short-term and thus using WM as a reference region in these studies seems reasonable. However, as participants age, the findings may be affected by changes in WM uptake. Changes in WM 11C-PiB uptake may relate to disease progression, warranting examination of the causes of WM 11C-PiB uptake.

SUBMITTER: Lowe VJ

PROVIDER: S-EPMC6167534 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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White Matter Reference Region in PET Studies of <sup>11</sup>C-Pittsburgh Compound B Uptake: Effects of Age and Amyloid-β Deposition.

Lowe Val J VJ Lundt Emily S ES Senjem Matthew L ML Schwarz Christopher G CG Min Hoon-Ki HK Przybelski Scott A SA Kantarci Kejal K Knopman David D Petersen Ronald C RC Jack Clifford R CR

Journal of nuclear medicine : official publication, Society of Nuclear Medicine 20180419 10

Amyloid-β (Aβ) deposition as seen on PET using an Aβ-binding agent is a critical diagnostic biomarker for Alzheimer disease (AD). Some reports suggest using white matter (WM) as a reference region for quantification of serial Aβ PET studies; however, nonspecific WM retention in Aβ PET in people with dementia or cognitively unimpaired (CU) has been widely reported and is poorly understood. <b>Methods:</b> To investigate the suitability of WM as a reference region and the factors affecting WM <sup ...[more]

PMID: 29674420

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Project description:Background White matter abnormalities are a common feature of aging and Alzheimer disease, and tend to be more severe among Black individuals. However, the extent to which white matter abnormalities relate to amyloid deposition, a marker of Alzheimer pathology, remains unclear. This cross-sectional study examined the association of white matter abnormalities with cortical amyloid in a community sample of older adults without dementia and examined the moderating effect of race. Methods and Results Participants from the ARIC-PET (Atherosclerosis Risk in Communities-Positron Emission Tomography) study underwent brain magnetic resonance imaging, which quantified white matter hyperintensity volume and microstructural integrity using diffusion tensor imaging. Participants received florbetapir positron emission tomography imaging to measure brain amyloid. Associations between measures of white matter structure and elevated amyloid status were examined using multivariable logistic regression. Among 322 participants (43% Black), each SD increase in white matter hyperintensity volume was associated with a greater odds of elevated amyloid (odds ratio [OR], 1.37; 95% CI, 1.03-1.83) after adjusting for demographic and cardiovascular risk factors. In race-stratified analyses, a greater white matter hyperintensity volume was more strongly associated with elevated amyloid among Black participants (OR, 2.00; 95% CI, 1.15-3.50), compared with White participants (OR, 1.29; 95% CI, 0.89-1.89). However, the race interaction was not statistically significant (P interaction=0.09). We found no association between white matter microstructure and elevated amyloid. Conclusions The results suggest a modest positive relationship between white matter hyperintensity and elevated amyloid in older adults without dementia. Although the results indicate that this association is nonsignificantly stronger among Black participants, these findings will need to be confirmed or refuted using larger multiracial cohorts.

Dataset Information

White Matter Reference Region in PET Studies of 11C-Pittsburgh Compound B Uptake: Effects of Age and Amyloid-? Deposition.

Publications

White Matter Reference Region in PET Studies of <sup>11</sup>C-Pittsburgh Compound B Uptake: Effects of Age and Amyloid-β Deposition.

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