Not quite PIB-positive, not quite PIB-negative: Slight PIB elevations in elderly normal control subjects are biologically relevant

• Published in: NeuroImage (Orlando, Fla.) Vol. 59; no. 2; pp. 1152 - 1160
• Main Authors: Mormino, Elizabeth C., Brandel, Michael G., Madison, Cindee M., Rabinovici, Gil D., Marks, Shawn, Baker, Suzanne L., Jagust, William J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16.01.2012; Elsevier Limited
• Subjects: Adult; Age; Aged; Aged, 80 and over; Aging; Aging - metabolism; Alzheimer Disease - diagnostic imaging; Alzheimer Disease - metabolism; Alzheimer's disease; Alzheimer's disease (AD); Aniline Compounds; Benzothiazoles - pharmacokinetics; Beta-amyloid; Brain - diagnostic imaging; Brain - metabolism; Female; Humans; Male; Medical imaging; Middle Aged; NMR; Nuclear magnetic resonance; PIB-PET imaging; PIB-positivity; Positron-Emission Tomography - methods; Preclinical AD; Radiopharmaceuticals - pharmacokinetics; Reproducibility of Results; Sensitivity and Specificity; Studies; Thiazoles; Tissue Distribution; Young Adult; Aging; Alzheimer's disease (AD); Preclinical AD; PIB-positivity; PIB-PET imaging; Beta-amyloid
• ISSN: 1053-8119; 1095-9572; 1095-9572
• DOI: 10.1016/j.neuroimage.2011.07.098

Researchers employing Pittsburgh Compound B positron emission tomography (PIB-PET) imaging have consistently indentified old normal control (oNC) subjects with elevated tracer uptake, suggesting the presence of beta-amyloid deposition in these individuals. However, a consensus regarding the level at which PIB reveals a biologically meaningful signal does not exist (ie. an appropriate cutoff value for PIB positivity remains unclear). In this exploratory study, we sought to investigate the range of PIB distribution volume ratio (DVR) values present in our oNC cohort (N=75, age range=58–97). oNC subjects were classified based on global PIB index values (average DVR across prefrontal, parietal, lateral temporal and cingulate cortices) by employing two approaches: (1) an iterative outlier approach that revealed a cutoff value of 1.16 (IO-cutoff) and (2) an approach using data from a sample of young normal control subjects (N=11, age range=20–30) that yielded a cutoff value of 1.08 (yNC-cutoff). oNC subjects falling above the IO-cutoff had values similar to AD subjects (“PIB+”, 15%). Subjects falling between the 2 cutoffs were considered to have ambiguous PIB status (“Ambig”, 20%) and the remaining oNC were considered “PIB-“ (65%). Additional measures capturing focal DVR magnitude and extent of elevated DVR values were consistent with the classification scheme using PIB index values, and revealed evidence for elevated DVR values in a subset of PIB- oNC subjects. Furthermore, there were a greater proportion of ambiguously elevated values compared to low values, and these elevated values were present in regions known to show amyloid deposition. The analyses presented in this study, in conjunction with recently published pathological data, suggest a biological relevance of slight PIB elevations in aging. ►Two cutoff approaches were employed to define PIB-positivity in elderly controls. ►A subset of elderly controls have PIB levels similar to Alzheimer's disease. ►A subset of elderly controls have ambiguously elevated PIB values. ►Ambiguously elevated PIB values may reflect early signs of amyloid deposition.