Objective: To compare approaches for defining PIB positivity, and investigate the relevance of elevated PIB in
elderly normal controls.
Methods: Seven young normal controls (yNC), 52 elderly normal controls (eNC) and 23 Alzheimer’s disease (AD)
subjects underwent PIB-PET scanning (mean age: yNC=25.2[3.5]; eNC=74.1[6.0]; AD=66.3[10.7]). Distribution
volume ratios (DVRs) were extracted using Logan plotting (35-90 min post-injection, cerebellum reference region)
and PIB index values were extracted (average DVR across prefrontal, lateral temporal, parietal, and cingulate). Two
methods were employed to determine a PIB positivity cut-off: Aizenstein 2008 iterative outlier approach using eNC PIB indices and 2 standard deviations (SDs) above the yNC PIB index mean. Resulting cut-offs were applied to
eNC and AD. Based on classification results, eNC subjects were further divided into 3 groups (PIB-: PIB- with both
approaches; PIB+: PIB+ with both approaches; “ambiguous”: classified differently). Age, hippocampus volume
(HV), episodic memory (EM) and APOE were investigated in these 3 eNC groups.
Results: PIB index values were highest in AD and lowest in yNC (yNC=1.025[0.024]; eNC=1.096[0.167];
AD=1.528[0.165]). The Aizenstein approach cut-off of 1.123 labeled 8/52 eNC and all AD cases as PIB+. Two SDs
above the young NC mean was 1.074 and classified 15/52 eNC and all AD cases as PIB+. Compared to the PIBgroup,
the PIB+ group showed higher age (p=0.08), smaller HV (p=0.05), reduced EM (p=0.10) and more APOE4
carriers (p=0.19). Differences were not detected between ambiguous and PIB- groups, however, the ambiguous
group was younger than the PIB+ group (p=0.01).
Conclusions: A more conservative cut-off had no effect on AD classification, and isolated eNC that were more
similar to AD subjects. Longitudinal follow up is needed to determine the biological relevance of “ambiguous”
eNC subjects. It is possible that these subjects show early amyloid deposition before downstream atrophy and
cognitive deficits are present.
