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Are low levels of PiB-PET signal clinically significant?

      Background

      In a previous study1 we suggested that the current SUVR thresholds of ∼1.4-1.5 are too high to capture early amyloid accumulation. We showed evidence that by the time a person reaches these thresholds, amyloid is already widespread throughout the cortex and suggested an SUVR value of 1.21 as an optimal cutoff to detect early PIB-PET signal using whole-brain [11C]PIB retention. The goal of this study was to characterize individuals with intermediate levels of amyloid on a variety of demographic, cognitive and brain markers (Table 1).

      Methods

      This study included 242 subjects (183 normal older adults and 59 adults with mild cognitive impairment). Group comparisons between PIB- (SUVRs < 1.21), PIBi (SUVRs ≥ 1.21 and <1.4) and PIB+ (SUVRs ≥ 1.4) were first restricted to cognitively normal individuals and then repeated in the total sample.

      Results

      In normal older adults, group differences were found for age, ApoE4 status and rate of amyloid accumulation. PIBi and PIB- individuals were younger than PIB+ individuals, and PIBi and PIB+ individuals had a higher frequency of ApoE4 carrier status and a higher rate of amyloid accumulation than PIB- individuals. When the analyses were performed in the total sample, the same results were found. Additionally, PIB+ individuals showed lower cortical thickness in AD-regions2 as well as lower global cognition (MMSE score) than PIBi and PIB-.

      Conclusions

      While PIBi individuals showed similar rate of amyloid accumulation and ApoE4 status to PIB+, they were comparable to PIB- on the other markers. These results suggest that low levels of PIB-PET signal are clinically relevant and that subjects with SUVR values between 1.21 and 1.4 are early accumulators. 1 Villeneuve et al., AAIC 2014; 2 Wirth et al., JAMA Neurol. 2013
      Table 1Variables of interest
      Demographic MarkersCognitive MarkersBrain Markers
      • Age
      • Gender
      • Education
      • ApoE e4 status
      • Mini-Mental Status Examination (MMSE)
      • 1 Memory complaint
      • 1 Factor Scores (baseline and change data)
        • o
          Episodic Memory
        • o
          Executive Function
      • Hippocampal Volume
      • FDG AD-regions
      • Cortical Thickness AD-regions
      • Amyloid accumulation2
      1Data only available in 127 cognitively normal older adults.
      2 Data only available in 55 cognitively normal older adults, rate of change in amyloid over 2 time points (3.4 years, 1.4 SD).