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PET amyloid imaging: Implications for estimating risk of progression to Alzheimer's disease in individuals with mild cognitive impairment

      Background

      In both clinical and research settings, there is an emerging need to provide evidence-based information about the risk of progressing to Alzheimer’s disease (AD) based on PET amyloid imaging results. Findings from meta-analyses can be difficult to translate into information that is relevant to patients because standard effect size indices (e.g., odds ratios) fail to account for varying length of follow-up among studies. The purpose of this analysis was to compute unambiguous AD risk estimates for use in pre-test counseling with persons affected by mild cognitive impairment (MCI) who are considering amyloid imaging.

      Methods

      We conducted a systematic literature review by searching for “mild cognitive impairment” and variations of “amyloid imaging,” “Pittsburgh Compound-B,” “florbetapir,” and “flutemetamol.” To account for differing follow-up length across studies, we calculated two-year person-time incidence rates for amyloid-negative and -positive MCI participants.

      Results

      Our search yielded 13 independent investigations following a total of 464 MCI participants for an average of 1.94 years (range: 0.68-2.68) after amyloid imaging. The meta-sample included various MCI subtypes and the proportion of APOE ε4 carriers ranged from 36.2%-66.7% across studies. Samples included both genders with study means ranging from 63.3-73.4 years for age, 11.8-17.2 years for education, and 25.1-28.2 for MMSE scores. Of the total 279 amyloid positive cases, 62% (n=172) converted to AD during follow-up, as to compared with 15% (n=28) of 191 amyloid negative cases. The overall person-time incidence rates were 0.297 (95%CI: 0.251-0.343)and 0.034 (95%CI: 0.015-0.054) per year for the amyloid positive and negative groups, respectively, suggesting that within 2 years, an estimated 59.4% of amyloid positive MCI cases and 6.8% of amyloid negative MCI cases progressed to AD.

      Conclusions

      Our synthesis of the available evidence suggests that, relative to a negative scan, a positive amyloid scan confers a high short-term risk of converting to AD. Given these striking prognostic implications, pre- and post-test counseling and the opportunities for reflection that they afford may be especially useful to persons with MCI who are considering PET amyloid imaging. The need to identify pertinent modifiers of clinical course that should be considered when tailoring risk information to individual cases remains.