IC-P-038: Identification of noninvasive screening variables for the prediction of amyloid accumulation in a population-based study of cognitively normal elderly individuals

The design of secondary Alzheimer's disease (AD) prevention trials in preclinical subjects will likely require documentation of brain amyloidosis for enrollment. The identification of inexpensive and non-invasive screening variables that could predict which individuals have significant amyloid accumulation would reduce screening costs. 483 cognitively normal (CN) individuals, aged 70-92, from the population-based Mayo Clinic Study of Aging underwent PIB-PET imaging. Logistic regression was used to determine whether age, sex, APOE genotype, family history, or cognitive performance were associated with increased odds of a PIB retention ratio>1.4 and >1.5. Area under the receiver operating characteristic curve (AUROC) evaluated the discrimination between PIB positive and negative subjects. Positive (PPV) and negative (NPV) predictive value was defined based on an estimated probability >0.50 who were PIB-positive. The estimated sample size for each characteristic, by age group (70-79 and 80-89 years), needed to screen to enroll 100 participants into a clinical trial with PIB>1.4 or >1.5 was determined based on the desired sample size divided by sample proportions in the MCSA data. Of 483 CN individuals, 151 (31%) had PIB>1.5 and 211 (44%)>1.4. In univariate and multivariate models, discrimination was modest (AUROC∼0.6-0.7). Multivariately, age and APOE best predicted odds of PIB>1.4 and >1.5. For PIB>1.5, the addition of all factors resulted in a PPV of 60% and NPV of 74%, and reduced the number needed to screen from 320 to 166 to enroll 100 individuals into a pre-clinical AD trial requiring brain amyloidosis. The predictability of some factors varied with age. For example, based on PIB>1.5, information on APOE genotype alone reduced the number needed to screen by 48% in persons aged 70-79 and 33% in those aged 80-89. Age and APOE genotype are useful predictors of amyloid accumulation, but discrimination is modest. Nonetheless, these results suggest that inexpensive and non-invasive measures could significantly reduce the number of CN individuals needed to screen with amyloid PET imaging or a lumbar puncture for CSF to identify a given number of amyloid positive subjects.