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• W2052632451 abstract "A recent hypothetical model of Alzheimer's disease (AD) biomarkers proposed that biomarker levels as function of disease stage follow a sigmoid-shaped trajectory. The basis for proposing a sigmoid shape for amyloid PET in particular was in part based on the observation that in most studies comparing PIB PET across clinical groups, the top (i.e., most abnormal values) in the distribution of cognitively normal subjects are no different than the top values in AD dementia subjects. This suggests that rates of PIB accumulation decrease as PIB accumulation reaches its highest levels. Our objective was to investigate this relationship. Subjects were enrolled in either the Mayo Clinic Study of Aging (n=177) or the Mayo Alzheimer's Disease Research Center (n=15). Subjects were aged 70-92, 145 subjects were classified as cognitively normal (CN) and 47 as cognitively impaired (38 Mild Cognitive Impairment (MCI) and 9 AD dementia). All subjects had undergone 2 or more serial PIB PET exams. We measured baseline PIB SUVR and for each subject estimated a slope representing the PIB accumulation rate. We then fit regression models predicting PIB accumulation rate given baseline PIB, age, sex, education, and APOE genotype. The PIB accumulation rate was strongly associated with baseline PIB (P<0.001) and had an inverted U shape (P<0.001, test of non-linearity). We observed low rates of accumulation at low baseline PIB values, rates increasing to a maximum at baseline SUVR values around 1.7-2.0, above which rates declined - reaching accumulation rates near 0 at baseline SUVR values of about 3.0. This non-linear relationship held across clinical subgroups. There was a significant interaction between APOE and clinical category (P=0.004) such that greater rates of PIB accumulation were found in MCI/AD APOE Îμ4 carriers compared to Îμ4 non-carriers. Our data is consistent with a recently published hypothetical model in which rates of amyloid PET accumulation accelerate early in the disease process, reach a peak, and then decline to near 0 at the highest levels of PIB accumulation measured. This produces a sigmoid shaped trajectory of PIB level as a function of disease progression." @default.
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• W2052632451 date "2012-07-01" @default.
• W2052632451 modified "2023-09-27" @default.
• W2052632451 title "O3-12-04: Rates of PIB accumulation do plateau" @default.
• W2052632451 doi "https://doi.org/10.1016/j.jalz.2012.05.1209" @default.
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