Plasma Transthyretin as a Predictor of Amnestic Mild Cognitive Impairment Conversion to Dementia

Amnestic mild cognitive impairment (MCI) is a prodromal stage of dementia, with a higher incidence of these patients progressing to Alzheimer's disease (AD) than normal aging people. A biomarker for the early detection and prediction for this progression is important. We recruited MCI subjects in three teaching hospitals and conducted longitudinal follow-up for 5 years at one-year intervals. Cognitively healthy controls were recruited for comparisom at baseline. Plasma transthyretin (TTR) levels were measured by ELISA. Survival analysis with time to AD conversion as an outcome variable was calculated with the multivariable Cox proportional hazards models using TTR as a continuous variable with adjustment for other covariates and bootstrapping resampling analysis. In total, 184 MCI subjects and 40 sex- and age-matched controls were recruited at baseline. At baseline, MCI patients had higher TTR levels compared with the control group. During the longitudinal follow-ups, 135 MCI patients (73.4%) completed follow-up at least once. The TTR level was an independent predictor for MCI conversion to AD when using TTR as a continuous variable (p = 0.023, 95% CI 1.001-1.007). In addition, in MCI converters, the TTR level at the point when they converted to AD was significantly lower than that at baseline (328.6 ± 66.5 vs. 381.9 ± 77.6 ug/ml, p < 0.001). Our study demonstrates the temporal relationship between the plasma TTR level and the conversion from MCI to AD.