T53. LTP-like cortical plasticity is associated with memory and predicts cognitive decline in Alzheimer’s disease patients

Abstract

To determine the ability of transcranial magnetic stimulation (TMS) in detecting synaptic impairment in Alzheimer’s disease (AD) patients and predicting cognitive decline since the early phases of the disease. We evaluated long-term potentiation (LTP)-like cortical plasticity in 60 newly diagnosed AD patients. Pearson r correlation coefficient or Kruskal-Wallis runk sum test explored any relationship between LTP, demographics, cognition and AD-related biomarkers. Univariable analyses examined the association between LTP (respect to other AD-related biomarkers) and cognitive decline. Multivariable regression model revealed the best parameters able to predict disease progression. LTP plasticity was not significantly associated with sex (z = 0.89, p = 0.37), age (r = −0.02, p = 0.75) or APOE genotype (z = −0.81, p = 0.41). We confirm a significant association between LTP and both CSF t-tau (r = −0.34, p < 0.01) and p-tau levels (r = −0.26, p = 0.04), while no significant association was find for Ab1–42 (r = −0.01, p = 0.89). Higher values of LTP were associated with higher long-term verbal memory performances (CVLT delayed: r = 0.45; p = 0.002), while neither visual-spatial long-term memory (RCF delayed: r = 0.08; p = 0.53), general intelligence (RPM test: r = 0.11; p = 0.45), executive functions (FVF: r = −0.13; p = 0.36) or visual-spatial abilities (RCF copy: r = −0.08; p = 0.54) showed any association. Among AD patients, higher values of LTP were associated with better long-term verbal memory performances (r = 0.45; p = 0.002). Notably, LTP was a significant predictor of disease progression (p = 0.02), while no other neurophysiological, neuropsychological and demographic parameters, was associated with cognitive decline, except for a trend regarding sex (p = 0.07), long-term verbal memory (p = 0.07), visuospatial abilities (p = 0.10) and CSF total-tau levels (p = 0.09). Multivariable analysis then promoted LTP as the best significant predictor of cognitive decline (p = 0.01). Synaptic dysfunction may be an early pathologic process in AD, and could be easily detected by means of TMS. Our data showed a significant correlation between episodic memory and LTP-like cortical plasticity, reinforcing the notion that this measure could be a neurophysiological surrogate of memory. Furthermore, our data show that LTP-like cortical plasticity is able alone to predict cognitive decline in AD patients. TMS could be a viable tool to assess synaptic impairment in AD patients, with LTP-like plasticity as the most sensitive marker of memory and predictor of cognitive decline progression.