Association between beta amyloid plaque deposition and neuronal activity measured by Resting‐state fMRI in Alzheimer’s Disease and mild cognitive impairment

Abstract

AbstractBackgroundDespite the important role of amyloid‐beta protein (Aβ) in the initiation and progression of Alzheimer’s Disease (AD), the precise mechanism by which Aβ disrupts neuronal activity (NA) and structure during disease development, and whether this protein is an appropriate therapeutic target is still controversial. Recently, we introduced several novel NA metrics (Kazemeifar, PLoS One 2017; Haddad, ISMRM 2019) based on specific spatiotemporal features of the resting‐state fMRI (rs‐fMRI) signal. These NA metrics are significantly lower in AD and mild cognitive impairment (MCI) compared to normal elderly controls. Here, we examine whether there is an association between resting‐state fMRI NA levels and Aβ deposition in grey matter (GM) measured by PET in AD and MCI.Method[18F]florbetapir Aβ PET images and rs‐fMRI data (TR = 3s, 197 volumes) in 9 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI, 3 early MCI (EMCI), 3 MCI, and 3 AD, aged 77 ± 7 years, 3 females) were included. The rs‐fMRI data was pre‐processed and decomposed into independent components (ICs) using IC analysis. The ICs associated with neuronal activity were identified using a support vector machine classifier (Demertzi, Cortex 2014). NA was quantified in each voxel using the magnitude of the neuronal ICs in the rs‐fMRI signal. This magnitude was calculated based on similarity (cross‐covariance) between each neuronal IC and rs‐fMRI signal (Haddad, ISMRM 2019). In each subject, the pre‐processed PET images (Jagust, Alzheimers. Dement. 2015) were registered to the T1‐weighted image to which the NA maps were already registered. GM voxelwise correlation was then conducted between the NA and [18F]florbetapir uptake maps in each subject.ResultThe NA and [18F]florbetapir uptake maps in one EMCI subject (Figure 1) and related scatter plot (Figure 2) show the correlation between NA and [18F]florbetapir uptake in GM. In all subjects studied, NA and [18F]florbetapir uptake were significantly negatively correlated (r = ‐0.25 ± 0.14) (Table 1).ConclusionThe negative correlation between NA and [18F]florbetapir uptake in this preliminary study indicates that Aβ deposition contributes to decreased neuronal activity in AD and MCI measured by rs‐fMRI. Future studies should determine the susceptibility of various brain regions to Aβ accumulation.