The Relationship Between Funcation Connectivity and Amyloid Accumulation in AD Continuum

Abstract

Alzheimer's disease (AD) is characterized by the pathology's amyloid-beta and tau, as the common form of neurodegenerative dementia. There has great challenge for the understanding of AD functional and metabolic pathological changes. In this study, we aimed to study the relationship between functional connectivity and amyloid metabolic activity in the whole AD continuum. The functional magnetic resonance imaging (fMRI) and amyloid positron emission tomography (PET) imaging data were collected from the ADNI database, including 43 normal controls (NCs), 37 patients with mild cognitive impairment (MCI), and 32 patients with AD. We calculated the functional and amyloid metabolic connectivity for each subject and group. To assess the relationship between the functional connectivity of specific region and amyloid regions, we used the general linear model (GLM) model to measure the association between region-to-region functional connectivity and amyloid PET metabolic connectivity, controlled with other variances (sex, age, education level). The results showed that the average amyloid uptake of AD patients was highest ( <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$1.62\pm 0.22,\ \mathrm{P} &lt; 0.001$</tex> ) rather than other groups (MCI: <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$1.41\pm 0.18$</tex> and NC: <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$1.13+0.21$</tex> ). The functional connectivity of default mode network showed that there was significant connectivity difference ( <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$\mathrm{P} &lt; 0.001$</tex> ), and the functional strength was decrease with disease severity. There was significant positive correlation between functional connectivity and amyloid metabolic connectivity in both NC group ( <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$\mathrm{r}=0.31,\ \mathrm{P} &lt; 0.001$</tex> ), MCI group ( <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$\mathrm{r}=0.42, \mathrm{P} &lt; 0.001$</tex> ), and AD group ( <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$\mathrm{r}=0.47,\ \mathrm{P} &lt; 0.001$</tex> ). This study showed that the higher amyloid metabolic connectivity in AD continuum maybe related with a higher AD-related functional connectivity strength, which may indicate the co-pathology of functional activity and amyloid accumulation might be caused using similar mechanisms.