Distinct Spontaneous Brain Activity Patterns in Different Biologically-Defined Alzheimer’s Disease Cognitive Stage: A Preliminary Study

Abstract

Background: The National Institute on Aging-Alzheimer's Association (NIA-AA) has proposed a biological definition of Alzheimer's disease (AD): individuals with both abnormal amyloid and tau biomarkers (A+T+) would be defined as AD. It remains unclear why different cognitive status is present in subjects with biological AD. Resting-state functional magnetic resonance imaging (rsfMRI) has provided an opportunity to reveal the brain activity patterns in a biologically-defined AD cohort. Accordingly, we aimed to investigate distinct brain activity patterns in subjects with existed AD pathology but in the different cognitive stages. Method: We selected individuals with AD pathology (A+T+) and healthy controls (HC, A−T−) based on the cerebrospinal fluid (CSF) biomarkers. According to the cognitive stage, we divided the A+T+ cohort into three groups: (1) preclinical AD; (2) prodromal AD; and (3) AD with dementia (d-AD). We compared spontaneous brain activity measured by a fractional amplitude of low-frequency fluctuation (fALFF) approach among four groups. Results: The analysis of covariance (ANCOVA) results showed significant differences in fALFF in the posterior cingulate cortex/precuneus (PCC/PCu). Further, compared to HC, we found increased fALFF values in the right inferior frontal gyrus (IFG) in the preclinical AD stage, whereas prodromal AD patients showed reduced fALFF in the bilateral precuneus, right middle frontal gyrus (MFG), right precentral gyrus, and postcentral gyrus. Within the dAD group, both hyperactivity (right fusiform gyrus, right parahippocampal gyrus (PHG)/hippocampus, and inferior temporal gyrus) and hypoactivity (bilateral precuneus, left posterior cingulate cortex, left cuneus and superior occipital gyrus) were detected.

A Comparative Study on the Predictive Value of Different Resting-State Functional Magnetic Resonance Imaging Parameters in Preclinical Alzheimer's Disease

“…Since the precuneus, along with the PCC, is well-known as an essential component of the DMN and brain network hub, it may be the earliest region showing the detrimental effect of Aβ cascade. On the other hand, our findings contradicted previous research by Zeng et al (37), which showed that fALFF values in the inferior frontal gyrus (IFG) were higher in cognitively normal adults with Aβ+ than those with Aβ−. Zeng et al speculated that, under the impact of Aβ pathology, increased neural activity in the IFG could be a compensational effect in an effort to maintain normal cognitive performance.…”

“…In line with our findings, rs-fMRI has consistently demonstrated decreased FC of the precuneus (17,36). Furthermore, a more recent study showed that subjects with Aβ pathology had significantly lowered fALFF in the bilateral PCC and precuneus (37). Since the precuneus, along with the PCC, is well-known as an essential component of the DMN and brain network hub, it may be the earliest region showing the detrimental effect of Aβ cascade.…”

Local Functional MR Change Pattern and Its Association With Cognitive Function in Objectively-Defined Subtle Cognitive Decline

“…The frontal lobe may be an essential area of cognitive maintenance associated with AD (Zeng et al, 2019). In terms of cognitive function, it may be involved in episodic memory and working memory (de Chastelaine et al, 2011;Matthews, 2015).…”

Distinct Brain Functional Impairment Patterns Between Suspected Non-Alzheimer Disease Pathophysiology and Alzheimer’s Disease: A Study Combining Static and Dynamic Functional Magnetic Resonance Imaging

“…Abnormalities in dynamic brain activity, including excessive variability (increased dALFF) and excessive stability (decreased dALFF), impair brain function (Christoff et al, 2016). These methods have been widely used in neurodegenerative diseases, like AD (Yang et al, 2018;de Vos et al, 2018;Li et al, 2019;Zeng et al, 2019), Parkinson's disease (Skidmore et al, 2013;Zhang et al, 2019) have been proven feasible and effective. Thus, combining the sALFF and dALFF may help to illuminate the underlying brain functional changes in SNAP.…”