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 d-AD 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.Conclusion: We found the distinct brain activity patterns in different cognitive stages among the subjects defined as AD biologically. Our findings may be helpful in understanding mechanisms leading to cognitive changes in the AD pathophysiological process.
Highlights
Alzheimer’s disease (AD) remains the most common cause of dementia and is characterized by cognitive impairment, in salient amnestic symptoms (Rogan and Lippa, 2002; Mucke, 2009)
The primary goal of Alzheimer’s Disease Neuroimaging Initiative (ADNI) has been to test whether serial MRI, positron emission tomography (PET), other biological markers, and clinical and neuropsychological assessment can be combined to measure the progression of mild cognitive impairment (MCI) and early AD
We found that the preclinical AD group has increased fALFF values in the right inferior frontal gyrus (IFG) than healthy controls (HC) (Figure 2)
Summary
Alzheimer’s disease (AD) remains the most common cause of dementia and is characterized by cognitive impairment, in salient amnestic symptoms (Rogan and Lippa, 2002; Mucke, 2009). Individuals with biomarker profile ‘‘A+T+’’ could be subdivided into three categories: (1) preclinical AD (A+T+, cognitively unimpaired); (2) prodromal AD [A+T+, mild cognitive impairment (MCI)]; and (3) AD with dementia (A+T+, dementia; Jack et al, 2018) It remains unclear why individuals with existed AD pathology show different cognitive statuses. 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. We aimed to investigate distinct brain activity patterns in subjects with existed AD pathology but in the different cognitive stages
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