Evaluating the association between brain atrophy, hypometabolism, and cognitive decline in Alzheimer’s disease: a PET/MRI study

Abstract

Glucose metabolism reduction and brain volume losses are widely reported in Alzheimer’s disease (AD). Considering that neuroimaging changes in the hippocampus and default mode network (DMN) are promising important candidate biomarkers and have been included in the research criteria for the diagnosis of AD, it is hypothesized that atrophy and metabolic changes of the abovementioned regions could be evaluated concurrently to fully explore the neural mechanisms underlying cognitive impairment in AD. Twenty-three AD patients and Twenty-four age-, sex- and education level-matched normal controls underwent a clinical interview, a detailed neuropsychological assessment and a simultaneous 18F-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET)/high-resolution T1-weighted magnetic resonance imaging (MRI) scan on a hybrid GE SIGNA PET/MR scanner. Brain volume and glucose metabolism were examined in patients and controls to reveal group differences. Multiple linear regression models were employed to explore the relationship between multiple imaging features and cognitive performance in AD. The AD group had significantly reduced volume in the hippocampus and DMN regions (P < 0.001) relative to that of normal controls determined by using ROI analysis. Compared to normal controls, significantly decreased metabolism in the DMN (P < 0.001) was also found in AD patients, which still survived after controlling for gray matter atrophy (P < 0.001). These findings from ROI analysis were further confirmed by whole-brain confirmatory analysis (P < 0.001, FWE-corrected). Finally, multiple linear regression results showed that impairment of multiple cognitive tasks was significantly correlated with the combination of DMN hypometabolism and atrophy in the hippocampus and DMN regions. This study demonstrated that combining functional and structural features can better explain the cognitive decline of AD patients than unimodal FDG or brain volume changes alone. These findings may have important implications for understanding the neural mechanisms of cognitive decline in AD.

Differential Effects of 2-Deoxyglucose and Glucose Deprivation on 4-Hydroxynonenal Dependent Mitochondrial Dysfunction in Primary Neurons

“…Mitochondrial dysfunction, which is associated with increased oxidative stress, is a major driving force of the progression of Alzheimer’s, Parkinson’s, and Huntington’s disease, as well as several other neurological disorders ( Lin and Beal, 2006 ; Austad et al, 2021 ). The progressive loss of glucose metabolism is also a prevalent feature of neurodegenerative disease, as indirectly shown by FDG-PET and MRI imaging, as well as measurement of concentrations of lactate, pyruvate, and TCA cycle metabolites in patient cerebrospinal fluid ( Parnetti et al, 1995 ; Redjems-Bennani et al, 1998 ; Buckner et al, 2005 ; Edison et al, 2007 ; Schroeter et al, 2009 ; La Joie et al, 2012 ; Liguori et al, 2016 ; Marchitelli et al, 2018 ; Chen et al, 2021 ). Therefore, a better understanding of the metabolic dysfunction that occurs in the brain during neurodegenerative disease progression is needed, at both the mitochondrial level, as well as upstream regarding the use of major metabolites such as glucose.…”

Cognitive Impairment and Brain Atrophy in Patients with Chronic Kidney Disease

“…The association between brain volume, brain atrophy, and cognitive function has been extensively investigated in studies involving Parkinson’s disease, multiple sclerosis, Alzheimer’s disease, and the general population; yet, few studies have explored the relationship between CI and white matter lesions, as well as brain atrophy, in CKD patients [ 28 , 35 , 36 , 37 , 38 ]. Yeh et al [ 39 ] found a significant correlation between attention and executive function and white matter lesions, but no correlation with brain atrophy.…”

Re-energising the brain: glucose metabolism, Tau protein and memory in ageing and dementia

“…In several studies, glucose hypometabolism follows a similar anatomical progression to the Braak stages of AD, and Tau pathology seen in Progressive Supranuclear Palsy and Corticobasal Degeneration [41][42][43] . However, it is noted that variations in the age of disease onset may have caused discrepancies between studies [44][45][46][47] . Furthermore, Tau pathology and glucose hypometabolism were shown to correlate with cognitive decline [48] .…”