Evidence of parietal hyperactivation in individuals with mild cognitive impairment who progressed to dementia: A longitudinal fMRI study

Abstract

Hyperactivation, which is defined as a higher level of activation in patients compared to cognitively unimpaired older adults (controls; CTL), might represent an early signature of Alzheimer's Disease (AD). The goal of this study was to assess the presence and location of hyperactivation in individuals with mild cognitive impairment (MCI) who were later diagnosed with dementia, examine how hyperactivation changes longitudinally, and whether it is related to time before dementia. Forty participants, 26 with MCI and 14 CTL were enrolled in the study. Magnetic resonance imaging was used to measure functional activation while participants encoded word-pairs as well as cortical thickness and regional brain volume at study entry (Y0) and two years later (Y2). Clinical follow-up was completed every two years following study entry to identify progressors (pMCI), that is, individuals who later received a diagnosis of dementia. Task-related activation was assessed in pMCI in both hippocampi and in regions showing greater cortical thinning from Y0 to Y2 compared to CTLs. Hyperactivation was found in pMCI individuals in the right supramarginal gyrus. Persons with pMCI also showed hypoactivation in the left hippocampus and left pars opercularis. Both hyper- and hypoactivation were present at Y0 and Y2 and did not change longitudinally. Activation was not associated with time before dementia diagnosis. Smaller volume and thinner cortical thickness were associated with shorter time to diagnosis in the left hippocampus and left pars opercularis. In conclusion, hyperactivation was found in individuals who later progressed to dementia, confirming that it might represent an early biomarker to identify individuals in the prodromal phase of AD and that its understanding could contribute to elucidate the key brain mechanisms that precede dementia.

Relationship of Parieto-Occipital Brain Energy Phosphate Metabolism and Cognition Using 31P MRS at 7-Tesla in Amnestic Mild Cognitive Impairment

“…Next, we investigated if the BEM indices derived from measuring the high-energy phosphates and membrane phospholipid metabolites at 7T showed a correspondence with cognitive performance (BEM-Cognitive correlates). Overall, we hypothesized an inverse relationship across BEM indicesenergy reserve, energy consumption, and metabolic statealong with regulatory co-factors pH and Mg 2+ and membrane phospholipid index with cognitive performance supported by previous work from Ashraf et al (2015), Croteau et al (2018), andCorriveau-Lecavalier et al (2019). Our results support our assumptions of an inverse relationship in aMCI with the exception of Mg 2+ and the membrane phospholipid index, which were positively associated with visuospatial domain and attention, respectively.…”

“… Ashraf’s et al (2015) research supported increased metabolism (hypermetabolism) in the occipital cortex in MCI compared to healthy controls using 18 FDG PET. Similarly, a longitudinal study in 26 MCI by Corriveau-Lecavalier et al (2019) found that parietal lobe hyperactivation in 13 MCI was an early indicator in individuals who progressed to dementia. In MCI, based on Ashraf’s and Corriveau’s findings in the parietal and occipital lobes separately, we hypothesized that there may be compensatory hyperactivation, which may be a proxy of higher cerebral blood flow and energy metabolism during the early phases of biological changes, which may be associated with worsening of cognitive performance.…”

“…The current study represents the first known project to test whether a methodology, previously shown to separate similar metabolites in the healthy young adult brain ( Ren et al, 2015 ), heart ( Rodgers et al, 2014 ), and muscles ( Ren et al, 2013 ) could be adapted to measure BEM using 31 P MRS at 7 Tesla in participants classified as aMCI. We selected parieto-occipital lobes as the region of interest based on two previous MCI studies ( Ashraf et al, 2015 ; Corriveau-Lecavalier et al, 2019 ). Ashraf’s et al (2015) research supported increased metabolism (hypermetabolism) in the occipital cortex in MCI compared to healthy controls using 18 FDG PET.…”

A quadratic function of activation in individuals at risk of Alzheimer's disease

“…In the presence of mild neurodegeneration, a high level of activation may be consistent with a higher risk of progression in cognitively intact older adults complaining about their memory. Furthermore, while some studies investigated fMRI dynamics in relation to amyloid and tau, 36 this is the first study to link a quadratic trajectory of brain activation with neurodegeneration, a recognized proxy of clinical severity 37,38 and time to dementia 5 …”

“…There has been growing interest in hyperactivation as an early signature of Alzheimer's disease (AD). This interest stems from the observation of higher task‐related functional magnetic resonance imaging (fMRI) activation in individuals with mild cognitive impairment (MCI) than in cognitively healthy controls (HC) 1–6 . This contrasts the observation of lower level of activation, or hypoactivation, in individuals with dementia or in the late stage of MCI 7–9 .…”