Metabolic Networks Underlying Cognitive Reserve in Prodromal Alzheimer Disease: A European Alzheimer Disease Consortium Project
Open Access
- 16 April 2013
- journal article
- Published by Society of Nuclear Medicine in Journal of Nuclear Medicine
- Vol. 54 (6), 894-902
- https://doi.org/10.2967/jnumed.112.113928
Abstract
This project aimed to investigate the metabolic basis for resilience to neurodegeneration (cognitive reserve) in highly educated patients with prodromal Alzheimer disease (AD). Methods: Sixty-four patients with amnestic mild cognitive impairment who later converted to AD dementia during follow-up, and 90 controls, underwent brain 18F-FDG PET. Both groups were divided into a poorly educated subgroup (42 controls and 36 prodromal AD patients) and a highly educated subgroup (48 controls and 28 prodromal AD patients). Brain metabolism was first compared between education-matched groups of patients and controls. Then, metabolism was compared between highly and poorly educated prodromal AD patients in both directions to identify regions of high education-related metabolic depression and compensation. The clusters of significant depression and compensation were further used as volumetric regions of interest (ROIs) in a brain interregional correlation analysis in each prodromal AD subgroup to explore metabolic connectivity. All analyses were performed by means of SPM8 (P < 0.001 uncorrected at peak level, P < 0.05 false discovery rate–corrected at cluster level; age, sex, Mini-Mental State Examination score, and center as nuisance). Results: Highly educated prodromal AD patients showed more severe hypometabolism than poorly educated prodromal AD patients in the left inferior and middle temporal gyri and the left middle occipital gyrus (ROI depression). Conversely, they showed relative hypermetabolism in the right inferior, middle, and superior frontal gyri (ROI compensation). The sites of compensation, mainly corresponding to the right dorsolateral prefrontal cortex (DLFC), showed wide metabolic correlations with several cortical areas in both hemispheres (frontotemporal cortex, parahippocampal gyrus, and precuneus) in highly educated prodromal AD patients but not in poorly educated prodromal AD patients. To provide evidence on whether these metabolic correlations represent preservation of the physiologic networks of highly educated control subjects (neural reserve) or rather the recruitment of alternative networks (neural compensation), or a combination of the two, we performed metabolic connectivity analysis of the DLFC in highly educated controls as well. The correlation sites of right DLFC partly overlapped those of highly educated prodromal AD patients but were less extended. Conclusion: The present findings suggest that highly educated prodromal AD patients can cope better with the disease thanks to neural reserve but also to the recruitment of compensatory neural networks in which the right DLFC plays a key role.This publication has 29 references indexed in Scilit:
- Measuring cognitive reserve based on the decomposition of episodic memory varianceBrain, 2010
- Cognitive reserve hypothesis: Pittsburgh Compound B and fluorodeoxyglucose positron emission tomography in relation to education in mild Alzheimer's diseaseAnnals of Neurology, 2007
- Education and dementiaNeurology, 2007
- Mapping the connections between education and dementiaJournal of Clinical and Experimental Neuropsychology, 2007
- Impact of Alzheimer's pathology on cognitive trajectories in nondemented elderlyAnnals of Neurology, 2006
- Cognitive impact of subcortical vascular and Alzheimer's disease pathologyAnnals of Neurology, 2006
- Neuropathology of older persons without cognitive impairment from two community-based studiesNeurology, 2006
- Brain Networks Associated with Cognitive Reserve in Healthy Young and Old AdultsCerebral Cortex, 2004
- Volumetric MRI predicts rate of cognitive decline related to AD and cerebrovascular diseaseNeurology, 2002
- What is cognitive reserve? Theory and research application of the reserve conceptJournal of the International Neuropsychological Society, 2002