Metabolic Networks Underlying Cognitive Reserve in Prodromal Alzheimer Disease: A European Alzheimer Disease Consortium Project

Journal of Nuclear Medicine

Silvia Morbelli¹  Bart N.M. van Berckel¹  Flavio Nobili¹  Eric Guedj¹  Robert Perneczky¹  Giovanni B. Frisoni¹  Marco Pagani¹  Andrea Brugnolo¹  Mira Didic¹  Rik Ossenkoppele¹  Alexander Drzezga¹  Gianmario Sambuceti¹  Anna Caroli¹  Mehrdad Naseri¹ 

关键词: Alzheimer’s disease;    mild cognitive impairment;    cognitive reserve;    positron emission tomography;    metabolic connectivity;   

DOI  :  10.2967/jnumed.112.113928

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

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.

【 授权许可】

Unknown