Metabolic networks underlying cognitive reserve in prodromal Alzheimer disease: A European Alzheimer Disease Consortium Project

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.

Tipo Pubblicazione: 
Author or Creator: 
Morbelli, Silvia D.
Perneczky, Robert
Drzezga, Alexander E.
Frisoni, Giovanni Battista
Caroli, Anna
Van Berckel, Bart NM M
Ossenkoppele, Rik
Guedj, Éric
Didic, Mira
Brugnolo, Andrea
Naseri, Mehrdad
Sambuceti, Gianmario
Pagani, Marco
Nobili, Flavio Mariano
Society of Nuclear Medicine., [New York], Stati Uniti d'America
The Journal of nuclear medicine (1978) 54 (2013): 894–902. doi:10.2967/jnumed.112.113928
info:cnr-pdr/source/autori:Morbelli, Silvia D.; Perneczky, Robert; Drzezga, Alexander E.; Frisoni, Giovanni Battista; Caroli, Anna; Van Berckel, Bart NM M; Ossenkoppele, Rik; Guedj, Éric; Didic, Mira; Brugnolo, Andrea; Naseri, Mehrdad; Sambuceti, Gianmari
Resource Identifier:
ISTC Author: 
Ritratto di Marco Pagani
Real name: