Decoupling of Local Metabolic Activity and Functional Connectivity Links to Amyloid in Alzheimer's Disease.
J Alzheimers Dis
; 64(2): 405-415, 2018.
Article
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| MEDLINE
| ID: mdl-29843243
ABSTRACT
BACKGROUND:
Both ongoing local metabolic activity (LMA) and corresponding functional connectivity (FC) with remote brain regions are progressively impaired in Alzheimer's disease (AD), particularly in the posterior default mode network (pDMN); however, it is unknown how these impairments interact. It is well known that decreasing mean synaptic activity of a region, i.e., decreasing LMA, reduces the region's sensitivity to afferent input from other regions, i.e., FC.OBJECTIVE:
We hypothesized progressive decoupling between LMA and FC in AD, which is linked to amyloid-ß pathology (Aß).METHODS:
Healthy adults (n=20) and Aß+patients without memory impairment (n=9), early MCI (n=21), late MCI (n=18) and AD (n=22) were assessed by resting-state fMRI, FDG-PET, and AV-45-PET to measure FC, LMA, and Aß of the pDMN. Coupling between LMA and FC (rLA/FC) was estimated by voxelwise correlation.RESULTS:
RLMA/FC decreased with disease severity (F=20.09, p<0.001). This decrease was specifically associated with pDMN Aß (r=-0.273, p=0.029) but not global Aß (r=-0.112, p=0.378) and with the impact of Aß on FC (i.e., rAß/FC,r=-0.339; p=0.006). In multiple regression models rLMA/FC was also associated with memory impairment, reduced cognitive speed and flexibility, outperforming global Aß, pDMN Aß, pDMN LMA, and pDMN FC, respectively.CONCLUSION:
Results demonstrate increasing decoupling of LMA from its FC in AD. Data suggest that decoupling is driven by local Aß and contributes to memory decline.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Péptidos beta-Amiloides
/
Enfermedad de Alzheimer
/
Disfunción Cognitiva
Tipo de estudio:
Diagnostic_studies
Límite:
Aged
/
Aged80
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
J Alzheimers Dis
Asunto de la revista:
GERIATRIA
/
NEUROLOGIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Austria