Interaction of caudate dopamine depletion and brain metabolic changes with cognitive dysfunction in early Parkinson's disease.
Damage to nonmotor dopamine (DA)-mediated frontostriatal circuits has been proposed as the main pathophysiological basis of cognitive dysfunction in Parkinson's disease (PD). In the present study, 18 early nondemented drug naive PD patients were investigated, by dual-tracer N-ω-fluoropropyl-2β-carbomethoxy-3β-4-[123I]iodophenyl-nortropane ([123I]FP-CIT) single-photon emission computed tomography (SPECT)/[18F] fluoro-deoxyglucose (FDG) positron emission tomography (PET) imaging, to test whether an early and not yet treatment-modulated relation exists between cognitive functions, caudate nucleus (CN) DA impairment and brain metabolism (CMRglc) in associative frontostriatal circuits. Verbal fluency performance correlated with DA impairment in CN, and with CMRglc in dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC). Further, CMRglc in orbitofrontal cortex, DLPFC, and ACC was shown to be early modulated by the level of DA impairment in CN. The present study demonstrates in vivo the early functional disruption of nonmotor frontostriatal circuits in PD. The effect of CN DA impairment on DLPFC and ACC metabolism is proposed as a possible early pathophysiological and functional substrate for executive dysfunction in PD.
Polito
Cristina
C
Department of Clinical Pathophysiology, University of Florence, Florence, Italy. cristina.polito@unifi.it
Berti
Valentina
V
Ramat
Silvia
S
Vanzi
Eleonora
E
De Cristofaro
Maria Teresa
MT
Pellicanò
Giannantonio
G
Mungai
Francesco
F
Marini
Paolo
P
Formiconi
Andreas Robert
AR
Sorbi
Sandro
S
Pupi
Alberto
A
D000368:Aged; D002421:Caudate Nucleus / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D003072:Cognition Disorders / Q000000981:diagnostic imaging / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000150:complications* / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D015899:Tomography, Emission-Computed, Single-Photon
D004298:Dopamine