Cortical hypometabolism and hypoperfusion in Parkinson's disease is extensive: probably even at early disease stages

TY - JOUR

T1 - Cortical hypometabolism and hypoperfusion in Parkinson's disease is extensive: probably even at early disease stages

AU - Borghammer, Per

AU - Chakravarty, Mallar

AU - Jonsdottir, Kristjana Yr

AU - Sato, Noriko

AU - Matsuda, Hiroshi

AU - Ito, Kengo

AU - Arahata, Yutaka

AU - Kato, Takashi

AU - Gjedde, Albert

PY - 2010/5

Y1 - 2010/5

N2 - Recent cerebral blood flow (CBF) and glucose consumption (CMRglc) studies of Parkinson's disease (PD) revealed conflicting results. Using simulated data, we previously demonstrated that the often-reported subcortical hypermetabolism in PD could be explained as an artifact of biased global mean (GM) normalization, and that low-magnitude, extensive cortical hypometabolism is best detected by alternative data-driven normalization methods. Thus, we hypothesized that PD is characterized by extensive cortical hypometabolism but no concurrent widespread subcortical hypermetabolism and tested it on three independent samples of PD patients. We compared SPECT CBF images of 32 earlystage and 33 late-stage PD patients with that of 60 matched controls. We also compared PET FDG images from 23 latestage PD patients with that of 13 controls. Three different normalizationmethods were compared: (1)GMnormalization, (2) cerebellum normalization, (3) reference cluster normalization (Yakushev et al.). We employed standard voxel-based statistics (fMRIstat) and principal component analysis (SSM). Additionally, we performed a meta-analysis of all quantitative CBF and CMRglc studies in the literature to investigate whether the global mean (GM) values in PD are decreased. Voxelbased analysis with GM normalization and the SSM method performed similarly, i.e., both detected decreases in small cortical clusters and concomitant increases in extensive subcortical regions. Cerebellum normalization revealed more widespread cortical decreases but no subcortical increase. In all comparisons, the Yakushev method detected nearly identical patterns of very extensive cortical hypometabolism. Lastly, the meta-analyses demonstrated that global CBF and CMRglc values are decreased in PD. Based on the results, we conclude that PD most likely has widespread cortical hypometabolism, even at early disease stages. In contrast, extensive subcortical hypermetabolism is probably not a feature of PD.

AB - Recent cerebral blood flow (CBF) and glucose consumption (CMRglc) studies of Parkinson's disease (PD) revealed conflicting results. Using simulated data, we previously demonstrated that the often-reported subcortical hypermetabolism in PD could be explained as an artifact of biased global mean (GM) normalization, and that low-magnitude, extensive cortical hypometabolism is best detected by alternative data-driven normalization methods. Thus, we hypothesized that PD is characterized by extensive cortical hypometabolism but no concurrent widespread subcortical hypermetabolism and tested it on three independent samples of PD patients. We compared SPECT CBF images of 32 earlystage and 33 late-stage PD patients with that of 60 matched controls. We also compared PET FDG images from 23 latestage PD patients with that of 13 controls. Three different normalizationmethods were compared: (1)GMnormalization, (2) cerebellum normalization, (3) reference cluster normalization (Yakushev et al.). We employed standard voxel-based statistics (fMRIstat) and principal component analysis (SSM). Additionally, we performed a meta-analysis of all quantitative CBF and CMRglc studies in the literature to investigate whether the global mean (GM) values in PD are decreased. Voxelbased analysis with GM normalization and the SSM method performed similarly, i.e., both detected decreases in small cortical clusters and concomitant increases in extensive subcortical regions. Cerebellum normalization revealed more widespread cortical decreases but no subcortical increase. In all comparisons, the Yakushev method detected nearly identical patterns of very extensive cortical hypometabolism. Lastly, the meta-analyses demonstrated that global CBF and CMRglc values are decreased in PD. Based on the results, we conclude that PD most likely has widespread cortical hypometabolism, even at early disease stages. In contrast, extensive subcortical hypermetabolism is probably not a feature of PD.

U2 - 10.1007/s00429-010-0246-0

DO - 10.1007/s00429-010-0246-0

M3 - Journal article

C2 - 20361208

SN - 1863-2653

VL - 214

SP - 303

EP - 317

JO - Brain Structure and Function

JF - Brain Structure and Function

IS - 4

ER -