Results of the whole-brain voxel-based analyses.

<p>First row: The brain regions that exhibited regional cerebral glucose metabolic reductions in the 60 PD patients relative to 14 normal volunteers (p<0.05 uncorrected, extent threshold of 100 voxels). Second row and below: The brain regions in which the resting CMRglc was correlated with the RTs in the various psychophysical tasks (Global: second row, Local: third row, Mixed: fourth row) and the shift cost (fifth row) (<i>p</i><0.001 uncorrected, extent threshold of 100 voxels). PD, Parkinson’s disease; R, right; L, left.</p

Brain regions in which regional cerebral glucose metabolism was negatively correlated with psychophysical task response time.

<p>Brain regions in which regional cerebral glucose metabolism was negatively correlated with psychophysical task response time.</p

Demographic and clinical characteristics of patients with PD and control participants.

<p>PD, Parkinson’s disease; MMSE, Mini Mental State Examination; CDR, Clinical Dementia Rating; NPI, Neuropsychiatric Inventory; UPDRS-III, Unified Parkinson’s Disease Rating Scale-motor score; L, left; R, right; B, bilateral.</p

Schematic illustrations of the psychophysical tasks.

<p>In both the Global and Local tasks, compound letter stimuli appeared after a 2-second presentation of a visual cue that indicated whether the target was a global or local letter. The subjects were instructed to respond orally to the target component of each compound letter stimulus as quickly as possible. In these tasks, the subjects maintained their attention on a single component of the compound letters (either the local or global component of the stimuli), and they were not required to reorient their attention. However, in the Mixed task, the cue that indicated the target component of the compound letter changed from trial to trial in a pseudorandom manner. The task required that the subjects switch their attention on the basis of the cue that was presented to them on each trial.</p

The results of the ROI-based stepwise multiple regression analyses.

<p>7 ROIs are shown in different colors: right DLPFC  =  red, left DLPFC  =  cyan, left VLPFC  =  yellow, right TPO  =  purple, left TPO  =  green, medial parietal cortex  =  white, and left posterior IT  =  blue. The scatterplots illustrate the relationship between the psychophysical task performance scores and the FDG-uptake values in the ROIs. DLPFC, dorsolateral prefrontal cortex; VLPFC, ventrolateral prefrontal cortex; TPO, temporo-parieto-occipital junction; posterior IT, posterior inferior temporal cortex; FDG, ¹⁸F-fluorodeoxyglucose.</p

Mean RTs and error rates in the psychophysical tasks.

<p>Comparisons that were significantly different are indicated with a * (p<0.05/3). There was a significant simple interaction between group and the Global/Mixed task factor (F = 5.99, p = 0.016), and there was a trend toward an interaction between the group and the Local/Mixed task factor (F = 5.63, p = 0.020). PD, Parkinson’s disease.</p

Group comparisons of regional cerebral glucose metabolism at baseline.

<p>(A) to (C) show the results of comparisons between patient groups with baseline Clinical Dementia Rating (CDR) 0, and (D) and (E) show the results of comparisons between groups with baseline CDR 0.5. Rendered images are shown in the order of the left lateral, left medial, right medial and right lateral. The left side of a coronal section corresponds to the left side of the brain.</p

Demographic and clinical profiles of patients with a Clinical Dementia Rating of 0.5 or more at baseline.

<p>Two-sample <i>t</i>-tests were used for group-wise comparisons of baseline scores and progression rates except for the UPDRS tremor/non-tremor scores. A two-way analysis of variance was used for the UPDRS tremor/non-tremor scores. No group-wise comparisons were performed for the backward digit-span owing to the small number of subjects. Data are given as the mean±SD except for the fields with asterisks. a and b indicate p<0.05 and p<0.01, respectively.</p><p>*Data are given as (the number of patients below −1 SD)/(the number of patients who underwent the test).</p>¶<p>The scores were calculated according to Lewis and colleagues. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0110547#pone.0110547-Lewis1" target="_blank">[5]</a> Data were obtained from 6 baseline memory-only and 6 baseline memory-plus patients.</p>†<p>The mean score of controls (n = 20, 65.5±4.8 years) is 21.3±3.5. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0110547#pone.0110547-Abe1" target="_blank">[49]</a>.</p>‡<p>The mean score of controls (n = 24, 66.1±5.3 years) is 32.9±4.4. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0110547#pone.0110547-Ishioka1" target="_blank">[32]</a>.</p>§<p>The mean score of controls (n = 20, 65.5±4.8 years) is 4.8±1.0. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0110547#pone.0110547-Abe1" target="_blank">[49]</a>; a statistical comparison was not performed owing to an insufficient number of subjects.</p><p>Abbreviations: UPDRS, Unified Parkinson's Disease Rating Scale; CDR, Clinical Dementia Rating; MMSE, Mini-Mental State Examination; ADAS, Alzheimer's Disease Assessment Scale; NE, not examined.</p><p>Demographic and clinical profiles of patients with a Clinical Dementia Rating of 0.5 or more at baseline.</p

Longitudinal changes in regional cerebral glucose metabolism.

<p>(A) to (E) show 3-year metabolic declines in the individual patient groups. (F) and (G) show group x time interactions between the non-converters and the memory-only converters and between the baseline memory-only patients and the baseline memory-plus patients, respectively. Rendered images show the left hemisphere. The left sides of coronal sections correspond to the left side of the brain.</p

Demographic and clinical profiles of patients with a Clinical Dementia Rating of 0 at baseline.

<p>Analysis of variance with post-hoc Tukey’s test was used for group-wise comparisons of baseline scores and progression rates except for the UPDRS tremor/non-tremor scores. Two-way analysis of variance with post-hoc Tukey’s test was used for the UPDRS tremor/non-tremor scores. Data are given as the mean±SD except for the fields with asterisks. a and b indicate p<0.05 and p<0.01, respectively.</p><p>*Data are given as (the number of patients below −1 SD)/(the number of patients who underwent the test).</p>¶<p>The scores were calculated according to Lewis and colleagues. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0110547#pone.0110547-Lewis1" target="_blank">[5]</a> Data were obtained from 21 non-converters, 6 memory-only converters and 5 memory-plus converters.</p>†<p>The mean score for controls (n = 20, 65.5±4.8 years) is 21.3±3.5. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0110547#pone.0110547-Abe1" target="_blank">[49]</a>.</p>‡<p>The mean score for controls (n = 24, 66.1±5.3 years) is 32.9±4.4. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0110547#pone.0110547-Ishioka1" target="_blank">[32]</a>.</p>§<p>The mean score for controls (n = 20, 65.5±4.8 years) is 4.8±1.0. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0110547#pone.0110547-Abe1" target="_blank">[49]</a>.</p><p>Abbreviations: UPDRS, Unified Parkinson's Disease Rating Scale; CDR, Clinical Dementia Rating; MMSE, Mini-Mental State Examination; ADAS, Alzheimer's Disease Assessment Scale; NE, not examined.</p><p>Demographic and clinical profiles of patients with a Clinical Dementia Rating of 0 at baseline.</p