Cerebral Glucose Metabolic Features of Parkinson Disease and Incident Dementia: Longitudinal Study

Abstract

Longitudinal studies in nondemented Parkinson disease (PD) subjects offer an opportunity to study the earliest regional cerebral subcortical and cortical metabolic changes underlying incident dementia in this disorder. Methods: Twenty-three PD subjects without dementia (Hoehn and Yahr stages I-III; age, 61.8 6 9.7 y; Mini-Mental State Examination, 28.0 6 1.4) and 27 controls (age, 59.8 6 11.5 y) underwent 18 F-FDG PET at study entry. PD subjects underwent yearly clinical assessment to determine conversion to dementia. The mean duration of follow-up was 3.9 6 1.2 y (range, 2.0-6.8 y). Follow-up 18 F-FDG PET was available in a subset of subjects at 2 or more years. Both volume-of-interest and 3-dimensional stereotactic surface projection (3D-SSP) analyses were performed. Results: Six subjects became demented (PDD), with a mean time of 3.8 6 1.7 y (range, 1.9-6.0 y) to development of dementia. Mean duration of disease before onset of dementia was 9.7 6 4.2 y (range, 3.1-14 y). There were significant metabolic reductions in the occipital (211.8% vs. controls, F (2,22) 5 7.0, P 5 0.002) and posterior cingulate (212.1% vs. controls, F (2,22) 5 5.2, P 5 0.009) cortices in PDD subjects at baseline, before diagnosis of dementia, compared with controls. Metabolism was most diminished in the visual association cortex (Brodmann area [BA] 18; 220.0% vs. control, F (2,22) 5 8.45, P 5 0.0007) of PDD subjects. There was mild hypometabolism in the caudate nucleus (28.4% vs. control, F (2,22) 5 3.2, P , 0.05). There was no significant hypometabolism in the temporal or frontal lobes. PD subjects who did not become demented (non-PDD), compared with controls, had reduced cerebral metabolism in the primary occipital cortex (BA 17) that was revealed only by 3D-SSP analysis. Follow-up scans in 5 PDD subjects at 2 y after study entry demonstrated a significant interval within-subject change in the thalamus (211.4%), posterior cingulate (29%), occipital (27%), parietal (27%), and frontal cortices (27%) and mild reductions in the temporal cortex (25%) and hippocampus (23%), compared with study entry scans. Conclusion: Incident dementia in idiopathic PD is heralded by decreased metabolism in the visual association (BA 18) and posterior cingulate cortices, with mild involvement also of the caudate nucleus. Two-year follow-up data from 5 PDD converters show that progression to dementia is associated with mixed subcortical and cortical changes that involve the mesiofrontal lobes also. These findings provide insights into early metabolic features of parkinsonian dementia.

Upregulation of a small vault RNA (svtRNA2-1a) is an early event in Parkinson disease and induces neuronal dysfunction

“…In addition, our observations indicate that svtRNA2-1a overexpression in differentiated SH-SY5Y impairs neuronal metabolism. It is worth noting that idiopathic PD is heralded by decreased glucose metabolism in different brain regions [62][63][64][65] and, therefore, svtRNA2-1a overexpression could contribute to metabolic impairment in PD. diffuse β-amyloid plaques and a few neurofibrillary tangles in the entorhinal cortex were the only abnormality in some cases.…”

Assessing cognitive dysfunction in Parkinson's disease: An online tool to detect visuo‐perceptual deficits

“…Converging evidence shows that PD patients with involvement of visual processing are at highest risk of PD dementia 2, 3. However, current measures of visuo‐perceptual function are poorly sensitive (eg, copying intersecting pentagons4 or clock drawing5 or require trained personnel and are time consuming to perform (such as the Vision Object and Space Perception battery6 or Benton's Judgment of Line Orientation7, 8.…”

Brain Energy Metabolism in Health and Disease

“…A hypometabolism of glucose has been described in Parkinson's disease patients (Huang et al, 2007;Yong et al, 2007;Perneczy et al, 2008;Hosokai et al, 2009;Lee et al, 2008;Lee et al, 2010;Bohnen et al, 2011;Borghammer et al, 2011). However, there is only limited molecular evidence to support this feature.…”

“…Glucose metabolism is decreased in the caudate, putamen and thalamus in a primate PD model. Bohnen et al, 2011;Borghammer et al, 2011Brownell et al, 2003Feng et al, 2008;Hattingen et al, 2009;Hou et al, 2010;Hyu Lee et al, 2009;Lee et al, 2010;Lyoo et al, 2008;Perneczky et al, 2008;Schapira et al, 1989. The Neuronal Doctrine recently reached its 100th year and together with the development of psychopharmacology by the middle of 20th century promoted spectacular developments in the knowledge of the biological bases of behavior.…”