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 ± 9.7 y; Mini-Mental State Examination, 28.0 ± 1.4) and 27 controls (age, 59.8 ± 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 ± 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 ± 1.7 y (range, 1.9-6.0 y) to development of dementia. Mean duration of disease before onset of dementia was 9.7 ± 4.2 y (range, 3.1-14 y). There were significant metabolic reductions in the occipital (-11.8% vs. controls, F((2,22)) = 7.0, P = 0.002) and posterior cingulate (-12.1% vs. controls, F((2,22)) = 5.2, P = 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; -20.0% vs. control, F((2,22)) = 8.45, P = 0.0007) of PDD subjects. There was mild hypometabolism in the caudate nucleus (-8.4% vs. control, F((2,22)) = 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 (-11.4%), posterior cingulate (-9%), occipital (-7%), parietal (-7%), and frontal cortices (-7%) and mild reductions in the temporal cortex (-5%) and hippocampus (-3%), 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.

FIGURE 1.

Metabolic reduction in PD. 3D-SSP t-statistic maps comparing PD[+]D and PD[−]D subjects with healthy controls (HC) at baseline. ¹⁸F-FDG-PET data are normalized within each subject to the pons. The most prominent metabolic reduction in PD[+]D is evident in the cuneus (especially BA 18; single-lined arrow) and precuneus (double-lined arrow). Mild-to-moderate reductions are also present in the mesiofrontal lobes (stippled arrow). In addition, the PD[+]D subjects demonstrate relative sparing of the primary sensorimotor cortex, a pattern similar to AD. In PD[−]D subjects, metabolic reduction in the posterior calcarine cortex (BA 17) is evident (arrow), while there is relative sparing of BA 18, 19, and the precuneus. RLAT = right lateral, LLAT = Left Lateral, RMED = Right Medial, LMED = Left Medial

FIGURE 2.

Progressive metabolic reduction in PD[+]D. 3D-SSP t-statistic maps comparing PD[+]D converters (n=5) to healthy controls (HC) at baseline (t1, upper row) and 2-year follow-up imaging (t2, lower row). FDG-PET data are normalized within each subject to the pons. There is progressive metabolic decline in the cuneus and precuneus and more widespread cortical hypometabolism including the mesiofrontal lobes in the follow-up ¹⁸F-FDG PET.RLAT = Right Lateral, LLAT = Left Lateral, RMED = Right Medial, LMED = Left Medial.

FIGURE 3.

Progressive metabolic reduction from within reference range at baseline (Year 0), through stages of mild cognitive impairment (Year 2, and Year 4), and clinical diagnosis of dementia (Year 5) in a PD[+]D converter. 3D-SSP t-statistic maps comparing a single PD[+]D converter to healthy controls (HC) with ¹⁸F-FDG PET data normalized to the pons. Progressive metabolic reductions in the cuneus and precuneus occur before less severe, but more widespread, cortical reductions. Sparing of the primary sensorimotor cortical strip is present. RLAT = Right Lateral, LLAT = Left Lateral, RMED = Right Medial, LMED = Left Medial, Yr = Year