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Neurodegeneration Across Stages of Cognitive Decline in Parkinson Disease

Daniel Weintraub, MD; Jimit Doshi, MS; Deepthi Koka, MS; Christos Davatzikos, PhD; Andrew D. Siderowf, MD, MSCE; John E. Duda, MD; David A. Wolk, MD; Paul J. Moberg, PhD; Sharon X. Xie, PhD; Christopher M. Clark, MD
Arch Neurol. 2011;68(12):1562-1568. doi:10.1001/archneurol.2011.725.
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Objective To assess regions and patterns of brain atrophy in patients with Parkinson disease (PD) with normal cognition (PD-NC), mild cognitive impairment (PD-MCI), and dementia-level cognitive deficits (PDD).

Design Images were quantified using a region-of-interest approach and voxel-based morphometry analysis. We used a high-dimensional pattern classification approach to delineate brain regions that collectively formed the Spatial Pattern of Abnormalities for Recognition of PDD.

Setting The Parkinson's Disease and Movement Disorders Center at the University of Pennsylvania.

Subjects Eighty-four PD patients (61 PD-NC, 12 PD-MCI, and 11 PDD) and 23 healthy control subjects (HCs) underwent magnetic resonance imaging of the brain.

Results The PD-NC patients did not demonstrate significant brain atrophy compared with HCs. Compared with PD-NC patients, PD-MCI patients had hippocampal atrophy (β = −0.37; P = .001), and PDD patients demonstrated hippocampal (β = −0.32; P = .004) and additional medial temporal lobe atrophy (β = −0.36; P = .003). The PD-MCI patients had a different pattern of atrophy compared with PD-NC patients (P = .04) and a similar pattern to that of PDD patients (P = .81), characterized by hippocampal, prefrontal cortex gray and white matter, occipital lobe gray and white matter, and parietal lobe white matter atrophy. In nondemented PD patients, there was a correlation between memory-encoding performance and hippocampal volume.

Conclusions Hippocampal atrophy is a biomarker of initial cognitive decline in PD, including impaired memory encoding and storage, suggesting heterogeneity in the neural substrate of memory impairment. Use of a pattern classification approach may allow identification of diffuse regions of cortical gray and white matter atrophy early in the course of cognitive decline.

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Figure 1. Hippocampus, insula, and putamen atrophy in patients with Parkinson disease (PD) and mild cognitive impairment compared with PD patients with normal cognition (uncorrected P = .01). A, Axial view. B, Coronal view. C. Sagittal view. The color scale indicates the amount of atrophy (in cubic millimeters) per cubic millimeter of tissue in the reference image at that voxel, adjusted by the intracranial volume.

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Figure 2. Hippocampus, amygdala, and globus pallidus atrophy in patients with Parkinson disease (PD) and mild cognitive impairment compared with PD patients with normal cognition (corrected P = .05). A, Sagittal view. B, Coronal view. The color scale indicates the amount of atrophy (in cubic millimeters) per cubic millimeter of tissue in the reference image at that voxel, adjusted by the intracranial volume.

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Figure 3. Scores for the Spatial Pattern of Abnormality for Recognition of Parkinson disease with dementia-level cognitive deficits (SPARE-PDD) instrument by cognitive subgroup. Data are presented as mean threshold scores; whiskers represent 95% CIs. HC indicates healthy controls; MCI, mild cognitive impairment; and NC, normal cognition.

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