Meles, S.K. (2013) An Abnormal Brain Network Associated with Cognitive Impairment in a Cohort of Dutch Patients with Parkinson’s Disease. thesis, Medicine.
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Abstract
Introduction: Cognitive symptoms are common in Parkinson’s disease (PD), even in early-stage patients. However, it is difficult to evaluate cognitive impairment with clinical measures alone. To date, the underlying mechanisms of cognitive deficits in PD remain largely unclear. Using ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET), an abnormal metabolic network associated with cognitive deficits in PD was previously identified in a North-Shore (NS) PD population (Huang et al., NeuroImage 2007). Nonetheless, this network has not been identified in a different PD population. Methods: Using network analysis, we derived a PD-related cognitive pattern (PDCP) from resting-state FDG-PET scans of 19 Dutch PD patients. Individual pattern scores were correlated to frontal assessment battery (FAB, a cognitive functioning measure) scores in this cohort. We also calculated PDCP scores in separate cohorts of PD patients without cognitive impairment (MCI-, n=20), with single-domain cognitive impairment (MCI-S, n=34), multiple-domain cognitive impairment (MCI-M, n=33), and dementia (PDD, n=13). Group differences were analyzed by one-way ANOVA and non-parametric trend analysis. Results: The PDCP derived in the Dutch cohort was characterized by decreased metabolism in the medial frontal and parietal cortical regions, with increased metabolism in the dentate nuclei of the cerebellum. Pattern scores correlated individually with FAB scores in PD subjects (p=0.003) but not in age-matched healthy controls (n=17, p=0.60). There was a significant trend of increase (p=0.004, one-way ANOVA; Kendall’s tau-b=0.261, p=0.001) across the MCI-, MCI-S, MCI-M and PDD groups. PDCP scores were significantly higher in the PDD group relative to both MCI- and MCI-S groups (p<0.05, Tukey test). These findings were comparable to the results from the original NS PDCP (p=0.01, one-way ANOVA). The Dutch PDCP is topographically comparable to the NS PDCP with overlapping network regions in the supplementary motor area (SMA), the inferior parietal lobule, and the dentate nuclei, although new regions were also identified, including metabolic reductions in the thalamus, caudate, the somatosensory association cortex and the posterior cingulate cortex. Moreover, the scores of the two patterns in the same PD subjects showed excellent correlation (R2=0.75, p<0.001). Conclusion: We found a metabolic basis for cognitive symptoms in Dutch PD subjects. The expression of this brain network is associated with individual performance on the behavioral test in PD patients. Overall, these findings substantiate the PDCP as a reproducible imaging marker of cognitive impairment in PD.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Leenders, K.L. MD and Kallenberg, C.G. MD |
| Supervisor name: | Eidelberg, D. MD and Tang, C.C. MD and The Feinstein Institute for Medical Research and Manhasset, NY |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 10:51 |
| Last Modified: | 25 Jun 2020 10:51 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/1186 |
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