Thomas G. Beach

Motor impairment in normal aging, clinically possible Parkinson's disease, and clinically probable Parkinson's disease: longitudinal evaluation of a cohort of prospective brain donors

This study presents data on the antemortem evaluations of a cohort of individuals registered in a brain donation program. Clinical evaluation determined that many individuals were unaware they had clinical signs of Parkinsons disease (PD) (rest tremor, bradykinesia, rigidity). Quantitative motor testing (timed tapping test and Purdue pegboard test) revealed a graded reduction in performance in those clinically found to have clinically possible and clinically probable PD. Longitudinal examinations over 4 years revealed some individuals progressed from control to clinically possible PD and clinically possible PD to clinically probable PD. This study underscores the importance of longitudinal antemortem testing of prospective brain donors as well as the potential value of quantitative motor testing.

Increased CSF biomarkers of angiogenesis in Parkinson disease.

Objective: To study biomarkers of angiogenesis in Parkinson disease (PD), and how these are associated with clinical characteristics, blood–brain barrier (BBB) permeability, and cerebrovascular disease. Methods: In this cross-sectional analysis, 38 elderly controls and 100 patients with PD (82 without dementia and 18 with dementia) were included from the prospective Swedish BioFinder study. CSF samples were analyzed for the angiogenesis biomarkers vascular endothelial growth factor (VEGF); its receptors, VEGFR-1 and VEGFR-2; placental growth factor (PlGF); angiopoietin 2 (Ang2); and interleukin-8. BBB permeability, white matter lesions (WMLs), and cerebral microbleeds (CMB) were assessed. CSF angiogenesis biomarkers were also measured in 2 validation cohorts: (1) 64 controls and 87 patients with PD with dementia; and (2) 35 controls and 93 patients with neuropathologically confirmed diagnosis of PD with and without dementia. Results: Patients with PD without dementia displayed higher CSF levels of VEGF, PlGF, and sVEGFR-2, and lower levels of Ang2, compared to controls. Similar alterations in VEGF, PlGF, and Ang2 levels were observed in patients with PD with dementia. Angiogenesis markers were associated with gait difficulties and orthostatic hypotension as well as with more pronounced BBB permeability, WMLs, and CMB. Moreover, higher levels of VEGF and PlGF levels were associated with increased CSF levels of neurofilament light (a marker of neurodegeneration) and monocyte chemotactic protein–1 (a marker of glial activation). The main results were validated in the 2 additional cohorts. Conclusions: CSF biomarkers of angiogenesis are increased in PD, and they are associated with gait difficulties, BBB dysfunction, WMLs, and CMB. Abnormal angiogenesis may be important in PD pathogenesis and contribute to dopa-resistant symptoms.

Probing the striatal dopamine system for a putative neuroprotective effect of deep brain stimulation in Parkinson's disease: Probing the striatal dopamine system

Pablo Martinez-Martin, MD, PhD,* Matej Skorvanek, MD, PhD, Jose Manuel Rojo-Abuin, PhD, Zuzana Gregova, MS, Glenn.T. Stebbins, PhD, Christopher G. Goetz, MD, and members of the QUALPD Study Group National Center of Epidemiology and CIBERNED, Carlos III Institute of Health, Madrid, Spain Department of Neurology, P. J. Safarik University, Kosice, Slovakia Department of Neurology, University Hospital of L. Pasteur, Kosice, Slovakia Department of Statistics, Center of Human and Social Sciences, Spanish Council for Scientific Research, Madrid, Spain Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA See Appendix