phenotype is based on a ratio, we evaluated the differential
influences of the nominator and denominator. We found that
this ratio is only driven by the denominator (PIGD score), and
hence reflects increasing disease progression. According to
Braak and colleagues,
the symptoms of PD parallel the
formation of Lewy bodies and Lewy neurites, and advance in
a topographically predictable sequence beginning in the
medulla oblongata/pontine tegmentum and olfactory bulb/
anterior olfactory nucleus with a subsequent spread to the
substantia nigra and other midbrain nuclei, forebrain and
neocortex. However, the clinical findings may also be explained
by a differential individual vulnerability of neuronal circuits for
the underlying disease process.
As such, neuronal circuits
underlying all impairment domains in PD may be affected
simultaneously, but because of different cell type vulnerability,
become clinically manifest at different stages.
D Verbaan, J Marinus, M Visser, S M van Rooden, J J van Hilten,
Department of Neurology, Leiden University Medical Centre, Leiden, the
A M Stiggelbout, Department of Medical Decision Making, Leiden
University Medical Centre, Leiden, the Netherlands
H A M Middelkoop, Department of Neuropsychology, Leiden University
Medical Centre, Leiden, the Netherlands
Funding/support: This work was supported by grants from the Prinses
Beatrix Fonds (PBF, project No WAR05-0120), the Netherlands
Organisation of Scientific Research (NWO, project No 0940-33-021),
the van Alkemade-Keuls Foundation and the Dutch Parkinson’s Disease
Competing interests: None.
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