Dysfunction of the locus coeruleus-norepinephrine system and related circuitry in Parkinson's disease-related dementia.
Although resting tremor, cogwheel rigidity, hypokinesia/bradykinesia and postural instability usually dominate the clinical picture of sporadic Parkinson's disease (PD), both clinical and epidemiological data reveal that a wide variety of additional symptoms impair patients' quality of life considerably, parallel to the chronic progressive neurodegenerative movement disorder. Autopsy based retrospective studies have shown that α-synuclein immunoreactive Lewy pathology (LP) develops in the locus coeruleus (LC) of patients with neuropathologically confirmed sporadic PD, as well as in individuals with incidental (prodromal or premotor) Lewy body disease but not in age and gender matched controls. Using five case studies, this review discusses the possible role of LP (axonopathy, cellular dysfunction and nerve cell loss) in the LC, catecholaminergic tract and related circuitry in the development of PD-related dementia. The contribution of noradrenergic deficit to cognitive dysfunction in PD has been underappreciated. Noradrenergic therapeutic interventions might not only alleviate depressive symptoms and anxiety but also delay the onset of cognitive decline.
Clinical Neuroanatomy Section, Center for Biomedical Research, Department of Neurology, University of Ulm, Helmholtzstrasse 8/1, Ulm 89081, Germany.
Kelly
K
Del Tredici
Heiko
H
Braak
D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000473:pathology; D001344:Autopsy; D001921:Brain / Q000473:pathology; D003704:Dementia / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D020961:Lewy Body Disease / Q000473:pathology; D008125:Locus Coeruleus / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009415:Nerve Net / Q000473:pathology*; D009638:Norepinephrine / Q000378:metabolism*; D010300:Parkinson Disease / Q000150:complications* / Q000378:metabolism / Q000473:pathology*; D020187:REM Sleep Behavior Disorder / Q000209:etiology; D007319:Sleep Initiation and Maintenance Disorders / Q000209:etiology; D051844:alpha-Synuclein / Q000378:metabolism
D051844:alpha-Synuclein; D009638:Norepinephrine