Non-motor dysfunctions in Parkinson's disease

Symposium — Wednesday, April 26, 2024 — 8:00 AM - 10:00 AM — , Room W193
CNS Section — Chair: R Alberto Travagli — Co-Chair:

Parkinsons disease (PD) has a lifetime risk of 2%, making it the 2nd most common neurodegenerative disease after Alzheimers disease. Idiopathic PD is generally considered to be a movement disorder characterized by bradykinesia, rigidity, tremor and gait/postural disorders related to the severe degeneration of the midbrain dopaminergic neurons in the substantia nigra pars compacta (SNpc). In recent years, however, several investigations, including laboratory, clinical and neuropathological studies, have led to the recognition that PD is a multi-system disorder. Indeed, PD patients experience a remarkably broad spectrum of early symptoms, including non-motor disorders, that still await classification into internationally established, temporally-staged clinical criteria. The non-motor symptoms include cognitive impairment, sleep disorders, orthostatic hypotension and gastrointestinal (GI) dysfunctions. These non-motor features of Parkinsons disease (PD) are often prodromic to the cardinal motor features and only recently has there been an increased awareness of the cognitive, psychiatric and autonomic dysfunctions associated with PD, many of these manifestations remain under-recognized and underestimated even by practicing neurologists. Among autonomic disorders, orthostatic hypotension is well recognized although it is often attributed to secondary effects of dopaminergic drugs rather than being caused by the disease itself. Similarly, gastrointestinal dysfunctions, such as severe constipation, gastroparesis and dysphagia, are very familiar to Parkinsonian patients and are often a source of considerable discomfort and disability and preclude in many cases the correct absorption of drugs. Many animal models have been used over the years, the experimental models currently available utilize a) either neurotoxins such as 6-OHDA, MPTP, or pesticides such as rotenone to more or less selectively destroy the dopaminergic neurons of the SNpc, or b) genetically modified animal models such as, for example, overexpression of ±-synuclein under the control of various promoters. The main drawbacks of these models, as well as in most animal models of diseases, are that they do not reproduce all the clinical features of PD and often a model can be useful for a particular feature of PD but not valid for another one.

Speakers

• Marie Chesselet — , UCLA


• R Alberto Travagli — Neural and Behavioral Sciences, Penn State College of Medicine


• David Goldstein — NINDS, NIH