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Mini Review

Current management of the Cognitive Dysfunction in Parkinson's disease: how far have we come?

¹ Laboratorios Trinidad

^* To whom correspondence should be addressed. E-mail: svalemayorga{at}yahoo.com.mx.

	Abstract

Parkinson's disease (PD) clinical features comprise both, motor and non-motor manifestations. Among the non-motor complications, dementia is the most important. In approximately 40% of the patients, PD is affected by cognitive impairment. Remarkably, in addition to age, dementia is an independent predictor of mortality while age at onset of PD and severity of neurological symptoms are not. In this review, I summarize the current knowledge of the pathogenesis of the PD cognitive impairment in relation to the therapies presently accessible and those that could become strategic in the near future. It is hypothesized that patients with PD show two components of cognitive dysfunction (CD): a generalized profile of subcortical dementia (PDsCD), and an overlapped pattern suggesting specific prefrontal damage with CD (PDpFCD). PDsCD is associated with structural neocortical/subcortical changes in the brain (in frontal, parietal, limbic and temporal lobes as well as in midbrain structures). In PDpFCD cognitive deficits comprise impairments in neuropsychological tests sensitive for frontal lobe function (discrete elements of episodic and working memory for instance), which are considered to be the consequence of dysfunction in neuronal loops connecting the prefrontal cortex and basal ganglia. Drugs reviewed for targeting PDsCD include: cholinesterase inhibitors, agents with mixed cholinergic and dopaminergic properties, anti-glutamatergic drugs, mixed antiglutamatergic/dopaminergic agents; antioxidants and enhancers of mitochondrial functions and anti-COX-2 as well as other anti-inflammatory mediators. Preliminary studies with vehicles that may target PDpFCD include piribedil, tolcapone, amantadine and farampator. Additional agents (citicoline and neuroimmuniphilines among others) will be outlined. A brief overview on neuroprotection and new biological promising advances in PD (deep brain stimulation, stem cells, gene therapy) also will be summarized.

Key Words: Parkinson, cognitive dysfunction, prefrontal cortex, dopamine, cholinesterase-inhibitors, ampakines