The role of acetylcholine and dopamine in dementia and psychosis in Parkinson's disease

Abstract

Parkinson's disease (PD) is a progressive neurological disorder in which there is abnormal degeneration of dopaminergic neurons in the substantia nigra and the ventral tegmental area combined with a varying degree of deterioration of the cholinergic, serotonergic and noradrenergic system, leading to a variety of motor and non-motor abnormalities. Dopamine (DA) depletion in nigrostriatal projections manifests with abnormal spontaneous motor behavior and (subtle) cognitive deficits, whereas more overt cognitive impairment may develop with concomitant DA-deficiency related mesocorticolimbic denervation. In combination with a progressive dysfunction of the ascending neocortical cholinergic (and serotonergic and noradrenergic) projections, mainly due to a loss of cholinergic neurons in the nucleus basalis of Meynert (NbM), these cognitive deficits may proceed into dementia sometimes in combination with psychotic behavior, which might also be associated with dopaminomimetic and/or anticholinergic treatment as well as with cholinergic deficit or dopaminomimetic induced REM sleep disturbances. As these psychiatric symptoms have a substantial negative effect on the patient's quality of life, contribute to caregiver distress and are predictive of nursing home placement, identification and adequate treatment is of great importance. Recent evidence supports a possible role for cholinomimetic therapy in alleviating cognitive dysfunction and psychotic symptoms in PD.