For many decades, PD was regarded as a unique entity, namely a sporadic neurodegenerative disease with its main lesion in the substantia nigra. The actual pathology was described as pathognomonic Lewy bodies in nigral dopaminergic cells, and the clinical abnormalities were thought to be due to insufficient dopamine release from nigrostriatal terminals, primarily in the putamen. It is now realized that the classical stereotypic description of PD starting with tremor or hypokinesia/rigidity and progressing to postural instability and eventually to cognitive decline is not the only scenario (although it may be the more common one). This latter observation led to a definition of the "Lewy body dementia" concept where motor symptoms may be minimal initially. In many patients, the disease starts with autonomic (particularly gastro-intestinal) or sensory (i.e., olfactory) manifestations. The identification of a-synuclein as a key constituent of Lewy bodies allowed the demonstration of specific changes in other areas such as the olfactory bulb and particularly the brain stem. Changes in the raphe nucleus and the locus coeruleus which antedate the substantia nigra lesions could explain some mental manifestations, particularly the depression which has been described prior to the first motor manifestations. Several behavioral disorders may be observed in people with PD. Hypodopaminergic states linked to the disease itself or associated with low levodopa levels may frequently contribute to symptoms such as anxiety, apathy, fatigue, sleep disruption. About twothirds of PD patients with fluctuations reported significant "on-off" mood swings. The excessive use of dopaminergic treatment may eventually lead to a pervasive behavioral syndrome termed homeostatic hedonistic dysregulation (HHD). We discuss these aspects with a particular interest in clinical practice.
