Clinical presentation
Depression and anxiety
Depression is common in PD-D, occurring in 30-60% of patients [4, 6, 8]. In addition, depression in PD patients without dementia is a risk factor for cognitive decline and development of PD-D [12-14]. This may be due in part to shared risk factors for dementia and depression in PD, including increasing age and more severe disease [13, 15]. Although not specifically examined in PD-D patients, in PD there is high co-morbidity between depression and anxiety disorders [16].
Most PD-D patients are on chronic levodopa treatment, and many experience motor fluctuations (MF), which involve ‘off’ periods characterized by worsening parkinsonism along with ‘on’ periods with improved motor function. In addition to MF, non-motor fluctuations (NMF) also occur. Increasing anxiety and discrete anxiety attacks have been associated with MF, particularly with the onset of ‘off’ periods, although this relationship does not hold for all patients [17]. When it does occur, patients often describe a sensation of feeling ‘trapped’ as they become increasingly immobilized, with anxiety symptoms typically resolving only after improvement in motor symptoms. Other NMF include slowness of thinking, fatigue, and dysphoria. NMF can be more disabling than MF for a substantial percentage of PD patients [18]. Patients may rarely experience hypomanic symptoms during ‘on’ periods [19].
A large national study in Germany assessing the frequency of NPS in 1449 PD patients found that at least one symptom occurred in 71% of PD patients. Depression was present in 23.8% of all PD patients and anxiety was present in 19.6%. Additionally, the co-morbidity of depression and dementia was analysed: patients experiencing both depression and dementia were more likely to experience additional NPS [20].
Apathy
Apathy is another common co-morbid condition in PD-D [1], one that overlaps with some motor symptoms of PD, but is a distinct clinical syndrome characterized by diminished spontaneous activity, motivation, and affect. It is common in a range of neurodegenerative diseases, including frontotemporal dementia (FTD) [21], PSP [9], DLB [21], and AD [22]; its frequency and severity increase with disease progression [22].
Studies have examined the prevalence of apathy in PD-D and determined that it affects 15-50% of patients [4, 6, 8, 9, 23]. In a study comparing PD patients with a similarly disabled group (osteoarthritis patients) [24], apathy was significantly more common in the PD group and was associated with cognitive impairment, but was not associated with either depression or anxiety. Another study reported similar findings using the Lille Apathy Rating Scale [25, 26], with apathy being more common in PD-D patients than in PD patients without dementia. All PD patients showed a decrease in action initiation compared with healthy controls, but PD-D patients were significantly more impaired in this regard. Additionally, they exhibited lower emotional responses and decreased self-awareness compared with PD patients without dementia.
A recent study assessed the association between the presence of apathy and the course of cognitive decline or dementia in 40 PD patients without depression or dementia. The patients were assessed twice over an 18-month period; over this time the rate of cognitive decline as well as conversion to dementia was found to be significantly higher in PD patients with apathy [27].
