Dissociating apathy and depression in Parkinson disease
Kirsch-Darrow L, Fernandez HF, Marsiske M, Okun MS, Bowers D;
Commented by , 27 Sep 2006
Background
Apathy is a common feature in neurodegenerative disorders, especially prominent in diseases such as Fronto-temporal dementia and Progressive Supranuclear Palsy. Apathy is also reported to be frequent in Parkinson's disease (PD), more so when cognitive impairment is present. At times it is difficult to differentiate apathy from lack of motivation due to depression, and the true extent of apathy in PD has not been studied using appropriate scales and a disease control group.
Objectives
The objective of this study was to examine the hypothesis that apahty is a core feature of PD and that it can be dissociated from depression.
Methods
Eighty consecutive patients in a Movement Disorder Clinic with a diagnosis of idiopathic PD and 20 patients with dystonia, which met the entry criteria, completed depression and apathy measures including the Marin Apathy Evaluation Scale, Beck Depression Inventory, and Centers for Epidemiological Studies-Depression Scale. The mean age was 69 and 61 years, and the mean disease duration was 6.4 and 8.0 years in PD and dystonia groups, respectively.
The mean Hoehn and Yahr stage was 2.4 and mean UPDRS score was 29.5 in the PD group, 91% of patients had a tremor-dominant disease.
Results
There was a significantly higher severity and frequency of apathy in PD (frequency = 51%, defined as apathy score equal to or more than 14 on MAE scale) than in dystonia (frequency 20%; p = 0.012). The mean apathy score in patients with PD (mean = 13.6) was higher than that in patients with dystonia (mean = 9.4; p= 0.041).
When those patients with a diagnosis of depression were excluded, apathy in the absence of depression was still frequent in PD, and did not occur in dystonia (PD= 28.8%, dystonia= 0%; p= 0.006). The authors concluded that patients with PD experienced significantly higher frequency and severity of apathy when compared with those with dystonia, and that apathy may be a core feature of PD occuring in the absence of depression.
Professor Emre's comments
Apathy is defined as a primary loss of motivation, loss of interest, and loss of effortful behaviour (ref. 1). As these features can also occur in patients with depression, at times it can be difficult to judge if these are simply manifestations of depression or stand by themselves as an independent feature. This is not trivial, as apathy can occur both as a symptom and as a syndrome in neurodegenerative diseases, which may also induce depression by their chronic disabling nature.
Apathy, with self-assessment, has been previously reported to be a common feature in PD, ranging from 38 to 43% (ref. 1, ref. 2, ref. 3). These figures are quite comparable to that found in this study (51%). The underlying mechanism for apathy in PD has been suggested to be disruption of non-motor basal ganglia connections to mesial frontal-anterior cingulate cortex, structures modulated by dopaminergic pathways arising from ventral tegmentum (ref. 4).
These areas are known to be involved in motivation and spontaneity, extreme clinical manifestation of their bilateral damage being akinetic mutism, with complete loss of spontaneity. In addition to degeneration of nigro-striatal pathways, dopaminergic pathways emanating from brainstem ventral tegmental area have also been reported to degenerate in patients with PD.
The novel feature of this study is that it assessed concomitantly the presence and severity of both apathy and depression, and used a disease control group in which basal ganglia are affected. The study found a clearly higher frequency and severity of apathy in PD as compared to dystonia. It also demonstrated that apathy is dissociated from depression and occurs in almost in 1/3 of PD patients in the absence of depression.
These results support the notion that apathy is a common non-motor manifestation of PD, possibly due to impairment in dopaminergic modulation of frontal-subcortical circuits subserving motivation.
References
1. Starkstein SE, Mayberg HS, Preziosi TJ, Andrezejewski P, Leiguarda R, Robinson RG. Reliability, validity, and clinical correlates of apathy in Parkinson's disease. Journal of Neuropsychiatry and Clinical Neurosciences 1992; 4 (2); 134-139
2. Isella V, Melzi P, Grimaldi M, Iurlaro S, Piolti R, Ferrarese C, et al. Clinical, neuropsychological, and morphometric correlates of apathy in Parkinson's disease. Movement Disorders 2002; 17 (2); 366-371
3. Pluck GC, Brown RG. Apathy in Parkinson's disease. Journal of Neurology, Neurosurgery and Psychiatry 2002; 73 (6); 636-642
4. Brown RG, Pluck G. Negative symptoms: the "pathology" of motivation and goal-directed behaviour. Trends in Neurosciences 2000; 23 (9); 412-417