We found that symptoms of anxiety, more than depression, overall cognitive status, or motor stage, affect health-related quality of life for nondemented patients with PD. The hypothesis that anxiety symptoms would significantly explain variance in overall quality of life (PDQ-39) in PD was supported, in that anxiety explained 29% of the variance beyond that explained by the other clinical variables in the model. Depression explained an additional 10% of the variance not accounted for by anxiety. Together, these mood symptoms accounted for 39% of the variance in quality of life. Although cognitive status (DRS scores) correlated significantly with quality of life scores, it did not explain any further variance when anxiety and depression were in the model, and in any case none of the participants met criteria for dementia.
Earlier studies describing quality of life in patients with PD did not include both anxiety and depression in the model. Without including anxiety scores, the majority of these studies found either depression [2
] or disease severity [3
] to be the most frequent associate of quality of life. Some previous studies have shown cognitive status, as measured by MMSE, to be an important predictor of quality of life in PD [5
], but others have not [4
Studies have found depression to explain up to 50% of the variance in PDQ-39 scores [1
]. The current study found depression symptoms to predict only 10% of the variance once anxiety was accounted for. Although differences in sample sizes from study to study may underlie some differences in the size of the contribution of depression, it may also be argued that, if previous studies had included an anxiety score in their model, their results may have been more similar to those of the present study. It is also possible that, because depression and anxiety symptoms often occur together in PD (e.g., [10
]), the measures used to capture anxiety and depression are not able to differentiate these two conditions, or an interaction between the two is present. Arguing against this interpretation is the fact that the Beck measures used in the present study have demonstrated good divergent validity between anxiety and depression [39
In spite of the relatively high mean DRS scores for the sample, cognitive status was significantly associated with quality of life, consistent with Schrag and colleagues [5
] even though it did not significantly contribute to the model once the mood measures were included. A sample comprising a larger range of cognitive impairment related to PD, including dementia, may show a greater impact of cognitive status on reported quality of life. It should also be noted that brief screening measures such as those used here do not capture more subtle cognitive changes that could contribute to patients' reported well-being. Future studies with tests that assess specific cognitive domains may not only further elucidate the relation of cognition to quality of life but also help determine whether various types of cognitive difficulties—for example, executive functioning versus attention—differentially impact reported quality of life in PD.
We did not find a relation between overall quality of life and motor stage, as measured by the Hoehn and Yahr (H/Y) scale. A study by Hobson and Meara [40
] did not find any significant correlation between motor stage, using the H/Y scale, and scores of the SF-36, the Short Form health related quality of life scale, whereas a study by the Global Parkinson's Disease Research Committee [6
] found H/Y scores and medication to explain up to 17.3% of the variance in the PDQ-39. In our recent study, we found correlations between only some aspects of motor severity as indexed by the UPDRS and some of the PDQ-39 subscales: specifically, the Rigidity and Dopamine-dependent subscales of the UPDRS with the ADL subscale of the PDQ-39; the Rigidity and Facial Expression subscales of the UPDRS and the Communication subscale of the PDQ-39 [41
]. A sample with a wider range of motor severity than represented in our present sample may well yield different results.
Anxiety is prevalent in PD, and this study highlights the dramatic impact it has on quality of life. Despite using conservative cut-off scores and using measures with few somatic items, clinically significant anxiety occurred in one-quarter to one-third of the participants of this study, depending on the measure used. Exactly how anxiety impacts quality of life has yet to be clearly determined. Anxiety symptoms are more prevalent in PD patients than in the general population or in individuals with other chronic illnesses but are not primarily a psychological reaction to the illness or side effects of levodopa treatment [42
]. Some investigators suggest that people with anxiety and people with PD share an underlying biological vulnerability. Anxiety and affective symptoms have been associated with striatal dopamine transporter (DAT) availability in the basal ganglia [43
] as well as with PD-related loss of catecholinergic cells of the locus ceruleus [12
] and abnormalities of serotonin production [13
]. It is of substantial interest that mood disorders may precede the onset of PD motor symptoms by several years—even 20 years in the case of anxiety—suggesting that mood disorders may be prodromal indicators of PD [44
]. Besides anxiety itself, an anxious (neurotic) personality has also been revealed as a risk factor for PD much later in life [46
], again suggesting a common pathophysiology for anxiety disorders and PD.
A more direct relation between anxiety symptom amelioration and improvement in PD symptoms may exist than previously recognized. Anecdotal evidence coupled with a study by Knight et al. [42
] suggests that motor symptoms themselves may be influenced by anxiety in PD. For example, the disabling motor symptoms such as tremor, rigidity, bradykinesia, and postural instability, which often occur intermittently, have been shown to increase when the patient is concentrating or feeling anxious [10
]. Further research exploring the direct relation of anxiety and motor symptoms and subsequent quality of life needs to be conducted. It is possible that treatment of anxiety in PD not only will increase the perceived quality of life but also may help reduce the frequency of the motor symptoms associated with the disease.
With 39% of the variance in quality of life accounted for by anxiety and depression symptoms, this study highlights the importance of treating anxiety symptoms as a means to improving the well-being of patients with PD as well as the importance of continued emphasis on the impact of depressive symptoms on their overall well-being. Some investigators have suggested a more pronounced increase in comorbidity of anxiety and depression in patients with PD than in healthy adults (19.3% comorbidity in PD versus 8.6% in control adults) [47
]. When depression and anxiety occur together, they are associated with increased impairment, a more chronic course, and poorer outcome, rendering treatment more complex [48
]. In PD, investigators have suggested that anxiety often presents before the onset of comorbid depression [51
]. The strong comorbidity between generalized anxiety disorder and major depression, the fact that most people with this type of comorbidity report that the onset of generalized anxiety disorder occurred before the onset of depression, and the fact that primary generalized anxiety disorder significantly predicts the subsequent onset of depression and other secondary disorders raise the question of whether early intervention and treatment of primary anxiety would effectively prevent the subsequent onset of secondary depression as well as improve PD patients' quality of life.
Limitations of this study include the use of patient self-report and the sample size. Future research can address this issue by including more participants and adding measures of participants' dispositional characteristics. The use of a brief self-report measure of anxiety and depression, although practical, does not allow us to clarify the nature of the anxiety and depressive disorder in this population or to determine whether the specific type of anxiety disorder has a differential impact on quality of life—for example, generalized anxiety disorder versus social phobia versus panic disorder, though all have been associated with PD [11
]. Replicating this study with a clinician-based interview would help elucidate whether certain types of anxiety disorders have greater impact on quality of life and more confidently clarify the frequency of general anxiety disorder and major depressive disorder in PD. It would also be worthwhile to include a more sensitive measure of PD motor symptoms, such as the UPDRS. In a larger sample, it would be of interest to examine data on disease characteristics associated with anxiety, such as motor fluctuations and dyskinesias. Although the results of this study indicate that mood symptoms are associated with reduced quality of life in patients with PD, this study is cross-sectional and the direction of causation among the variable examined cannot be determined. Longitudinal studies would help clarify the causal relation between the variables in this study and help us to assess how quality of life may change following treatment of anxiety and depression in this population.
A better understanding of the factors that have the greatest impact on a patient's well-being is important to informing new and improved treatment management plans in PD. The findings of the present study support those of other studies in the literature that mood symptoms are better predictors of quality of life than is motor symptom stage [1
]. The primary difference between this study and previous studies is the inclusion of standard anxiety measures here and the finding that anxiety, in addition to depression, is associated with quality of life using a PD-specific quality of life measure.
Despite the prevalence of anxiety and depression in PD, mood symptoms are often not addressed in individuals with this disease. In a chronic and disabling illness such as PD, improving the aspects of well-being that most significantly impact their perceived quality of life is vital [12
]. Empirical studies confirm that cognitive behavioral therapy (CBT) is an effective form of therapy for the treatment of anxiety and depression in the general population [55
]. Dobkin et al. (1997) demonstrated the effectiveness of CBT for the treatment of depression in PD [57
], but further studies are needed to also address the effectiveness of CBT and other therapies for the treatment of anxiety in PD. The findings of the present study suggest that primary assessment and management of the anxiety and depression associated with the disease may be needed to optimize the quality of life of patients with PD, and we accordingly call for more clinical work and research in this area. As there is no cure for PD, empirically supported treatment of distressing neuropsychiatric symptoms is of paramount importance in the quest to improve the quality of life of individuals with this disorder.