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From: Current Clinical Neurology: Atypical Parkinsonian Disorders Edited by: I. Litvan © Humana Press Inc., Totowa, NJ
17
Quality of Life Assessment in Atypical Parkinsonian Disorders
Anette Schrag and Caroline E. Selai
INTRODUCTION
Assessing the health-related quality of life (Hr-QoL) of patients with atypical parkinsonism disor- ders is important yet no validated measures are currently available. The atypical parkinsonian disor- ders are chronic progressive conditions, which not only shorten life expectancy but affect many aspects of patients’ and their carers’ lives. No curative treatment for these disorders is available, and management of these patients largely has to concentrate on amelioration of symptoms, such as falls, immobility, autonomic features or dysphagia, activities of daily living and (in)dependence, and pa- tients’ social and emotional well-being; in short, the improvement of patients’ quality of life. Assess- ment of patients with atypical parkinsonism has concentrated on objective measures such as mortality and clinical evaluation of impairment and physical functioning, supplemented by laboratory test re- sults. However, a large literature shows that patients’ own assessments of their health, their prefer- ences, and their views regarding health often differ significantly from physicians’ objective assessments (1). Where possible, treatment decisions should focus on health outcomes of value to the individual patient.
Scales to measure Hr-QoL, fully psychometrically tested and validated, are now used in a number of clinical and research contexts. Some types of Hr-QoL scale yield information that, combined with economic data, can be used to assess the cost benefit of health interventions and to inform decisions about the allocation of scarce health care resources. There are currently no validated measures to assess Hr-QoL in patients with atypical Parkinsonian disorders.
This chapter starts with a general overview of some of the conceptual and methodological issues relating to the measurement of subjective health assessment and Hr-QoL. Section two gives an over- view of Hr-QoL instruments that have been used in Parkinson’s disease (PD) and the impact of PD on Hr-QoL. The third section addresses what is known about the Hr-QoL of patients with atypical par- kinsonism, in particular multiple system atrophy (MSA) and progressive supranculear palsy (PSP).
The chapter concludes with some comments about future research in this area.
HEALTH-RELATED QUALITY OF LIFE: CONCEPTUAL AND METHODOLOGICAL ISSUES
What Is Quality of Life?
Although the definition of this somewhat elusive term is still occasionally discussed in the litera-
ture, there is general consensus on some fundamental points. First, although the phrases “quality of
life,” “health-related quality of life,” and health status are used somewhat interchangeably, there is broad agreement that, in the medical context, Hr-QoL should be regarded as a multidimensional construct (2), comprising physical, psychological, and social well-being. Within these three broad dimensions, most Hr-QoL scales have items on physical health and functioning, activities of daily living, mental health (e.g., perceived stigma, anxiety, depression), social activities, family relation- ships, and cognitive functioning. Because of these multiple factors, it has been argued that although it may be helpful to derive a summary index of Hr-QoL, the different aspects of Hr-QoL as measured by the scale domains should also be presented separately in order to better understand the precise impact of interventions (3).
Second, since quality of life is highly subjective, any appraisal of Hr-QoL should rely, where possible, on the perception of the individual patient. Many groups of patients cannot, however, assess their own Hr-QoL, e.g., those with severe dementia, and there is a growing literature on the use of proxy ratings.
Third, no quality of life instrument can comprehensively cover all aspects of Hr-QoL. Although some scales attempt to comprehensively assess all aspects of Hr-QoL, such instruments are often lengthy and burdensome and so are not feasible in clinical practice, particularly where patients have disabling conditions. Therefore, most measures focus on a limited number of specific aspects of Hr-QoL. The choice of instrument will be determined by the precise aim of the study.
Finally, in order to provide meaningful data for research and clinical practice, Hr-QoL measures need to be carefully developed and validated and there is now a large literature on the validation and psychometric properties that need to be demonstrated before the scientific community will accept that an instrument has been shown to be appropriately validated. Before considering psychometric testing in more detail, it is useful to consider next why Hr-QoL might be measured.
Why Assess Health-Related Quality of Life?
Though Hr-QoL measures have been developed for a number of reasons, two basic aspects of health care underlie most of the questions that Hr-QoL appraisals set out to answer: outcome of treatment and cost. As discussed above, Hr-QoL has emerged as an important outcome that incorpo- rates patients’ views of their health. Also, since no country in the world can afford to do all that it is technically possible to do to improve the health of its citizens, the need has arisen for some system of setting priorities. The assessment of the Hr-QoL of patients with atypical parkinsonian disorders will become increasingly important if and when new drug treatments and other therapies for these disor- ders are developed. Trials will need to address the benefit of therapeutic interventions and measure change of symptoms in relation to Hr-QoL.
HEALTH-RELATED QUALITY OF LIFE MEASURES: DEVELOPMENT AND VALIDATION
All clinical assessment measures need to be shown to be valid and reliable. In addition, self-com- pleted measures for patients with a disabling disease need to be short and feasible. Instrument devel- opers must test the psychometric properties of a new instrument, which is a labor-intensive exercise, involving a series of studies to obtain data on the performance of the measure in different situations.
For a comprehensive review of the statistical procedures, see Streiner and Norman (4). In brief, valid-
ity is how well the instrument measures what it purports to measure. There are various statistical
procedures for testing different aspects of an instrument’s validity. The terminology is somewhat
confusing but Streiner and Norman provide a useful guide to the various types (e.g., face validity,
construct validity, criterion validity, concurrent validity, and predictive validity). Reliability assesses
whether the same measurement can be obtained on other occasions and concerns the amount of error
inherent in any measurement. Two basic tests are the internal consistency of a test, measured by
coefficient alpha, and test–retest reliability where scores taken on two occasions are compared. Sensi-
tivity or responsiveness to change is concerned with how sensitive the measure is to detecting clini- cally relevant changes in Hr-QoL. This is important for monitoring benefits of treatment. Newer meth- ods that allow further improvement of scales include Rasch analysis and Item Response Theory, a discussion of which is beyond the scope of this chapter.
This psychometric testing has not uniformly been conducted with all instruments, particularly older instruments.
Types of Hr-QoL Measures
There is no “gold standard” for measuring Hr-QoL and there is a wide range of instruments avail- able, or in development. The categories of Hr-QoL measures have been comprehensively reviewed elsewhere (5). In brief, generic instruments cover a broad range of Hr-QoL domains in a single instrument. Their chief advantage is in facilitating comparisons among different disease groups. Dis- ease-specific instruments reduce patient burden by including only relevant items for a particular illness but their main disadvantage is the lack of comparability of results with those from other dis- ease groups. Health profiles provide separate scores for each of the dimensions of Hr-QoL, whereas a health index, a type of generic instrument, gives a single summary score, usually from 0 (death) to 1 (perfect health). A further category, developed within the economic tradition, is that of utility mea- sures, which are based on preferences for health states. Preference weighted measures are required when the focus is on society as a whole and the societal allocation of scarce resources. The choice of measure will depend upon the goal of the study.
Preference-Based Outcome Measures
Preference-based outcome measures are a particular type of measure used in economic analyses, such as cost-utility analyses. Cost-utility analysis is a technique that uses the quality adjusted life year (QALY) as an outcome measure. For its calculation, the QALY requires well-being or Hr-QoL to be expressed as a single index score. The three most commonly used preference measurement techniques are visual analog scales, time trade-off, and standard gamble. A review of the literature on the use of Hr-QoL life data in economic studies is beyond the scope of this chapter, but interested readers can consult a series of chapters on this topic in ref. 6. As treatments for atypical parkinsonisan disorders become available, they will undoubtedly be subject to economic appraisal and robust, pro- spectively collected Hr-QOL data will be important for the calculation of QALYs and for other eco- nomic analyses.
Which Outcome Measure to Use?
The choice of instrument depends on the purpose of the study. A common recommendation is to include both disease-specific and generic measures in an investigation. The generic measure facili- tates comparisons of the target group with the normal population and/or other patient groups whereas the disease-specific instrument provides more sensitivity and is therefore usually more responsive to change in health status. If pharmaco-economic evaluation or a comparison of two or more treatment options is the aim of the study, incorporation of an additional utility measure is recommended. In atypical parkinsonism no disease-specific instruments are available to date but disease-specific instru- ments for MSA and PSP are currently being developed.
HEALTH-RELATED QUALITY OF LIFE IN PARKINSON’S DISEASE Health-Related Quality of Life Instruments Used in Parkinson’s Disease
A number of studies have assessed Hr-QoL in idiopathic PD. The authors of the first of these
studies used generic instruments including the Sickness Impact Profile (SIP) (7), the Nottingham
Health Profile (NHP) (8), the Medical Outcomes Short Form (SF 36) (9), and EQ-5D (10). These
measures were shown to be valid to varying degrees. However, the older instruments, such as the SIP and the NHP have been criticized for their content and their psychometric properties. For example, the NHP is skewed toward the severe end of disability and worse functional status and is therefore less likely to capture subtle changes in early stages of disease. The questions in the SIP have been felt to be offensive to patients by some (11), and the SF 36 may have limited feasibility and validity in patients with parkinsonism (12). However, the SF 36, a widely used Hr-QoL instrument, which has been translated in several languages and been validated for use in many cultures, enables compari- sons across cultures and disease groups. The EQ-5D has also been shown to be valid in patients with PD (12), and its brevity of five questions and a visual analog scale is an advantage in disabled patients. In addition, its summary index yields a utility score that can be used in pharmaco-economic analyses.
The EQ-5D has also been translation into many languages.
More recently, PD-specific Hr-QoL measures have been developed. Table 1 briefly describes the PD-specific Hr-QoL measures, showing the scale domains. All of the PD-specific instruments have been shown to have good psychometric properties, but only the Parkinson’s Disease Ques- tionnaire (PDQ 39; ref. 13) and the Parkinson’s Disease Quality of Life Questionnaire (PDQL; ref.
14) have been validated by researchers independent of the developers (15). The PDQ 39 is the most widely used Hr-QoL instrument in Parkinson’s disease. It has been translated in several languages, and has been shown to be valid, reliable and sensitive to change. An abbreviated format, the PDQ 8, which has been shown to have comparable validity (16), is also available. Although PDQ 39 has been validated in some cultures, including Britain, the United States, Spain, France, China, and Japan, its validity in other cultures needs to be established. The PDQL is similar to the PDQ 39 in content and format, but includes some questions that are missing in the PDQ 39, e.g., on sexuality. It has been validated in The Netherlands and Britain, but it has not been translated into other languages and no validation studies in other cultures are currently available. Its psychometric properties are less well tested than those of the PDQ 39 and some issues such as self-care, role functions, and close relation- ships are not addressed (15).
The Parkinson’s Impact Scale (PIMS) was developed to identify the major problems in patients’
lives in a clinical setting. It is based on consensus rather than testing in a patient sample and its content validity has been criticized (15). However, it is the only instrument that distinguishes between on and off periods and has been reported to be valid, reliable, and sensitive to change (17). The Parkinson’s Disease Quality of Life Scale (PDQUALIF) includes questions on fatigue and driving ability, concentrates on the nonmotor symptoms of Parkinson’s disease, and has more emphasis on social functioning than other scales (18). The Parkinson’s Disease Symptom Inventory (PDSI; ref.
19) has a larger number of questions (51 items) and asks patients to indicate the frequency as well as the distress caused by each item. There is also a German questionnaire, the ParkinsonLebensqualität (PQL), which has been psychometrically tested in a German population (20). The differences between some of these scales are discussed in an excellent review by Marinus et al. (15).
Finally, a number of measures that assess only the psychosocial aspects of Hr-QoL, excluding
items relating to physical impairment, have recently been developed and validated (21,22). The choice
of instrument in each setting will be guided by the differences between the content of the question-
naires, published data on the psychometric testing, and, if relevant to the study, the availability of
translations and cultural adaptation. For specific interventions different aspects of Hr-QoL will be
important and as no instrument can be both completely comprehensive and feasible, the selection of
the instrument will be based on the particular aim of the study. As discussed above, whereas generic
instruments can be used in patients with Parkinson’s disease, PD-specific instruments are likely to be
more valid, sensitive, and responsive to change.
Table 1 D isease-Spec if ic Hr-QoL Measures Developed for Park inson ’s D isease PD-Specific Measure Number of Items Domains of Hr-QoL Covered by Scale Reference Parkinson’ Disease Questionnaire 39 mobility, activities of daily living, emotional well-being, stigma, Peto et al. 1995 (13) 39-item version (PDQ-39) social support, cognition, communications, bodily discomfort Parkinson’ Disease Questionnaire 8 mobility, activities of daily living, emotional well-being, stigma, Peto et al. 1998 (16) 8-item version (PDQ-8) social support, cognition, communications, bodily discomfort™ Parkinson’ Disease Quality of Life 37 Parkinsonian symptoms, systemic symptoms, emotional functioning, De Boer et al. 1996 (14) Questionnaire (PDQL) social functioning Parkinson’s Impact Scale (PIMS) 10 Work, finance, leisure, safety, travel, self, feel, family, friend, Schulzer et al. 2002 (17) sexuality; differentiates between on- and off-states Parkinson’s Disease Quality of Life 33 Social/role function, self-image/sexuality, sleep, outlook, physical Welsh et al. 2003 (18) Scale (PDQUALIF) function, independence, urinary function, global HrQoL Parkinson’s Disease Symptom 51 Frequency and distress of symptoms; further analysis on scoring Hogan et al. 1999 (19) Inventory (PDSI) ongoing Fragebogen Parkinson 44 Depression, physical achievement, leisure, concentration, social Van den Berg, 1998 (20) LebensQualität (PLQ) integration, insecurity, restlessness, activity limitation, anxiety
THE IMPACT OF PARKINSONISM ON HEALTH-RELATED QUALITY OF LIFE
Parkinson’s Disease
The only parkinsonian disorder that has been assessed in detail with regard to Hr-Qol is PD.
Studies on Hr-QoL of patients with PD have improved our understanding of subjectively experienced difficulties associated with this disease, and we now have a clearer understanding of what aspects of Hr-QoL are most important to patients with PD. A full review of the expanding Hr-QoL literature in PD is beyond the scope of this chapter. However, it has consistently been found that all areas of Hr-QoL are affected by PD, not merely the physical impairment or functioning (23,25,26). The main areas of impairment in PD are in physical functioning, emotional reactions, social isolation, and energy. Other domains of impairment of Hr-QoL in PD, include bodily discomfort/pain, self-image, cognitive function, communication, sleep, role function, and sexual function (23,25–27). It has also become clear that in PD, it is not primarily disease severity and presence of the symptoms of PD that determine Hr-QoL, but the disability associated with these symptoms and, more than any other fac- tor, the presence and severity of depression (24,25,28). Further symptoms, which have also been found to be highly relevant to Hr-QoL of patients with PD, are postural instability and falls, impaired cognition, and insomnia. Other factors, including motor complications of treatment, may also be associated with poorer Hr-QoL in subgroups of patients, but this association is no longer significant once other important factors such as depression and disability due to parkinsonism are accounted for.
Potentially Important Quality-of-Life Issues in Atypical Parkinsonian Disorders A wide range of symptoms are likely to be associated with impaired Hr-QoL in atypical parkinso- nian disorders, including the cardinal features of parkinsonism, nonmotor symptoms such as sexual and autonomic dysfunction, postural instability and falls, cognitive impairment, and visual distur- bances.
Some analogies can usefully be drawn from Hr-QoL studies in PD. The degree of disability in atypi- cal parkinsonism is at least as great as in PD and depression occurs in all atypical parkinsonian disor- ders (29,30). It is therefore likely that these factors are also important in atypical parkinsonian disorders. However, these are likely not to be the only difficulties encountered by patients with atypi- cal parkinsonism in whom, frequently, many systems are affected. The impact of features such as greater autonomic dysfunction, higher rate of falls, behavioral changes, or cognitive impairment, will depend on the type of atypical parkinsonism. In addition, the shortened life expectancy, greater dis- ability, lack of response to treatment, associated nonmotor features, cognitive impairment, and behavioral disturbances in atypical parkinsonian disorders will all impact on patients’ subjective evaluation of their Hr-QoL. On the other hand, symptoms that occur less frequently in atypical par- kinsonism than in PD, such as tremor, hallucinations, dyskinesias, and motor fluctuations, are likely to be of lesser importance to the Hr-QoL in patients with atypical parkinsonian disorders.
All of these symptoms may lead to increased dependence on others, a diminished sense of autonomy and self-image (31), impairment of role functioning, emotional disturbances, fear of social stigma asso- ciated with physical symptoms, and impairment of social functioning. Table 2 gives examples of features of atypical parkinsonism, domains of Hr-QoL, which can be affected, and demographic and psycho-social variables, which may influence Hr-QoL in patients with atypical parkinsonism.
Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP)
We have recently undertaken in-depth interviews with patients with MSA and PSP and their car- ers, and conducted a large survey on issues relevant to patients with atypical parkinsonian disorders, with the aim of developing disease-specific Hr-QoL questionnaires for patients with MSA and PSP.
There was considerable overlap in reported areas of health-related quality of life issues relevant to
patients with PSP and MSA, but also some differences.
Table 2 Examples of Factors Relevant to Hr-Qol in Atyp ical Park inson ian D isorders Domains of HR-QoL That May Be Affected Features of Atypical Parkinsonian Disorders Demographic Variables Psychosocial Variables Physical function, e.g., mobility, bodily Motor symptoms Age Personal, e.g., coping discomfort, bladder problems strategies, personal attitudes, expectation of optimism Activites of daily living, e.g., self-care, Speech impairment Gender Social and environmental, communication, difficulties eating, reading e.g., social support, health care difficulties resource circumstances, e.g., family or in nursing home Psychological, e.g., stigma, self-image, Autonomic dysfunction Socioeconomic class depression, isolation, fear of future Social, e.g., family life, social interaction, Visual impairment Area of residence dependence on others Role functioning, e.g., emotional, physical Sexual dysfunction Insomnia Cognitive impairment, including bradyphrenia, executive dysfunction, retrieval difficulties, apraxia, neglect Affect, e.g., depression, anxiety Behavioral disturbances, e.g., apathy, disinhibition
The main presentations of MSA, which include autonomic dysfunction and cerebellar symptoms in addition to parkinsonism, were reflected in our preliminary Hr-QoL interviews. Patients with MSA reported difficulties with bladder and autonomic dysfunction among their most common and severe problems, which were not reported as commonly by patients with PSP, or those with PD (32). Lack of coordination, which was also more commonly reported in MSA patients than in PSP patients, is likely to reflect not only parkinsonism but also cerebellar dysfunction, which also results in “diffi- culty walking” and “balance problems.” The reported items “transferring from lying down to sitting”
or “difficulty standing up without support” may reflect orthostatic hypotension in addition to bradyki- nesia. Other issues more often rated as important by patients with MSA such as “worrying about the family,” “worrying about the future,” or “change of role within the family” may reflect the younger age group affected by MSA. Although these issues can also be important to patients with PSP, other items were rated as more important by patients with PSP.
Problems commonly reported in PSP but rare in Parkinson’s disease or MSA include early pos- tural impairment and falls, visual impairment owing to supranuclear gaze palsy, eyelid apraxia or photophobia, clinically relevant cognitive impairment, personality change, swallowing difficulties, and speech disturbances (33). In addition, patients with PSP may develop neuropsychiatric complica- tions, including apathy, inhibition, and depression (29,30). From the patients’ point of view, these issues are also particular problems, although apathy and personality change were less problematic from the patients than from the carers’ point of view (34).
In patients with MSA as well as PSP, difficulties beyond those of physical and mental symptoms of the disease were rated as important. Patients in both groups not only reported difficulties in daily activities but patients with MSA reported being anxious and worried about the future, had experi- enced loss of self-esteem and confidence, felt ignored or that nobody could understand their difficul- ties. Patients with PSP reported difficulties in showing their emotions, frustration and isolation, difficulties in communication, and worrying about others’ reactions. Without doubt, the impact on the emotional and social aspects of Hr-QoL goes beyond that of physical impairment and disability in both disorders.
Other Parkinsonian Disorders
For other atypical parkinsonism such as corticobasal degeneration there are currently no data avail- able on Hr-QoL. However, it is likely that, as in the other atypical parkinsonian disorders, there is considerable overlap of Hr-QoL issues, but that some features specific to this syndrome are also particularly relevant to their Hr-QoL, e.g., loss of hand function owing to alien limb, and impairment of activities of daily living because of apraxia. Other features important to PSP or MSA, such as bladder dysfunction or visual disturbances, are likely to have less impact in this patient group.
CARER BURDEN
It is not only the lives of patients that are severely affected by the chronic progressive disease
course, by decreased life expectancy, and by the multiple consequences of atypical parkinsonian
disorders; the lives of each family member and, particularly their carers, are also affected. It is likely
that atypical parkinsonian disorders affect carers’ physical functioning (e.g., caring affecting the
carer’s own health), emotional well-being (e.g., response to change in role, feelings of hopelessness
and depression), and social functioning (limitations on social life), but no studies to date have
assessed the different aspects of caregiver burden in these disorders. However, one study investi-
gated the correlates and determinants of carer burden in PSP (35). In this study, the impact of PSP on
carers increased with advancing disease severity and disability. Interestingly, this was most pro-
nounced in the first 18 mo after diagnosis, but carer burden plateaued after this initial increase. The
presence of affective and behavioral problems such as depression and aggression was associated with
greater carer burden, and women reported greater carer burden then men, even when disease severity
and behavioral disturbances were accounted for. The overall degree of carer burden appeared similar to that reported in carers of patients with Alzheimer’s disease.
CONCLUSION
The assessment of Hr-QoL in patients with atypical parkinsonian disorders is important for clini- cal research, surveys, and clinical trials. Since there is no cure, the management and current treatment of these chronic, disabling disorders is aimed at improving patients’ subjective Hr-QoL. The impact of these disorders on an individual is complex, comprising multiple aspects of physical, cognitive, emotional, and social functioning. The patient’s rating of their own Hr-QoL may vary considerably from their physician’s assessment. The valid and reliable assessment of patient-rated health status and Hr-QoL will become even more relevant as treatments for these disorders become available and the benefits of treatment need to be rigorously assessed. Generic Hr-QoL instruments can be used, but their validity and feasibility in patients with atypical parkinsonism is not known. PD-specific Hr-QoL instruments, although incorporating a number of features of relevance to atypical parkin- sonism, have not been validated in any of the atypical parkinsonian disorders and are likely to lack some of the salient features. The particular manifestations of each of the atypical parkinsonian disor- ders, e.g., the specific cognitive impairments in PSP or the autonomic features in MSA together with the features of parkinsonism, are not adequately reflected in any of these instruments. Hr-QoL instru- ments specifically for patients with MSA and PSP and for their carers are currently being developed.
FUTURE RESEARCH
Little information is available on the impact of atypical parkinsonism on specific domains of Hr-QoL. Our starting point must be to ask the patients what factors are most important to their Hr-QoL. It is anticipated that, analogous to the clinical presentations, some aspects of Hr-QoL, such as mobility, will be common to all of these disorders, whereas specific aspects will be associ- ated with particular disorders, e.g., bladder function in patients with MSA. Identifying the most important aspect of Hr-QoL in these disorders, from the patient’s perspective, will assist in the man- agement of these patients and will inform debate about the provision of health care resources. Finally, but perhaps most importantly, if and when symptomatic treatments for these disorders become available, their efficacy and relevance can be assessed by arguably the most important outcome measure: the effect on patients’ Hr-QoL as rated by the patients themselves.
MAJOR QUESTIONS FOR FUTURE RESEARCH
• What aspects of Hr-QOL are important in atypical parkinsonian disorders, as judged by the patients them- selves?
• Which instruments are most useful to assess Hr-QoL in atypical parkinsonian disorders?
• Which areas of Hr-QoL are most affected in each of the atypical parkinsonian disorders and what are the implications for the allocation of health care resources?
• Which demographic, clinical, and environmental factors have the greatest influence on patients’s subjec- tive Hr-QoL?
• What is the effect of potential symptomatic treatments for atypical parkinsonian disorders on patients’
Hr-QoL as rated by the patients themselves?
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