Quality of Life in Atypical Parkinsonian Disorders
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Quality of Life Assessment in Atypical Parkinsonian
Disorders
Anette Schrag and Caroline E. Selai
INTRODUCTION
The atypical parkinsonian disorders 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 patients’ social and emotional well-being; in short, the improvement
of patients’ quality of life. Assessment 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 results. However, a large literature shows that patients’ own assessments of their health, their preferences, 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 overview 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 parkinsonism, 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 literature, there is general consensus on some fundamental points. First, although the phrases “quality of
From: Current Clinical Neurology: Atypical Parkinsonian Disorders
Edited by: I. Litvan © Humana Press Inc., Totowa, NJ
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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 relationships, 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 incorporates 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 disorders 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-completed measures for patients with a disabling disease need to be short and feasible. Instrument developers 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, validity 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-
Quality of Life in Atypical Parkinsonian Disorders
279
tivity or responsiveness to change is concerned with how sensitive the measure is to detecting clinically relevant changes in Hr-QoL. This is important for monitoring benefits of treatment. Newer methods 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 available, 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. Disease-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 disease 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 measures, 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, prospectively collected Hr-QOL data will be important for the calculation of QALYs and for other economic 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 facilitates 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 instruments 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
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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 comparisons 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 Questionnaire (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
relationships 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 questionnaires, 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.
PD-Specific Measure
Number of Items
Domains of Hr-QoL Covered by Scale
Parkinson’ Disease Questionnaire
39-item version (PDQ-39)
39
mobility, activities of daily living, emotional well-being, stigma,
social support, cognition, communications, bodily discomfort
Peto et al. 1995 (13)
Parkinson’ Disease Questionnaire
8-item version (PDQ-8)
8
mobility, activities of daily living, emotional well-being, stigma,
social support, cognition, communications, bodily discomfort™
Peto et al. 1998 (16)
Parkinson’ Disease Quality of Life
Questionnaire (PDQL)
37
Parkinsonian symptoms, systemic symptoms, emotional functioning,
social functioning
De Boer et al. 1996 (14)
Parkinson’s Impact Scale (PIMS)
10
Work, finance, leisure, safety, travel, self, feel, family, friend,
sexuality; differentiates between on- and off-states
Schulzer et al. 2002 (17)
Parkinson’s Disease Quality of Life
Scale (PDQUALIF)
33
Social/role function, self-image/sexuality, sleep, outlook, physical
function, independence, urinary function, global HrQoL
Welsh et al. 2003 (18)
Parkinson’s Disease Symptom
Inventory (PDSI)
51
Frequency and distress of symptoms; further analysis on scoring
ongoing
Hogan et al. 1999 (19)
Fragebogen Parkinson
LebensQualität (PLQ)
44
Depression, physical achievement, leisure, concentration, social
integration, insecurity, restlessness, activity limitation, anxiety
Van den Berg, 1998 (20)
Reference
Quality of Life in Atypical Parkinsonian Disorders
Table 1
Disease-Specific Hr-QoL Measures Developed for Parkinson’s Disease
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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 factor, 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 parkinsonian disorders, including the cardinal features of parkinsonism, nonmotor symptoms such as sexual
and autonomic dysfunction, postural instability and falls, cognitive impairment, and visual disturbances.
Some analogies can usefully be drawn from Hr-QoL studies in PD. The degree of disability in atypical parkinsonism is at least as great as in PD and depression occurs in all atypical parkinsonian disorders (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 atypical 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 disability, 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 parkinsonism 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 associated 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 carers, 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.
Domains of HR-QoL That May Be Affected
Features of Atypical Parkinsonian Disorders
Demographic Variables
Physical function, e.g., mobility, bodily
discomfort, bladder problems
Motor symptoms
Age
Personal, e.g., coping
strategies, personal attitudes,
expectation of optimism
Activites of daily living, e.g., self-care,
communication, difficulties eating, reading
difficulties
Speech impairment
Gender
Social and environmental,
e.g., social support, health care
resource circumstances, e.g., family
or in nursing home
Psychological, e.g., stigma, self-image,
depression, isolation, fear of future
Autonomic dysfunction
Socioeconomic class
Social, e.g., family life, social interaction,
dependence on others
Visual impairment
Area of residence
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
Psychosocial Variables
Quality of Life in Atypical Parkinsonian Disorders
Table 2
Examples of Factors Relevant to Hr-Qol in Atypical Parkinsonian Disorders
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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 “difficulty 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 bradykinesia. 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 postural 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 complications, 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 experienced loss of self-esteem and confidence, felt ignored or that nobody could understand their difficulties. 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 available 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 investigated 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 pronounced 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
Quality of Life in Atypical Parkinsonian Disorders
285
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 clinical 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 parkinsonism, 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 disorders, 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 instruments 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 associated 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 management 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 themselves?
• 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 subjective Hr-QoL?
• What is the effect of potential symptomatic treatments for atypical parkinsonian disorders on patients’
Hr-QoL as rated by the patients themselves?
REFERENCES
1. Slevin ML, Plant H, Lynch D, Drinkwater J, Gregory WM. Who should measure quality of life, the doctor or the
patient? Br J Cancer 1988;57:109–112.
2. Spilker B, Revicki DA. Taxonomy of quality of life. In: Spilker B, ed. Quality of Life and Pharmacoeconomics in
Clinical Trials, 2nd ed. Philadelphia: Lippincott-Raven, 1996:25–31.
3. McDowell I, Newell C. Measuring Health: A Guide to Rating Scales and Questionnaires. New York: Oxford University
Press, 1987.
4. Streiner,DL, Norman GR. Health Measurement Scales: A Practical Guide to Their Development and Use, 2nd ed.
Oxford: Oxford Medical Publications, 1995.
286
Schrag and Selai
5. Brooks RG. Health Status Measurement: A Perspective on Change. Philadelphia: Macmillan, 1995.
6. Spilker B, ed. Quality of Life and Pharmacoeconomics in Clinical Trials, 2nd ed. Philadelphia: Lippincott-Raven,
1996.
7. Bergner M, Bobbitt RA, Carter WB, et al. The Sickness Impact Profile: development and final revision of a health
status measure. Med Care 1981;19:787–805.
8. Hunt SM, McEwen J, McKenna SP. Measuring health stats: a new tool for clinicians and epidemiologists. J Royal Coll
Gen Pract 1985;35:185–188.
9. Ware JE, Sherbourne CD. The MOS 36-item short form health survey (SF 36). I. Conceptual framework and item
selection. Med Care 1992;30:473–483.
10. EuroQoL Group. EuroQoL: a new facility for the measurement of health-related quality of life. Health Policy
1990;16:199–208.
11. Mitchell JD, O’Brien MR. Quality of life in motor neurone disease—towards a more practical assessment tool? J Neurol
Neurosurg Psychiatry. 2003;74:287–288.
12. Schrag A, Selai C, Jahanshahi M, Quinn NP. The EQ-5D—a generic quality of life measure—is a useful instrument to
measure quality of life in patients with Parkinson’s disease. J Neurol Neurosurg Psychiatry 2000;69:67–73
13. Peto V, Jenkinson C, Fitzpatrick R, Greenhall R. The development and validation of a short measure of functioning
and well being for individuals with Parkinson’s disease. Qual Life Res 1995;4:241–248.
14. de Boer AG, Wijker W, Speelman JD, de Haes JC . Quality of life in patients with Parkinson’s disease: development of
a questionnaire. J Neurol Neurosurg Psychiatry 1996;61:70–74.
15. Marinus J, Ramaker C, van Hilten JJ, Stiggelbout AM. Health related quality of life in Parkinson’s disease: a systematic review of disease specific instruments. J Neurol Neurosurg Psychiatry 2002;72:241–248.
16. Peto V, Jenkinson C, Fitzpatrick R. PDQ-39: a review of the development, validation and application of a Parkinson’s
disease quality of life questionnaire and its associated measures. J Neurol 1998;245(Suppl 1):S10–S14.
17. Schulzer M, Mak E, Calne SM. The psychometric properties of the Parkinson’s Impact Scale (PIMS) as a measure of
quality of life in Parkinson’s disease. Parkinsonism Relat Disord 2003;9:291–294.
18. Welsh M, McDermott MP, Holloway RG, Plumb S, Pfeiffer R, Hubble J, The Parkinson Study Group development and
testing of the Parkinson’s Disease Quality of Life Scale. Mov Disord 2003;18:637–645.
19. Hogan T, Grimaldi R, Dingemanse J, Martin M, Lyons K, Koller W. The Parkinson’s disease symptom inventory
(PDSI): a comprehensive and sensitive instrument to measure disease symptoms and treatment side-effects. Parkinsonism Relat Disord 1999;5:93–98.
20. Van den Berg M. Leben mit Parkinson: Entwicklung und psychometrische Testung des Fragenbogens PLQ. Neurol
Rehabil 1998;4:221–226.
21. Marinus J, Visser M, Martinez-Martin P, van Hilten JJ, Stiggelbout AM. Questionnaire for patients with Parkinson’s
disease: the SCOPA-PS. J Clin Epidemiol 2003;56:61–67.
22. Spliethoff-Kamminga NGA, Zwinderman AH, Springer MP, Roos RAC. Psychosocial problems in Parkinson’s disease: evaluation of a disease-specific questionnaire. Mov Disord 2003;18: 503–509.
23. Schrag A, Jahanshahi M, Quinn N. How does Parkinson’s disease affect quality of life? A comparison with quality of
life in the general population. Mov Disord 2000;15:1112–1118.
24. Schrag A, Jahanshahi M, Quinn N.What contributes to quality of life in patients with Parkinson’s disease? J Neurol
Neurosurg Psychiatry 2000;69:308–312.
25. Karlsen KH, Larsen JP, Tandberg E, Maland JG. Quality of life measurements in patients with Parkinson’s disease: a
community-based study. Eur J Neurol 1998;5:443–450.
26. Kuopio AM, Marttila RJ, Helenius H, Toivonen M, Rinne UK. The quality of life in Parkinson’s disease. Mov Disord
2000;15:216–223.
27. Damiano AM, McGrath MM, Willian MK, et al. Evaluation of a measurement strategy for Parkinson’s disease: assessing patient health-related quality of life. Qual Life Res 2000;9:87–100.
28. Global Parkinson’s Disease Survey Steering Committee. Factors impacting on quality of life in Parkinson’s disease:
results from an international survey. Mov Disord 2002;17:60–67.
29. Litvan I, Mega MS, Cummings JL, Fairbanks L. Neuropsychiatric aspects of progressive supranuclear palsy. Neurology 1996;47:1184–1189.
30. Aarsland D, Litvan I, Larsen JP. Neuropsychiatric symptoms of patients with progressive supranuclear palsy and
Parkinson’s disease. J Neuropsychiatry Clin Neurosci 2001;13:42–49.
31. Fitzsimmons B, Bunting LK. Parkinson’s disease—quality of life issues. Nurs Clin North Am 1993;28:807–818
32. Fitzpatrick R, Peto V, Jenkinson C, Greenhall R, Hyman N. Health-related quality of life in Parkinson’s disease: a
study of outpatient clinic attenders. Mov Disord 1997;12:916–922.
33. Nath U, Ben-Shlomo Y, Thomson RG, Lees AJ, Burn DJ. Clinical features and natural history of progressive supranuclear palsy: a clinical cohort study. Neurology 2003;60:910–916.
34. Schrag A, Selai D, Davis J, Lees A, Jahanshahi M, Quinn N. Health-related quality of life in patients with progressive
supranuclear palsy (PSP). Mov Disord 2003;18:1464–1469.
35. Uttl B, Santacruz P, Litvan I, Grafman J. Caregiving in progressive supranuclear palsy. Neurology 1998;51:1303–1309.