Fear of Progression is Determined by Anxiety and Self-Efficacy but not Disease-Specific Parameters in Patients with Parkinson’s Disease: Preliminary Data from a Multicenter Cross-Sectional Study

Abstract

Background:

Fear of progression (FoP) is a reactive, conscious concern about chronic disease progression and its consequences which may limit quality of life substantially. Only one study has examined FoP in Parkinson’s disease (PD), showing the second highest FoP scores among chronic diseases.

Objective:

To examine FoP prevalence and to exploratorily analyze determinants of FoP in PD.

Methods:

Within a multicenter cross-sectional study, 120 PD inpatients (age: 64.45±9.20; 60.8% male; UPDRS-III: 28.86±16.12) were examined with the FoP questionnaire (FoP-Q; max. 20 points). Stepwise multiple linear regression analysis examined sociodemographic, clinical, and (neuro-) psychological determinants of FoP.

Results:

With a mean FoP-Q score of 8.08±2.17, 63.0% of the patients were classified with moderate FoP and 17.6% with dysfunctional (i.e., severe) FoP. The highest scores were shown for the subscale ‘loss of autonomy’. Increased levels of anxiety, less self-efficacy, female gender, current employment, and lower health literacy were identified as significant determinants associated with FoP.

Conclusion:

With more than 80% of patients showing moderate to dysfunctional FoP, it must be regarded as a frequent symptom in PD, which needs to be further understood and addressed in clinical practice. Clinical parameters like PD duration and severity were no determinants for FoP, indicating that FoP awareness must be considered by professionals at all disease stages.

Keywords

Parkinson’s disease fear of progression disease progression anxiety self-efficacy health literacy cross-sectional study

INTRODUCTION

Parkinson’s disease (PD) is a complex, progressive neurodegenerative disorder characterized by motor and non-motor symptoms, leading to heterogeneous courses that are currently relatively unpredictable [1]. While some patients develop early complications such as postural instability leading to a higher risk of falling, or dementia affecting activities of daily living and entailing loss of independence and autonomy, others have a relatively benign course even at 10 years of PD [2]. Therefore, both immediately after PD diagnosis and during the course of the disease, patients and their relatives have to deal with questions: How quickly does the disease progress? What symptoms do I have to expect? How long will I be able to continue in my job and live an independent life? These worries about disease progression— which can also affect the relatives of chronically ill patients— can be described using the term ’fear of progression’ (FoP) (synonymous terms are ’fear of reoccurrence’ and ’health anxiety’[3]). FoP is defined as a conscious fear that arises from the real experience of a serious, potentially life-threatening or disabling disease, and its diagnosis and therapy [4]. FoP shows a continuum between ’functional’ and ’dysfunctional’ [5]. Functional FoP is understood as normative, rational, and adequate concerns, which can lead to an increased therapy adherence by patients. By contrast, patients with dysfunctional FoP experience quality of life reductions [6, 7] and increased suffering with effects on their social and occupational life due to a lack of well-functioning coping mechanisms, leading to higher utilization of medical and psychological care [8, 9], reduced therapy adherence [9], and higher health costs.

FoP should not be confounded with anxiety disorders involving irrational, often unspecific, and free-floating anxiety that leads to reactions that are recognizably inappropriate [10]. However, there can be an overlap between FoP, anxiety, and depression including emotional, cognitive, behavioral, and somatic aspects [4 , 10–13]. Dysfunctional FoP carries an increased risk for developing anxiety/depression. Lebel et al. [3] described this continuum between realistic health concerns and the psychiatric perspective including symptom misinterpretation and excessive thoughts and feelings about the disease leading to avoidance and reassurance-seeking behavior in their conceptual framework of health anxiety.

FoP has been examined in cancer patients [3 , 14–16]. However, FoP research in the field of neurodegenerative diseases is very limited [13 , 18]. So far, only one study examined FoP in PD patients (n = 54) in comparison to other chronic diseases [17], demonstrating that PD patients showed the second highest FoP scores after rheumatic diseases. Studies examining factors that specifically examine variables associated with and determinants for FoP in PD patients, in order to identify those with an increased risk, are missing. However, studies with other progressive diseases (i.e., cancer, multiple sclerosis [MS], and chronic diseases in general) revealed several factors associated with FoP. These include sociodemographic (younger age [17 , 19–21], female gender [17], less education [20], and being employed [17]), health-related and psychiatric (general health/physical symptoms [14 , 19–21], anxiety [6, 18], and depression/psychological distress [13 , 21]), and psychological variables (lower social support/family distress [14 , 20], self-efficacy [22, 23]) as well as disease knowledge and health literacy [18, 24].

Thus, the aim of this study was to investigate the prevalence of FoP in a large sample of PD patients as well as to explore sociodemographic, clinical, and (neuro-) psychological determinants for FoP.

MATERIAL AND METHODS

Study design

The recruitment for this multicenter cross-sectional study took part in three German hospitals/rehabilitation clinics (the Centre of Parkinsonism and Movement Disorders, Paracelsus-Elena Hospital, Kassel; the Movement Disorders Clinic, Beelitz-Heilstaetten; and the Neurological Rehabilitation Centre Godeshoehe e.V., Bonn) from January 2019 to July 2020. The study was preregistered in the German Clinical Trials Register (DRKS00016021) and was approved by the ethics committees of the Faculty of Medicine of the University of Cologne (master vote) and of the Hessian State Chamber of Physicians. Research was conducted in accordance with the Declaration of Helsinki. The reporting of this trial follows the STROBE statement [25].

After checking PD patients’ files, participants were invited to take part in this study by psychologists and/or neurologists at the recruiting centers. Individual appointments were scheduled during which patients gave written informed consent. After assessing study eligibility, clinical evaluation and neuropsychological testing was conducted in the medication ON state; short breaks were offered to avoid excessive strain. Afterwards, the participants were requested to complete further psychological questionnaires. Patients received no financial reimbursement.

Participants

The sample size calculation indicated that n = 120 participants should be recruited for this study. Inclusion criteria were 1) an inpatient stay in the recruiting hospitals/rehabilitation clinics, 2) a clinical diagnosis of idiopathic PD confirmed by a neurologist, 3) ability to follow instructions and to independently answer questionnaires, 4) age 50 years and older, 5) unrestricted or sufficiently corrected vision and hearing abilities, and 6) German as a native language or very good knowledge of German to follow study procedures. Exclusion criteria encompassed 1) severe cognitive impairment indicated by≤12 points in the Montreal Cognitive Assessment (MoCA) [26], 2) lack of capacity to consent, and 3) severe comorbidities affecting life expectancy or acute suicidal tendencies.

Clinical and (neuro-) psychological assessment

Besides demographic (age, gender, education, occupational, family status, and living situation) and PD- and health-relevant data (PD duration and severity assessed with the Unified Parkinson’s Disease Rating Scale III [UPDRS III] and Hoehn and Yahr stage [27], motor subtype, medication/levodopa equivalent daily dose [LEDD], comorbidities and pain level, care degree [German classification for the need of informal or formal care between I and V], need for support in everyday life, and activities of daily living assessed with the UPDRS II [27]), the following established standardized (neuro-) psychological assessments and questionnaires with good reliability and validity were conducted in interview format.

FoP was measured with the 43-item FoP questionnaire (FoP-Q) [28] comprising five subscales: affective reactions (13 items), partnership/family (7 items), work (7 items), loss of autonomy (7 items), and coping (9 items). The items of the first four subscales were answered on a 5-point Likert scale (1 = never to 5 = very often; higher scores indicating more FoP); the scoring for the coping subscale was the reverse (1 = very often to 5 = never). A FoP sum score was calculated as the sum of the subscales’ mean scores (affective reactions, partnership/family, work, and loss of autonomy). As a cut-off score for dysfunctional (i.e., severe) FoP is lacking, we used a threshold based on the mean value (±1 SD) of our sample for low, moderate, and dysfunctional FoP [14]. For the coping subscale, a separate sum score was calculated. Items that did not apply (e.g., questions on occupational life for retired patients) were answered with ‘1 = never’. We also used a semi-structured interview on PD-specific FoP components and aspects causing the greatest concerns; results will be reported elsewhere. For reliability analysis, Cronbach’s alpha was calculated to assess the internal consistency of the FoP questionnaire including 34 items (excluding items of the coping subscale). The internal consistency of the questionnaire is high, with Cronbach’s alpha = 0.883.

Global cognition was measured with the MoCA [26] (max. 30 points; cut-off for cognitive impairment≤26 points; higher scores indicating better performance). The MoCA includes subtests on the cognitive domains short-term memory, orientation, executive functions, working memory, attention, visuocognition, and language) and is administered in 10 min. Anxiety and depression were examined with the German version of the Hospital Anxiety and Depression Scale (HADS-D) [29]. The 14-item HADS-D includes two subscales for anxiety and depression (each 7 items) with higher scores indicating more symptoms. Therefore, each item is scored between 0 and 3 leading to a total score between 0 and 21 for either anxiety or depression; a cut-off value of 8 points or above on both subscales defines clinically relevant anxiety or depressive symptoms.

After the interview, the 66-Items self-assessment Questionnaire for the Assessment of Resources and Self-management Skills (FERUS) [30] was done by patients themselves including 7 subscales to measure motivation-to-change, coping, self-observation, self-efficacy, self-verbalization, hope and social support on a 5-point Likert scale (1 = not true to 5 = very true) with higher scores indicating more resources and self-management skills. Here, we only report on the self-efficacy scale.

Finally, the 47-item European Health Literacy Survey Questionnaire (HLS-EU-Q47) [31] was used to assess patients’ health literacy on a 4-point Likert scale (1 = very difficult to 4 = very easy; higher scores describing better health literacy). A general health literacy index with a maximum score of 50 points was calculated (cut-off score for problematic and inadequate health literacy < 33 points).

Further outcomes not reported here, but considered in future papers, were subjective cognitive impairment as well as further cognitive domains (i.e., executive functions and reasoning), hypochondria, personality, quality of life, self-management strategies (FERUS scales motivation-to-change, coping, self-observation, self-verbalization, hope, and social support), sense of coherence, and PD information level.

The outcome assessors were gerontologists and supervised psychology/medicine students who were trained in sensitive conversation skills in order to deal with patients’ stress resulting from the FoP interview. The clinical examinations (UPDRS III) were conducted by neurologists, physicians in neurological training, and physiotherapists (the rating was partly based on recorded videos).

Statistical analysis

Statistical analyses were performed using IBM SPSS Statistics (27.0). Single missing values in the self-administered questionnaires FERUS and HLS-EU-Q47 were imputed for 12 patients based on the means of the other items of the respective scale. The alpha level was set at 0.05 for all analyses.

The sample size calculation was guided by the aim to exploratorily examine sociodemographic, clinical, and (neuro-) psychological determinants for FoP by using regression analyses. We identified 12 variables to be included in the stepwise multiple linear regression analysis leading to a sample size of n = 120 (i.e., 10 observations per variable [32]).

The Kolmogorov-Smirnov test revealed that not all variables were normally distributed. Thus, for the descriptive statistics of the sociodemographic, clinical, and (neuro-) psychological data mean scores, standard deviations as well as median and corresponding minimum and maximum scores, or frequencies with percentages were indicated, as appropriate.

To analyze determinants for the FoP sum score and the respective subscales affective reactions, partnership/family, work, and loss of autonomy as the dependent variables, a stepwise multiple linear regression analysis with computerized forward selection and mean substitution was performed for exploratory model building [33]. For the selection of potentially determinants for FoP, we followed previous FoP reports in other patient groups and included further PD-relevant variables that were discussed and determined in an expert panel. The analysis included sociodemographic (age, gender, family, and occupational status), PD-related (disease duration and severity [UPDRS III]), psychiatric and cognitive (HADS-D anxiety and depression scores, and MoCA total score), and further psychological (FoP subscale coping, HLS-EU-Q47 total score, and FERUS self-efficacy) variables. The assumptions of multiple regressions were checked according to Field [33].

Since FoP and anxiety as well as depression have been demonstrated to be overlapping constructs in previous research, the FoP-Q sum score as well as the HADS-D subscales for anxiety and depression were correlated using Pearson correlation coefficients.

RESULTS

Patients’ characteristics

The patients were recruited during their inpatient stay in the cooperating hospitals. Unfortunately, it was not documented how many patients were identified as eligible for study participation, but declined to participate. In total, N = 122 PD patients were finally included (Bonn: n = 55; Kassel: n = 36; and Beelitz: n = 29; Table 1). Two data sets were excluded from the analyses because the PD diagnosis was revised by the diagnosis of atypical parkinsonism following the assessments. Thus, the total sample included N = 120 PD patients who were between 50 and 88 years old, around 60% were male, and they were on average in moderate PD disease stages (H&Y) and had no to mild cognitive impairment (MoCA). Around 40% of the sample had undergone deep brain stimulation (DBS) surgery in the past. The HLS-EU-Q47 score indicated a mean problematic health literacy.

Table 1

Sociodemographic and clinical characteristics of the sample (N = 120)

	N	%	M	SD	Median	Min.	Max.
Age (y)			64.45	9.204	64.00	50	88
Gender
Male	73	60.8
Female	47	39.2
Family status
Single	9	7.5
Married	88	73.3
In a relationship	4	3.3
Separated	2	1.7
Divorced	12	10.0
Widowed	5	4.2
Living situation
Alone	25	20.8
Two-person-household	68	56.7
Multi-person-household	24	20.0
Nursing home	3	2.5
Education (school and training years in total)			14.95	3.59	15.00	7	25
Current occupation
Employed	45	38.1
Unemployed/non-working	4	3.4
Retired	69	58.5
PD duration (y)			8.94	6.39	8.00	<1	30
Age at PD diagnosis (y)			55.54	11.03	54.00	31	86
Hoehn and Yahr stage			2.82	0.77	3.00	1	5
UPDRS II			12.22	5.99	12.00	0	30
UPDRS III			28.86	16.12	27.00	1	83
LEDD (in mg)			760.60	454.41	711.50	0	2347.50
DBS
Yes	51	42.5
MoCA total score (max. 30 points)²			24.78	3.22	25.00	14	30
HADS-D Depression (max. 21 points)¹			4.97	3.59	5.00	0	16
HADS-D Anxiety (max. 21 points)¹			5.34	3.11	4.00	0	15
FERUS Self-efficacy (max. 45 points)²			31.33	5.98	32.00	12	43
HLS-EU-Q47 total score (max. 50 points)²			30.83	6.79	29.35	15.25	48.58

Values are presented as the mean±standard deviation (including median as well as minimum and maximum scores) or frequency with percentages, as appropriate. ¹Higher scores indicate worse performance; ²Higher scores indicate better performance. DBS, Deep brain stimulation; FERUS, Questionnaire for the assessment of resources and self-management skills; HADS-D, Hospital Anxiety and Depression Scale (German version); HLS-EU-Q47, Health Literacy Survey European Questionnaire 47; LEDD, Levodopa equivalent daily dose; MoCA, Montreal Cognitive Assessment; PD, Parkinson’s disease; SCI, subjective cognitive impairment; UPDRS, Unified Parkinson’s Disease Rating Scale.

Prevalence of FoP

The total mean score on the FoP-Q sum score was 8.08±2.17 (range: 4.29–15.24) out of a maximum of 20 points. Using the cutoff value based on the mean (±1 SD), 23 patients (19.3%) were classified with low, 75 patients (63.0%) with moderate, and 21 patients (17.6%) with dysfunctional FoP. The highest scores were shown for the FoP subscale ‘loss of autonomy’, followed by ‘partnership/family’ and ‘affective reactions. When considering only the employed patients, the score of the subscale ‘work’ was comparable to the score of the subscale ‘partnership/family’ (Table 2).

Table 2

Results of the Fear of Progression-Questionnaire (FoP-Q)

FoP-Q scale	N	M	SD	Median	Min.	Max.
Affective reactions (max. 5 points)¹	119	2.02	0.59	1.92	1.00	3.62
Partnership/family (max. 5 points)¹	120	2.08	0.69	2.00	1.00	4.14
Work (max. 5 points)¹	120	1.53	0.81	1.14	1.00	5.00
Work (max. 5 points)¹ –employed patients only	45	2.08	1.03	1.86	1.00	5.00
Loss of autonomy (max. 5 points)¹	120	2.45	0.85	2.43	1.00	4.43
Sum score (max. 20 points]¹	119	8.08	2.17	7.91	4.29	15.24
Coping (max. 5 points)²	119	2.62	0.67	2.56	1.33	4.56

Values are presented as the mean±standard deviation (including median as well as minimum and maximum scores). ¹Higher scores indicate more FoP; ²Higher scores indicate better coping mechanisms regarding FoP. FoP-Q, Fear of progression questionnaire.

Analysis of determinants for FoP

Multiple regression analysis (Table 3) indicated that five variables explained 51.0% of the variance of FoP (F(5,114) = 25.81, R² = 0.531, p = 0.012). Significant determinants for FoP were higher levels of anxiety (β= 0.487, p < 0.001) and less self-efficacy (β= –0.247, p = 0.001), as well as currently being employed (β= 0.286, p < 0.001), female gender (β= 0.216, p = 0.002), and lower health literacy (β= –0.179, p = 0.012).

Table 3

Stepwise multiple linear regression analysis with forward selection: Determinants of the FoP-Q sum score

		B	SE B	β	T	p	R²	R² change	Adjusted R²
Step 1	HADS-D Anxiety	0.414	0.052	0.591	7.962	<0.001	0.349	0.349	0.344
Step 2	HADS-D Anxiety	0.359	0.051	0.512	7.015	<0.001
	FERUS Self-efficacy	–0.108	0.028	–0.285	–3.911	<0.001	0.425	0.075	0.415
Step 3	HADS-D Anxiety	0.380	0.050	0.543	7.619	<0.001
	FERUS Self-efficacy	–0.111	0.027	–0.293	–4.149	<0.001
	Current occupation (yes/no)	0.940	0.307	0.210	3.061	0.003	0.468	0.043	0.454
Step 4	HADS-D Anxiety	0.356	0.049	0.508	7.248	<0.001
	FERUS Self-efficacy	–0.113	0.026	–0.298	–4.359	<0.001
	Current occupation (yes/no)	1.104	0.303	0.247	3.646	<0.001
	Gender	0.878	0.301	0.199	2.916	0.004	0.504	0.037	0.487
Step 5	HADS-D Anxiety	0.342	0.048	0.487	7.103	<0.001
	FERUS Self-efficacy	–0.094	0.026	–0.247	–3.539	0.001
	Current occupation (yes/no)	1.279	0.304	0.286	4.186	<0.001
	Gender	0.953	0.296	0.216	3.206	0.002
	HLS-EU-Q47 total score	–0.060	0.024	–0.179	–2.465	0.012	0.531	0.027	0.510

Summary of the final model: F(5,114) = 25.81, R² = 0.531, p = 0.012. FERUS, Questionnaire for the assessment of resources and self-management skills; HADS-D, Hospital Anxiety and Depression Scale (German version); HLS-EU-Q47, Health Literacy Survey European Questionnaire 47.

The analyses for the FoP subscales affective reactions, partnership/family, work, and loss of autonomy revealed further significant determinants for FoP (Supplementary Tables 1–4). For affective reactions, alongside higher anxiety scores (β= 0.503, p < 0.001), lower self-efficacy (β= –0.223, p = 0.001), and female gender (β= 0.293, p < 0.001), a lower cognitive performance (β= –0.135, p = 0.040) was identified as a significant determinant. Together, these variables explained 52.6% of the variance (F(4,115) = 34.05, R² = 0.542, p = 0.040).

For FoP with regard to partnership/family, four variables— i.e., anxiety (β= 0.354, p < 0.001) and depression (β= 0.257, p = 0.008), being in a relationship (β= 0.259, p = 0.001), and younger age (β= –0.186, p = 0.014)— explained 37.0% of the variance (F(4,115) = 18.44, R² = 0.391, p = 0.014).

Overall, 39.6% of the variance for the FoP-Q subscale ‘work’ (F(4,115) = 20.50, R² = 0.416, p = 0.022) was explained by the four determinants currently being employed (β= 0.562, p < 0.001), lower self-efficacy (β= –0.254, p = 0.001), not being in a relationship (β= –0.183, p = 0.012), and higher anxiety scores (β= 0.175, p = 0.022).

Four variables explained 39.3% of the variance (F(4,115) = 20.09, R² = 0.411, p = 0.010) of the FoP subscale ‘loss of autonomy’, with higher levels of anxiety (β= 0.361, p < 0.001) as well as less self-efficacy (β= –0.249, p = 0.002) and health literacy (β= –0.202, p = 0.009), and female gender (β= 0.191, p = 0.010) being significant determinants.

Disease duration and severity (UPDRS III), as well as the FoP subscale coping, were no significant determinants for the FoP-Q sum score or any subscale.

Visual inspection of histograms and residual plots revealed no systematic patterns or violations of the normal distribution assumption or homoscedasticity, except for the FoP subscale ‘work’, which showed a tendency to deviate from the normal distribution.

Correlation sub-analysis for FoP-Q and HADS-D

The FoP-Q sum score correlated significantly with both the HADS-D anxiety (r = 0.59, p < 0.001), and depression subscale (r = 0.53, p < 0.001).

DISCUSSION

This paper investigated the prevalence of FoP in PD patients and explored determinants for FoP. We found the following: 1) FoP was a frequently occurring symptom in PD patients and more than 80% showed moderate to dysfunctional FoP; 2) FoP was determined by several sociodemographic (age, gender, family, and occupational status), and psychiatric and cognitive (anxiety and depressive symptoms, and cognitive performance) as well as psychological (self-efficacy and health literacy) variables; and 3) no disease-related parameters (disease severity and duration) were identified as meaningful variables associated with FoP in PD patients.

FoP prevalence in PD patients

Our data demonstrated that FoP was of high prevalence in PD patients, making it important to identify predictors to determine high-risk constellations for dysfunctional FoP requiring treatment. Comparing our FoP scores with other studies and chronic diseases was challenging, as a clear cut-off for dysfunctional FoP as measured with the FoP-Q is lacking [10], several definitions and questionnaires exist [3], and studies often use the short form of the FoP-Q [6 , 35]. Nevertheless, compared to cancer patients undergoing acute inpatient care [12], this PD sample showed higher FoP sum scores (8.1 vs. 7.1); by contrast, in comparison to a mixed sample of chronically ill patients including cancer, diabetes mellitus and rheumatic diseases [28], our sample reported lower FoP sum scores (8.8 vs. 8.1). Notably, the only study considering PD patients so far [17] also found higher scores for the FoP sum score (10.7±1.6). However, Berg et al. [17] included an atypical PD sample with a mean age of 47.3 years and around 65% women, while our sample involved a general PD population with more men (60%) and patients who were on average 17 years older. Therefore, we assume that the study of Berg et al. [17] was biased towards age and gender, and the results cannot be transferred to a general PD population. This argument is strengthened by our regression analyses showing that female gender as well as younger age were significant determinants for higher FoP.

Regarding the FoP-Q subscales, this PD sample was most concerned about ‘loss of autonomy’, which is a common fear in any elderly population. This finding was consistent with a recent qualitative study on experiences of late-stage PD patients and their informal caregivers, demonstrating that maintaining autonomy even in late disease stages was perceived as one of the most important factors [36]. Our inpatient recruitment settings (i.e., specialized PD hospitals and rehabilitation clinics) could have had an additional impact on FoP symptoms in terms of encounters with other patients who may be in advanced disease stages and already in need of care. Thus, future studies comparing inpatients and outpatients could clarify the influence of clinical setting and encounters with other PD patients on FoP.

Determinants for FoP in PD patients

As the most robust variables throughout the regression analyses for the FoP-Q sum score and its subscales, higher levels of anxiety and less self-efficacy were identified, which have also been described as associated factors for FoP in cancer [6 , 23] and MS [18]. Anxiety overlaps with the FoP concept (which is also underlined by a significant positive correlation between the HADS-D anxiety scale and the FoP sum score), which could explain the regression results; however, they should be addressed as different entities, which also holds true for depression [12]. Depression was identified as a determinant for the FoP-Q subscale ‘partnership/family”, which was also in line with results from FoP trials with cancer [14, 21] and MS patients [13], and is also underlined by a significant positive correlation analysis between the HADS-D depression subscale and the FoP sum score. Thus, when patients report health-related worries during routine clinical contact, anxiety and depression need to be considered as well.

Self-efficacy is conceptualized as personal beliefs about one’s capabilities for managing— e.g., in chronic and progressive diseases— and represents an important resource for adequate coping behavior [22, 23]. In line with this notion, self-efficacy was a significant FoP determinant in our regression analysis. Also, lower health literacy was identified as a significant determinant, which was in line with studies of other chronically ill patients [18, 24]. Ghojazadeh et al. [18] demonstrated that limited disease knowledge, which is highly associated with health literacy, is associated with higher FoP in MS patients. Thus, promoting health literacy, together with strengthening self-efficacy, should be considered as important determinants when developing psychosocial intervention programs for FoP prevention and treatment. Also, coping mechanisms to deal with FoP as normative and rational concerns regarding disease progression are possible intervention components to prevent or treat dysfunctional FoP, although the FoP-Q coping scale was no significant determinant FoP in this study. One explanation might be that the scale does not cover specific problem-, emotion-, and appraisal-focused coping mechanisms that might be specifically helpful for PD patients. Thus, future studies should apply questionnaires examining coping styles in a more differentiated way and consider them as single variables in the regression analysis to gain a more distinct insight in the role of FoP coping.

Regarding sociodemographics, we found female gender and younger age to be significantly associated with FoP. Higher FoP scores in female patients may be related to findings showing that women with PD have significantly more anxiety and depressive symptoms [37]. Age-related differences in FoP severity could be explained by different living situations between younger and older patients, with the former having different family obligations (e.g., caring for children). Berg et al. [17] also showed that in their sample of younger PD patients, questions around family life were associated with the strongest concerns. Also, current occupation and career status may have a different influence on FoP in younger compared to older patients. However, for the FoP-Q subscale ‘work’, age was not identified as a significant determinant, which could be related to this samples’ demographics with more than 60% of the patients being retired or unemployed. Also, the family and occupational status were determinants for FoP. The role of partnership and family was striking as contradictory results were found for the FoP-Q subscales ‘partnership/family’ and ‘work’. With regard to FoP in the occupational context, family, financial and emotional security could be helpful when dealing with a progressive disease like PD. This explanation is strengthened by study results showing that lower social support and family distress is associated with higher FoP [14 , 20]. Currently being employed leads to further concerns when dealing with a chronic disease in terms of PD-related occupational disability and financial security [17]. Taken together, these easy-to-assess sociodemographic data are helpful for identifying patients at risk for dysfunctional FoP during routine clinical contact.

We also identified the MoCA total score as a further factor for higher FoP scores, which could be explained by the link between cognitive dysfunction and anxiety as well as depression [38]. However, the MoCA total score was the only significant clinical variable. PD duration and severity were no significantly determinants for FoP. This was in line with a study by Nielsen et al. [13] who showed that disease duration was not linked with FoP in MS patients. This indicates that FoP is an ongoing symptom that can be found at all disease stages (e.g., immediately after diagnosis or in advanced PD).

Limitations

The recruitment was conducted by hospital staff, and it was not documented how many patients were identified as being eligible but declined to participate in the study. Thus, it was not possible to compile a patient flow diagram. This information could be helpful for planning FoP trials in general and should be part of future studies.

Although the range of disease duration and severity, including patients who had undergone DBS surgery, and the gender and age distribution reflected clinical reality, the generalizability was limited to this inpatient collective. Thus, future studies need to examine FoP in different PD groups, including younger samples of PD patients as well as outpatients, along with regression analyses, to further understand the underlying mechanisms resulting in FoP differences, in order to develop suitable prevention and therapy programs for different target groups.

We found that PD duration and severity were no determinants for FoP, indicating that FoP is not limited to specific PD stages. However, only longitudinal studies that optimally follow PD patients during the course of the disease will clarify the evolution of FoP symptoms.

For the regression analysis of the FoP subscale ‘work’, a tendency for violations of the normal distribution assumption was revealed, which was related to the fact that less than 40% of the patients were employed. Therefore, the results for the FoP subscale ‘work’ need to be reevaluated in further studies with a higher percentage of employed patients.

Cut-off scores for dysfunctional FoP are still lacking due to the absence of established external criteria to define the clinical stage of dysfunctional FoP [10]. Therefore, our staging of low, moderate, and dysfunctional FoP, based on the sample’s normal distribution (i.e., mean value [±1 SD]) as proposed by Mehnert et al. [14], might be questionable and the categorization should be considered as preliminary. Thus, it is of high importance to determine a cut-off for clinically relevant FoP to re-evaluate the categorization into low, moderate and dysfunctional FoP in PD patients in future studies when clinical criteria are defined. Further research should develop clinical diagnostic criteria for dysfunctional FoP, which will also be of relevance for the implementation of a clinical FoP assessment routine.

CONCLUSION

This is the first study examining the prevalence of FoP and its sociodemographic, clinical, and (neuro-) psychological determinants in a large PD sample reflecting the age and gender distribution of a European PD population. Our preliminary data indicate awareness of FoP at all PD disease stages, with patients showing higher levels of anxiety, less self-efficacy, lower health literacy, and female gender being at greater risk for dysfunctional FoP. Although no established cut-off values exist, the short or long version of the FoP-Q may be helpful for assessment. Existing psychosocial services should be extended for PD patients at risk of dysfunctional FoP [39, 40].

Footnotes

ACKNOWLEDGMENTS

We thank all patients for their participation in our study. Furthermore, we give our thanks to Carolina Habbel, Annika Rosenow, Pia Wagner, and Sarah Wendland for helping with data collection.

This study was financed by the budgets of the participating study centers. Two students who wrote their master’s theses within this project received a student grant from the Center for Social and Economic Behavior (S-SEB) of the University of Cologne, Cologne, Germany.

CONFLICT OF INTEREST

AKF has received grants from the German Parkinson Society and the German Alzheimer’s Society, as well as honoraria from Springer Medizin Verlag GmbH, Heidelberg, Germany; Springer-Verlag GmbH, Berlin; ProLog Wissen GmbH, Cologne, Germany; pro audito Switzerland, Zürich, Switzerland; Seminar- und Fortbildungszentrum Rheine, Germany; and LOGOMANIA, Fendt & Sax GbR, Munich, Germany. AFK is author of the cognitive intervention programs “NEUROvitalis” but receives no corresponding honoraria.

NA has received honoraria from Medtronic for lecturing and consulting and from Boston Scientific and Merz Pharmaceuticals for lecturing.

CT has received grants from the Michael J. Fox Foundation and Horizon 2020 (PROPAG-AGEING), as well as honoraria for educational lectures from UCB Pharma GmbH. CT is on advisory boards for UCB Pharma GmbH, and ROCHE.

GE has received honoraria for advisory boards and consultancy from AbbVie Pharma, BIAL Pharma, Biogen GmbH, Desitin Pharma, and STADA Pharma, speakers’ honoraria from AbbVie Pharma, BIAL Pharma, Britannia Pharma, Desitin Pharma, Licher GmbH, UCB Pharma, and Zambon Pharma, and royalties from Kohlhammer Verlag and Thieme Verlag.

EK has received grants from the German Ministry of Education and Research, ParkinsonFonds Deutschland gGmbH, the German Parkinson Society, and the German Alzheimer’s Society, and honoraria from Oticon GmbH, Hamburg, Germany; Lilly Pharma GmbH, Bad Homburg, Germany; Bernafon AG, Bern, Switzerland; and Desitin GmbH, Hamburg, Germany. EK is author of the cognitive intervention programs “NEUROvitalis” but receives no corresponding honoraria.

No other authors have any conflicts of interest to report.

The supplementary material is available in the electronic version of this article: .

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