A four-year trajectory of Alexithymia in Parkinson’s disease patients

Abstract

The aim of this study was to assess the presence of Alexithymia in Parkinson’s disease (PD) patients compared to their caregivers (CG) and to investigate whether Alexithymia progressed over a 4-year observational period. Alexithymia in PD is a cognitive affective disturbance resulting in difficulty to identify, distinguish and describe feelings and it is known to be strongly associated with health-related quality of life and other cognitive/ neuropsychiatric symptoms. So far, there have been no longitudinal investigations of Alexithymia in PD. We recruited 34 moderately progressed PD patients (mean disease duration of 8.9 ± 5.3 years) and their caregivers in our neurological department and did a baseline and follow-up assessment using the validated Toronto Alexithymia Scale-26 (TAS-26). Our data show that Alexithymia is more abundant in the PD cohort compared to their caregivers (p = 0.007, PD 21 %, CG 6 % at follow-up). In the 4-year observational period, Alexithymia did not increase significantly in PD patients or caregivers. However, there was a high variance in Alexithymia scores in both groups. It remains unclear when Alexithymia appears during the disease course and whether there is a dynamic in Alexithymia scores later in PD progression. This should be the objective for future studies of Alexithymia in advanced PD patients.

1. Introduction

Parkinson’s disease (PD) leads to several non-motor symptoms including Alexithymia [5], [3]. It is considered as the inability to identify and describe feelings, accompanied by difficulties to distinguish between feelings and bodily sensations of emotional arousal, imaginative restrictions, lack of emotional awareness and an externalized way of living and thinking [12]. Individuals with Alexithymia are more likely to develop hypochondriasis and somatization [12]. In PD patients, Alexithymia was found to be about twice as abundant as in control subjects (about 20 % in PD and about 10 % in control subjects) [5], [3]. However, two studies found that about 20–35 % of the general population in Finland had Alexithymia measured by TAS-26 [13], [7]. Previously, Poletti et al., investigated 42 untreated de novo PD patients and 30 healthy controls and found that Alexithymia was not more abundant in the de novo PD patients[10]. Thus, it remains unclear, when PD patients develop more Alexithymia than healthy controls during the disease course.

Especially the Alexithymia subdomain depicting difficulties describing and communicating feelings differed between PD patients and control subjects[5]. In line with that, PD patients also show differences in processing emotional prosody compared to healthy controls and suffer from impairments in facial emotion recognition [1], [11]. In PD, Alexithymia and disturbed facial emotion recognition were strongly associated with lower quality of life and difficulties in interpersonal relationships, making them noteworthy symptoms also in the longer trajectory [1], [6], [8]. In a previous report we focused on the correlations between Alexithymia in PD and other clinical parameters. Apart from the influence on the quality of life, we found an association between Alexithymia in PD patients and caregiver burden[8]. Furthermore, Alexithymia in PD showed a connection to other neuropsychiatric symptoms like depression, apathy, anxiety and impulsivity [2], [10]. Poletti et al., reported an especially strong association between Alexithymia and depression in PD patients as well as in healthy control subjects [10]. It would be interesting, whether a successful treatment of depression can also result in less Alexithymia. Regarding neurocognitive functions, Alexithymia is associated with frontal and parietal lobe dysfunctions, especially executive functions of the non-verbal domains [2], [4]. One study showed a beneficial effect of deep brain stimulation in the subthalamic nucleus on Alexithymia in PD patients [6].

A previous investigation of a large cohort of Finish men (n = 755) revealed that Alexithymia is relatively stable in the general (male) population over a period of eleven years[13]. So far, there are no reports on long-term observations of Alexithymia in PD patients. Since we explored the associations of Alexithymia in PD patients with other clinical parameters [8], the aim of this study was to investigate a 4-year trajectory of Alexithymia in a cohort of PD patients.

We recruited 34 PD patients and their caregivers (CG) as a control group and did a baseline and follow-up investigation after four years comprising background and demographic data, disease duration and severity measured by Hoehn and Yahr score and degree of depression (measured by Beck’s depression inventory – BDI). To assess Alexithymia in both groups we used the validated TAS-26 scale at baseline and follow-up. The TAS-26 contains three subdomains: I. difficulties identifying feelings, II. difficulties describing feelings, III. externally oriented thinking. A sum score of ≥3 is indicative of Alexithymia. We performed an analysis of the subdomain- and total scores to compare PD patients to caregivers and in order to investigate the longitudinal development of Alexithymia.

The PD cohort had a mean age of 64.8 ± 10.1 years and a mean disease duration of 8.5 ± 5.1 years at baseline. The disease severity was moderate (Hoehn and Yahr 2.8 ± 1.0, median = 3). The caregivers had a mean age of 61.5 ± 8.6 years. The gender distribution differed between the groups, as there were only 29 % females in the PD group opposed to 68 % females in the CG group.

Depressive symptoms were present in both experimental groups (BDI scores 10.2 ± 6.9 in PD patients and 7.7 ± 5.1 in caregivers). However, there was no significant difference regarding depression between PD patients and caregivers (Table 1). Neither PD patients nor caregivers exhibited a significant increase of depression in the four-year trajectory (Table 1).

Table 1.

Demographic data of PD patients and caregivers, analysis of TAS-26 baseline and follow-up scores.

	PD patients n = 34	Caregivers n = 34	p-value
Age	64.8 ± 10.1	61.5 ± 8.6
Sex distribution	29 % female	68 % female
Disease duration baseline	8.5 ± 5.1 years	−
BDI baseline	10.2 ± 6.9	7.7 ± 5.1
BDI follow-up	11.8 ± 5.1	8.7 ± 6.4
TAS-26 I baseline	2.2 ± 0.75	1.8 ± 0.73	*(p = 0.036)
TAS-26 II baseline	2.8 ± 0.87	2.5 ± 0.76	*(p = 0.049)
TAS-26 III baseline	2.6 ± 0.54	2.5 ± 0.70
TAS-26 total baseline	2.5 ± 0.56	2.2 ± 0.55	*(p = 0.018)
Total score ≥ 3 at baseline	9/34 (26 %)	1/34 (3 %)	#(p = 0.013)
TAS-26 I follow-up	2.3 ± 0.75 (4/1)	1.9 ± 0.72 (1/3)	*(p = 0.013)
TAS-26 II follow-up	2.9 ± 0.85 (5/6)	2.3 ± 0.65 (2/3)	**(p = 0.006)
TAS-26 III follow-up	2.6 ± 0.54 (5/5)	2.7 ± 0.71 (6/3)
TAS-26 total follow-up	2.6 ± 0.51 (3/5)	2.3 ± 0.46 (1/0)	**(p = 0.007)
Total score ≥ 3 at follow-up	7/34 (21 %)	2/34 (6 %)

Data are shown as mean ± standard deviation. P values are only presented for significant results. A Wilcoxon-signed-rank test was performed to compare baseline- to follow-up scores for each group (no significant results). To compare the TAS-26 scores/ BDI scores of the PD and CG (caregiver) group, a Mann-Whitney test was performed (significant results shown as *). The fractions of patients with a positive Alexithymia total score (≥3) were compared with a Fisher’s exact test (significant results shown as #). In brackets behind the follow-up scores, we present the number of participants who passed over the cutoff score of 3 (positive for Alexithymia) from baseline to follow-up. The first number represents the participants that changed from < 3 to ≥ 3 (newly alexithymic) and the second number represents the participants who changed from ≥ 3 to < 3 (newly non-alexithymic).

Our data show that PD patients exhibited more Alexithymia than their caregivers (26 % of PD patients and 3 % of caregivers at baseline, comparison of total scores p = 0.018, comparison of fractions with total TAS-26 score ≥ 3, p = 0.013 (Table 1)). This result was slightly less prominent at the follow-up investigation after 4 years (Alexithymia in 21 % of PD patients and 6 % of caregivers, comparison of total scores p = 0.007, comparison of fractions with total TAS-26 score ≥ 3, p = 0.15 not significant). The subscores I and II differed significantly between the groups compared by non-parametric t-test at baseline and follow-up investigation, while the scores in subdomain III were similar (Table 1). Over the 4-year trajectory, Alexithymia did not increase in PD patients or caregivers neither in total scores nor in any subdomain score (Table 1). However, our data show that the scores in all subdomains are variable in both groups (SD between 0.51 and 0.87 in PD and 0.44 and 0.76 in CG) and that participants TAS-26 results changed over the cutoff of 3 (indicative of Alexithymia) in both directions in all subdomains and the total score over time. This suggests that there are participants who started non-alexithymic at baseline and converted to Alexithymia during 4 years as well as participants who started alexithymic but did not reach a positive Alexithymia score after 4 years any more. The overall proportion remained stable, as described before in the Finish male population[13]. Therefore, more studies on the longitudinal development of Alexithymia in healthy individuals and in PD patients are necessary to understand the construct of Alexithymia and its change over time better.

Additionally, it remains interesting, when Alexithymia appears during PD progression as it was already clearly present in our moderately advanced cohort and could not be detected in one study on de novo PD patients [10]. Future investigations should focus on the time of occurrence of Alexithymia in the disease course (e.g. analysis of patients with REM-sleep-behavior disorder and early as well as advanced PD patients). Furthermore, the neurobiological characteristics of Alexithymia are still not fully understood, so it remains to be elucidated whether it is associated with a specific PD phenotype. To investigate this, deep and specific phenotyping of the patients would be necessary. Then, imaging studies of those well characterized patients would help to gain insight into Alexithymia neurobiology.

Our study shows that overall Alexithymia is stable in moderately progressed PD patients over four years. It would be interesting to see if this is also true for even longer trajectories or whether PD patients at severe disease stage display more Alexithymia. This should be an objective of future investigations.

2. Material and methods

The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Ethics Committee of Hannover Medical School (No. 3178-2016, Amendment 2018).

Parkinson’s disease (PD) patients and their caregivers (CG) were recruited at the neurological department of Hanover Medical School between 2019 (baseline, n = 47) and 2023 (follow up) and gave written informed consent prior to their study participation. Movement disorder specialists confirmed PD diagnosis and were involved in clinical scoring. We did a baseline assessment including demographic characteristics (PD and CG), disease duration (PD), Hoehn and Yahr (PD), degree of depression measured by BDI (PD and CG) and Alexithymia score (PD and CG) as described below. Four years later, we repeated the assessment in both patients and caregivers. Only pairs of PD patient and caregiver, whose TAS-26 data were complete in baseline and follow-up, were included into the analysis (n = 34).

The German version of the Toronto Alexithymia Scale 26 (TAS-26) is a validated score to assess Alexithymia in different diseases and healthy participants[9]. It contains 26 items that were rated on a five-point Likert scale. There are three subdomains (1. difficulties identifying feelings, 2. difficulties describing feelings, 3. externally oriented thinking). Sum scores were divided by the number of completed items to obtain average scores for the total scale and the three subdomains. With a total score of ≥ 3 the participant is considered to have Alexithymia. The TAS-26 scale was completed by the patients and the caregivers by themselves. In more advanced PD patients who had difficulties to complete the TAS-26 questionnaire, caregivers were allowed to help. A bias due to that is possible in those cases.

Data were anonymized and analyzed in GraphPad Prism (Version 10.2.0, Boston, MA). We used a Wilcoxon-signed rank test to compare baseline to follow-up TAS-26/ BDI scores of PD patients and CG in the three TAS-26 subdomains and the total score, respectively. To investigate whether Alexithymia total scores/ BDI scores differ between PD patients and their caregivers, we performed a Mann-Whitney-U-Test. Additionally, we compared the fractions of PD patients and CG with and without Alexithymia (total score ≥ 3) with a Fisher’s exact test.

3. Limitations

The study was designed to assess the longitudinal development of Alexithymia in PD patients and their caregivers. Therefore, no data on cognitive impairments, impulsive-compulsive disorders, motor symptoms of PD patients, medication and device-aided therapies were acquired. Investigations including those clinical parameters in relation to Alexithymia should be the objective of future studies. Furthermore, the amount of patients in the study was limited. 47 patient/caregiver- pairs were included in the baseline assessment, due to missing TAS-26 data at the follow-up investigation, 34 patient/ caregiver-pairs could be included into the final data analysis. Another limitation of this study is that we did not address gender differences. It was reported that male PD patients tend to show more Alexithymia than females [10]. Our cohort comprised male patients predominantly, whereas the CG cohort consisted of more females, a gender bias is thus possible. More investigations on gender phenomena in Alexithymia are necessary.

4. Authors’ contribution

MK designed the study. AHR and TS were responsible for recruitment and data acquisition. LK performed the statistical analysis. MK and LK interpreted the data. LK wrote the first draft of the manuscript. All authors coedited the manuscript. All authors had access to the data generated in the study including the statistical analysis and decided to submit the paper for publication.

5. Author’s disclosure

The authors have nothing to declare concerning the research project. There were no conflicts of interest concerning this research topic.

CRediT authorship contribution statement

Lea Krey: Writing – original draft, Supervision, Methodology, Funding acquisition, Formal analysis, Conceptualization. Annika Heike Ritzrau: Writing – review & editing, Project administration, Investigation, Data curation. Theresa Schnur: Project administration, Investigation, Data curation. Stephan Greten: Writing – review & editing, Supervision, Methodology. Florian Wegner: Writing – review & editing, Validation, Supervision. Martin Klietz: Writing – review & editing, Validation, Supervision, Resources, Methodology, Formal analysis, Conceptualization.

Funding

Dr. Lea Krey was supported by PRACTIS – Clinician Scientist Program of Hannover Medical School, funded by the German Research Foundation (DFG, ME 3696/3-1).

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.