
==== Front
Sci Rep
Sci Rep
Scientific Reports
2045-2322
Nature Publishing Group UK London

39266657
72742
10.1038/s41598-024-72742-z
Article
Increased risk of depression and associated symptoms in poststroke aphasia
Kao Shih-Kai 1
Chan Chia-Ta M007356@ms.skh.org.tw

234
1 grid.415755.7 0000 0004 0573 0483 Department of General Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
2 grid.415755.7 0000 0004 0573 0483 Department of Psychiatry, Shin Kong Wu Ho-Su Memorial Hospital, No. 95, Wenchang Rd., Shilin Dist., Taipei, 111 Taiwan
3 grid.145695.a 0000 0004 1798 0922 School of Medicine, College of Medicine, Fu Jen University, Taipei, Taiwan
4 https://ror.org/00se2k293 grid.260539.b 0000 0001 2059 7017 Institute of Brain Science and Brain Research Center, School of Medicine, National Yang-Ming Chiao-Tung University, Taipei, Taiwan
12 9 2024
12 9 2024
2024
14 2135229 6 2024
10 9 2024
© The Author(s) 2024
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
Poststroke aphasia hinders patients’ emotional processing and social adaptation. This study estimated the risks of depression and related symptoms in patients developing or not developing aphasia after various types of stroke. Using data from the US Collaborative Network within the TriNetX Diamond Network, we conducted a retrospective cohort study of adults experiencing their first stroke between 2013 and 2022. Diagnoses were confirmed using corresponding International Classification of Diseases, Tenth Revision, Clinical Modification codes. Patients were stratified by poststroke aphasia status and stroke type, with propensity score matching performed to control for confounders. The primary outcome was depression within one year post-stroke; secondary outcomes included anxiety, fatigue, agitation, emotional impact, and insomnia. Each matched group comprised 12,333 patients. The risk of depression was significantly higher in patients with poststroke aphasia (hazard ratio: 1.728; 95% CI 1.464–2.038; p < 0.001), especially those with post-hemorrhagic-stroke aphasia (hazard ratio: 2.321; 95% CI 1.814–2.970; p < 0.001). Patients with poststroke aphasia also had higher risks of fatigue, agitation, and emotional impact. Anxiety and insomnia risks were higher in those with post-hemorrhagic-stroke aphasia. Poststroke aphasia, particularly post-hemorrhagic-stroke aphasia, may increase the risks of depression and associated symptoms, indicating the need for comprehensive psychiatric assessments.

Keywords

Stroke
Aphasia
Depression
Anxiety
Hemorrhagic stroke
Subject terms

Neuroscience
Psychology
Diseases
Health care
Neurology
Signs and symptoms
http://dx.doi.org/10.13039/501100004319 Shin Kong Wu Ho-Su Memorial Hospital SKH-8302-103-DR-04 Kao Shih-Kai issue-copyright-statement© Springer Nature Limited 2024
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pmcIntroduction

Stroke is a leading cause of long-term disability and mortality globally, and it has profound implications for affected individuals and their family members. Approximately 85% and 12% of all stroke cases involve ischemic and hemorrhagic strokes, respectively1. Hemorrhagic stroke involves hematoma formation and inflammation, potentially raising intracranial pressure, while ischemic stroke features a necrotic core and an ischemic penumbra with preserved neuronal function due to collateral circulation2.

Among the various sequelae of stroke, poststroke depression, which typically occurs within the first year, is the most common and burdensome neuropsychiatric complication, affecting recovery, rehabilitation, and overall quality of life3. Relevant meta-analyses have reported that the cross-sectional prevalence of poststroke depression ranges from 18 to 33%4,5. Poststroke depression not only prolongs the process of recovery but also increases the risks of morbidity and mortality6. Although commonly linked to ischemic stroke, poststroke depression is also prevalent in hemorrhagic stroke, with a prospective cohort study showing that the risk of depression is more than twice as high in patients with intracerebral hemorrhage compared to those with ischemic stroke7.

Aphasia is a disorder that is characterized by an acquired loss or impairment of language after brain damage. Approximately one-third of all stroke survivors develop aphasia8, which complicates the recovery process. Individuals with aphasia are at high risks of complications and neurological disability, which lead to functional limitations and reduced quality of life compared with the outcomes in individuals without poststroke aphasia9. Notably, aphasia not only hampers communication but also hinders emotional processing and social adaptation10.

Small-scale studies have shown that depression is more prominent among patients with aphasia than those without aphasia, and that depressive symptoms do not appear to diminish over time for individuals with chronic aphasia11,12. Lin et al. recently conducted a population-based cohort study involving Taiwanese individuals, and they reported that the incidence of depression was higher in individuals with poststroke aphasia than in those without it, regardless of sex or stroke type13; in their study, the adjusted hazard ratio (HR) for the risk of depression was 1.21 (95% confidence interval [CI] 1.15–1.29).

Anxiety is the feeling of fear that occurs when faced with threatening or stressful situations14. Comorbid depression and anxiety disorders are present in up to 25% of patients in general practice15. Insomnia, anxiety, and depression commonly co-occurred and were closely related16. A prospective cohort study reported anxiety and insomnia complicate poststroke recovery, especially in hemorrhagic stroke aphasia patients who face higher risks than those with ischemic stroke7. In addition, depression and anxiety can contribute to reduced appetite, which is a common issue in patients with aphasia17,18.

Fatigue, a prevalent symptom among stroke survivors, is particularly pronounced in patients with aphasia19,20. Fatigue is also a clinical symptom of depression21. Individuals with aphasia exhibiting higher levels of fatigue are inclined to report reduced social participation20. Agitation, characterized by irritability or severe restlessness, is a common physiological process related to depression and is also prevalent in poststroke aphasia patients22. Previous studies have shown that the risk of agitation is significantly higher in patients with aphasia23. Suicidal ideation, characterized by thoughts of self-harm, represents a serious mental health concern with potentially severe consequences if left untreated24. This depression-related issue is also common among patients with language impairment in clinical practice25.

The emotional impact of aphasia extends beyond symptoms related to depression and anxiety, encompassing a broad and profound range of effects. Aphasia can elicit both positive and negative emotions, such as agitation, apathy, irritability, and unhappiness. These emotional responses significantly influence an individual's psychological state and overall well-being, highlighting the complex interplay between aphasia and mental health26.

Evidence suggests an association between depression risk and poststroke aphasia. In their stroke genetics network study, Wassertheil-Smoller et al. demonstrated that the risk of poststroke depression is influenced by not only stroke types and genetic factors but also ethnicity27. Therefore, findings from studies associating depression risk with poststroke aphasia must be confirmed using larger databases. Furthermore, the associations of poststroke aphasia with the risks of anxiety and other depression-related symptoms, such as poor appetite, fatigue, agitation, insomnia, self-harm behavior, and emotional impact, remain unclear.

To bridge the aforementioned knowledge gap, the present study evaluated the risks of depression and associated symptoms in patients with poststroke aphasia and investigated the effects of different strokes, particularly ischemic and hemorrhagic strokes, on these risks.

Methods

Study design and ethics declarations

This retrospective, observational cohort study was conducted using data from the US Collaborative Network within the TriNetX Diamond Network, a comprehensive repository of electronic medical records, medical claims, and pharmacy claims. The data set included comprehensive information on patient demographics, diagnoses, medication records, laboratory test results, and health-care utilization, coded in accordance with standard systems. Notably, TriNetX curates longitudinal data every 3 months from 92 sites, representing more than 212 million patients.

The TriNetX platform adheres to the US Health Insurance Portability and Accountability Act (HIPAA) and the General Data Protection Regulation. The present study was conducted in accordance with relevant regulations and standards. Data de-identification is formally attested as per section §164.514(b)(1) of the HIPAA Privacy Rule. The requirement for informed consent was waived because of the anonymized nature of the data (the TriNetX platform stores deidentified data) and the retrospective nature of this study. Additionally, the use of TriNetX in the current study was approved by the Institutional Review Board of the Shin Kong Wu Ho-Su Memorial Hospital.

Study cohort

A flowchart of the patient selection process is presented in Fig. 1. This study included adult (aged ≥ 18 years) patients who had their first-ever stroke between January 1, 2013, and December 31, 2022. The diagnoses of various strokes were confirmed using the following International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes: I63 (cerebral infarction), I60 (nontraumatic subarachnoid hemorrhage), and I61 (nontraumatic intracerebral hemorrhage). The diagnoses of aphasia were confirmed using the following ICD-10-CM codes: R47.01 (aphasia), I69.920 (aphasia after unspecified cerebrovascular disease), and I69.320 (aphasia after cerebral infarction). Notably, in our cohort, aphasia was diagnosed within 3 months after the stroke event. The patients were stratified into two groups according to poststroke aphasia status: a case group (comprising patients with aphasia) and a control group (comprising those without aphasia). We excluded patients who were aged < 18 years; died before aphasia diagnosis; or had a history of depression (ICD-10-CM codes: F32 and F33), anxiety (ICD-10-CM codes: F40 and F41), schizophrenia (ICD-10-CM codes: F20–F29), bipolar disorder (ICD-10-CM code: F31), intellectual disabilities (ICD-10-CM codes: F70–F79), suicidal ideation and attempts (ICD-10-CM codes: R45.851 and T14.91, respectively), or prestroke aphasia.Fig. 1 A flow chart showing the selection of patients.

The patients were divided into subgroups according to stroke type (ischemic stroke [ICD-10-CM code: I63 excluding I60 and I61] vs. hemorrhagic stroke [ICD-10-CM codes: I60 and I61]) for analysis.

Study outcomes

The primary study outcome was the development of depression within 1 year after stroke (during the follow-up period). The secondary study outcomes were the development of anxiety and other depression-related symptoms within 1 year after stroke. The other symptoms included poor appetite (ICD-10-CM code: R63.0), fatigue (ICD-10-CM codes: R53.81 and R53.83), insomnia (ICD-10-CM code: G47.0), self-harm ideation (ICD-10-CM codes: X71–X83, R45.851, T14.91, and R45.88), agitation (ICD-10-CM codes: R45.1 and R45.4), and emotional impact (ICD-10-CM code: R45).

Statistical analysis

To mitigate the effects of confounding factors, we performed propensity score matching (PSM) to establish groups with balanced baseline characteristics. Through greedy nearest neighbor matching, 1:1 PSM was performed using a built-in function within TriNetX. Specifically, the groups were matched by age, sex, race (White, African American, Hispanic or Latino, and Asian), marital status (never married), low income (ICD-10-CM code: Z59.6), hypertension (ICD-10-CM code: I10), atrial fibrillation (ICD-10-CM code: I48), heart failure (ICD-10-CM code: I50), chronic kidney disease (ICD-10-CM code: N18), diabetes mellitus (ICD-10-CM code: E08–E13), hyperlipidemia (ICD-10-CM code: E78.5), overweight and obesity (ICD-10-CM code: E66), epilepsy (ICD-10-CM code: G40), chronic pain (ICD-10-CM code: G89.2), dementia (ICD-10-CM code: F03), smoking (ICD-10-CM code: F17), alcohol use (ICD-10-CM code: F10), hypnotic use, antidepressant use, antipsychotic use, and anticonvulsant use before the index date (stroke diagnosis). Standardized differences were calculated to examine the balance of baseline characteristics between the propensity score–matched groups. A standardized difference of < 0.1 was considered to indicate a small between-group difference. HRs with 95% CI values were calculated for all outcomes. The TriNetX user interface was used for risk analysis and Kaplan–Meier survival analysis. In the Kaplan–Meier survival analysis, between-group differences were determined using a log-rank test and a Cox proportional-hazards model.

Results

Patient groups

Table 1 presents the baseline characteristics of the study cohort. After the application of the exclusion criteria, the case and control groups comprised 12,337 and 937,883 patients, respectively. After PSM, each group comprised 12,333 patients. The median follow-up time is 365 days for both groups.Table 1 Baseline characteristics of case group (post-stroke patients with aphasia) and control group (post-stroke patients without aphasia). SMD Standardized mean difference.

	Before matching	After matching	
Case (N = 12,337)	Control (N = 937,883)	SMD	Case (N = 12,333)	Control (N = 12,333)	SMD	
Demographic data	
 Age (years)	65.8 ± 13.1	64.0 ± 14.3	0.130	65.8 ± 13.1	66.4 ± 12.9	0.045	
 Male	6862 (55.6%)	512,648 (54.7%)	0.019	6862 (55.6%)	6940 (56.3%)	0.013	
 Race	
 White	6312 (51.2%)	456,495 (48.7%)	0.050	6312 (51.2%)	6405 (51.9%)	0.015	
 African American	2555 (20.7%)	124,058 (13.2%)	0.200	2551 (20.7%)	2472 (20.0%)	0.016	
 Hispanic or Latino	700 (5.7%)	50,691 (5.4%)	0.012	700 (5.7%)	650 (5.3%)	0.018	
 Asian	512 (4.2%)	40,019 (4.3%)	0.006	512 (4.2%)	510 (4.1%)	0.001	
Baseline comorbidities	
 Hypertension	6439 (52.2%)	280,149 (29.9%)	0.466	6435 (52.2%)	6558 (53.2%)	0.020	
 Diabetes mellitus	3369 (27.3%)	148,956 (15.9%)	0.280	3365 (27.3%)	3423 (27.8%)	0.011	
 Hyperlipidemia	4005 (32.5%)	154,941 (16.5%)	0.377	4001 (32.4%)	4035 (32.7%)	0.006	
 Overweight and obesity	1446 (11.7%)	64,526 (6.9%)	0.167	1445 (11.7%)	1432 (11.6%)	0.003	
 Atrial fibrillation	2081 (16.9%)	69,989 (7.5%)	0.291	2078 (16.8%)	2095 (17.0%)	0.004	
 Heart failure	1625 (13.2%)	65,388 (7.0%)	0.207	1622 (13.2%)	1519 (12.3%)	0.025	
 Chronic kidney disease	1589 (12.9%)	69,280 (7.4%)	0.183	1588 (12.9%)	1629 (13.2%)	0.010	
 Epilepsy	919 (7.4%)	19,720 (2.1%)	0.253	915 (7.4%)	885 (7.2%)	0.009	
 Dementia	498 (4.0%)	11,413 (1.2%)	0.177	495 (4.0%)	454 (3.7%)	0.017	
 Chronic pain	664 (5.4%)	35,170 (3.7%)	0.078	663 (5.4%)	649 (5.3%)	0.005	
 Smoke	1274 (10.3%)	55,325 (5.9%)	0.163	1272 (10.3%)	1248 (10.1%)	0.006	
 Alcohol	495 (4.0%)	19,086 (2.0%)	0.116	494 (4.0%)	468 (3.8%)	0.011	
Socioeconomic status	
 Never married	1330 (10.8%)	86,008 (9.2%)	0.054	1329 (10.8%)	1239 (10.0%)	0.024	
 Low income	10 (0.1%)	88 (0.0%)	0.034	10 (0.1%)	10 (0.1%)	 < 0.001	
Medication	
 Hypnotics	3674 (29.8%)	167,189 (17.8%)	0.283	3670 (29.8%)	3685 (29.9%)	0.003	
 Antidepressants	1871 (15.2%)	70,921 (7.6%)	0.241	1868 (15.1%)	1894 (15.4%)	0.006	
 Antipsychotics	1002 (8.1%)	30,968 (3.3%)	0.209	1000 (8.1%)	925 (7.5%)	0.023	
 Anticonvulsants	2710 (22.0%)	94,051 (10.0%)	0.330	2706 (21.9%)	2710 (22.0%)	0.001	

Patient characteristics at baseline and after PSM

Before PSM, the case group was older than the control group (65.8 ± 13.1 vs. 64.0 ± 14.3 years, respectively). The proportion of men was slightly higher in the case group than in the control group (55.6% vs. 54.7%, respectively; p = 0.093). White patients constituted the majority of both groups, followed by African American patients. The proportion of White patients was higher in the case group than in the control group (51.2% vs. 48.7%, respectively). After PSM, the two groups were well-matched regarding the distribution of demographic variables, comorbidities, and drug usage (standardized differences < 0.1).

Risks of depression and associated symptoms in the study cohort

Table 2 presents the risks of depression, anxiety, and other depression-related symptoms in patients with poststroke aphasia. During the 1-year follow-up period, the incidence rates for the case group and the control group are 44.4 and 28.3 per 1,000 person-years, respectively. The risk of depression was significantly higher in the case group than in the control group (HR: 1.728; 95% CI 1.464–2.038; p < 0.001). However, the risk of anxiety did not differ significantly between the two groups (HR: 1.160; 95% CI 0.969–1.390; p = 0.106). The risks of poor appetite, fatigue, agitation, and emotional impact were significantly higher in the case group than in the control group. However, no significant between-group difference was observed in insomnia or self-harm ideation.Table 2 Depression, anxiety, and other depression-related symptoms in post-stroke aphasia after propensity score matching. *Significant difference with p < 0.001.

	Case
(N = 12,333)	Control
(N = 12,333)	Hazard ratio (95% CI)	P value	
Depression	371	226	1.728 (1.464, 2.038)	 < 0.001*	
Anxiety	249	224	1.160 (0.969, 1.390)	0.106	
Poor appetite	101	75	1.405 (1.042, 1.894)	0.025	
Fatigue	1,009	758	1.392 (1.267, 1.530)	 < 0.001*	
Agitation	217	129	1.714 (1.378, 2.131)	 < 0.001*	
Insomnia	352	322	1.136 (0.977, 1.322)	0.098	
Self-harm ideation	22	17	1.357 (0.720, 2.555)	0.343	
Emotional impact	311	199	1.603 (1.342, 1.916)	 < 0.001*	

Risks of depression and associated symptoms in patients stratified by stroke type

Figure 2 illustrates Kaplan–Meier curves depicting the risks of depression in patients with poststroke aphasia stratified by stroke type. Significant differences were noted in the risks of depression between patients with poststroke aphasia compared to those without aphasia across different stroke types (log-rank test, p < 0.001). Figure 3 revealed the Kaplan–Meier curves depicting depression in post-ischemic-stroke aphasia compared to post-hemorrhagic-stroke aphasia. Figure 4 showed risks of depression and associated symptoms in patients stratified by stroke type. There were 9,456 individuals in both the case and control groups for post-ischemic stroke and 3,158 individuals in both the case and control groups for post-hemorrhagic stroke. The risk of depression was higher in patients with post-hemorrhagic-stroke aphasia than in those with post-ischemic-stroke aphasia (HR: 2.321 [95% CI 1.814–2.970; p < 0.001] and 1.543 [95% CI 1.277–1.865; p < 0.001], respectively). In addition, the risks of fatigue, agitation, and emotional impact were significantly elevated in both groups. Although the risk of poor appetite was significantly higher in the overall case group compared to the control group, subgroup analyses of post-hemorrhagic stroke and post-ischemic stroke revealed no significant difference in poor appetite between both groups. Notably, the risk of anxiety was significantly higher in patients with post-hemorrhagic-stroke aphasia than in those without it (HR: 1.494; 95% CI 1.135–1.967; p = 0.004); however, no significant difference in anxiety risk was observed between patients with post-ischemic-stroke aphasia and those without it. Furthermore, the risk of insomnia was significantly higher in patients with post-hemorrhagic-stroke aphasia than in those without it (HR: 1.480; 95% CI 1.126–1.944; p = 0.005). Depression in post-stroke aphasia before and after PSM stratified by stroke type was presented in Table 3.Fig. 2 The Kaplan–Meier curves depicting depression in post-stroke patients with aphasia compared to those without aphasia after propensity score matching across different stroke types. Upper total stroke patients, Middle: ischemic stroke patients, Lower: hemorrhagic stroke patients.

Fig. 3 The Kaplan–Meier curves depicting depression in post-ischemic-stroke aphasia compared to post-hemorrhagic-stroke aphasia.

Fig. 4 Analysis of depression, anxiety, and other depression-related symptoms in post-stroke aphasia after propensity score matching stratified by ischemic stroke (N = 9,456) and hemorrhagic stroke (N = 3,158). HR Hazard ratio, CI Confidence interval.

Table 3 Depression in post-stroke aphasia before and after propensity score matching stratified by stroke type. *Significant difference with p < 0.001.

	Case#	Control#	Hazard ratio (95% CI)	P value	
Before propensity score matching	
 Total stroke	373/12,337	15,247/963,680	1.918 (1.730, 2.125)	 < 0.001*	
 Ischemic stroke	261/9,460	11,408/708,249	1.773 (1.568, 2.004)	 < 0.001*	
 Hemorrhagic stroke	213/3,160	4,709/240,027	3.151 (2.747, 3.615)	 < 0.001*	
After propensity score matching	
 Total stroke	371/12,333	226/12,333	1.728 (1.464, 2.038)	 < 0.001*	
 Ischemic stroke	261/9,456	182/9,456	1.543 (1.277, 1.865)	 < 0.001*	
 Hemorrhagic stroke	212/3,158	90/3,158	2.321 (1.814, 2.970)	 < 0.001*	
#Due to the statistical settings of TriNetX, each analysis before and after propensity score matching is computed independently, including different time points and subgroup analyses. Although all data were analyzed in July 2024, the numbers for ischemic and hemorrhagic stroke may not perfectly add up to the total stroke count.

Discussion

We investigated the risks of depression and associated symptoms in patients with poststroke aphasia. The risk of depression was significantly higher in patients with poststroke aphasia than in those without it. Regarding depression-related symptoms, the risks of fatigue, agitation, and emotional impact were significantly elevated in patients with poststroke aphasia. Notably, patients with post-hemorrhagic-stroke aphasia were at increased risks of depression, anxiety, and insomnia.

In our study, the risk of depression during the 1-year follow-up period was significantly higher in patients with poststroke aphasia than in those without it. Emotional responses such as sadness and grief are common after poststroke aphasia and other impairments. These responses can hinder recovery, rehabilitation, and psychosocial adjustment28. Patients with poststroke aphasia typically encounter considerable functional limitations and experience reduced quality of life29. Furthermore, communication barriers stemming from poststroke aphasia may exacerbate patients’ emotional distress, compounded by a reluctance among stroke practitioners to offer interventions such as counseling30. The substantially elevated risk of depression in patients with poststroke aphasia highlights the need for addressing not only the physical but also the emotional and psychological consequences of stroke-related impairments.

Our study revealed considerable increases in the risks of fatigue, agitation, and emotional impact in patients with poststroke aphasia. Recent evidence suggests that patients with aphasia frequently experience an increased level of fatigue, which consequently reduces their levels of social engagement and participation20. Fatigue management is crucial for stroke survivors with aphasia; fatigue management strategies often involve medication, exercise, and psychological interventions31–33. Regarding agitation and emotional impact, the inability to control anger and aggressive behaviors is common in patients with aphasia34,35. Angelelli et al. indicated that the risk of agitation is fourfold higher in patients with aphasia than in those without it23. Another study evaluating anger in acute stroke survivors reported that 31% of all patients with poststroke aphasia exhibited irritability and aggression36. Because daily functional communication is impaired in these patients, they may become disheartened, less tolerant, and prone to becoming angry over trivial matters37. To avoid these problems, patients with poststroke aphasia must be evaluated for fatigue, agitation, and emotional impact and treated as necessary.

Our subgroup analysis revealed a strong association between depression risk and post-hemorrhagic-stroke aphasia. In their recent cohort study involving Taiwanese patients, Lin et al. demonstrated that the incidence of depression was higher in patients with poststroke aphasia than in those without it, regardless of sex or stroke type13. Our study, which was conducted using a relatively large database, revealed that the risk of depression was substantially elevated in patients with post-hemorrhagic-stroke aphasia. In a prospective cohort study, Zeng et al. reported that the odds ratio for poststroke depression was 2.65 (95% CI 1.34–5.24; p = 0.005) in patients with intracerebral hemorrhage when compared with those with ischemic stroke7. These findings are corroborated by results. Hemorrhagic strokes may induce biochemical changes in the brain, affecting areas involved in emotional processing, which, combined with a poor quality of life, can lead to depression7,38.

In our subgroup analysis, patients with post-hemorrhagic-stroke aphasia had significantly higher risks of anxiety and insomnia than did those without aphasia. However, no significant difference in the risk of anxiety or insomnia was noted between patients with post-ischemic-stroke aphasia and those without it. A prospective cohort study revealed that the risks of anxiety and insomnia were significantly higher in patients with hemorrhagic stroke than in those with ischemic stroke (61.8% vs. 44.7% [p = 0.006] and 50.1% vs. 31.8% [p = 0.003], respectively)7; these findings are consistent with ours. Another study indicated that anxiety persists throughout the poststroke recovery phase and may be more prevalent in patients with aphasia than in those without it39. Patients with poststroke aphasia develop linguistic anxiety, which is characterized by an abnormal stress response elicited by situations associated with poor language performance. However, the acute state of performance anxiety relative to the symptoms of generalized anxiety disorder remains to be comprehensively explored40. In our study, an end point was the development of anxiety within 1 year after stroke. In the future, the follow-up period should be extended to ≥ 5 years; this is because long-term observations may provide valuable insights into the trajectory and persistence of anxiety following stroke, particularly in patients with aphasia.

Notably, although we excluded patients with pre-existing diagnoses of depression and anxiety, some patients were still taking antidepressants. This may be due to antidepressants being prescribed for other indications, such as chronic pain conditions including back pain, knee osteoarthritis, postoperative pain, fibromyalgia, and neuropathic pain41. Additionally, patients may have experienced depressive or anxiety symptoms without a formal diagnosis. To address this potential confounder, we included antidepressant use in the PSM analysis.

This study has several limitations. First, aphasia can be classified as motor, sensory, or mixed aphasia; such variations make it challenging to perform subgroup analyses. Although we predicted that the risk of depression would be higher in patients with Broca’s aphasia than in those with Wernicke’s aphasia21,42, we could not investigate this notion because of data limitations. Second, although the severity of aphasia may be correlated with the risk of post-stroke depression43, our data does not include information on the severity of aphasia, making it difficult to analyze its relationship with the risk of depression. Third, depression is often diagnosed through language-based assessments, such as questionnaires and verbal interviews; such a diagnostic approach poses major challenges for patients with aphasia. Recent research has focused on developing non-language-based screening tools for depression but is limited by the noninclusion of patients with aphasia44. In the present study, although the conditions were diagnosed using ICD-10-CM codes, we could not ascertain whether depression was evaluated consistently and appropriately in our patients; therefore, the possibility of a bias cannot be eliminated. Future research should consider the development and utilization of more detailed and aphasia-sensitive instruments to better capture the symptomatology in this population. Fourth, stroke severity at baseline, low social support at three months, and loneliness and low satisfaction may be the predictors of psychological distress post stroke45. However, we could not adjust for factors not included in the patients’ electronic health records, such as their scores on the National Institutes of Health Stroke Scale, Barthel Index, modified Rankin Scale, and degree of social support. Fifth, the depression-related symptoms included in this study are also crucial for diagnosing depression, as these symptoms may be integral to the depressive disorder itself. However, distinguishing between depression and depression-related symptoms using ICD-10-CM codes proves challenging. Additionally, it is difficult to determine whether certain symptoms are attributable to the effect of depression or stroke itself. For instance, post-stroke fatigue is an independent symptom and should be differentiated from fatigue associated with post-stroke depression46. Sixth, the prevalence of post-stroke aphasia in our sample, at 1.3%, is significantly lower than the generally reported prevalence of up to one-third. This discrepancy may be attributable to the fact that aphasia is a symptom that is challenging to obligatorily document using standard coding systems, potentially leading to an underestimation of its true prevalence. Seventh, the retrospective nature of this study made it susceptible to potential biases from unadjusted confounders. Finally, we excluded many underlying major psychological diseases, which limited our ability to explore certain aspects. Therefore, a cautious interpretation of the results and consideration of potential uncertainties are imperative for drawing accurate conclusions from our findings.

Despite the aforementioned limitations, our study has several strengths. Very few studies linking depression risk to poststroke aphasia have analyzed data from large databases. The present study was conducted using a large database. We found a substantially high risk of depression in patients with post-hemorrhagic-stroke aphasia. In addition to analyzing the risk of depression, we analyzed those of anxiety and other depression-related symptoms in patients with poststroke aphasia. Future studies may extend the observation period to ≥ 5 years, explore the associations between various mental illnesses and poststroke aphasia, and investigate the correlations between depression-related symptoms and poststroke aphasia.

Conclusion

The risk of depression may be considerably high in patients with poststroke aphasia, particularly those with post-hemorrhagic-stroke aphasia. Patients with aphasia are also at elevated risks of fatigue, agitation, and emotional impact. Furthermore, the risks of anxiety and insomnia are substantially higher in patients with post-hemorrhagic-stroke aphasia than in those without it. In summary, our findings suggest that poststroke aphasia increase the risks of depression and associated symptoms. Therefore, comprehensive psychiatric assessments are necessary for patients with poststroke aphasia.

Supplementary Information

Supplementary Information.

Supplementary Information

The online version contains supplementary material available at 10.1038/s41598-024-72742-z.

Acknowledgements

This manuscript was edited by Wallace Academic Editing. This study was supported by the Shin Kong Wu Ho-Su Memorial Hospital (Grant Number: SKH-8302-103-DR-04).

Author contributions

S.-K.K.: Conceptualization, Methodology, Formal analysis, Writing—Original Draft, Writing—Review & Editing, and Visualization; C.-T.C.: Investigation, Resources, Writing—Review & Editing, Supervision, and Project administration. Both authors have approved the final version of the manuscript.

Data availability

The data that support the findings of this study are available on request from the corresponding author upon reasonable request.

Declarations

Competing interests

The authors declare no competing interests.

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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References

1. Mozaffarian D Heart disease and stroke statistics–2015 update: A report from the American Heart Association Circulation 2015 131 e29 322 10.1161/cir.0000000000000152 25520374
Mozaffarian, D. et al. Heart disease and stroke statistics–2015 update: A report from the American Heart Association. Circulation 131, e29-322. 10.1161/cir.0000000000000152 (2015).25520374 10.1161/cir.0000000000000152
2. Zhou H Wei YJ Xie GY Research progress on post-stroke depression Exp. Neurol. 2024 373 114660 10.1016/j.expneurol.2023.114660 38141804
Zhou, H., Wei, Y. J. & Xie, G. Y. Research progress on post-stroke depression. Exp. Neurol. 373, 114660. 10.1016/j.expneurol.2023.114660 (2024).38141804 10.1016/j.expneurol.2023.114660
3. Shi Y Yang D Zeng Y Wu W Risk factors for post-stroke depression: A meta-analysis Front. Aging Neurosci. 2017 9 218 10.3389/fnagi.2017.00218 28744213
Shi, Y., Yang, D., Zeng, Y. & Wu, W. Risk factors for post-stroke depression: A meta-analysis. Front. Aging Neurosci. 9, 218. 10.3389/fnagi.2017.00218 (2017).28744213 10.3389/fnagi.2017.00218
4. Taylor-Rowan M Prevalence of pre-stroke depression and its association with post-stroke depression: A systematic review and meta-analysis Psychol. Med. 2019 49 685 696 10.1017/s0033291718002003 30107864
Taylor-Rowan, M. et al. Prevalence of pre-stroke depression and its association with post-stroke depression: A systematic review and meta-analysis. Psychol. Med. 49, 685–696. 10.1017/s0033291718002003 (2019).30107864 10.1017/s0033291718002003
5. Mitchell AJ Prevalence and predictors of post-stroke mood disorders: A meta-analysis and meta-regression of depression, anxiety and adjustment disorder Gen. Hosp. Psychiatry 2017 47 48 60 10.1016/j.genhosppsych.2017.04.001 28807138
Mitchell, A. J. et al. Prevalence and predictors of post-stroke mood disorders: A meta-analysis and meta-regression of depression, anxiety and adjustment disorder. Gen. Hosp. Psychiatry 47, 48–60. 10.1016/j.genhosppsych.2017.04.001 (2017).28807138 10.1016/j.genhosppsych.2017.04.001
6. Hackett ML Pickles K Part I: Frequency of depression after stroke: An updated systematic review and meta-analysis of observational studies Int. J. Stroke 2014 9 1017 1025 10.1111/ijs.12357 25117911
Hackett, M. L. & Pickles, K. Part I: Frequency of depression after stroke: An updated systematic review and meta-analysis of observational studies. Int. J. Stroke 9, 1017–1025. 10.1111/ijs.12357 (2014).25117911 10.1111/ijs.12357
7. Zeng YY Comparison of poststroke depression between acute ischemic and hemorrhagic stroke patients Int. J. Geriatr. Psychiatry 2021 36 493 499 10.1002/gps.5444 33108011
Zeng, Y. Y. et al. Comparison of poststroke depression between acute ischemic and hemorrhagic stroke patients. Int. J. Geriatr. Psychiatry 36, 493–499. 10.1002/gps.5444 (2021).33108011 10.1002/gps.5444
8. Brady MC Kelly H Godwin J Enderby P Campbell P Speech and language therapy for aphasia following stroke Cochrane Database Syst. Rev. 2016 2016 Cd000425 10.1002/14651858.CD000425.pub4 27245310
Brady, M. C., Kelly, H., Godwin, J., Enderby, P. & Campbell, P. Speech and language therapy for aphasia following stroke. Cochrane Database Syst. Rev. 2016, Cd000425. 10.1002/14651858.CD000425.pub4 (2016).27245310 10.1002/14651858.CD000425.pub4
9. Lazar RM Boehme AK Aphasia as a predictor of stroke outcome Curr. Neurol. Neurosci. Rep. 2017 17 83 10.1007/s11910-017-0797-z 28929424
Lazar, R. M. & Boehme, A. K. Aphasia as a predictor of stroke outcome. Curr. Neurol. Neurosci. Rep. 17, 83. 10.1007/s11910-017-0797-z (2017).28929424 10.1007/s11910-017-0797-z
10. Thomas SA Lincoln NB Predictors of emotional distress after stroke Stroke 2008 39 1240 1245 10.1161/strokeaha.107.498279 18292381
Thomas, S. A. & Lincoln, N. B. Predictors of emotional distress after stroke. Stroke 39, 1240–1245. 10.1161/strokeaha.107.498279 (2008).18292381 10.1161/strokeaha.107.498279
11. Shehata GA El Mistikawi T Risha AS Hassan HS The effect of aphasia upon personality traits, depression and anxiety among stroke patients J. Affect. Disord. 2015 172 312 314 10.1016/j.jad.2014.10.027 25451431
Shehata, G. A., El Mistikawi, T., Risha, A. S. & Hassan, H. S. The effect of aphasia upon personality traits, depression and anxiety among stroke patients. J. Affect. Disord. 172, 312–314. 10.1016/j.jad.2014.10.027 (2015).25451431 10.1016/j.jad.2014.10.027
12. Pompon RH Associations among depression, demographic variables, and language impairments in chronic post-stroke aphasia J. Commun. Disord. 2022 100 106266 10.1016/j.jcomdis.2022.106266 36150239
Pompon, R. H. et al. Associations among depression, demographic variables, and language impairments in chronic post-stroke aphasia. J. Commun. Disord. 100, 106266. 10.1016/j.jcomdis.2022.106266 (2022).36150239 10.1016/j.jcomdis.2022.106266
13. Lin HL Sung FC Muo CH Chen PC Depression risk in post-stroke aphasia patients: A nationwide population-based cohort study Neuroepidemiology 2023 57 162 169 10.1159/000530070 36972565
Lin, H. L., Sung, F. C., Muo, C. H. & Chen, P. C. Depression risk in post-stroke aphasia patients: A nationwide population-based cohort study. Neuroepidemiology 57, 162–169. 10.1159/000530070 (2023).36972565 10.1159/000530070
14. Dean E Anxiety Nurs. Stand. 2016 30 15 10.7748/ns.30.46.15.s17 27507366
Dean, E. Anxiety. Nurs. Stand. 30, 15. 10.7748/ns.30.46.15.s17 (2016).27507366 10.7748/ns.30.46.15.s17
15. Tiller JW Depression and anxiety Med. J. Aust. 2013 199 S28 31 10.5694/mja12.10628 25370281
Tiller, J. W. Depression and anxiety. Med. J. Aust. 199, S28-31. 10.5694/mja12.10628 (2013).25370281 10.5694/mja12.10628
16. Mao X The impact of insomnia on anxiety and depression: A longitudinal study of non-clinical young Chinese adult males BMC Psychiatry 2023 23 360 10.1186/s12888-023-04873-y 37226120
Mao, X. et al. The impact of insomnia on anxiety and depression: A longitudinal study of non-clinical young Chinese adult males. BMC Psychiatry 23, 360. 10.1186/s12888-023-04873-y (2023).37226120 10.1186/s12888-023-04873-y
17. Engel JH Hardiness, depression, and emotional well-being and their association with appetite in older adults J. Am. Geriatr. Soc. 2011 59 482 487 10.1111/j.1532-5415.2010.03274.x 21391938
Engel, J. H. et al. Hardiness, depression, and emotional well-being and their association with appetite in older adults. J. Am. Geriatr. Soc. 59, 482–487. 10.1111/j.1532-5415.2010.03274.x (2011).21391938 10.1111/j.1532-5415.2010.03274.x
18. Edelkraut L Spectrum of neuropsychiatric symptoms in chronic post-stroke aphasia World J. Psychiatry 2022 12 450 469 10.5498/wjp.v12.i3.450 35433325
Edelkraut, L. et al. Spectrum of neuropsychiatric symptoms in chronic post-stroke aphasia. World J. Psychiatry 12, 450–469. 10.5498/wjp.v12.i3.450 (2022).35433325 10.5498/wjp.v12.i3.450
19. Alghamdi I Ariti C Williams A Wood E Hewitt J Prevalence of fatigue after stroke: A systematic review and meta-analysis Eur. Stroke J. 2021 6 319 332 10.1177/23969873211047681 35342803
Alghamdi, I., Ariti, C., Williams, A., Wood, E. & Hewitt, J. Prevalence of fatigue after stroke: A systematic review and meta-analysis. Eur. Stroke J. 6, 319–332. 10.1177/23969873211047681 (2021).35342803 10.1177/23969873211047681
20. Quique YM Ashaie SA Babbitt EM Hurwitz R Cherney LR Fatigue influences social participation in aphasia: A cross-sectional and retrospective study using patient-reported measures Arch. Phys. Med. Rehabil. 2023 104 1282 1288 10.1016/j.apmr.2023.02.013 36921833
Quique, Y. M., Ashaie, S. A., Babbitt, E. M., Hurwitz, R. & Cherney, L. R. Fatigue influences social participation in aphasia: A cross-sectional and retrospective study using patient-reported measures. Arch. Phys. Med. Rehabil. 104, 1282–1288. 10.1016/j.apmr.2023.02.013 (2023).36921833 10.1016/j.apmr.2023.02.013
21. Mohr B Stahl B Berthier ML Pulvermüller F Intensive communicative therapy reduces symptoms of depression in chronic nonfluent aphasia Neurorehabil. Neural Repair. 2017 31 1053 1062 10.1177/1545968317744275 29192534
Mohr, B., Stahl, B., Berthier, M. L. & Pulvermüller, F. Intensive communicative therapy reduces symptoms of depression in chronic nonfluent aphasia. Neurorehabil. Neural Repair. 31, 1053–1062. 10.1177/1545968317744275 (2017).29192534 10.1177/1545968317744275
22. Siddiqui, W., Gupta, V. & Huecker, M. R. In StatPearls (StatPearls PublishingCopyright © 2024, StatPearls Publishing LLC., 2024).
23. Angelelli P Development of neuropsychiatric symptoms in poststroke patients: A cross-sectional study Acta Psychiatr. Scand. 2004 110 55 63 10.1111/j.1600-0447.2004.00297.x 15180780
Angelelli, P. et al. Development of neuropsychiatric symptoms in poststroke patients: A cross-sectional study. Acta Psychiatr. Scand. 110, 55–63. 10.1111/j.1600-0447.2004.00297.x (2004).15180780 10.1111/j.1600-0447.2004.00297.x
24. Harmer, B., Lee, S., Rizvi, A. & Saadabadi, A. In StatPearls (StatPearls PublishingCopyright © 2024, StatPearls Publishing LLC., 2024).
25. Costanza A "Hard to say, hard to understand, hard to live": possible associations between neurologic language impairments and suicide risk Brain Sci. 2021 10.3390/brainsci11121594 34942896
Costanza, A. et al. “Hard to say, hard to understand, hard to live”: possible associations between neurologic language impairments and suicide risk. Brain Sci.10.3390/brainsci11121594 (2021).34942896 10.3390/brainsci11121594
26. Code C Hemsley G Herrmann M The emotional impact of aphasia Semin. Speech Lang. 1999 20 19 31 10.1055/s-2008-1064006 10100374
Code, C., Hemsley, G. & Herrmann, M. The emotional impact of aphasia. Semin. Speech Lang. 20, 19–31. 10.1055/s-2008-1064006 (1999).10100374 10.1055/s-2008-1064006
27. Wassertheil-Smoller S Polygenic risk for depression increases risk of ischemic stroke: From the stroke genetics network study Stroke 2018 49 543 548 10.1161/strokeaha.117.018857 29438084
Wassertheil-Smoller, S. et al. Polygenic risk for depression increases risk of ischemic stroke: From the stroke genetics network study. Stroke 49, 543–548. 10.1161/strokeaha.117.018857 (2018).29438084 10.1161/strokeaha.117.018857
28. Code C Herrmann M The relevance of emotional and psychosocial factors in aphasia to rehabilitation Neuropsychol. Rehabil. 2003 13 109 132 10.1080/09602010244000291 21854330
Code, C. & Herrmann, M. The relevance of emotional and psychosocial factors in aphasia to rehabilitation. Neuropsychol. Rehabil. 13, 109–132. 10.1080/09602010244000291 (2003).21854330 10.1080/09602010244000291
29. Hilari K The impact of stroke: Are people with aphasia different to those without? Disabil. Rehabil. 2011 33 211 218 10.3109/09638288.2010.508829 20712416
Hilari, K. The impact of stroke: Are people with aphasia different to those without?. Disabil. Rehabil. 33, 211–218. 10.3109/09638288.2010.508829 (2011).20712416 10.3109/09638288.2010.508829
30. Sekhon JK Douglas J Rose ML Current Australian speech-language pathology practice in addressing psychological well-being in people with aphasia after stroke Int. J. Speech Lang. Pathol. 2015 17 252 262 10.3109/17549507.2015.1024170 25936387
Sekhon, J. K., Douglas, J. & Rose, M. L. Current Australian speech-language pathology practice in addressing psychological well-being in people with aphasia after stroke. Int. J. Speech Lang. Pathol. 17, 252–262. 10.3109/17549507.2015.1024170 (2015).25936387 10.3109/17549507.2015.1024170
31. Kirkevold M Christensen D Andersen G Johansen SP Harder I Fatigue after stroke: Manifestations and strategies Disabil. Rehabil. 2012 34 665 670 10.3109/09638288.2011.615373 21995298
Kirkevold, M., Christensen, D., Andersen, G., Johansen, S. P. & Harder, I. Fatigue after stroke: Manifestations and strategies. Disabil. Rehabil. 34, 665–670. 10.3109/09638288.2011.615373 (2012).21995298 10.3109/09638288.2011.615373
32. Nadarajah M Goh HT Post-stroke fatigue: A review on prevalence, correlates, measurement, and management Top. Stroke Rehabil. 2015 22 208 220 10.1179/1074935714z.0000000015 25779764
Nadarajah, M. & Goh, H. T. Post-stroke fatigue: A review on prevalence, correlates, measurement, and management. Top. Stroke Rehabil. 22, 208–220. 10.1179/1074935714z.0000000015 (2015).25779764 10.1179/1074935714z.0000000015
33. De Groot MH Phillips SJ Eskes GA Fatigue associated with stroke and other neurologic conditions: Implications for stroke rehabilitation Arch. Phys. Med. Rehabil. 2003 84 1714 1720 10.1053/s0003-9993(03)00346-0 14639575
De Groot, M. H., Phillips, S. J. & Eskes, G. A. Fatigue associated with stroke and other neurologic conditions: Implications for stroke rehabilitation. Arch. Phys. Med. Rehabil. 84, 1714–1720. 10.1053/s0003-9993(03)00346-0 (2003).14639575 10.1053/s0003-9993(03)00346-0
34. Osa García A Predicting early post-stroke aphasia outcome from initial aphasia severity Front. Neurol. 2020 11 120 10.3389/fneur.2020.00120 32153496
Osa García, A. et al. Predicting early post-stroke aphasia outcome from initial aphasia severity. Front. Neurol. 11, 120. 10.3389/fneur.2020.00120 (2020).32153496 10.3389/fneur.2020.00120
35. Ferro JM Santos AC Emotions after stroke: A narrative update Int. J. Stroke 2020 15 256 267 10.1177/1747493019879662 31581930
Ferro, J. M. & Santos, A. C. Emotions after stroke: A narrative update. Int. J. Stroke 15, 256–267. 10.1177/1747493019879662 (2020).31581930 10.1177/1747493019879662
36. Santos CO Caeiro L Ferro JM Albuquerque R Luísa Figueira M Anger, hostility and aggression in the first days of acute stroke Eur. J. Neurol. 2006 13 351 358 10.1111/j.1468-1331.2006.01242.x 16643312
Santos, C. O., Caeiro, L., Ferro, J. M., Albuquerque, R. & Luísa Figueira, M. Anger, hostility and aggression in the first days of acute stroke. Eur. J. Neurol. 13, 351–358. 10.1111/j.1468-1331.2006.01242.x (2006).16643312 10.1111/j.1468-1331.2006.01242.x
37. Benson DF Psychiatric aspects of aphasia Br. J. Psychiatry 1973 123 555 566 10.1192/bjp.123.5.555 4766654
Benson, D. F. Psychiatric aspects of aphasia. Br. J. Psychiatry 123, 555–566. 10.1192/bjp.123.5.555 (1973).4766654 10.1192/bjp.123.5.555
38. Wen QH Relationship between depression after hemorrhagic stroke and auditory event-related potentials in a Chinese patient group Neuropsychiatr. Dis. Treat. 2022 18 1917 1925 10.2147/ndt.S362824 36065387
Wen, Q. H. et al. Relationship between depression after hemorrhagic stroke and auditory event-related potentials in a Chinese patient group. Neuropsychiatr. Dis. Treat. 18, 1917–1925. 10.2147/ndt.S362824 (2022).36065387 10.2147/ndt.S362824
39. Campbell Burton CA Frequency of anxiety after stroke: A systematic review and meta-analysis of observational studies Int. J. Stroke 2013 8 545 559 10.1111/j.1747-4949.2012.00906.x 23013268
Campbell Burton, C. A. et al. Frequency of anxiety after stroke: A systematic review and meta-analysis of observational studies. Int. J. Stroke 8, 545–559. 10.1111/j.1747-4949.2012.00906.x (2013).23013268 10.1111/j.1747-4949.2012.00906.x
40. Cahana-Amitay D Language as a stressor in aphasia Aphasiology 2011 25 593 614 10.1080/02687038.2010.541469 22701271
Cahana-Amitay, D. et al. Language as a stressor in aphasia. Aphasiology 25, 593–614. 10.1080/02687038.2010.541469 (2011).22701271 10.1080/02687038.2010.541469
41. Micó JA Ardid D Berrocoso E Eschalier A Antidepressants and pain Trends Pharmacol. Sci. 2006 27 348 354 10.1016/j.tips.2006.05.004 16762426
Micó, J. A., Ardid, D., Berrocoso, E. & Eschalier, A. Antidepressants and pain. Trends Pharmacol. Sci. 27, 348–354. 10.1016/j.tips.2006.05.004 (2006).16762426 10.1016/j.tips.2006.05.004
42. Starkstein SE Robinson RG Aphasia and depression Aphasiology 1988 2 1 19 10.1080/02687038808248883
Starkstein, S. E. & Robinson, R. G. Aphasia and depression. Aphasiology 2, 1–19. 10.1080/02687038808248883 (1988).10.1080/02687038808248883
43. Zanella C Laures-Gore J Dotson VM Belagaje SR Incidence of post-stroke depression symptoms and potential risk factors in adults with aphasia in a comprehensive stroke center Top. Stroke Rehabil. 2023 30 448 458 10.1080/10749357.2022.2070363 35543182
Zanella, C., Laures-Gore, J., Dotson, V. M. & Belagaje, S. R. Incidence of post-stroke depression symptoms and potential risk factors in adults with aphasia in a comprehensive stroke center. Top. Stroke Rehabil. 30, 448–458. 10.1080/10749357.2022.2070363 (2023).35543182 10.1080/10749357.2022.2070363
44. Townend E Brady M McLaughlan K A systematic evaluation of the adaptation of depression diagnostic methods for stroke survivors who have aphasia Stroke 2007 38 3076 3083 10.1161/strokeaha.107.484238 17932334
Townend, E., Brady, M. & McLaughlan, K. A systematic evaluation of the adaptation of depression diagnostic methods for stroke survivors who have aphasia. Stroke 38, 3076–3083. 10.1161/strokeaha.107.484238 (2007).17932334 10.1161/strokeaha.107.484238
45. Hilari K Psychological distress after stroke and aphasia: The first six months Clin. Rehabil. 2010 24 181 190 10.1177/0269215509346090 20103578
Hilari, K. et al. Psychological distress after stroke and aphasia: The first six months. Clin. Rehabil. 24, 181–190. 10.1177/0269215509346090 (2010).20103578 10.1177/0269215509346090
46. Chen W Jiang T Huang H Zeng J Post-stroke fatigue: A review of development, prevalence, predisposing factors, measurements, and treatments Front. Neurol. 2023 14 1298915 10.3389/fneur.2023.1298915 38187145
Chen, W., Jiang, T., Huang, H. & Zeng, J. Post-stroke fatigue: A review of development, prevalence, predisposing factors, measurements, and treatments. Front. Neurol. 14, 1298915. 10.3389/fneur.2023.1298915 (2023).38187145 10.3389/fneur.2023.1298915
