Depression,Anxiety,and Stress After Acquired Brain Injury: The Role of Cognitive Reserve in Patients and Caregivers ’Symptoms

Abstract

Objectives

Severe acquired brain injury (sABI) can impact the psychological health not only in patients, but also in their caregivers. The present study was aimed at examining depression, anxiety and stress symptoms in patients with sABI and in their caregivers, exploring differences and correlations between the two, and investigating the role of cognitive reserve as potential predictor of patients and caregiver’s psychological wellbeing.

Methods

Fifty-four individuals (27 patients-caregiver’s dyads) took part in the present study. All patients had a severe injury and data were collected approximately five years post-injury. During a telemedicine assessment, the Depression Anxiety Stress Scale (DASS-21), the Caregiver Burden Inventory (CBI) and the Cognitive Reserve Index questionnaire (CRIq) were administered.

Results

Results show higher levels of anxiety and perceived stress in caregivers, when compared with patients. Significant associations emerged between patients and caregivers’ symptoms of depression and anxiety. Furthermore, cognitive reserve emerged as a significant modulator of caregivers’ emotional burden and depressive symptoms.

Conclusion

Findings highlight the interconnection between patients’ and caregivers’ psychological wellbeing and suggest that cognitive reserve might be considered a predictor of caregivers’ mental health.

Plain Language Summary

After an acquired brain injury, such as a trauma or a stroke, symptoms of depression, anxiety and stress can be present, both in patients and in their family members. The present study focused on those aspects, and involved twenty-sevent patient-caregiver couples, around five years after the brain injury. Results showed that patients and and caregiver's psychological well-being are significantly correlated. Moreover, Cognitive Reserve emerged as significant predictor of emotional burden and depressive symptoms in caregivers.

Keywords

acquired brain injury anxiety stress caregivers burden cognitive reserve

1. Introduction

Severe acquired brain injury (sABI) can have profound consequences on the psychological health of both patients and of their caregivers. In patients, the extensively studied cognitive outcomes^1-3 can be accompanied by the relatively less studied affective sequelae, such as symptoms of depression and anxiety.^4,5 Negative affect symptoms may result directly from brain damage, particularly when it affects frontal circuits, or stem from adaptive and reactive responses to the trauma and its functional long-term consequences.^6,7 Cohort studies and systematic reviews consistently indicate that depression, anxiety, and stress-related disorders are frequently observed 1–10 years following acquired brain injury, irrespective of traumatic or non-traumatic aetiology, with clinically meaningful incidence rates.^6-11 Multiple factors have been shown to influence the onset and persistence of these conditions, including coping style, individual characteristics, severity of injury-related consequences, and premorbid emotional vulnerability.^8,9,12-14

Importantly, sABI affective outcomes can have a considerable impact not only on patients’ recovery, but also on the health of their caregivers.

Indeed, caregivers of people with sABI who experience both physical and psychological sequelae might suffer from the so-called “caregiver burden”, a term referring to the state of prolonged physical, psychological, social, and financial stress experienced by individuals providing care.¹⁵ Indeed, as informal caregivers are typically family members, they not only attend to needs such as hygiene and basic home life activities, but also engage in the challenging task of “renegotiating relationships” in cognitive, emotional, and/or economic family dynamics. The emotional distress that caregivers can feel may also trigger symptoms of depression and anxiety,^16-18 with the label “hidden patients”¹⁹ referring to the need of taking care of both patients and caregivers, rather than only of the first.

Typically, the psychological wellbeing of patients and their caregivers has been investigated separately in the literature,^20-23 with very few studies that have enrolled patients-caregivers’ dyads comparing their level of wellbeing.^18,24,25

Studying patients-caregivers’ dyads is however of crucial importance, as the quality of life of patients and of their families is influenced not only by social and economic factors, but is also determined by the psychological health of both parties, which are closely interconnected and reciprocally influence each other.^26-33

Hence, the first aim of the present study is to investigate the relationship between patients and caregiver’s psychological health, by exploring the association between symptoms of depression, anxiety and stress, and caregiver burden. Our hypothesis is that more severe patients’ affective sequelae would be associated to greater emotional distress and burden in caregivers.

The second aim of the study is to shed light on the predictors of patients and caregivers’ psychological wellbeing, by testing the hypothesis that Cognitive Reserve (CR) might play a role. For the sake of clarity, the concept of CR refers to the individual’s adaptation to the cumulative environmental, biological, behavioural, and psychosocial exposures experienced across the lifespan, which dynamically shapes brain structure through functional brain use and contributes to the brain’s capacity to withstand damage or change.^34,35

Importantly, CR has been traditionally studied in the context of cognitive functions after brain damage, resulting as a factor underlying resilience against cognitive deficits and decline.^2,36,37 Only more recently, CR has been also studied in the context of affective functions, both in healthy individuals, and in clinical and at-risk populations.

Specifically, recent evidence from healthy individuals indicated that CR was positively related to global measures of psychological wellbeing assessing symptoms of depression, anxiety and stress³⁸ Consistently, evidence collected in patients with multiple sclerosis and with chronic migraine indicates that high CR is associated with more favourable affective outcomes, such as lower levels of depression, anxiety, and stress^39-41 Finally, recent evidence collected on caregivers of patients with sABI and with dementia also indicates that CR buffers against stress-related cognitive and emotional disorders^42,43

Hence, in light of these findings, our hypothesis is that CR will be associated with measures of psychological wellbeing in both patients with sABI and their caregivers, such as higher levels of CR will correspond to lower levels of depression, anxiety and stress symptoms, and with lower caregiver burden.

2. Method

2.1. Participants

2.1.1. Patients

Patients were recruited within the group of participants of our previous studies (^1,2), i.e., patients who had been admitted to intensive care rehabilitation centre (Centro Cardinal Ferrari, Fontanellato, Parma, Italy) after an acute neurological event causing altered consciousness for >24 hours (Glasgow Coma Scale⁴⁴ ≤ 8) and discharged after rehabilitation. Inclusion criteria for the present study were: 1) being part of our previous study¹; 2) having a Level of Cognitive Functioning (LCF) of at least 6; 3) providing consent to participate in the present study.

Exclusion criteria were: 1) occurrence of a new neurological disorder or major life event after discharge; 2) having a Level of Cognitive Functioning (LCF) below 6; 3) unavailability to participate and to provide informed consent.

Twenty-seven patients with sABI (7 females; mean age 45.9 ± 14.6 years) participated in the present study. On average, the time elapsed from the brain injury was approximately five years (mean= 5.03/St.dev= 0.8 years; range 4-7 years), and LCF ranged from 6 to 8 (6 patients scored 6; 18 patients scored 7, and 3 patients scored 8). sABI had the following aetiologies: traumatic brain injury (N=14), haemorrhagic stroke (N=7), ischemic stroke (N=3), anoxic damage (N=2), brain tumour (N=1). Other demographical and clinical characteristics of the sample are detailed in Table 1.

Table 1.

Demographics and Clinical Characteristics of Patients and Caregivers

	sABI patients		Caregivers		Mann-whitney U	Hodges-lehmann estimate	95% confidence interval (lower, upper)	p-value	Effect size (rank-biserial correlation)
	Mean (SD)	Range	Mean (SD)	Range	Mann-whitney U	Hodges-lehmann estimate	95% confidence interval (lower, upper)	p-value	Effect size (rank-biserial correlation)
Age	45.9 (14.6)	20-70	56.5 (8.85)	39-72	210	10.000	2000, 17000	0.007**	-.425
Education	13.3 (3.43)	8-21	11.6 (3.7)	5-20	277	-1000	-4000, 0.000	0.122	.247
DASS-21 total score	14.7 (12.2)	0-52	22 (14.7)	0-70	251.5	6000	0.00, 12000	0.051	-.310
DASS-depression	5.48 (5.99)	0-22	6.52 (6.6)	0-26	337	0.00	-2000, 4000	0.636	-.075
DASS-anxiety	2.44 (2.68)	0-10	4.52 (3.62)	0-12	244	2000	0.00, 4000	0.033*	-.331
DASS-stress	6.81 (6.08)	0-26	11.9 (8.21)	0-42	206	4000	2000, 8000	0.006**	-.435
CBI	/	/	14.3 (10.9)	0-46	/			/
CRIq total score	100.78 (12.4)	83-139	103.41 (13.71)	79-130	330	3000	-4000, 10000	0.556	-.108
CRI education	99.41 (11.86)	80-133	101.26 (12.04)	79-131	322	3000	-3000, 9000	0.467	-.139
CRI working activities	101.26 (12.54)	77-135	101.93 (15.97)	74-132	358	1000	-8000, 11000	0.917	-.019
CRI leisure time	100.56 (12.19)	76-122	104.63 (12.43)	85-139	300.5	4000	-3000, 11000	0.917	-.169

Note. SD= standard deviation; *p<.05; ** p<.001; DASS-21= Depression, Anxiety and Stress Scale – 21 items; CBI = Caregiver Burden Inventory; CRIq = Cognitive Reserve Index questionnaire.

2.1.2. Caregivers

Caregivers were recruited within the family members of the patients who agreed to take part in the current study. Inclusion criteria for this group were: 1) being caregiver of a patient taking part in the present study; 2) being available to participate and provide informed consent. Exclusion criteria were: 1) presence of any neurological condition; 2) being unable to participate or provide informed consent.

Twenty-seven family members (19 females; mean age 56.5 ± 8.5 years) acting as caregivers for the involved patients voluntarily participated in the present study. Among them, nine out of 27 (33.3%) were the patients’ parents, 14 were the patients’ partners (51.9%), 2 were the patients’ siblings, and 2 were the patients’ children (7.4%). On average, they had cared for their loved ones for approximately 5.04 ± 0.8 years (range 4-7; median 5). Other demographical and characteristics of the sample are detailed in Table 1.

2.2. Procedure

Patients and their caregivers were contacted by a clinical neuropsychologist member of the research team who explained the study, proposed participation, and assessed inclusion and exclusion criteria. Participants were asked whether any major life event or illness had occurred between discharge and the present follow-up; none reported any significant events or illness. After providing informed consent, both patients and caregivers were invited to participate in a video call, which took place in a quiet environment, ensuring minimal external noise and interruptions and providing the ideal setting for psychological testing. Online data collection has been employed because the study was conducted during the third and fourth COVID-19 pandemic wave in 2021.

The overall data collection lasted approximately three months (from April to June 2021).

2.3. Measures

Affective status of both patients and caregivers was assessed through the Depression Anxiety Stress Scale 21 (DASS-21^45,46). This tool assesses the presence and severity of symptoms of depression, anxiety, and stress, experienced in the last week. It yields three sub-scores, namely DASS-Depression, DASS-Anxiety and DASS-Stress, as well as a total score (DASS-total score), providing a comprehensive index of overall psychological distress. Previous research has supported the validity of the DASS-21 for assessing emotional symptoms in individuals with traumatic brain injury, confirming its suitability as a measure in sABI of traumatic aetiology.^44,47

In the group of caregivers only, levels of burden were assessed though the Caregiver Burden Inventory (CBI⁴⁸), which yields a total score (CBI total) and five sub-scores, related to different burden dimensions: time-dependence, developmental, physical, social, and emotional burden.

In both groups, CR was evaluated through the Cognitive Reserve Index questionnaire (CRIq⁴⁹), which provides a total score (CRI-total) and three sub-scores, reflecting the impact of education (CRI-education), working activities (CRI-working activities), and leisure time activities (CRI-leisure time). The CRIq has been validated in healthy adult samples and has been previously employed in studies involving patients with sABI.^1,2,50 Importantly, the in the patient’s group, CRIq was administered at hospital discharge; hence CRIq scores for this sample were derived from their neuropsychological assessment conducted in our previous study.¹

2.4. Data Analysis

Descriptive statistics were computed for each measure collected in both groups. Results of the Shapiro-Wilk normality test indicated that most of the measures were not normally distributed (p<.05). Hence, non-parametric analyses were conducted. Between-group differences were assessed using Mann-Whitney U and Chi-Square tests, while correlations between measures were assessed through Spearman’s rank correlation coefficient. Main statistical analyses were conducted using JAMOVI software, version 1.6. Effect sizes and 95% confidence intervals were computed in JASP using bootstrap procedures.

3. Results

3.1. Demographic and Clinical Characteristics of the Group of Patients With sABI

As shown in Table 1, the mean age of patients with sABI was 45.8 years (±14.6; range 20 - 70) and their mean education level was 13.3 years (±3.4; range 8 - 21). With regard to educational attainment, 4 patients completed 8 years of formal education, 14 completed between 8 and 13 years, and 9 completed more than 13 years.

Regarding the clinical characteristics of the patients, the data collected with the DASS-21 showed that 11.1% (N=3) reported severe to extremely severe depressive symptoms, 7.4% (N=2) reported mild to moderate depressive symptoms, and the majority (85.2%; N=23) fell within the normal range. As regards anxiety, mild symptoms were observed in one patient (3.7%), with the rest of the sample (96.3%; N=26) scoring within the normal range. Concerning perceived stress (DASS-stress), 11.1% of patients (N=3) showed mild to moderate levels, while none reported severe to extremely severe levels.

3.2. Demographic and Clinical Characteristics of the Group of Caregivers

As shown in Table1, caregivers’ average age was 56.5 years (±8.85; range 39 - 72) and their average education level was 11.6 years (±3.7; range 5 - 20). Regarding educational attainment, 2 caregivers had 5–6 years of education, 7 had 8 years, 13 had 9–13 years, and 5 had more than 13 years of education.

Data collected with the DASS-21 showed that 25.9 % (N=7) reported severe to extremely severe levels of depressive symptoms, 18.5% (N=5) indicated mild to moderate depressive symptoms, while almost half the sample (55.5%; N=15) obtained a score within the normal range (Table 1).

As to anxiety symptoms, severe to extremely severe levels were reported by 29.6% of the sample (N=8), mild to moderate by 37% (N=10), and normal levels by 33.3% (N=9) of caregivers. As concerns perceived stress (DASS-stress), levels were severe to extremely severe in 33.3% of the sample (N= 9), mild to moderate in 44.4% (N=12), and normal in 22.2% (N= 6). Regarding CBI scores, most caregivers (81.5%, N= 22) obtained a normal score, 14.8% (N= 4) could be considered at risk, and only 3.7% (N=1) of caregivers reported burnout (Table 1).

3.3. Comparisons Between Patients’ and Caregivers’ Demographics and Psychological Wellbeing Measures

Comparing the demographics of the two groups, results indicated the presence of a significant difference age, with patients being significantly younger than their caregivers (p <.01), and sex, with the group of caregivers being formed by more females respect to the patient’s group (X² = 10.7; p <.001).

Comparing the standardized psychological measures, results indicate the presence of significant differences in the DASS-anxiety and DASS-stress scores, with caregivers reporting higher levels of anxiety (p <.05) and higher levels of perceived stress (p <.01) when compared with patients. No other difference emerged as significant (details about all the results obtained are reported in Table 1).

3.4. Correlations Between Patients’ and Caregivers’ Psychological Wellbeing

Results of the correlation indicated a significant positive association between patients’ and caregivers’ anxiety levels (Rho = .418; p<.05; Fishers’s Z=.445; 95% Confidence Interval .045, .689), patients’ and caregivers’ depressive symptoms (Rho = .455; p<.05, Fishers’s Z=.490; 95% Confidence Interval .089, .711) as well as between patients’ anxiety and caregivers’ depressive symptoms (Rho = .459; p<.05, Fishers’s Z=.496; 95% Confidence Interval .096, .714). Non-significant correlations emerged between patient’s stress levels and caregiver’s wellbeing, and viceversa (for all, p>.1).

3.5. Correlations Between CR and Psychological Wellbeing of Patients and Caregivers

Results showed the presence of significant associations between CR and psychological wellbeing in caregivers only. Specifically, CRI-leisure time sub-score was negatively correlated with caregivers’ DASS-depression scores, indicating that higher engagement in leisure time activities was associated with lower levels of depressive symptoms (Rho=-.398; p>.05; Fishers’s Z=.-.42; 95% Confidence Interval -.67, -.021; see Figure 1A). On the contrary, scores at the emotional burden CBI subscale were negatively correlated with CRIq scores, namely CRI-education (Rho=.450; p <.05; Fishers’s Z=.485; 95% Confidence Interval .084, -.709; see Figure 1B) and CRI-working activities (Rho=.583; p <.05; Fishers’s Z=.667; 95% Confidence Interval .261, .788 see Figure 1C) indicating that higher levels of education and cognitively demanding jobs were associated with higher levels of emotional caregiver burden. This negative association also emerged when correlating the same CBI subscore (emotional burden) and the CRI-total score (Rho=.574; Fishers’s Z=.654; 95% Confidence Interval .248, .783; p <.05). In the patient group, no significant associations were observed between CR and psychological wellbeing measures.

Figure 1.

Panel A: Significant relationship between Cognitive Reserve Index (CRI) Leisure time activity and depressive symptoms (DASS_depression subscale) in caregivers; Panel B: Significant relationship between Cognitive Reserve Index Working activity and emotional caregiver burden; Panel C: Significant relationship between Cognitive Reserve Index Education and emotional caregiver burden

4. Discussion

In this study, we delved into the long-term psychological wellbeing of patients with sABI and of their caregivers, aiming to explore the reciprocal influence between the two groups, and to assess the role of CR as a psychological protective factor against symptoms of depression, anxiety, stress, and caregiver burden.

To achieve these goals, we recruited 27 patients with sABI in their chronic phase, i.e., approximately 5 years after the event, together with their 27 caregivers.

Employing standardized psychometric tools, we collected data on stress, anxiety, depressive symptoms, caregiver burden, and CR, and we aimed at assessing differences and correlations between the two groups, and at exploring the association between CR and psychological wellbeing measures in each group. Results will be discussed addressing these two main aims.

4.1. Psychological Wellbeing of Patients With sABI and Their Caregivers: Differences and Correlations

Our first set of findings revealed that most patients with sABI obtained scores within the normal range for depressive and anxiety symptoms, and for perceived stress. These results are both consistent and in contrast with previous studies. Specifically, they are in line with evidence reporting normal levels of depression and anxiety symptoms five years post-injury in patients with persisting concussion symptoms.^51,52 However, they are not consistent with evidence from cohort studies and systematic reviews reporting clinically relevant levels of depression, anxiety, and stress-related disorders in patients with ABI, both in the short and in the long-term.^7,8,10,53 These discrepancies may be attributed to sample characteristics (including ABI severity, aetiology, age and clinical history), to the psychometric instruments employed, as well as to the diagnostic criteria and follow-up time of each studies. Moreover, our results might be explained by a potential reduced level of insight and self-awareness that sABI patients might present, despite we did not formally assess awareness in the present study. This hypothesis, however, might be compatible with the results we have obtained in the assessment of caregivers’ psychological wellbeing, and in the comparison between patients and caregivers.

Indeed, results of the present study also show that caregivers revealed more depressive and anxiety symptoms, and higher levels of perceived stress than the patient they cared for, ranging from mild to extremely severe levels. This is in line the with literature on caregivers of patients with sABI, which consistently reports high rates of affective disorders and stress, although also in this case percentages vary depending on aetiology, follow-up, and measurement instruments.^54-57 Moreover, this is in line with the above-mentioned hypothesis of a reduced awareness in sABI patients. Indeed, it is well documented that, in people with ABI, the ability to estimate their own capabilities might be altered,^58,59 with severity of brain damage being negatively associated with disease awareness. Furthermore, while greater disease awareness may increase anxiety and depressive symptoms,⁶⁰ the presence of anosognosia is related to less frequent negative affect manifestations.^59,61

On the contrary, caregivers are often more aware of patients’ disorders, and for this reason might experience higher stress and affective disorders when compared with patients^24, Moreover, patients’ impaired self-awareness is suggested to be associated with increased family members’ distress and caregiver burden.^62,63 Despite we did not collect data on self and disease-awareness, this set of evidence might provide a valid explanation for our results, which showed lower levels of psychological wellbeing in caregivers, when compared with patients.

Importantly, caregiver burden levels were generally low in our sample, with the majority of family caregivers who did not obtain clinically significant scores on the CBI. This result might appear in contradiction with a recent study conducted employing the same tool and in caregivers of patients with mild/moderate ABI, which reported high levels of burden two years after injury.⁶² However, despite the difference in ABI severity, the discrepancy between our results and this previous study may be attributable to the different time-window considered, with longer follow-up time employed in the current study being associated with lower lever of burden.

At the same time, we need to be cautious in interpreting this result, as the relatively low scores obtained at the CBI are not in line either with the ones obtained at the DASS-21 from the same participants. Specifically, while only five family members showed significant burden, DASS-21 data revealed clinically relevant anxiety, depression, and stress symptoms in at least half of the sample. Hence, this discrepancy between CBI and DASS-21 scores obtained in the caregivers group suggest caution in the interpretation of CBI scores and highlights the importance of using multiple, validated instruments in long-term assessments of psychological wellbeing of caregivers. Indeed, the CBI alone might be not sensitive enough to detect the complexity of emotional distress in this sample, which DASS-21 seems to have better detected. Indeed, the existing literature confirms the enduring psychological impact of caregiving a patient with ABI,^64-66 suggesting similarities in the psychological impact on family members of acute injuries and chronic neurological conditions, such Parkinson’s disease, or dementias.^67-71 Results of the present study also revealed the presence of significant correlations between patients’ and caregivers’ psychological wellbeing. Specifically, significant positive association emerged between patients’ and caregivers’ anxiety levels, patients’ and caregivers’ depressive symptoms, and patients’ anxiety and caregivers’ depressive symptoms. This reciprocal influence may be attributed to the intricate dynamics of the physical and emotional care relationship,⁷² and is coherent with previous evidence showing an association between the psychological state of caregivers and the affective outcomes in patients with cancer and dementia.^73,74 Despite correlations cannot speak about directionality of the relationships that emerged, results confirm the hypothesis of a reciprocal influence between patients and caregiver’s affective status, highlighting the importance of considering the patients-caregivers dyad, rather than the two groups separately, both in the short and in the long-term assessment and management of sABI consequences.

4.2. CR and Psychological Wellbeing of Patients With sABI and Their Caregivers

Our second set of findings indicates the presence of an association between CR and psychological wellbeing, even if only in the group of caregivers and not in patients with sABI.

Specifically, our results highlight the differential role that distinct dimensions of CR can have in predicting different aspects of psychological functioning.

Indeed, the leisure-time dimension of the CRIq was negatively associated with caregivers’ depressive symptoms. This is in line with Behavioural Activation Therapy principles: being engaged in activities rather than remaining inactive improves mood and typically reduces symptoms in people with depression thanks to positive reinforcement processes. This finding confirms the protective role of diverse and enriching experiences against depressive symptoms, laying the groundwork for the development of functional coping skills, facilitating adaptation to the outcomes of pathology, and encouraging caregivers to look for social support.^75-78

On the contrary, other aspects related to CR seems to play a different role in emotional burden, which resulted to be higher in individuals with high levels of education and who are engaged in cognitively demanding jobs.

This set of results, which apparently are in contrast with each other, can indeed been explained by examining more in depth the changes that the caregiving role might bring in lifestyle and daily habits.^79,80 Specifically, individuals who remain actively employed in high-level positions while facing caregiving demands may experience higher levels of burden, with jobs that are typically characterized by greater responsibilities and longer working hours that might prevent them engaging in leisure time activities.

Conversely, those who are able to devote part of their free time to enriching and stimulating activities may be protected against the development of negative affective manifestations.

Finally, individuals with higher levels of education may not only be more frequently engaged in high-level occupations, but may also have greater awareness of both their own difficulties and those of the patient, thereby experiencing a greater emotional burden.

Overall, our data suggest to further explore the role of CR, and of its different proxies, as a modulating factor of affective functioning and caregiver burden, suggesting differential roles of education, working and leisure time activities.

The lack of significant correlations between CR and affective symptoms in the patient group may, at least in part, reflect the potential underestimation of self-reported wellbeing due to the above hypothesized diminished insight and self- and disease-awareness. However, new evidence will need to be collected to further explore this relationship.

4.3. Limitations and Future Directions

When interpreting our results, some limitations need to be considered. First, the relatively small sample size and the heterogeneity in terms of brain injury aetiology represent important limitations of the study, which might limit generalizability. Specifically, we included both traumatic and non-traumatic aetiologies, despite they might be associated with distinct forms of affective outcomes and different risk factors for emotional distress. These limitations should be addressed in future studies by considering larger samples that will allow to conduct stratified analyses for different aetiologies.

Second, the use of psychometric tools that were not specifically developed for ABI patients and caregivers. Although these instruments were chosen due to their widespread use in clinical studies conducted in the Italian population, and their previous employment in studies involving patients with ABI and their caregivers, the fact that those instruments were not specifically developed for these populations may have at least partially affected the methodological reliability of our results.

Hence, future studies will be needed to replicate and confirm our findings.

Last, the cross-sectional design employed prevents us from drawing causal inferences about the relationship between CR and psychological wellbeing, as well as about the relationship between patients and caregiver affective status. Longitudinal studies will be needed to disentangle these dynamics and assess the evolution of affective symptoms over time.

5. Conclusions

This study highlights the importance of examining patients and caregivers as a psychologically interdependent dyad in the context of chronic sABI. Our findings emphasize the need of a thorough examination of caregiver wellbeing and provide preliminary evidence of the differential association between proxies of CR, burden and emotional distress in caregivers.

Footnotes

ORCID iDs

Debora Bertoni

Elisa Di Rosa

Ethical Considerations

The study was conducted in accordance with the Declaration of Helsinki. Ethical approval was obtained from the Ethics Committee of the School of Psychology, University of Padua (protocol n.4028).

Consent to Participate

Written informed consent was obtained from all participants involved in the study. For participants with cognitive impairments, consent was also obtained from their legal guardians.

Consent for Publication

No individual participant data are included that would require consent for publication.

Author Contributions

All authors conceptualized the study. D.B., B.B. and E.D.R. designed the methodology. D.B. collected the data. S.M. and A.DT. supervised the overall research process. E.DR. analyzed the data. D.B., S.M. and E.DR. wrote the first draft of the manuscript. S.M., B.B. and A.DT contributed to data interpretation and critically revised the manuscript for important intellectual content. All authors reviewed, edited, and approved the final version of the manuscript.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Data Availability Statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.*

References

Bertoni

Petraglia

Basagni

, et al. Cognitive reserve index and functional and cognitive outcomes in severe acquired brain injury: A pilot study. Applied Neuropsychology: Adult. 2022;29(4): 684-694. doi:10.1080/23279095.2020.1804910.

Basagni

Di Rosa

Bertoni

Mondini

De Tanti

. Long term effects of severe acquired brain injury: A follow-up investigation on the role of cognitive reserve on cognitive outcomes. Appl Neuropsychol Adult. 2025;32(1): 162-167. doi:10.1080/23279095.2022.2160251.

Avesani

Roncari

Khansefid

, et al. The Italian National Registry of severe acquired brain injury: epidemiological, clinical and functional data of 1469 patients. Eur J Phys Rehabil Med. 2013;49(5):611-618.

Gómez-de-Regil

Estrella-Castillo

Vega-Cauich

. Psychological intervention in traumatic brain injury patients. Behavioural neurology. 2019;2019:6937832. doi:10.1155/2019/6937832.

Molaie

Maguire

. Neuroendocrine abnormalities following traumatic brain injury: an important contributor to neuropsychiatric sequelae. Frontiers in Endocrinology. 2018;9:176. doi:10.3389/fendo.2018.00176.

Igoe

Twomey

Allen

, et al. Psychological outcomes following moderate-to-severe acquired brain injury: A longitudinal study. Appl Neuropsychol Adult. 2025;16:1-10. doi:10.1080/23279095.2025.2513620. Epub ahead of print. PMID: 40521926.

Singh

Humphries

Dawson

Tiupin-Szulc

Mason

Lecky

. Changes in depression symptoms over 10 years after TBI; a long-term prospective study. Brain Inj. 2025;39(2):154-161. doi:10.1080/02699052.2024.2413639. Epub 2024 Oct 13. PMID: 39396206.

Carmichael

Hicks

Gould

Ponsford

Spitz

. Ten-Year Cohort Study of Emotional Distress Trajectories After Moderate-Severe Traumatic Brain Injury. Arch Phys Med Rehabil. 2023;104(7):1081-1090. doi:10.1016/j.apmr.2023.02.008. Epub 2023 Mar 4. PMID: 36878378.

Scholten

Haagsma

Cnossen

Olff

van Beeck

Polinder

. Prevalence of and Risk Factors for Anxiety and Depressive Disorders after Traumatic Brain Injury: A Systematic Review. J Neurotrauma. 2016;33(22):1969-1994. doi:10.1089/neu.2015.4252. Epub 2016 Apr 29. PMID: 26729611.

10.

Naghedi

Delgado-Mederos

Vives-Bauza

. Stroke Survivors Have Almost Three Times Higher Risk of Depression: A Systematic Review and Meta-Analysis. J Clin Med. 2025;14(23):8410. doi:10.3390/jcm14238410. PMID: 41375712; PMCID: PMC12693352.

11.

Janssen

EPJ

Spauwen

PJJ

Bus

BAA

Rijnen

SJM

Ponds

RWHM

. Prevalence of posttraumatic stress disorder after stroke: A systematic literature review. J Psychosom Res. 2024;187:111914. doi:10.1016/j.jpsychores.2024.111914. Epub 2024 Sep 3. PMID: 39306898.

12.

Cole

Bailie

. Neurocognitive and Psychiatric Symptoms following Mild Traumatic Brain Injury. In: Laskowitz

Grant

, eds. Translational Research in Traumatic Brain Injury. Boca Raton (FL): CRC Press/Taylor and Francis Group; 2016. Chapter 19.

13.

Torregrossa

Raciti

Rifici

, et al. Behavioral and Psychiatric Symptoms in Patients with Severe Traumatic Brain Injury: A Comprehensive Overview. Biomedicines. 2023;11(5):1449. doi:10.3390/biomedicines11051449. PMID: 37239120; PMCID: PMC10216807.

14.

Liu

. Risk factors for psychiatric disorders following traumatic brain injury: a multivariate logistic regression analysis. Front Psychiatry. 2024;15:1499894. doi:10.3389/fpsyt.2024.1499894. PMID: 39664324; PMCID: PMC11631929.

15.

Gwyther

George

. Caregivers for dementia patients: complex determinants of wellbeing and burden. Gerontologist. 1986;26(3):245-266. doi:10.1093/geront/26.3.245.

16.

Norup

Welling

Qvist

Siert

Mortensen

. Depression, anxiety and quality-of-life among relatives of patients with severe brain injury: the acute phase. Brain Injury. 2012;26(10):1192-1200. doi:10.3109/02699052.2012.672790.

17.

Norup

Petersen

Mortensen

. Relatives of patients with severe brain injury: Growth curve analysis of anxiety and depression the first year after injury. Brain injury. 2015;29(7-8):822-829. doi:10.3109/02699052.2015.1016451.

18.

Ponsford

Schönberger

. Family functioning and emotional state two and five years after traumatic brain injury. Journal of the international neuropsychological society. 2010;16(2):306-317. doi:10.1017/S1355617709991342.

19.

Roche

Palmer

. The hidden patient: addressing the caregiver. The American journal of the medical sciences. 2009;337(3):199-204. doi:10.1097/MAJ.0b013e31818b114d.

20.

Williams

. An updated model of perceived stress in caregivers for acquired brain injury. Drexel University; 2023.

21.

Butler

. How People Make Sense of their Partner’s Cognitive and Emotional Difficulties Following Acquired Brain Injury. United Kingdom: Lancaster University; 2022.

22.

McIntyre

Rice

Janzen

, et al. Anxiety, depression, and quality of life among subgroups of individuals with acquired brain injury: The role of anxiety sensitivity and experiential avoidance. NeuroRehabilitation. 2020;47(1):45-53. doi:10.3233/NRE-203080.

23.

Nelson

Temkin

Barber

, et al. Functional Recovery, Symptoms, and Quality of Life 1 to 5 Years After Traumatic Brain Injury: Findings From the TRACK-TBI Study. JAMA Netw Open. 2023;6(3):e233660. doi:10.1001/jamanetworkopen.2023.3660.

24.

Formisano

Longo

Azicnuda

, et al. Quality of life in persons after traumatic brain injury as self-perceived and as perceived by the caregivers. Neurological Sciences. 2017;38:279-286. doi:10.1007/s10072-016-2755-y.

25.

Smeets

van Heugten

Geboers

Visser-Meily

Schepers

. Respite Care After Acquired Brain Injury: The Wellbeing of Caregivers and Patients. Archives of Physical Medicine and Rehabilitation. 2012;93(5):834-841. doi:10.1016/j.apmr.2011.10.029.

26.

Guldager

Nordentoft

Poulsen

Aadal

Loft

. Wants and needs for involvement experienced by relatives of patients with an acquired brain injury: a scoping review. JBI evidence synthesis. 2023;21(5):886-912. doi:10.11124/JBIES-22-00022.

27.

Allonsius

de Kloet

van Markus-Doornbosch

Vliet Vlieland

TPM

Van Der Holst

. A longitudinal follow-up study of parent-reported family impact and quality of life in young patients with traumatic and non-traumatic brain injury. Disability and rehabilitation. 2024;46(11): 2240-2250. doi:10.1080/09638288.2023.2218657.

28.

Giovanis

Menon

Perali

. Disability specific equivalence scales: a case–control approach applied to the cost of acquired brain injuries. International Journal of Health Economics and Management. 2023;23(4):643-672. doi:10.1007/s10754-022-09332-x.

29.

Norman

Curro

Holloway

Percuklievska

Ferrario

. Experiences of individuals with acquired brain injury and their families interacting with community services: a systematic scoping review. Disability and rehabilitation. 2023;45(4):739-751. doi:10.1080/09638288.2022.2043465.

30.

Bivona

Azicnuda

Rapiti

Silvestro

. Psycho-educational intervention on caregivers within the rehabilitation process: From the post-acute to the homecoming phases. In: Diagnosis and Treatment of Traumatic Brain Injury. Academic Press; 2022:531-541.

31.

Acord-Vira

Davis

Boyd

Wheeler

. Relationship Building Interventions for Caregivers of Adults With Traumatic Brain Injury (2013-2020). Am J Occup Ther. 2022;76(Suppl 2):7613393110. doi:10.5014/ajot.2022/76S2011.

32.

Rickardsson

Scotland

Poveda

Gillanders

. Caring for someone with an acquired brain injury: The role of psychological flexibility. Journal of Contextual Behavioral Science. 2022;23:151-164.

33.

Bivona

Villalobos

De Luca

, et al. Psychological status and role of caregivers in the neuro-rehabilitation of patients with severe Acquired Brain Injury (ABI). Brain Inj. 2020;34(13-14):1714-1722.

34.

Verkhratsky

Zorec

. Neuroglia in cognitive reserve. Mol Psychiatry. 2024;29(12):3962-3967. doi:10.1038/s41380-024-02644-z. Epub 2024 Jul 2. PMID: 38956370; PMCID: PMC11609093.

35.

Stern

. What is cognitive reserve? Theory and research application of the reserve concept. Journal of the international neuropsychological society. 2002;8(3):448-460.

36.

Fraser

Downing

Biernacki

McKenzie

Ponsford

. Cognitive reserve and age predict cognitive recovery after mild to severe traumatic brain injury. Journal of neurotrauma. 2019;36(19):2753-2761. doi:10.1089/neu.2019.6430.

37.

Nunes

Silva Nunes

. The influence of cognitive reserve in the protection of the cognitive status after an acquired brain injury: A systematic review. Journal of clinical and experimental neuropsychology. 2021;43(9):839-860. doi:10.1080/13803395.2021.2014788.

38.

Porricelli

Tecilla

Pucci

Di Rosa

Mondini

Cappelletti

. Cognitive reserve modulates mental health in adulthood. Aging Clinical and Experimental Research. 2024;36(1):139.

39.

Biasi

Taurisano

Manni

, et al. The protective role of cognitive reserve in moderating depressive symptomatology in patients with multiple sclerosis. BMC Psychol. 2025;13(1):843. doi:10.1186/s40359-025-03162-5. PMID: 40722207; PMCID: PMC12306131.

40.

Cancino

Rehbein-Felmer

Ortiz

. Funcionamiento cognitivo en adultos mayores: rol de la reserva cognitiva, apoyo social y depresión [Cognitive reserve, depression and social support. Analysis of 206 older adults]. Rev Med Chil. 2018;146(3):315-322. doi:10.4067/s0034-98872018000300315. PMID: 29999101.

41.

Chen

Wang

. Cognitive Reserve and Its Associations with Pain, Anxiety, and Depression in Patients with Chronic Migraine: A Retrospective Study. J Clin Med. 2025;14(15):5193. doi:10.3390/jcm14155193. PMID: 40806814; PMCID: PMC12347591.

42.

Formica

La Face

Buono

, et al. Factors related to cognitive reserve among caregivers of severe acquired brain injury. Journal of Clinical Neuroscience. 2020;77:94-97. doi:10.1016/j.jocn.2020.05.027.

43.

Pertl

Hannigan

Brennan

Robertson

Lawlor

. Cognitive reserve and self-efficacy as moderators of the relationship between stress exposure and executive functioning among spousal dementia caregivers. Int Psychogeriatr. 2017;29(4):615-625. doi:10.1017/S1041610216002337.

44.

Randall

Thomas

Whiting

McGrath

. Depression Anxiety Stress Scales (DASS-21): Factor Structure in Traumatic Brain Injury Rehabilitation. J Head Trauma Rehabil. 2017;32(2):134-144. doi:10.1097/HTR.0000000000000250. PMID: 27455437.

45.

Lovibond

. The structure of negative emotional states: Comparison of the Depression Anxiety Stress Scales (DASS) with the Beck Depression and Anxiety Inventories. Behaviour research and therapy. 1995;33(3):335-343. doi:10.1016/0005-7967(94)00075-u.

46.

Bottesi

Ghisi

Altoè

Conforti

Melli

Sica

. The Italian version of the Depression Anxiety Stress Scales-21: Factor structure and psychometric properties on community and clinical samples. Comprehensive psychiatry. 2015;60:170-181. doi:10.1016/j.comppsych.2015.04.005.

47.

Dahm

Wong

Ponsford

. Validity of the Depression Anxiety Stress Scales in assessing depression and anxiety following traumatic brain injury. J Affect Disord. 2013;151(1):392-396. doi:10.1016/j.jad.2013.06.011. Epub 2013 Jul 4. PMID: 23830002.

48.

Novak

Guest

. Application of a multidimensional caregiver burden inventory. The gerontologist. 1989;29(6):798-803. doi:10.1093/geront/29.6.798.

49.

Nucci

Mapelli

Mondini

. Cognitive Reserve Index questionnaire (CRIq): a new instrument for measuring cognitive reserve. Aging clinical and experimental research. 2012;24(3):218-226. doi:10.3275/7800.

50.

Hakiki

Pancani

Romoli

, et al. Cognitive reserve index and long-term disability in patients with severe traumatic brain injury discharged from the intensive rehabilitation unit. Front Neurol. 2023;14:1106989. doi:10.3389/fneur.2023.1106989.

51.

Doroszkiewicz

Gold

Green

Tartaglia

Tator

. Anxiety, Depression, and Quality of Life: A Long-Term Follow-Up Study of Patients with Persisting Concussion Symptoms. J Neurotrauma. 2021;38(4):493-505. doi:10.1089/neu.2020.7313.

52.

Heath

Kidwai

Colella

, et al. Predictors and Functional Outcomes Associated With Longitudinal Trajectories of Anxiety and Depression from 2 to ≥36 Months After Moderate to Severe Traumatic Brain Injury. J Neurotrauma. 2023;40(21-22):2311-2320. doi:10.1089/neu.2023.0003. Epub 2023 May 5. PMID: 36927109.

53.

Delmonico

Theodore

Sandel

Armstrong

Camicia

. Prevalence of depression and anxiety disorders following mild traumatic brain injury. PM R. 2022;14(7):753-763. doi:10.1002/pmrj.12657.

54.

Özcan

Gürçay

Kalem Özgen

Demir

. Outcomes and predictors of stress among Turkish family caregivers of patients with acquired brain injury. Appl Neuropsychol Adult. 2024;31(6):1225-1233. doi:10.1080/23279095.2022.2115909. Epub 2022 Sep 8. PMID: 36075221.

55.

Kreutzer

Rapport

Marwitz

, et al. Caregivers' wellbeing after traumatic brain injury: a multicenter prospective investigation. Arch Phys Med Rehabil. 2009;90(6):939-946. doi:10.1016/j.apmr.2009.01.010. PMID: 19480869.

56.

Sander

Maestas

Clark

Havins

. Predictors of Emotional Distress in Family Caregivers of Persons with Traumatic Brain Injury: A Systematic Review. Brain Impairment. 2013;14(1):113-129. doi:10.1017/BrImp.2013.12.

57.

Ennis

Rosenbloom

Canzian

Topolovec-Vranic

. Depression and anxiety in parent versus spouse caregivers of adult patients with traumatic brain injury: a systematic review. Neuropsychol Rehabil. 2013;23(1):1-18. doi:10.1080/09602011.2012.712871. Epub 2012 Aug 17. PMID: 22897335.

58.

Dromer

Kheloufi

Azouvi

. Impaired self-awareness after traumatic brain injury: A systematic review. Part 2. Consequences and predictors of poor self-awareness. Annals of Physical and Rehabilitation Medicine. 2021;64(5):101542. doi:10.1016/j.rehab.2021.

59.

Bivona

Costa

Contrada

, et al. Depression, apathy and impaired self-awareness following severe traumatic brain injury: a preliminary investigation. Brain Inj. 2019;33(9):1245-1256. doi:10.1080/02699052.2019.1641225.

60.

Lambert

Sheldrake

Deneault

Wheeler

Burke

Scratch

. Depressive Symptoms in Individuals With Persistent Postconcussion Symptoms: A Systematic Review and Meta-Analysis. JAMA Netw Open. 2022;5(12):e2248453. doi:10.1001/jamanetworkopen.2022.48453.

61.

Smeets

Vink

Ponds

Winkens

van Heugten

. Changes in impaired self-awareness after acquired brain injury in patients following intensive neuropsychological rehabilitation. Neuropsychological rehabilitation. 2017;27(1):116-132. doi:10.1080/09602011.2015.1077144.

62.

McCabe

Sica

Doody

Fortune

. Self-awareness and quality of relationships after acquired brain injury: Systematic review without meta-analysis (SWiM). Neuropsychol Rehabil. 2023;12:1-27. doi:10.1080/09602011.2023.2186437.

63.

Rubin

Klonoff

Perumparaichallai

. Does self-awareness influence caregiver burden? NeuroRehabilitation. 2020;46(4):511-518. doi:10.3233/NRE-203093.

64.

Laratta

Lucca

Tonin

Cerasa

. Factors influencing burden in spouse‐caregivers of patients with chronic‐acquired brain injury. BioMed research international. 2020;2020(1):6240298.

65.

Walker

Schlebusch

Gaede

. The impact of stress on depression, ill health and coping in family members caring for patients with acquired brain injury. South African Family Practice. 2020;62(4):e1-e6. doi:10.4102/safp.v62i1.5149.

66.

Yan

Cai

, et al. Mood assessments of family caregivers of patients with severe brain injury in China. Quality of Life Research. 2023;33:1-10. doi:10.1007/s11136-023-03539-2.

67.

Auclair-Pilote

Lalande

Tinawi

Feyz

De Guise

. Satisfaction of basic psychological needs following a mild traumatic brain injury and relationships with post-concussion symptoms, anxiety, and depression. Disability and rehabilitation. 2021;43(4):507-515. doi:10.1080/09638288.2019.1630858.

68.

Tramonti

Bonfiglio

Bongioanni

, et al. Caregiver burden and family functioning in different neurological diseases. Psychol Health Med. 2019;24(1):27-34. doi:10.1080/13548506.2018.1510131. Epub 2018 Aug 24. PMID: 30141703.

69.

Chen

Zou

Teng

, et al. A systematic review and meta-analysis of psychological burden in family caregivers of patients with brain tumors. Sci Rep. 2025;15:39694. doi:10.1038/s41598-025-23331-1.

70.

Pugh

McCoy

Williams

Pienaar

Bentley

Monterosso

. Neurological patient and informal caregiver quality of life, and caregiver burden: A cross-sectional study of postdischarge community neurological nursing recipients. Contemp Nurse. 2022;58(2-3):138-152. doi:10.1080/10376178.2022.2086892. Epub 2022 Aug 17. PMID: 35670272.

71.

Vescovelli

Ruini

. The wellbeing and burden of caregiving for patients with Parkinson's disease. Scand J Caring Sci. 2022;36(1):49-58. doi:10.1111/scs.12962. Epub 2021 Feb 9. PMID: 33559921.

72.

Schönberger

Ponsford

Olver

Ponsford

. A longitudinal study of family functioning after TBI and relatives' emotional status. Neuropsychol Rehabil. 2010;20(6):813-829. doi:10.1080/09602011003620077.

73.

Ketcher

Otto

Vadaparampil

Heyman

Ellington

Reblin

. The Psychosocial Impact of Spouse-Caregiver Chronic Health Conditions and Personal History of Cancer on Wellbeing in Patients With Advanced Cancer and Their Caregivers. J Pain Symptom Manage. 2021;62(2):303-311. doi:10.1016/j.jpainsymman.2020.12.008. Epub 2020 Dec 19. PMID: 33348028; PMCID: PMC8213866.

74.

Safavi

Wearden

Berry

. Psychological wellbeing in persons with dementia: The role of caregiver expressed emotion. Br J Clin Psychol. 2023;62(2):431-443. doi:10.1111/bjc.12416. Epub 2023 Feb 24. PMID: 36840348.

75.

Martell

Addis

Jacobson

. Depression in context: Strategies for guided action. WW Norton & Co; 2001.

76.

Kusec

Methley

Murphy

Peers

Carmona

Manly

. Developing behavioural activation for people with acquired brain injury: a qualitative interpretive description study of barriers and facilitators to activity engagement. BMC psychology. 2023;11(1):207. doi:10.1186/s40359-023-01230-2.

77.

Zabihi

Lemmel

Orgeta

. Behavioural Activation for Depression in Informal Caregivers: A Systematic Review and Meta-Analysis of Randomised Controlled Clinical Trials. Journal of affective disorders. 2020;274:1173-1183. doi:10.1016/j.jad.2020.03.124.

78.

Oates

Moghaddam

Evangelou

das Nair

. Behavioural activation treatment for depression in individuals with neurological conditions: a systematic review. Clinical rehabilitation. 2020;34(3):310-319. doi:10.1177/0269215519896404.

79.

Bermejo-Toro

Sánchez-Izquierdo

Calvete

Roldán

. Quality of life, psychological wellbeing, and resilience in caregivers of people with acquired brain injury (ABI). Brain Injury. 2020;34(4):480-488. doi:10.1080/02699052.2020.1725127.

80.

D’Ippolito

Aloisi

Azicnuda

, et al. Changes in Caregivers Lifestyle after Severe Acquired Brain Injury: A Preliminary Investigation. Biomed Res Int. 2018;3:2824081. doi:10.1155/2018/2824081.