Caregiver burden and quality of life associated with behavioral and psychological symptoms of Alzheimer's disease: A web-based cross-sectional survey study

Abstract

Background

Behavioral and psychological symptoms of dementia (BPSD) in patients with Alzheimer's disease (AD) may seriously impact caregiver burden and, therefore, quality of care.

Objective

To clarify the association of BPSD and BPSD subtypes with caregiver burden and quality of life (QOL) among caregivers of patients with AD in Japan in a multidimensional manner.

Methods

This descriptive, cross-sectional, community-based survey involved administering a web-based questionnaire to live-in caregivers of patients with AD registered with Macromill Inc. BPSD prevalence was measured using the Japanese version of the Neuropsychiatric Inventory-Questionnaire Form. The Japanese version of the Zarit Caregiver Burden Scale (J-ZBI), EQ-5D-5L, and Adult Social Care Outcomes Toolkit for Carers (ASCOT-Carer) were used to assess caregiver burden, health-related QOL, and social care-related QOL, respectively.

Results

Of 705 survey responders, 639 (90.6%) and 66 (9.4%) cared for patients with and without BPSD, respectively. Mean caregiver age was 54.6 years, 56.9% were male, and 84.0% cared for parents or in-laws. In the “with BPSD” group, the J-ZBI score was higher (mean difference [95% confidence interval], 6.7 [4.5, 9.0]; p < 0.001), while EQ-5D-5L and ASCOT-Carer scores were lower (–0.076 [–0.134, −0.018; p = 0.010] and −0.101 [–0.168, −0.033]; p = 0.003, respectively) than in the “without BPSD” group.

Conclusions

A significant association between increased caregiver burden and BPSD in patients with AD was demonstrated, which may be associated with decreased caregiver healthcare and social care-related QOL.

Keywords

Alzheimer's disease behavioral symptoms caregiver burden caregivers dementia psychomotor agitation quality of life

Introduction

Alzheimer's disease (AD) is the most common cause of dementia.¹ Several previous studies have provided insights into the relationship between behavioral and psychological symptoms of dementia (BPSD) and the burden of caregivers of patients with AD.^2–4 However, these findings may be influenced by patient/caregiver attributes, cultural factors unique to each country, and the sampling method used (clinical-based or population/community-based study).

BPSD, including delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, nighttime behaviors, and appetite/eating, are common in patients with dementia. The course of these symptoms may vary over time.⁵ As dementia progresses, BPSD tends to increase,⁶ leading to greater caregiver burden and stress. This, in turn, can decrease the quality of care and worsen BPSD in patients with dementia, ultimately reducing the quality of life (QOL) for both patients with dementia and their caregivers.^7–9

It is important to understand the impact of BPSD on QOL not only for patients with dementia, but also their caregivers. Recent studies have shown that specific BPSD symptoms, such as agitation, irritability, and sleep disturbances, are significantly associated with caregiver depression, burden, and reduced QOL.^10,11 For example, Pinyopornpanish et al. found that agitation and sleep disorders were linked to higher levels of caregiver distress, which negatively impacted QOL.¹⁰ Similarly, Baharudin et al. reported that symptoms such as irritability and apathy strongly correlate with caregiver burden, with coping strategies and personality traits mediating the relationship between BPSD and QOL.¹¹ Moreover, unmet needs expressed through BPSD, such as aggression, psychosis, and mood disturbances, can compromise care quality and strain caregiver-patient relationships.¹² These findings highlight the importance of examining BPSD subtypes in relation to caregiver QOL, particularly in aging societies where informal caregiving remains prevalent.

A Delphi Consensus identified patient and caregiver QOL as key effectiveness measures for AD, and the Zarit Caregiver Burden Interview (ZBI) was the highest-ranked outcome measure for caregiver and family QOL.¹³ However, few studies have focused specifically on the QOL of caregivers of patients with AD. In a systematic review and meta-analysis of dyadic psychological interventions in dementia or mild cognitive impairment,¹⁴ only six of 14 studies reported measures on caregiver QOL or burden. While QOL assessment tools such as the QOL-AD,^15–17 the Perceived Change Index,¹⁸ the SF-12,¹⁶ the EQ-5D-5L,¹⁶ and the EQ-VAS¹⁹ have been used, the results varied across the studies. Furthermore, there is no standardized method to measure the QOL of caregiving service users or to attribute changes or improvements in QOL to the use of caregiving services.^20–22

In Japan, standard health-related QOL measures are often used but may be limited as they tend to conceptualize QOL too narrowly. Therefore, the Adult Social Care Outcomes Toolkit for Carers (ASCOT-Carer) was developed as an index to measure the social care-related QOL of caregivers in Japan.²³

Given Japan's growing aging population and unique cultural context, further investigation into the relationship between BPSD and caregiver burden is needed. Few Japanese studies have examined how caregiver burden, QOL, and BPSD in patients with AD interrelate, despite the potential influence of cultural factors that may affect this relationship. Additionally, there is a gap in research focusing on caregiver QOL among those caring for patients with AD, a measure recognized as a priority effectiveness measure by a Delphi consensus.²⁴

The present study aimed to clarify the multidimensional association between BPSD, caregiver burden, and QOL among caregivers of patients with AD in Japan using multiple rating scales, including the ASCOT-Carer. By using a web-based tool to enroll a Japanese community-based population, this study characterizes the challenges faced by caregivers in Japan, independent of cross-cultural or regional influences.

Methods

Study design

This descriptive, cross-sectional survey was conducted from 13–27 November 2023. A web-based questionnaire was distributed via the Internet to a panel of approximately 8000 enrolled participants (Supplemental Text). Of these, 4944 caregivers accessed the survey, and 705 participants who met the eligibility criteria completed the main survey questionnaire. The questionnaire gathered information on BPSD presence, the severity of illness, caregiver burden, caregiver QOL, labor productivity, AD patient background, and status of anti-dementia and antipsychotic medications.

The protocol was approved by the Ethics Committee of the Research Division of Otsuka Pharmaceutical Co., Ltd (Reception number: 230928). The study was conducted in accordance with the Declaration of Helsinki (1975), which outlines ethical principles for medical research involving human subjects, including respect for individuals, informed consent, and risk minimization. It also adhered to the Ethical Guidelines for Medical and Biological Research Involving Human Subjects, issued by Japan's Ministry of Health, Labour and Welfare, which provide detailed standards for participant protection, data handling, and transparency in biomedical research. All family caregivers provided written informed consent prior to participation. This study was registered with the University hospital Medical Information Network (UMIN) under the identifier number UMIN000053306, ensuring public accessibility and research accountability.

Enrolled participants

Participants registered as caregivers with Macromill, Inc. (Tokyo, Japan; https://www.macromill.com/), were included if they met the following three criteria: aged 19–79 years, living with a family member with AD and within the second degree of kinship, and were the primary or partial caregiver of a patient with AD. Respondents were excluded from the study if they closed their web browsers at any point during the survey. All participants received financial compensation from Otsuka Pharmaceutical Co., Ltd for their involvement in this research. Rewards were paid based on the number of questions answered, with participants earning 2–82 points per question, equivalent to 1 yen per point.

Measurements

The prevalence of BPSD was measured using the Japanese version of the Neuropsychiatric Inventory-Questionnaire Form (NPI-Q).²⁵ The NPI-Q assesses 12 neuropsychiatric symptoms, with each symptom rated for frequency (0–4) and severity (0–3). A total NPI-Q score, ranging from 0 to 144 points, is calculated by summing the products of frequency and severity scores for each symptom, with higher scores indicating greater severity and impact of BPSD. Caregiver burden was measured using the eight-item short Japanese version of the ZBI (J-ZBI), which scores range from 0 to 32 points, with higher scores indicating greater caregiver burden.²⁶ Health-related QOL was measured using the EQ-5D-5L, which describes health status across five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each with five severity levels.¹⁶ The EQ-5D-5L generates a single health utility index score, typically ranging from 0 to 1, with higher scores indicating better health-related QOL.²⁷ Social care-related QOL was measured using the Japanese version of the ASCOT-Carer. This measure assesses eight domains of social care-related QOL (e.g., control over daily life, personal dignity, safety) and the resulting scores range from 0 to 1 points, with higher scores indicating greater QOL.²³

Statistical methods

Background characteristics were summarized using frequencies for categorical variables and mean ± standard deviation for continuous variables. Individuals caring for AD patients with BPSD were categorized as the “with BPSD” group, and those caring for AD patients without BPSD as the “without BPSD” group. A general linear regression model was used to evaluate differences between the “with BPSD” and “without BPSD” groups, with J-ZBI, EQ-5D-5L, and ASCOT-Carer as dependent variables; the presence of BPSD as an independent variable; and patient/caregiver age, patient/caregiver sex, patient comorbidities, and caregiver annual income as variables to obtain point estimates (β) and 95% confidence intervals (CI) for “with BPSD” versus “without BPSD.” For the multivariable analysis, models were established as follows: No adjustments were made for model 0 (crude analytical model); model 1 was adjusted for patient age, sex, and comorbidities; model 2 was adjusted for caregiver age, sex, and income; and model 3 was adjusted for factors in model 1 plus variables in model 2.

To evaluate the effects of BPSD on caregiver burden, BPSD was further divided into four sub-syndrome categories in the Neuropsychiatric Inventory based on symptoms relating to: Hyperactivity (agitation/aggression, disinhibition, irritability, and aberrant motor behavior), Psychosis (hallucination, delusion, and night-time behavior disturbances), Affective symptoms (depression and anxiety), and Apathy (apathy and appetite and eating abnormalities), according to a previous study.²⁸ This approach was taken to ensure the internal consistency of the comparison groups. While the presence of any BPSD symptoms qualified individuals for inclusion in the “with BPSD” group, some of these symptoms did not fall into any of the four predefined subcategories of Hyperactivity, Psychosis, Affective symptoms, and Apathy. Including individuals with no BPSD symptoms would have introduced a fundamentally different reference group, potentially confounding the interpretation of the subcategory-specific effects. By restricting the analysis to individuals with BPSD, the estimated effects more accurately reflected the differential impact of each subcategory within a population consistently affected by BPSD.

The statistical significance level was set at 0.05, and a 95% CI was used for interval estimation. The web-based questionnaire was designed to prevent the inclusion of missing values; therefore, there were essentially no missing data for any variable except for comorbidity and the presence of neuropsychiatric symptoms in the NPI-Q. Any responses of ‘I don’t know’ in the comorbidity or ‘Not applicable’ in the neuropsychiatric symptoms were treated as missing values, and no imputation was performed. All statistical analyses were performed using Stata 18/MP8 (StataCorp LLC, College Station, TX, USA), SAS 9.4 (SAS Institute Inc., Cary, NC, USA), or Python version 3.10 (Python Software Foundation, Wilmington, DE, USA).

Results

Characteristics of the caregiver cohort

Of the 705 caregivers who answered the survey (Figure 1), 639 (90.6%) cared for AD patients with BPSD, and 66 (9.4%) cared for AD patients without BPSD. Most caregivers were male (56.9%), with a mean ± standard deviation age of 54.6 ± 11.5 years. Most (84.0%) cared for their parents and in-laws, and 60.7% were the primary caregivers (Table 1).

Figure 1.

Participant flowchart from panel registration to final response.

Table 1.

Background characteristics of patients with AD and their caregivers.

	OverallN = 705	With BPSDN = 639	Without BPSDN = 66
Caregiver sex, n (%)
Male	401 (56.9)	352 (55.1)	49 (74.2)
Caregiver age, years, mean ± SD	54.6 ± 11.5	54.30 ± 11.5	57.7 ± 11.7
Relationship to the patient, n (%)
Spouse/partner	39 (5.5)	33 (5.2)	6 (9.1)
Siblings and siblings-in-law	3 (0.4)	3 (0.5)	0 (0)
Parents and in-laws	592 (84.0)	534 (83.6)	58 (87.9)
Grandparents and grandparents-in-law	65 (9.2)	64 (10.0)	1 (1.5)
Other	6 (0.9)	5 (0.8)	1 (1.5)
Primary caregiver, n (%)
Respondent	428 (60.7)	391 (61.2)	37 (56.1)
Other family member	277 (39.3)	248 (38.8)	29 (43.9)
Patient age, years, mean ± SD	84.2 ± 8.8	84.3 ± 8.8	82.9 ± 9.1
Patient sex, n (%)
Male	185 (26.2)	170 (26.6)	15 (22.7)
Patient's last level of education, n (%)
Common elementary school	41 (5.8)	39 (6.1)	2 (3.0)
Junior high school	196 (27.8)	178 (27.9)	18 (27.3)
High school	272 (38.6)	247 (38.7)	25 (37.9)
College of technology and junior college	79 (11.2)	69 (10.8)	10 (15.2)
Tertiary education institutions, including universities and colleges.	95 (13.5)	87 (13.6)	8 (12.1)
Graduate school	4 (0.6)	4 (0.6)	0 (0)
Other	18 (2.6)	15 (2.3)	3 (4.5)

AD: Alzheimer's disease; BPSD: behavioral and psychological symptoms of dementia; SD: standard deviation.

Characteristics of the patient cohort

Among the 705 patients with AD included in this study, 639 (90.6%) had BPSD, and 66 (9.4%) did not have BPSD. Patients with AD had a mean ± standard deviation age of 84.2 ± 8.8 years, and 73.8% were female (Table 1).

Association between BPSD and caregiver burden and QOL

The association between BPSD and caregiver burden (J-ZBI), health-related QOL (EQ-5D-5L), and social care-related QOL (ASCOT-Carer) were assessed using models 0–3, representing the crude analysis; adjustments for patient age, sex, and comorbidities; adjustments for caregiver age, sex, and income; and adjustments for the factors in models 1 and 2; respectively (Table 2).

Table 2.

Association between BPSD and caregiver burden, health-related QOL, and social care-related QOL.

Outcome		Model 0^aEstimate, β (95% CI)N = 705	Model 1^bEstimate, β (95% CI)N = 672	Model 2^cEstimate, β (95% CI)N = 705	Model 3^dEstimate, β (95% CI)N = 672
J-ZBI	E value	3.99	3.94	3.63	3.64
	Without BPSD	ref.	ref.	ref.	ref.
	With BPSD	7.3 (5.3, 9.4)	7.3 (5.1, 9.5)	6.7 (4.6, 8.7)	6.7 (4.5, 9.0)
	p	<0.001	<0.001	<0.001	<0.001
EQ-5D-5L	E value	1.83	2.07	1.88	2.14
	Without BPSD	ref.	ref.	ref.	ref.
	With BPSD	−0.053 (−0.106, 0.000)	−0.070 (−0.127, −0.014)	−0.057 (−0.110, −0.003)	−0.076 (−0.134, −0.018)
	p	0.049	0.015	0.037	0.010
ASCOT-Carer	E value	2.48	2.34	2.34	2.27
	Without BPSD	ref.	ref.	ref.	ref.
	With BPSD	−0.117 (−0.179, −0.056)	−0.107 (−0.175, −0.040)	−0.106 (−0.168, −0.044)	−0.101 (−0.168, −0.033)
	p	<0.001	0.002	<0.001	0.003

Bold font is used to indicate significant associations.

^aNo adjustments were made for Model 0 (crude analytical model).

^bModel 1 was adjusted for patient age, sex, and comorbidities.

^cModel 2 was adjusted for caregiver age, sex, and income.

^dModel 3 was adjusted for factors in models 1 and 2.

ASCOT-Carer: Adult Social Care Outcomes Toolkit for Carers; BPSD: behavioral and psychological symptoms of dementia; CI: confidence interval; J-ZBI: eight-item short Japanese version of the Zarit Caregiver Burden Interview; QOL: quality of life.

The J-ZBI score estimate (95% CI) in the “with BPSD” group was significantly higher than in the “without BPSD” group across all models, at 7.3 (5.3, 9.4), 7.3 (5.1, 9.5), 6.7 (4.6, 8.7), and 6.7 (4.5, 9.0), respectively (p < 0.001 for all models).

Across all models, the EQ-5D-5L scores were significantly lower in the “with BPSD” group than in the “without BPSD” group, with estimates (95% CIs) of −0.053 (−0.106, 0.000), p = 0.049; −0.070 (−0.127, −0.014), p = 0.015; −0.057 (−0.110, −0.003), p = 0.037; and −0.076 (−0.134, −0.018), p = 0.010; respectively.

Similarly, ASCOT-Carer scores were significantly lower in the “with BPSD” group than in the “without BPSD” group, with estimates (95% CIs) of −0.117 (−0.179, −0.056), p < 0.001; −0.107 (−0.175, −0.040), p = 0.002; −0.106 (−0.168, −0.044), p < 0.001; and −0.101 (−0.168, −0.033), p = 0.003; respectively.

Table 3 shows the association between the primary outcome (caregiver burden and QOL) and the four BPSD categories: Hyperactivity, Psychosis, Affective symptoms, and Apathy. This analysis used a single, fully adjusted model controlling for patient age, sex, and comorbidities, and caregiver age, sex, and income. Multicollinearity was not detected using variance inflation factors.

Table 3.

Association between BPSD and caregiver burden and QOL by BPSD sub-syndrome categories.

	Outcome
Variables	J-ZBI Estimate, β (95% CI)N = 672	EQ-5D-5L Estimate, β (95% CI)N = 672	ASCOT-Carer Estimate, β (95% CI)N = 672
Hyperactivity (−)^a	ref.	ref.	ref.
Hyperactivity (+)	2.7 (1.3, 4.1)	−0.011 (−0.049, 0.028)	−0.052 (−0.098, −0.007)
p	<0.001	0.593	0.025
Psychosis (−)^b	ref.	ref.	ref.
Psychosis (+)	3.9 (2.7, 5.2)	−0.045 (−0.080, −0.009)	−0.040 (−0.081, 0.002)
p	<0.001	0.013	0.063
Affective symptoms (−)	ref.	ref.	ref.
Affective symptoms (+)	1.8 (0.5, 3.0)	−0.039 (−0.073, −0.005)	−0.057 (−0.097, −0.016)
p	0.006	0.025	0.006
Apathy (−)	ref.	ref.	ref.
Apathy (+)	2.7 (1.3, 4.0)	−0.029 (−0.067, 0.008)	−0.041 (−0.085, 0.003)
p	<0.001	0.123	0.069

Bold font is used to indicate significant associations.

^aIncludes agitation/aggression, disinhibition, irritability, and aberrant motor behavior.

^bIncludes hallucinations, delusion, and night-time behavior disturbances.

^cIncludes depression and anxiety.

^dIncludes apathy and appetite and eating abnormalities.

The model was adjusted for patient age, sex, comorbidities, and caregiver age, sex, and income.

All BPSD sub-syndrome categories were significantly associated with caregiver burden (J-ZBI scores) and the magnitude of association was highest for symptoms of psychosis (3.9 [2.7, 5.2], p < 0.001), followed by hyperactivity (2.7 [1.3, 4.1], p < 0.001) and apathy (2.7 [1.3, 4.0], p < 0.001), then affective symptoms (1.8 [0.5, 3.0], p = 0.006).

Regarding QOL, the EQ-5D-5L was significantly associated with psychosis (−0.045 [−0.080, −0.009], p = 0.013) and affective symptoms (−0.039 [−0.073, −0.005], p = 0.025). In contrast, QOL as assessed using ASCOT-Carer was significantly associated with symptoms related to hyperactivity (−0.052 [−0.098, −0.007], p = 0.025) and affective symptoms (−0.057 [−0.097, −0.016], p = 0.006).

Discussion

The present study found that the majority of the caregivers surveyed were caring for AD patients with BPSD, with a prevalence of 90.6%. This finding is consistent with current clinical trends in Japan and aligns with multicenter and longitudinal studies that, using NPI-based assessments, have reported a similar high prevalence.^29,30 The relatively small proportion of caregivers supporting AD patients without BPSD (9.4%) may limit the statistical power and generalizability of between-group comparisons.

The results showed that caregiver burden (J-ZBI) was significantly higher in the group of caregivers caring for AD patients with BPSD compared with the group without BPSD. The J-ZBI score proved to be a sensitive measure as it showed a significant increase in caregiver burden across all the BPSD sub-syndrome groups. Notably, psychosis was most strongly associated with the degree of caregiver burden, followed by hyperactivity, apathy, appetite and eating abnormalities, and affective symptoms. This association between BPSD and caregiver burden is consistent with previous research from Brazil, Spain, Korea, Turkey, and the US,^3,31–33 in which various BPSD symptoms, such as irritability, aberrant motor behavior, delusions, and agitation, were significant predictors of caregiver burden. In a longitudinal study from the CATIE-AD trial in the US, reductions in symptom severity and improvements in patients’ QOL were associated with decreased caregiver burden.³⁴ The present study findings are aligned with the results of a systematic review and meta-analysis in which depression, agitation/aggression, and apathy were the most distressing symptoms for caregivers.³⁵ A study of 1437 pairs of dementia patient–family caregivers in Japan showed that 69% of caregivers of patients with dementia reported a high levels of distress, and that verbal abuse, wandering, and refusal of care were associated with caregiver distress.³⁶ Another Japanese study reported significant correlations between BPSD symptoms of delusion, agitation/aggression, apathy/indifference, irritability/lability, and aberrant motor behavior and caregiver burden.³⁷ A survey study of caregivers of patients with dementia showed that lower coping skills for managing stress were associated with higher caregiver burden.³⁸ These studies consistently demonstrate that BPSD, regardless of symptom type or severity, is positively associated with increased caregiver burden.

Health-related QOL (EQ-5D-5L) was significantly decreased in the “with BPSD” group compared with the “without BPSD” group. However, the BPSD sub-syndromes were associated differently with each QOL measure. The EQ-5D-5L score was associated only with symptoms of psychosis and affective symptoms (depression and anxiety). It was shown that lower EQ-5D-5L score and severity of psychotic or affective sub-symptoms in AD reflect an increase in caregivers’ levels of anxiety. The reason the estimated mean difference in EQ-5D was smaller than in other measures (e.g., the ASCOT-Carer) is that some sub-items in the EQ-5D questionnaire may not accurately reflect the actual condition of caregivers in the present study (Tables 2 and 3). Among the five items of the EQ-5D, only “daily activities” and “anxiety” might reflect the actual condition of caregivers dealing with BPSD. In contrast, the remaining items, such as “mobility”, “personal care”, and “pain” may not be relevant in the context of the present study. In other words, the different results obtained for EQ-5D-5L may be attributed to the various aspects of caregiver QOL that each tool measures. The EQ-5D-5L primarily evaluates an individual's health-related QOL, and only one of its five dimensions specifically addresses an individual's anxiety.²⁷ It is unlikely that other dimensions were affected by the patient's symptoms, such as pain, movement, or management of daily life.

Regarding other caregiver QOL measures, social care-related QOL (ASCOT-Carer) was significantly decreased in the “with BPSD” group compared with the “without BPSD” group. Furthermore, the ASCOT-Carer score was only associated with hyperactivity and affective symptoms and was not associated with symptoms of psychosis. The ASCOT-Carer captures broader aspects of an individual's QOL related to social connectedness and personal satisfaction, as well as aspects pertaining to social functioning and daily living.³⁹ These differences may have influenced the differences in the association between QOL indicators and each BPSD sub-syndrome category in the present study. Consequently, it may have acquired new evaluative significance in the evaluation of caregivers.

Our findings, supported by existing literature, suggest distinct mechanisms through which BPSD contribute to caregiver burden. Specific BPSD such as hyperactivity and affective symptoms may result in potentially harmful behavior (PHB) by caregivers toward patients with dementia. In turn, PHB may worsen the severity of BPSD,⁴⁰ leading to further suboptimal caregiving practices, creating a vicious cycle of escalating symptoms and inadequate care. This is a potential mechanism by which hyperactivity and affective symptoms can disproportionally affect daily living and social-related QOL, as measured by the ASCOT-Carer score. A Japanese study of 133 pairs of patients with dementia who saw a psychiatrist and their caregivers reported that the caregiver's Zarit Caregiver Burden Interview total score, Neuropsychiatric Inventory scores for patient irritability (odds ratio, 1.22 per unit increase; 95% CI, 1.06–1.40) and appetite/eating disorders (odds ratio, 1.41 per unit increase; 95% CI, 1.08–1.84), and daughter-in-law caregivers were associated with PHB.⁴⁰ Another study involving family caregivers of patients with dementia receiving home nursing services in Japan, more than 30% of caregivers were found to have exhibited PHB. The risk of PHB was particularly higher among caregivers of patients with BPSD compared with those caring for patients without BPSD (odds ratio, 3.61; 95% CI, 1.65–7.90; p < 0.01).⁴¹

While there is no conclusive explanation for how symptoms of psychosis and affective symptoms relate to the QOL of individual caregivers, one possibility is that each BPSD sub-syndrome category tends to appear at a different disease stage.^42,43 A survey of patients with dementia and their caregivers showed that agitation/aggression and related symptoms, with associated symptoms of psychosis, were associated with lower EQ-VAS scores.⁴⁴ In contrast, agitation/aggression and related symptoms without symptoms of psychosis were not associated with EQ-VAS.⁴⁴ It is suggested that symptoms of psychosis and symptoms related to agitation are essential factors that affect caregiver QOL. In addition, hallucinations, delusions, and depressive symptoms appear early during AD and decrease in severity with disease progression, while other symptoms (such as agitation/aggression and apathy and eating behavior) increase over time.⁴³

An analysis of social media data from AD-related stakeholders (patients, caregivers, and healthcare providers) showed that caregiver anxiety is a major challenge in all AD illnesses.⁴⁵ In other words, the observed association of symptoms of psychosis and affective symptoms with EQ-5D-5L may reflect an underlying phenotype of anxiety, possibly due to caregivers’ limited knowledge and experience with early-stage AD. Notably, among the ZBI, ASCOT, and EQ-5D instruments, only the EQ-5D includes a domain specifically designed to assess caregiver anxiety.

The characteristics of BPSD, such as hyperactivity, psychosis, and affective symptoms, significantly contribute to caregiver burden.⁴⁶ These symptoms not only affect caregivers’ daily functioning but also disrupt nighttime sleep.⁴⁷ Sleep disturbances in caregivers are often exacerbated by patients’ insomnia and the psychological stress associated with caregiving, including depressive symptoms and perceived burden.⁴⁸ While there is no direct evidence in the literature supporting this specific pathway, the association between mood disorders and sleep disturbances in patients with dementia has been established.⁴⁹ Moreover, sleep disturbances are frequently cited as a major source of burden among caregivers of individuals with young-onset AD.⁵⁰ Interventions targeting sleep disorders in patients with dementia have been shown to reduce caregiver burden. Sleep disturbances and nighttime behavioral problems in patients with dementia can significantly impair caregivers’ sleep quality, further increasing their levels of burden and risk for depression.⁵¹ In contrast to these symptoms, apathy appears to be more directly related to the intrinsic challenges of caregiving itself. BPSD encompasses a broad range of symptoms, each of which may impose a different type or level of burden on caregivers. Therefore, it is essential to accurately assess each symptom and implement early and consistent interventions where treatment is possible. Emotional disturbances are associated with nearly all aspects of caregiver burden and QOL; however, there is currently no established treatment for these symptoms. Conversely, the efficacy of psychotropic medications has been demonstrated in managing hyperactivity and psychosis in patients with dementia.^52,53

This study has some limitations that should be considered. It is cross-sectional in design and the results do not infer causality; a longitudinal study may be warranted in the future. This study employed a web-based survey, and the respondents may be biased toward younger or technologically literate caregivers, limiting generalizability. Furthermore, the respondents may be biased toward caregivers living in urban areas. However, given Japan's population distribution, residents of urban areas constitute the majority,^54,55 and therefore the findings of this study can be considered to have a certain degree of generalizability to the digitally engaged caregiver population. Although reports indicate that regional disparities in Japan's internet penetration rate are minimal (e.g., fiber-optic coverage is 99.84% of households⁵⁶), the realities of caregiving in areas with limited internet access—such as mountainous regions and remote islands—may not have been fully captured in this survey. We note that a gap in internet usage rates by prefecture still exists (overall, 85.6%; lowest, 72.2% in Iwate; highest, 90.1% in Kanagawa and Fukuoka).⁵⁷ Thus, while digital accessibility is high nationally, the exclusion of caregivers in the lowest usage areas remains a limitation. Most participating caregivers (over 80%) were the sons/daughters/in-laws of the patients with AD, limiting the generalization of the results to other caregiver groups such as spouses, siblings, or professional caregivers. As the diagnosis of AD was self-reported by caregivers, there is uncertainty about the accuracy of the diagnosis, and some patients with dementia with Lewy bodies and vascular dementia may have been included in the analysis. The lack of information on the stage of dementia prevents the examination of potential confounding by temporal factors in the relationship between BPSD, caregiver burden, and QOL. Additionally, the substantial discrepancy in group sizes—639 participants in the BPSD group versus 66 in the non-BPSD group—may limit the statistical power and generalizability of between-group comparisons. While this imbalance reflects the high prevalence of BPSD in dementia populations, consistent with epidemiological data indicating that over 80% of individuals with dementia develop BPSD over the course of their illness,⁵⁴ it may influence variance assumptions and compromise the reliability of confidence intervals. Sensitivity analyses using Huber-White robust standard errors yielded comparable results, and statistical power for the J-ZBI and ASCOT-Carer models exceeded 99% under one-sided test conditions using Cohen's d. However, the power for EQ-5D-5L was approximately 60%, indicating that results should be interpreted with caution. Finally, the classification of the sub-syndrome categories into four groups was done arbitrarily, based on findings from previous studies and not by using statistical methods such as factor analysis or principal component analysis, which could potentially affect the accuracy and generalizability of our findings.

Notably, the present study has several strengths worth highlighting. First, a web-based system with a community-based population enabled us to capture authentic perspectives of a broader, more diverse range of caregivers. Additionally, this study evaluated the QOL of caregivers of patients with AD using the ASCOT-Carer questionnaire, which evaluates social-care related QOL and may be considered a more comprehensive assessment tool to assess caregiver QOL (compared with the EQ-5D-5L) as it evaluates social connectedness and personal satisfaction.

Conclusion

This study found that BPSD in patients with AD was associated with more severe caregiver burden and lower health-related QOL and social care-related QOL among caregivers. Therefore, accurately assessing each symptom and implementing early interventions is essential where treatment is possible. The impact of different BPSD sub-syndrome categories may differ between indicators related to personal health and those that include a social perspective. Further investigation is needed to explore potential confounding factors and interactions between BPSD symptoms. Given the limited research on this topic to date, further studies on the association between BPSD and caregiver QOL using QOL-specific measures are warranted. Additional evidence is needed to understand this relationship better and optimize targeted interventions.

Supplemental Material

sj-docx-1-alz-10.1177_13872877261415637 - Supplemental material for Caregiver burden and quality of life associated with behavioral and psychological symptoms of Alzheimer's disease: A web-based cross-sectional survey study

Supplemental material, sj-docx-1-alz-10.1177_13872877261415637 for Caregiver burden and quality of life associated with behavioral and psychological symptoms of Alzheimer's disease: A web-based cross-sectional survey study by Shunichiro Shinagawa, Tomoyuki Nagata, Shinichi Noto, Kentaro Yamato, Naoki Mori and Keisuke Onuki in Journal of Alzheimer's Disease

Footnotes

Acknowledgements

We thank Macromill, Inc., for providing assistance with the data collection and some of the analysis. We also thank Michelle Belanger, MD, of Edanz (www.edanz.com), for providing medical writing support, which was funded by Otsuka Pharmaceutical Co., Ltd, Tokyo, Japan, in accordance with Good Publication Practice guidelines ().

ORCID iDs

Shunichiro Shinagawa

Tomoyuki Nagata

Shinichi Noto

Kentaro Yamato

Naoki Mori

Keisuke Onuki

Ethical considerations

The protocol was approved by the Ethics Committee of the Research Division of Otsuka Pharmaceutical Co., Ltd (Reception number: 230928), and the study was conducted in accordance with the Declaration of Helsinki of 1975 and adhered to Good Clinical Practice guidelines. This study was registered at the University hospital Medical Information Network under the identifier number UMIN000053306.

Consent to participate

All family caregivers provided written informed consent to participate in the present study.

Consent for publication

Not applicable

Author contribution(s)

Shunichiro Shinagawa: Conceptualization; Methodology; Writing – review & editing.

Tomoyuki Nagata: Conceptualization; Methodology; Writing – review & editing.

Shinichi Noto: Conceptualization; Methodology; Writing – review & editing.

Kentaro Yamato: Conceptualization; Funding acquisition; Methodology; Supervision; Writing – review & editing.

Naoki Mori: Conceptualization; Funding acquisition; Methodology; Writing – review & editing.

Keisuke Onuki: Data curation; Formal analysis; Funding acquisition; Methodology; Visualization; Writing – original draft; Writing – review & editing.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was funded by Otsuka Pharmaceutical Co., Ltd, Tokyo, Japan. The study sponsor, Otsuka Pharmaceutical Co., Ltd, participated in the writing, editing, and approval of this manuscript.

Declaration of conflicting interests

The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Shunichiro Shinagawa has received speaking and manuscript fees from Otsuka Pharmaceutical, Kowa, Sumitomo Pharma, Eisai, Takeda Pharmaceutical, MSD, Lundbeck, and Viatris Pharmaceutical. He has also served advisory roles for Eisai, Otsuka Pharmaceutical, and Ono Pharmaceutical. Tomoyuki Nagata has received a Grant-in-Aid for Scientific Research (grant number 25893251) from the Ministry of Education, Culture, Sports, Science and Technology, Japan, and a Chiba health preventive fund from Chiba Foundation for Health Promotion & Disease Prevention. Dr Nagata has not received honoraria, including speaker honoraria, from pharmaceutical companies. Shinichi Noto has received speaker honoraria from Otsuka Pharmaceutical Co., Ltd Kentaro Yamato, Naoki Mori, and Keisuke Onuki are employees of Otsuka Pharmaceutical Co., Ltd.

Data availability statement

The data collected and analyzed in the present study are not publicly available due to contractual agreements and privacy considerations. The survey results are intended for use by Otsuka Pharmaceutical Co., Ltd, and were obtained under conditions that do not permit sharing with third parties without additional consent. As participant consent for broader data sharing was not obtained, access to the dataset is restricted. Requests for data access may be considered on a case-by-case basis, subject to approval by the vendor and compliance with data protection measures. Any potential data sharing would require an opt-out mechanism for participants and strict safeguards to prevent unauthorized disclosure. For further inquiries, please contact the corresponding author.

Supplemental material

Supplemental material for this article is available online.

References

Feng

Sun

, et al. Global, regional, and national burden of Alzheimer’s disease and other dementias, 1990–2019. Front Aging Neurosci 2022; 14: 937486.

Grossberg

Urganus

Schein

, et al. A real-world assessment of healthcare costs associated with agitation in Alzheimer’s dementia. J Med Econ 2024; 27: 99–108.

Shim

Kang

Kim

, et al. Factors associated with caregiver burden in dementia: 1-year follow-up study. Psychiatry Investig 2016; 13: 43–49.

Liu

Jin

Shi

, et al. The effects of behavioral and psychological symptoms on caregiver burden in frontotemporal dementia, Lewy body dementia, and Alzheimer’s disease: clinical experience in China. Aging Ment Health 2017; 21: 651–657.

van der Linde

Dening

Stephan

, et al. Longitudinal course of behavioural and psychological symptoms of dementia: systematic review. Br J Psychiatry 2016; 209: 366–377.

Brodaty

Connors

, et al. The course of neuropsychiatric symptoms in dementia: a 3-year longitudinal study. J Am Med Dir Assoc 2015; 16: 380–387.

Terum

Andersen

Rongve

, et al. The relationship of specific items on the neuropsychiatric inventory to caregiver burden in dementia: a systematic review. Int J Geriatr Psychiatry 2017; 32: 703–717.

Rinaldi

Spazzafumo

Mastriforti

, et al. Predictors of high level of burden and distress in caregivers of demented patients: results of an Italian multicenter study. Int J Geriatr Psychiatry 2005; 20: 168–174.

Annerstedt

Elmståhl

Ingvad

, et al. Family caregiving in dementia—an analysis of the caregiver’s burden and the “breaking-point” when home care becomes inadequate. Scand J Public Health 2000; 28: 23–31.

10.

Pinyopornpanish

Soontornpun

Wongpakaran

, et al. Impact of behavioral and psychological symptoms of Alzheimer's disease on caregiver outcomes. Sci Rep 2022; 12: 14138.

11.

Baharudin

Din

Subramaniam

, et al. The associations between behavioral-psychological symptoms of dementia (BPSD) and coping strategy, burden of care and personality style among low-income caregivers of patients with dementia. BMC Public Health 2019; 19: 447.

12.

Warren

. Behavioral and psychological symptoms of dementia as a means of communication: considerations for reducing stigma and promoting person-centered care. Front Psychol 2022; 13: 875246.

13.

Ellison

Cappa

Garrett

, et al. Outcome measures for Alzheimer’s disease: a global inter-societal Delphi consensus. Alzheimers Dement 2023; 19: 2707–2729.

14.

Poon

. A systematic review and meta-analysis of dyadic psychological interventions for BPSD, quality of life and/or caregiver burden in dementia or MCI. Clin Gerontol 2022; 45: 777–797.

15.

Judge

Yarry

Looman

, et al. Improved strain and psychosocial outcomes for caregivers of individuals with dementia: findings from project ANSWERS. Gerontologist 2013; 53: 280–292.

16.

Orrell

Yates

Leung

, et al. The impact of individual cognitive stimulation therapy (iCST) on cognition, quality of life, caregiver health, and family relationships in dementia: a randomized controlled trial. PloS Med 2017; 14: e1002269.

17.

Phung

Waldorff

Buss

, et al. A three-year follow-up on the efficacy of psychosocial interventions for patients with mild dementia and their caregivers: the multicentre, rater-blinded, randomised Danish Alzheimer intervention study (DAISY). BMJ Open 2013; 3: e003584.

18.

Gitlin

Winter

Dennis

, et al. Targeting and managing behavioral symptoms in individuals with dementia: a randomized trial of a nonpharmacological intervention. J Am Geriatr Soc 2010; 58: 1465–1474.

19.

EuroQol Group. Euroqol—a new facility for the measurement of health-related quality of life. Health Policy 1990; 16: 199–208.

20.

Nakamura-Thomas

Morikawa

Moriyama

, et al. Japanese Translation and cross-cultural validation of the adult social care outcomes toolkit (ASCOT) in Japanese social service users. Health Qual Life Outcomes 2019; 17: 59.

21.

Itoh

Kondoh

. Quality assessment and goal of care and issues. J Natl Inst Popul Soc Secur Res 2012; 48: 120–132 [In Japanese].

22.

Tsutsui

. Quality assessment of care: current achievements in an international context and the future direction of Japan. Soc Secur Res 2016; 1: 129–147 [In Japanese].

23.

Shiroiwa

Nakamura-Thomas

Yamaguchi

, et al. Japanese Preference weights of the adult social care outcomes toolkit for carers (ASCOT-carer). Qual Life Res 2022; 31: 2143–2151.

24.

Ellison

Cappa

Garrett

, et al. Outcome measures for Alzheimer's disease: a global inter-societal delphi consensus. Alzheimers Dement 2023; 19: 2707–2729.

25.

Matsumoto

Ikeda

Fukuhara

, et al. Validity and reliability of the Japanese version of the neuropsychiatric inventory caregiver distress scale (NPI-D) and the neuropsychiatric inventory brief questionnaire form (NPI-Q). No To Shinkei 2006; 58: 785–790 [In Japanese].

26.

Arai

Tamiya

Yano

. The short version of the Japanese version of the zarit caregiver burden interview (J-ZBI): its reliability and validity. Nihon Ronen Igakkai Zasshi 2003; 40: 497–503 [In Japanese].

27.

Shiroiwa

Fukuda

Ikeda

, et al. Japanese Population norms for preference-based measures: eQ-5D-3L, EQ-5D-5L, and SF-6D. Qual Life Res 2016; 25: 707–719.

28.

Aalten

Verhey

Boziki

, et al. Neuropsychiatric syndromes in dementia. Results from the European Alzheimer disease consortium: part I. Dement Geriatr Cogn Disord 2007; 24: 457–463.

29.

Kazui

Yoshiyama

Kanemoto

, et al. Differences of behavioral and psychological symptoms of dementia in disease severity in four major dementias. PLoS One 2016; 11: e0161092.

30.

Imamura

Kato

Sato

, et al. Annual rate of change in behavioral and psychological symptoms of dementia (BPSD) in Alzheimer's disease. Jpn J Neuropsychol 2017; 33: 44–55.

31.

Sousa

Santos

Turró-Garriga

, et al. Factors associated with caregiver burden: comparative study between Brazilian and Spanish caregivers of patients with Alzheimer’s disease (AD). Int Psychogeriatr 2016; 28: 1363–1374.

32.

Bozgeyik

Ipekcioglu

Yazar

, et al. Behavioural and psychological symptoms of Alzheimer’s disease associated with caregiver burden and depression. Psychiatry Clin Psychopharmacol 2019; 29: 656–664.

33.

Mohamed

Rosenheck

Lyketsos

, et al. Effect of second-generation antipsychotics on caregiver burden in Alzheimer’s disease. J Clin Psychiatry 2012; 73: 121–128.

34.

Mohamed

Rosenheck

Lyketsos

, et al. Caregiver burden in Alzheimer disease: cross-sectional and longitudinal patient correlates. Am J Geriatr Psychiatry 2010; 18: 917–927.

35.

Feast

Moniz-Cook

Stoner

, et al. A systematic review of the relationship between behavioral and psychological symptoms (BPSD) and caregiver well-being. Int Psychogeriatr 2016; 28: 1761–1774.

36.

Shikimoto

Sado

Ninomiya

, et al. Predictive factors associated with psychological distress of caregivers of people with dementia in Japan: a cross-sectional study. Int Psychogeriatr 2018; 30: 1089–1098.

37.

Matsumoto

Ikeda

Fukuhara

, et al. Caregiver burden associated with behavioral and psychological symptoms of dementia in elderly people in the local community. Dement Geriatr Cogn Disord 2007; 23: 219–224.

38.

Lloyd

Muers

Patterson

, et al. Self-compassion, coping strategies, and caregiver burden in caregivers of people with dementia. Clin Gerontol 2019; 42: 47–59.

39.

Rand

Malley

Vadean

. Measuring the outcomes of long-term care for unpaid carers: comparing the ASCOT-carer, carer experience scale and EQ-5D-3 L. Health Qual Life Outcomes 2019; 17: 184.

40.

Toda

Tsukasaki

Itatani

, et al. Predictors of potentially harmful behaviour by family caregivers towards patients treated for behavioural and psychological symptoms of dementia in Japan. Psychogeriatrics 2018; 18: 357–364.

41.

Sasaki

Arai

Kumamoto

, et al. Factors related to potentially harmful behaviors towards disabled older people by family caregivers in Japan. Int J Geriatr Psychiatry 2007; 22: 250–257.

42.

Tanaka

Hashimoto

Fukuhara

, et al. Relationship between dementia severity and behavioural and psychological symptoms in early-onset Alzheimer’s disease. Psychogeriatrics 2015; 15: 242–247.

43.

Castillo-García

López-Álvarez

Osorio

, et al. Clinical trajectories of neuropsychiatric symptoms in mild-moderate to advanced dementia. J Alzheimers Dis 2022; 86: 861–875.

44.

Chekani

Pike

Jones

, et al. Impact of dementia-related behavioral symptoms on healthcare resource use and caregiver burden: real-world data from Europe and the United States. J Alzheimers Dis 2021; 81: 1567–1578.

45.

Tahami Monfared

Stern

Doogan

, et al. Understanding barriers along the patient journey in Alzheimer’s disease using social media data. Neurol Ther 2023; 12: 899–918.

46.

García-Martín

de Hoyos-Alonso

Delgado-Puebla

, et al. Burden in caregivers of primary care patients with dementia: influence of neuropsychiatric symptoms according to disease stage (NeDEM project). BMC Geriatr 2023; 23: 525.

47.

Chen

Sung

Wang

. The impact of behavioral and psychological symptoms of dementia on mental health, sleep quality, and caregiver's burden. Int J Geriatr Psychiatry 2025; 40: e70080.

48.

McCurry

Logsdon

Teri

, et al. Sleep disturbances in caregivers of persons with dementia: contributing factors and treatment implications. Sleep Med Rev 2007; 11: 143–153.

49.

Kolberg

Hjetland

Thun

, et al. The effects of bright light treatment on affective symptoms in people with dementia: a 24-week cluster randomized controlled trial. BMC Psychiatry 2021; 21: 377.

50.

Cole

Ito

Chen

, et al. Impact of Alzheimer’s disease on caregiver questionnaire: internal consistency, convergent validity, and test-retest reliability of a new measure for assessing caregiver burden. Health Qual Life Outcomes 2014; 12: 114.

51.

Kim

Richards

. Sleep disturbance, nocturnal agitation behaviors, and medical comorbidity in older adults with dementia: relationship to reported caregiver burden. Res Gerontol Nurs 2014; 7: 206–214.

52.

Sink

Holden

Yaffe

. Pharmacological treatment of neuropsychiatric symptoms of dementia: a review of the evidence. JAMA 2005; 293: 596–608.

53.

Kales

Gitlin

Lyketsos

, et al. Management of neuropsychiatric symptoms of dementia in clinical settings: recommendations from a multidisciplinary expert panel. J Am Geriatr Soc 2014; 62: 762–769.

54.

Anantapong

Jiraphan

Aunjitsakul

, et al. Behavioural and psychological symptoms of people with dementia in acute hospital settings: a systematic review and meta-analysis. Age Ageing 2025; 54: afaf013.

55.

United Nations. World Urbanization Prospects 2025. https://population.un.org/wup/countryprofiles?country=Japan&mainCategory=Countries%20and%20Aggregates&subCategory=Urbanization%20-%20International%20definition (2025, accessed 4 December 2025).

56.

Ministry of Internal Affairs and Communications, Japan. Information and Communications in Japan. White Paper 2024. https://www.soumu.go.jp/johotsusintokei/whitepaper/eng/WP2024/2024-index.html (2024, accessed 4 December 2025).

57.

Ministry of Internal Affairs and Communications, Japan. Telecommunications Usage Trends Survey, https://www.soumu.go.jp/johotsusintokei/statistics/pdf/HR202400_001.pdf (2025, accessed 4 December 2025). [In Japanese]

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.05 MB