Influence of Behavioral and Psychological Symptoms on Caregiver Burden for Different Types of Dementia: Clinical Experience in Lima, Peru Free

Caregiver burden can be understood as a multidimensional concept that refers to the caregiver’s perceived level of strain from caring for a patient over time [1], and it has been associated with negative outcomes for caregivers and patients in terms of poorer general health, decreased quality of life, and increased risk of morbidity [2]. Furthermore, it is often a forgotten variable in the doctor-patient relationship, as caregivers play an essential role in the well-being of patients in the community [3].

The care of patients with dementia can often be a challenging and demanding task, particularly for those who act as informal care partners. Taking care of persons with Alzheimer’s disease (AD) is often associated with a high burden of care [4], reducing the quality of life and work productivity of caregivers due to depressive symptoms [5]. The factors associated with caregiver burden related to the patients include behavioral and psychological symptoms of dementia (BPSD), daily functional limitations, duration/severity of illness, cognitive impairment, and comorbidities [2]. Most of the studies that have compared the burden of caregivers between different types of dementia showed contradictory results; for example, caregivers taking care of patients with dementia with Lewy bodies (DLB) or frontotemporal dementia (FTD) experienced more burden than those caring for patients with AD [6, 7], or caregivers of persons living with DLB reported higher levels of burden than those caring for persons living with AD and vascular dementia (VD) [8, 9] and less than those persons living with FTD [10]. Another study reported that VD caregivers in Italy had a lower care burden than AD caregivers [11]. On the other hand, some reports did not observe any differences in caregiver burden between dementia subtypes [12‒14]. American researchers reported there were no differences in the burden of care between VD and AD dementia [12]. Oliveira et al. [13] in Brazil also reported that caregivers of DLB and AD have no statistical difference in caregiving burden. A Taiwanese longitudinal study comparing AD, FTD, DLB, VD, and mixed dementia concluded that caregivers of DLB patients have a higher burden than those of AD patients, which may be due to the increased rate of BPSD observed in DLB patients [5].

It is very important to determine factors that predict the burden of caregiving for addressing care needs for both people living with dementia and their care partners [15], particularly in Latin America and Caribbean countries, a region with challenges that include the scarcity of formal long-term care, socioeconomic and social determinants of health disparities, gender-biased burdens, growing dementia prevalence, and the effect of the recent COVID-19 pandemic on families affected by dementia [16]. Usually, the caregivers spend more than 8 h a day with the patient [17], and they are mainly women with low education comparting multiple roles [18]. In Brazil, caregivers of patients with behavioral variant frontotemporal dementia (bvFTD) experienced higher levels of distress than caregivers of AD patients, and patients’ functional limitations were associated with the burden of caregivers of bvFTD patients, whereas BPSD were associated with caregiver strain in both groups [19]. In a cross-sectional study, Peruvian informal caregivers of patients with AD, FTD, VD, and mixed dementia showed significant levels of burden and depression was a consistent predictor [20].

To the best of our knowledge, in Latin America and Caribbean countries, there has not been a study discussing caregiver burden in different types of dementia. This cross-sectional study had the following objectives: (1) determine which BPSD have the greatest impact on caregiver burden for Peruvian patients with AD, bvFTD, DLB, and VD and (2) compare the effects of BPSD on caregiver burden across AD, bvFTD, DLB, and VD. We hypothesized that DLB patients would have higher rates of BPSD than AD, bvFTD, and VD patients; moreover, we hypothesized that caregivers of DLB patients would have higher levels of burden than those with AD, bvFTD, and VD patients.

We included patients with AD (n = 88), VD (n = 52), bvFTD (n = 49), and DLB (n = 42) and their caregivers, who were recruited consecutively at the Instituto Peruano de Neurociencias (IPN) in Lima, Peru, between June 2019 and May 2023. Eligible patients with AD, VD, bvFTD, and DLB were invited to participate, according to the following diagnostic criteria: McKhann criteria for AD [21], National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l’Enseignement en Neurosciences (NINDS-AIREN) criteria for VD [22], Rascovsky et al. [23] criteria for bvFTD, and McKeith et al. [24] consensus of diagnosis for DLB. Exclusion criteria included a prior history of head trauma resulting in loss of consciousness, active epilepsy, a prior history of stroke, or a person unable to undergo an MRI due to metal in the body or severe claustrophobia. In addition, we excluded participants with any abnormal findings on MRI that would suggest prior lacunar ischemic infarcts, brain tumors, traumatic brain injury, or other pathology on neuroimaging deemed by the investigators to confound the results of neurocognitive testing or the MRI visual rating scale scores and caregivers who were paid or who interacted with patients less than 8 h/day were excluded. All participants were evaluated by neurologists and geriatricians with expertise in dementia, and the standardized neuropsychological battery was applied by experienced neurologists and two expert neuropsychologists based on the core clinical criteria for dementia [25] and the score of the Clinical Dementia Rating scale (CDR) [26]. Additionally, all patients completed a brain MRI utilizing the standardized protocol defined by the Center for Radiology (DPI) in Lima, Peru.

Sociodemographic characteristics included age, gender, years of education, and duration of disease in years. Cognitive performance was measured with a standardized neuropsychological battery and cognitive brief screening tools using the Mini-Mental State Examination (MMSE) and the Rowland Universal Dementia Assessment Scale (RUDAS), both of which have been previously validated in Peru and have been shown to appropriately discriminate between cognitively healthy individuals and those with dementia [27]. The neuropsychological battery included the following tests: Rey Auditory Verbal Learning Test, Logical Memory Subtest of the Revised Wechsler Memory Scale, Trail Making Tests A and B, Rey Complex Figure, Boston Naming Test, Wisconsin Card Sorting Test, Letter-Number (subtest of the Wechsler Adult Intelligent Scale III), Digit Span, and the WAIS-III Cubes Test. Functional impairment was examined using the Pfeffer Functional Activities Questionnaire (PFAQ) [28]. The PFAQ consists of 11 questions about activities of daily living, with scores ranging from 0 to 3 according to the functional disability severity for each activity assessed. The maximum score is 33, and a score greater than 6 indicates functional impairment.

The BPSD were assessed using the Neuropsychiatric Inventory (NPI) via an interview with their caregivers [29], including delusions, hallucinations, agitation/aggression, dysphoria/depression, anxiety, euphoria, apathy, disinhibition, irritability, aberrant motor behavior, sleep disturbances, and eating abnormalities. The score for each item is the product of the severity (1–3) multiplied by the frequency (1–4) (range 0–12). The total score (range 0–144) was assessed by caregiver observations of the patient’s behavioral disturbances during the previous 4 weeks, with higher scores indicating stronger behavioral symptoms.

The dementia’s severity was assessed by CDR [26] via an interview with the patient and the caregiver. The CDR is a widely used 5-point scale that evaluates 6 domains (memory, orientation, judgment and problem-solving, ability to work in the community, ability to complete daily tasks at home, and hobbies and self-care). Those in the cognitively healthy control group had a score of “0” (no dementia). Those with MCI had a CDR score of 0.5 (“suspected dementia” or “questionable dementia”). Those in the AD, bvFTD, DLB, and VD groups had CDR scores of 1, 2, and 3 representing mild, moderate, and severe stages, respectively.

Sociodemographic characteristics included age, gender, years of education, type of relationship to the patient, years of caring for the patient, and time spent in patient-related activities (e.g., communication, feeding, dressing, transportation, and supervision). The caregiver’s burden was evaluated using the Zarit Burden Inventory [30]. The scale comprises 22 items evaluating both the physical and emotional burden, such as the caregiver’s quality of life, psychological suffering, financial difficulties, shame, guilt, and difficulties in social and family relationships (range 0–88). The higher the score, the greater the burden.

Data were analyzed using the statistical package STATA version 17. Kolmogorov-Smirnov tests were used to check for normal distribution. For normally distributed data, we used analysis of variance (ANOVA) to compare groups (AD, bvFTD, DLB, and VD), followed by post hoc tests (the least significant difference [LSD] method) to investigate group differences. Given the non-normal distribution of NPI subscale scores for AD, bvFTD, DLB, and VD groups, correlations between Zarit Burden Inventory scores and NPI subscale scores were evaluated using Spearman’s correlation coefficient. To compare each NPI subscale score across AD, bvFTD, DLB, and VD, we used the nonparametric Kruskal-Wallis H test, following Bonferroni corrections. We considered a p value <0.05 as statistically significant. Bonferroni corrections with a significance level set at 0.0042 were used for multiple comparisons. Categorical variables were analyzed using χ² tests.

Tables 1 and 2 show demographic characteristics and clinical variables for the caregivers and patients in the four diagnostic groups. The groups were well matched for caregiver age, years of education, years of caregiving, hours of caregiving/day, and relationship to patients. About eighty percent of caregivers were female. Approximately sixty percent of the caregivers were spouses. The average education of caregivers was 11.8 years. ANOVA revealed a group difference in Zarit Burden Inventory scores (F = 13.049, p < 0.001), and post hoc tests (LSD method) showed that DLB caregivers had significantly higher levels of burden than the other patient groups (p < 0.05). No other group differences were found. Patients were similar in terms of gender, years of education, disease duration, severity of dementia, and brief cognitive assessment scores. The severity of dementia within each group ranged from mild to severe on all measures. Patient age and onset age were lower in bvFTD than in AD, DLB, and VD. ANOVA revealed a group difference in total NPI scores (AD: 23.5, bvFTD: 30.4, DLB: 40.7, VD: 18.2, F = 5.114, p < 0.001), and post hoc tests (LSD method) showed that DLB patients had significantly higher total NPI scores than other patient groups (p < 0.05) and bvFTD patients had significantly higher total NPI scores than AD and VD patients (p < 0.05).

Table 3 shows Spearman’s correlations between Zarit Burden Inventory scores and the 12 NPI subscale scores. Hallucinations, aberrant motor behavior, and apathy were the symptoms most significantly correlated with caregiver burden in those caring for DLB, bvFTD, and AD patients, respectively. Agitation and anxiety were also the symptoms most significantly correlated with DLB caregiver burden.

The current study found that the dementia subtype influenced the degree of caregiver burden and that some BPSD contributes to caregiver burden. For DLB, bvFTD, and AD patients, the BPSD that were most highly correlated with caregiver burden were hallucinations, aberrant motor behavior, and apathy, respectively; however, total NPI scores also increased caregiver burden for all four forms of dementia in Peru.

In line with previous reports, caregivers taking care of DLB patients had a significantly increased burden compared with those taking care of patients with other dementias exhibiting increased higher Zarit Burden Inventory scores associated with a higher frequency of hallucinations [5, 6, 31]; however; in a recent publication from Brazil, the caregiver burden was more affected by depression and motor features in the DLB group [32]. Additional possible explanations included the significantly higher risk of falls and functional impairment in patients with DLB. A prospective DLB cohort showed clinically relevant associations between symptomatology and disease burden; specifically cognitive and motor symptoms were related functionally, while negative neuropsychiatric symptoms and functional dependency were important determinants of quality of life and caregiver burden [33]. Independent activity of daily living function has been reported to be a risk factor associated with the burden of care [5, 7, 34, 35]. Additionally in this study, unlike Asian [5, 6, 10] and US [36] reports, the older age of caregivers may be an additional factor to burden. Older caregivers of older demented patients experience a higher care burden when patients have greater impaired functional autonomy and the presence of BPSD [35]. The influence of the COVID-19 pandemic in this sample cannot be ruled out, since an increase in BPSD in Peruvian patients with Alzheimer’s disease has been previously demonstrated [37, 38].

In this study, caregivers of bvFTD patients revealed a higher care burden compared with caregivers of AD patients, a similar finding previously reported by Huang et al. [5] and Liu et al. [6, 10]. Consistent with previous observations, aberrant motor behavior in bvFTD patients was the most frequent symptom [31] and was strongly associated with caregiver burden [10]. The evidence suggests that the increased burden is due to the higher rate of BPSD observed in bvFTD; in this case, hyperactivity symptoms may be the result of increased vulnerability to stressors and a higher susceptibility to over- or under-stimulation in individuals with dementia, which can lead to dysfunctional reactions, for example, agitation or irritability. However, a potential overlap of pathophysiological mechanisms between different dementia subtypes could explain these results [31]. Medial frontal degeneration and fronto-insular degeneration are common in bvFTD, a diagnosis characterized by disinhibition and poor social functioning [23]. We found in AD patients that apathy, delusions, agitation, depression, anxiety, irritability, aberrant motor behavior, and sleep disturbance were related with caregiver burden, in line with a systematic review study in 2017 [39].

A principal strength of this study is the inclusion of the dementia subtypes. Studies comparing caregiver burden across different etiological diagnoses are scarce [5‒7, 14], and this is the first in Latin America and Caribbean countries; nevertheless, there were several study limitations. First, the number of study participants was lower in bvFTD and DLB groups than in AD and VD groups; the relatively small sample size of the two groups influenced the representativeness of this study. Second, the study was cross-sectional and the caregiver burden assessment metric was unidimensional. A longitudinal study following caregivers from diagnosis to the end stages of the disease would likely provide an enhanced understanding of caregiver burden as the disease progresses and elucidate the impact of time on caregiver burden. Also, our sample is from a single center in our country; therefore, our results may not be valid for all the cities. Third, the diagnosis of groups was based on clinical, laboratory, and neuroimaging criteria; this may limit the interpretability of the results, as some participants may have been incorrectly classified, particularly in combination with a lack of pathological or genetic data to aid diagnosis. Identifying the dementia type that generates more caregiver stress based on behavioral symptoms can help professionals identify the needs of caregivers and propose non-pharmacological measures to modify patients’ behaviors according to the type of dementia. It is important that caregivers have the opportunity to learn and accept BPSD and their accompanying behavioral changes. This will lead caregivers toward acceptance of the diagnosis, allowing them to adjust their expectations and helping them to overcome the difficulties associated with caring for those suffering from neurodegenerative and neurovascular diseases [40].

We found that informal caregivers of patients with AD, FTD, VD, and mixed dementia had high levels of burden; moreover, depression was associated with it. Few papers have assessed this comparison because most papers are focused on AD and not on the other types of dementia due to their relatively low frequencies. Depression is commonly associated with high levels of burden; therefore, interventions on mental health factors deserve more attention.

In our cohort of Peruvian patients with different types of dementia, we found that neuropsychiatric symptoms are higher in DLB caregivers. Hallucinations, aberrant motor behavior, and apathy are the main symptoms correlated with burden. Our results show that the caregiver’s burden differs across the type of dementia. It is important to work on interventions on neuropsychiatric symptoms that have an impact on caregiver burden.

This study was performed in accordance with the Helsinki Declaration and was approved by the Committee for Medical and Health Research Ethics, Hospital Nacional Docente Madre-Niño-HONADOMANI “San Bartolomé” (10360-18). Written informed consent was obtained from all patients and caregivers enrolled in the study.

The authors have no conflicts of interest to declare.

This work was self-funded. NC and RM were supported by the National Institute of Health (R56AG069118-01) and Multi-Partner Consortium to Expand Dementia Research in Latin America (ReDLat), supported by the National Institutes of Health, National Institutes of Aging (R01 AG057234).

N.C. and B.C. designed the study. N.C., R.M., B.C., and D.C.-M. supervised data collection. R.M., G.V.-A., K.A., J.A.-Z., L.A.-V., and W.-S. collected the data. M.M., D.C.-M., and B.C. were responsible for the statistical design of the study. N.C. carried out the statistical analysis. R.M., B.C., and N.C. wrote the paper. M.M., D.C.-M., G.V.-A., K.A., J.A.-Z., L.A.-V., and W.S. critically reviewed the manuscript. All authors agreed to the final version.

Authors confirm that the data supporting the findings of this study are available within reasonable request. Data are not publicly available due to ethical reasons. Further inquiries can be directed to the corresponding author.