Dementia with Lewy bodies (DLB) represents the second most common type of neurodegenerative dementia after Alzheimer's disease dementia (ADD) among older people. Patients with DLB present with not only cognitive impairment as do patients with ADD, but also various symptoms such as Parkinsonism, visual hallucinations, REM sleep behavioral disorder (RBD), cognitive fluctuation, and depressive mood from early stages onwards (1). Therefore, various factors contribute to deficits in activities of daily living (ADL) (2), and family caregivers experience a high burden (3–5) in cases of patients with DLB rather than those with ADD, although there is a report that shows no difference in caregiver burden between DLB and ADD (6).

Previous studies have documented that the high caregiver burden in DLB is affected by behavioral and psychological symptoms of dementia (BPSD) in addition to impaired ADL (4, 5). However, it is still unclear what kind of BPSD affects caregiver burden in DLB. The variety and interaction of symptoms in DLB may render it difficult to shed light on the relationship between caregiver burden and BPSD. Previous studies of ADD and mild cognitive impairment (MCI) revealed that BPSD consists of three factors of hyperactivity, and affective and psychotic symptoms, resulting from factor analysis of the 12-item Neuropsychiatric Inventory (NPI) (7, 8). Similar clusters of BPSD in DLB are considered to exist, but have not yet been confirmed.

The present study sought to verify the factors of BPSD in DLB using an exploratory factor analysis of NPI, and to evaluate the association between caregiver burden and each factor of BPSD in DLB.

This study sheds light on the characteristics of BPSD and the association between BPSD and caregiver burden in DLB. The factor analysis revealed four factors of BPSD in DLB, namely “psychosis,” “affection,” “wakefulness,” and “hyperactivity.” Caregiver burden was linked to a number of symptoms, and multivariate regression analyses revealed that each BPSD factor affected different aspects of caregiver burden.

The exploratory factor analysis revealed that BPSD was classified into four factors. Three of them, “psychosis,” “affection,” and “hyperactivity,” were reported in previous studies on ADD, MCI, and vascular cognitive impairment (7, 8, 17, 18) and were considered to be common factors of DLB and other dementia. The other “wakefulness” factor consisted of nighttime behaviors and cognitive fluctuation, which are specific symptoms in DLB compared with other types of dementia. We previously reported that increased limb movement during nighttime sleep, as measured by actigraphy, was related to cognitive fluctuation (19). The characteristics of cognitive fluctuation in DLB have been reported as disturbed arousal, such as excessive daytime sleepiness (20). As such, cognitive fluctuation is considered to be caused by sleep–wake disorder, and the “wakefulness” factor would be reasonable as a factor characteristic of DLB.

Alongside MMSE, IADL, and PSMS, the factors of “psychosis” and “affection” in BPSD were positively associated with caregiver burden in DLB. “Wakefulness” factor tended to be associated with the RS score in ZBI. These factors are frequently observed in DLB (10). These results are consistent with those of previous studies showing a relationship between BPSD and caregiver burden in DLB (3, 4). However, “hyperactivity” factor was not related to caregiver burden. In general, hyperactivity symptoms have been reported to affect caregiver burden in patients with dementia (21, 22), which is contrary to the present results. This may be influenced by the fact that motor disturbance and disinhibition in “hyperactivity” were less common in the current participants, which is consistent with the results of a previous multicenter study on BPSD (23). A systematic review showed that irritability, sleep disturbances, and anxiety were the most reported symptoms to impact caregivers, and that irritability, agitation, delusions, and apathy contribute the most to overall caregiver burden in patients with dementia (24). These symptoms were included in the “psychosis,” “affection,” and “wakefulness” factors, suggesting that the present results are consistent with the findings of this study. A study examining the impact of BPSD on caregiver distress in DLB and ADD reported that disinhibition, apathy, irritability, agitation, and aberrant motor behavior were important contributors to caregiver distress in ADD, whereas apathy, sleep disturbances, and aberrant motor behavior affected caregiver distress in DLB (25). Compared with ADD, “affection” and “wakefulness” factors may have more impact on caregiver burden in DLB.

Multiple regression analyses demonstrated that deficits in IADL were independently associated with all of the total, PS, and RS scores in ZBI after correcting various patient's conditions. The results agree with the relationship between caregiver burden and IADL reported in previous studies on dementia (21, 26) including DLB (3, 27). Multiple regression analyses also revealed that the “psychosis” factor was also associated with the total score in ZBI, and that the “affection” factor was independently associated with the total and PS scores in ZBI. A previous study examining the relationship between caregiver burden and symptoms in Lewy body dementia reported that IADL and non-motor symptoms were related to caregiver burden in DLB, whereas motor symptoms and IADL were related to caregiver burden in Parkinson's disease dementia (28). The previous and the present results are consistent in suggesting that non-motor symptoms, including BPSD, have a greater impact on the caregiver burden in DLB than motor symptoms. A previous validation study of ZBI reported that PS was related to BPSD, while RS was related to ADL deficits in impaired older people (29). We also reported that an improvement in BPSD was related to a decrease in PS in ZBI after shunt surgery in patients with iNPH (30). Therefore, these results replicate the association between BPSD and PS of ZBI in DLB. By contrast, the “wakefulness” factor was associated with the RS score in ZBI. As previously mentioned, the “wakefulness” factor is considered to be strongly related to daytime excessive sleepiness and to be more closely related to ADL than other BPSD. Therefore, this factor may be more related to RS than to PS.

In the present study, about 53% of the participants were females. Originally, it was often reported that males were more common in DLB in the 1990s (31–34). However, it has also been reported that females are more prevalent in DLB since 2000 (35–37). Gender difference in DLB may be debatable. In addition, it was reported that DLB patients with auditory hallucinations as their first symptom were more likely to be female (38). Since the patients with DLB in the present study were recruited from our outpatient clinic in Department of Psychiatry, it is possible that the number of patients with such psychiatric symptoms as their first symptoms was relatively high.

This study has several key strengths. First, we recruited over 100 patients with probable DLB, which is a sufficient number to perform a factor analysis on 12 variables and multivariate regression analyses. Second, we evaluated cognitive fluctuations in the same manner as the NPI. Therefore, we conducted a factor analysis with cognitive fluctuation in addition to various BPSDs and could reveal the “wakefulness” factor specific to DLB.

This study is also limited in a number of ways. First, this was a single-center, retrospective, cross-sectional study, which may have incurred a certain degree of bias. Second, we used two diagnostic criteria for probable DLB depending on when the patient visited our clinic. However, most current participants who were diagnosed until July 2017 also met the 2017 version of the diagnostic criteria for probable DLB. Third, we did not conduct confirmatory factor analysis because there were no previous studies that conducted a factor analysis of BPSD in DLB alone. Finally, some patients were prescribed choline esterase inhibitors and/or memantine, which might affect BPSD. However, the number of patients actually being prescribed these was relatively small. This may be due to the fact that many patients were undiagnosed in the early stages due to the nature of the facilities from which they were recruited. In fact, 38 of the participants were judged 0.5 in CDR, 39 were judged 1 in CDR, and more than 2/3 of the participants were very mild to mild stage of DLB. It should be noted that the results of this study are the findings in patients with these characteristics.

In conclusion, this study demonstrated that BPSD in DLB consists of four factors: “psychosis,” “affection,” “wakefulness,” and “hyperactivity.” Three factors were common to other dementia, and the “wakefulness” factor was considered to extract the characteristics of BPSD in DLB. In addition to IADL, “psychosis,” “affection,” and “wakefulness” factors of BPSD could affect caregiver burden. It is clinically noteworthy that factors of BPSD other than “hyperactivity,” which is generally reported to influence caregiver burden, may influence caregiver burden in DLB.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by the Research Ethical Committee of the Osaka University Hospital (Suita, Japan). Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.

HK designed the study and wrote the initial draft of the article. MI contributed to the interpretation of data and assisted in the preparation of the article. SS, YS, FK, DT, AK, TW, and KY have contributed to data collection, interpretation, and reviewed the article. All authors approved the article and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

This work was supported by JSPS KAKENHI under Grant No. T21K157300 and AMED under Grant No. JP21dk0207056.

HK, KY, and MI report grants and personal fees from Eisai Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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