Caregiving and Caregiver Burden in Dementia Home Care: Results from the Prospective Dementia Registry (PRODEM) of the Austrian Alzheimer Society

Abstract

Background:

Comprehensive studies on caregiver burden (CB) of persons caring for dementia patients differ methodologically and show variable results.

Objective:

Analysis of known and hypothesized factors of CB in home care of dementia patients.

Methods:

Multicenter longitudinal study comprising 585 persons caring mostly for Alzheimer’s disease patients (age median 77.25 years, Mini-Mental State Examination raw score median 23) using the Zarit Caregiver Burden Interview (CBI). Known patient-related determinants of CB were studied, such as dementia severity (Clinical Dementia Rating, CDR), neuropsychological deficits (CERAD-Plus), neuropsychiatric symptoms (Neuropsychiatric Inventory, NPI), disability (Disability Assessment for Dementia, DAD), dependency (Dependency Scale, DS), and moreover, unclarified potential factors (age, sex, education of patients; age, sex, occupational status of the caregivers; family relationship). Psychological and somatic effects of CB were analyzed (factor analysis).

Results:

Caregiver age was median 61. Female caregivers prevailed (67.8%). Median CBI sum score (CBIss) was 16 at baseline. After two years, CBIss was 22 and 37% of the caregivers reported mild to moderate (CBIss 21–40), 16.8% moderate to severe or severe (≥41), and 46.2% absent to little CB (CBIss ≤ 20). CB correlated positively with NPI, CDR, DS scores, disability (DAD), years of education of the patients, and proximity of patient and caregiver sex (female), and negatively with caregiver age. Caregivers reported restrictions of time, health problems, and negative emotions.

Conclusion:

The findings are applicable to identify persons at risk for substantial CB and its consequences. There is demand for personal, psychological, and medical support of caregivers and increasing male participation.

Keywords

Caregiver burden dementia dementia severity dependency home care Zarit Caregiver Burden Interview neuropsychiatric symptoms

INTRODUCTION

Patients with mild or moderate dementia are mostly cared for by informal caregivers in their homes [1]. Some thirty years ago caregiver burden (CB) was addressed for the first time in the medical literature and since then has been of ongoing interest [2]. Comparative studies on CB, its determinants, and negative consequences for caregivers have been performed in several European countries [3 –7]. In most countries caregiving of dementia patients is informal and a female domain. Neuropsychiatric symptoms and abnormal behavior of the patient, dementia severity, low level of education and family income, impaired health status of the caregiver and lack of support including deficits in dementia care organization are known determinants of CB [1 , 3–8]. Whether family relationship, age, sex, education, degree of dependency of the patient, and age, sex and occupational status of the caregiver are determining factors of CB has not been addressed in these studies or was viewed differently [1 , 3–8]. Consequences of long-term caregiving, such as psychological distress, restrictions in occupation, family life and social activities or health problems have been highlighted in recent studies [3 –8]. Severity of CB seems to vary between countries [3 –8]. Except for studies in small collectives of caregivers [3] comprehensive data from Austria is missing.

The objective of this multi-center longitudinal study was to analyze the burden of caregiving of persons caring for dementia patients in their homes in Austria. We hypothesized that caregiving is mainly informal and a female domain. CB was hypothesized to increase over time in relation to dementia progression, neuropsychological and behavioral deterioration, disability, and dependency, as demonstrated in recent studies, but may also stabilize in response to treatment [3 –10]. Moreover, analysis of so far uncertain factors of CB, such as demographic parameters, education, occupation of the patient and the caregiver, dependency, and family relationship could contribute to a better understanding of CB. Another aim was to analyze caregiving-related stressors and to compare the findings to other studies. Finally, we hypothesized that global severity of CB might be similar to that in other western countries.

METHODS

The PRODEM study

The Prospective Registry on Dementia Austria (PRODEM) is an ongoing study of the Austrian Alzheimer’s Disease Society, initiated in 2008. Thirteen memory clinics in six of nine states of Austria participate and analyze various aspects of dementia, such as dementia progression, neuropsychological and neuropsychiatric deterioration, disability, activities of daily living, dependency, medication, MRI findings, EEG, and aspects of personal care including CB. Included patients live at home and are part-time supervised or cared for. The local ethics committees of the state of Upper Austria (Vote code 2008.04.25) and the Medical Universities of Innsbruck (UN3259/2009), Vienna (176/2008) and Graz (19–135 ex 07/08) approved the study. Informed written consent was obtained from the patient and the caregiver. Follow-up (FU) examinations are scheduled 6, 12, and 24 months after baseline (BL; FU 1, 2, and 3, respectively). The study ends after two years or earlier due to loss to FU, withdrawal of consent, death or institutionalization of the patient.

Diagnostic procedures, and scales

For dementia diagnosis, dementia onset and symptoms, concomitant and previous diseases, medication, and family history are assessed at BL. Patients are clinically examined including routine blood laboratory, vitamin B12 and folate serum levels, HIV and TPHA serology and cerebral MRI or CT. In accordance with previous studies [3 –9] and for diagnostic reasons, parameters are assessed that are hypothesized or known to determine CB, such as dementia severity, neuropsychological deficits, neuropsychiatric symptoms, disability, and dependency, using the following inventories and tests at BL and at the FU 1, 2, and 3.

The Clinical Dementia Rating (CDR [11]): The examiner evaluates impairment of memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care of the patient using semi-structured questionnaires addressed to the caregiver and the patient. An algorithm results in scores ranging from 0 to 3 (0, normal cognition; 0.5, mild cognitive impairment; 1, mild; 2, moderate; 3, severe dementia).

The Consortium on the Establishment of a Registry in Alzheimer’s Disease (CERAD)-Plus neuropsychological battery [12] which tests performance in frontal-executive functions, recognition, language, verbal learning and short-term memory, visuospatial and visual-motor functions and short-term memory, processing speed, divided attention and global intellectual performance (Mini-Mental State Examination; MMSE). Z scores are calculated for each subtest in relation to healthy control persons matched for age, sex and education years [12].

The Neuropsychiatric Inventory (NPI, [13]): Caregivers rate presence, frequency (range: 1–4 points) and severity (1–3 points) of twelve categories of neuropsychiatric symptoms and behavioral abnormalities of the patient. The products of frequency and severity of these categories are added. The total score reflects overall severity of neuropsychiatric impairment (range: 0, symptomless, to 144 points, maximum impairment).

The Disability Assessment for Dementia (DAD, [14]): This questionnaire addresses 40 questions to the caregiver on initiation, planning, organization, and effective performance in daily living and leisure time activities of the patient. Ratings are converted to a percentage score, with higher scores representing less disability.

The Dependency Scale (DS, [15]) is a 13-item caregiver survey about the patient’s need for help in daily living. The higher the sum score (range: 0–15) the more dependent the patient is.

In accordance with recent studies age, sex, education, occupation and marital status of the patients, demographic data and occupational status of the caregivers and relationship of the caregivers were also noted and analyzed [3 –9].

The Caregiver Burden Interview (CBI): Felt burden of caregiving was rated at BL and at FU visits using the CBI [16], a self-rating questionnaire comprising 21 questions on the felt frequency of limitations in personal and social life, health strain, feelings of insufficiency and guilt, and one question on general (overall) CB. Each question is scaled from 0 to 4 (range score 0, “never”, score 4, “nearly always”). The sum scores of the 22 questions (CBIss) were classified according to the literature: CBIss 0–20 indicate absent or little CB, for better readability designated as little CB in this article, 21–40 mild to moderate CB, designated as mild CB, 41–60 moderate to severe CB, moderate CB, and 61–88, severe, severe CB [17]. CBIss of 26 or higher suggest harmful effects of the CB for mental health [18].

From 2008 to 2015, 239 male and 346 female (40.8% and 59.1%), altogether 585 patients and their caregivers were recruited. Demographic data, clinical diagnoses and the results of the clinical ratings and the neuropsychological tests at BL are summarized in Table 1. Probable Alzheimer’s disease (AD) was diagnosed according to the NINCDS-ADRDA criteria of 1984 [19]. Patients with the clinical diagnosis of AD, but MRI evidence of confluent cerebrovascular pathology were classified as possible AD. Possible AD and probable AD prevailed (together 571 out of 585 patients). The remaining patients suffered from frontotemporal dementia, behavioral variant, semantic dementia, dementia with Lewy bodies, vascular and unclassified dementia [20 –22] (Table 1).

Table 1

Patients: Demographic and clinical data at baseline (means, standard deviations, medians)

Variable	Male patients		Female patients		All patients
	Mean±SD	Median	Mean±SD	Median	Mean±SD	Median
Age	75.32±11.40	77.00	76.04±10.94	77.58	75.74±11.12	77.25
Dementia	30.47±23.71	24.00	29.20±26.55	24.00	29.71±25.43	24.00
Duration (mo)
CDR Scores	0.91±0.5	1.00	0.90±0.53	1.00	0.91±0.54	1.00
MMSE raw scores	22.22±4.55	23	21.94±4.04	23	22.06±4.26	23
MMSE Z-sum scores^*	–3.14±1.97	–3.05	–3.53±2.08	–3.50	–3.37±2.04	–3.30
CERAD-Plus	–9.38±9.40	–8.71	–10.81±5.38	–10.50	–10.23±7.30	–9.70
Z-sum scores
DAD	73.05±25.36	76.92	78.95±22.63	84.62	76.53±24.36	84.62
Percentage scores^***
DS	6.15±3.23	6.0	6.01±3.37	6.0	6.07±3.31	6.0
Sum scores
NPI	13.63±16.73	7.0	13.18±17.18	7.0	13.36±16.98	7.0
Total scores
Diagnosis (N/%)
Probable AD	147 (61.5)		237 (68.5)		384 (65.6)
Possible AD	86 (36.0)		101 (29.2)		187 (32.0)
Other dementias^#	6 (2.5)		8 (2.3)		14 (2.4)
All	239 (100)		346 (100)		585 (100)

AD, Alzheimer’s disease; CDR, Clinical Dementia Rating; CERAD-Plus, Consortium on the Establishment of a Registry in Alzheimer’s Disease-Plus neuropsychological battery; DAD, Disability Assessment for Dementia questionnaire; DS, Dependency Scale; MMSE, Mini-Mental State Examination; mo, months; NPI, Neuropsychiatric Inventory; SD, standard deviation. ^#see section Methods: The PRODEM study. text. Comparison of the parameters for differences between male and female patients (Student t-test). Only significant differences are indicated. ^*p < 0.05, ^***p < 0.0001.

Statistical analysis

The demographic and clinical parameters of male and female patients were compared using Student t, Mann Whitney U, and G-tests. CB was analyzed with respect to demographic and clinical parameters (tests and inventories), education and occupation of the patients, relationship between patient and caregiver, and demographic parameters and occupational status of the caregivers. From the longitudinal data containing information about patients and caregivers, the evolution of potential influential factors over time was assessed using the McNemar or Wilcoxon test. To characterize dependencies between caregiver burden and covariates, the G test was used. Factor analysis was applied as an explorative tool to evaluate dimensions of CB in agreement with the literature [23]. After identifying risk factors for CB according to the literature [3 , 6–9], ordinal regression analysis was applied to estimate the effects of these covariates. Finally, a linear mixed model was estimated to investigate in more detail the development of CB over time. The analysis was performed with statistics software R [24]); packages used for regression analysis were MASS and regr0, for factor analysis nFactors, the package Deducer for the G tests and nlme for fitting a mixed model.

RESULTS

Patients

Median age was 77.25 and median MMSE raw sum score 23. Age, dementia duration, and the test scores with the exception of the MMSE-z-sum and the DAD percentage scores were not statistically different in male and female patients (p > 0.05, t-tests, Table 1). MMSE z-sum scores were significantly lower (p < 0.05, t-test) and the DAD percentage scores significantly higher (less disability; p < 0.0001, t-test, Table 1) in female compared to male patients. The highest educational levels and the occupational categories of the patients are summarized in Table 2. The educational level was in general lower in female than in male patients. There was a higher proportion of male than female patients with white collar occupations and self-employment.

Table 2

Patients: Highest levels of education (years of education and school type) and occupational categories

	Male patients	Female patients	All patients
	n (%)	n (%)	n (%)
Years of formal education
9, ES, elementary school	57 (23.8)	188 (54.3)	245 (41.9)
11, ES+apprenticeship	76 (31.8)	58 (16.7)	134 (22.9)
12, high school	29 (12.1)	30 (8.6)	59 (10.1)
13, vocational secondary high school	41 (17.1)	42 (12.1)	83 (14.2)
14, teachers college	8 (3.3)	13 (3.7)	21 (3.5)
17, university	27 (11.3)	12 (3.4)	39 (6.6)
missing data	1 (0.4)	3 (0.8)	4 (0.6)
all	239 (100)	346 (100)	585 (100)
Occupational categories (longest - occupation in life)
1 blue collar	88 (37.1)	127 (37.0)	215 (37.1)
2 white collar	133 (56.1)	149 (43.4)	282 (48.6)
3 self-employed	16 (6.8)	12 (3.5)	28 (4.8)
4 household	0 (0.0)	55 (16.0)	55 (9.5)
all	237 (100)	343 (100)	580 (100)

Indicated are numbers of male, female and all patients and percentages (in brackets).

Caregivers

Demographic data of the caregivers, CBIss, occupational status, and relationship of the caregiver to the patient are summarized in Table 3. Age was mean 60.65±14.01(SD), median 61 years. Informal caregiving (95.7%) and female caregivers (68%) prevailed. Female caregivers were younger (p < 0.0001, t-test) than caregiving men. Larger proportions of female than male caregivers were employed (38.1% versus 31.8%). Part-time employment was more prevalent in female than male caregivers (16.2 versus 1.6%), in contrast to full-time employment (30.2% in male, 21.8% in female caregivers). Retired persons prevailed among male compared to female caregivers (60.4 versus 53.2%). Partners were the largest subgroups of caregivers in both sexes. Among female caregivers the proportion of caregiving partners was smaller (46.5 versus 56.7%) and the proportion of “other relatives” (sons or daughters-in-law, cousins, nephews, nieces, or grandchildren) larger than among male caregivers (13.3 versus 5.4%).

Table 3

Caregivers: Age, sex, Caregiver Burden Interview sum score, occupational status, relationship to patient

	Mean±SD	Median	Mean±SD	Median	Mean±SD	Median
	Male (n = 183)		Female (n = 397)		All (n = 580)
Age^**	63.67±14.91	65	59.36±13.48	60	60.65±14.01	61
CBIss^**	17.13±13.45	14	20.32±14.26	18	19.28±14.01	16
	n (%)		n (%)		n (%)
Occupational status
Unemployed	3 (1.6)		5 (1.2)		8 (1.4)
Full-time employed	55 (30.2)		84 (21.8)		139 (24.5)
Part-time employed	3 (1.6)		63 (16.2)		66 (11.2)
Student	1 (0.5)		2 (0.5)		3 (0.5)
Retired	110 (60.4)		205 (53.2)		315 (55.5)
Other	1 0 (5.4)		26 (6.7)		36 (6.3)
All	182 (100)		385 (100)		567 (100)
Relation caregiver and patient
Partner	105 (56.7)		181 (46.5)		286 (49.7)
Child	63 (34.0)		138 (35.5)		201 (35.0)
Other relatives	10 (5.4)		52 (13.3)		62 (10.8)
Other relationship	6 (3.2)		19 (4.6)		25 (4.3)
All	184 (100)		390 (100)		574 (100)

CBIss, Caregiver Burden interview sum score; SD, standard deviation. Male caregivers were compared to female caregivers for differences of age (Student t-test), Caregiver Burden Interview sum score (Student t test). Only significant differences are indicated. ^**p < 0.01.

The number of participating caregivers and patients decreased with duration of FU. Four hundred fifteen patients and caregivers were re-examined six months (FU1), 332, twelve months (FU2), and 208, two years after BL (FU3). Part of the caregivers were active in the study and had not yet completed FU evaluations. Other caregivers and patients had dropped-out because of trauma, illness, death or institutionalization of the patient, were lost to FU, or had withdrawn their consent to the study.

Caregiver burden at baseline and during follow-up

At BL, CBIss was median 16, mean±SD 19.28±14.01, and was significantly lower in male than in female caregivers (median 14 versus 18, mean±SD 17.13±13.45 versus 20.32±14.26, Table 3, t test, p = 0.005). It significantly increased to a median of 22 at FU3 (McNemar test, Table 4, p < 0.0001). CB at BL was classified as little (CBIss ≤20, The Caregiver Burden Interview) in 342 caregivers (59%), mild (CBIss 21–40) in 177 (31%), moderate (41–60) in 49 (8%), and severe (>60) in 3 (0.5%, Fig. 1). At FU1 CB was little in 56.5% patients, mild in 32.2%, moderate in 10.8% , severe in 0.5%, at FU2, in 50.1%, 34.3%, 14.1% and 1.5%, at FU3, in 46.2%, 37%, 14.9%, and 1.9%, respectively. A CBIss of 26 or higher is considered harmful for mental health [18] and was reported by 25% of the caregivers at BL and by 44% at FU 3.

Fig.1

Caregiver burden (Caregiver Burden Interview sum scores) at baseline and at follow-up visits, bar plots. BL, baseline; CBIss, Caregiver Burden Interview sum score; FU, follow-up; NA, not applicable. Bars indicate proportions of patients at baseline and at the follow-up visits allocated to different classes of caregiver burden: CBIss 0–20 indicate little, 21–40 mild, 41–60 moderate, and 61–88, severe CB. Statistics see Legend Table 4.

Table 4

Caregiver Burden Interview sum scores, Clinical Dementia Rating scores, CERAD-Plus z sum scores, and Mini-Mental State Examination z scores, Neuropsychiatric Inventory total scores, Dependency Scale sum scores at baseline and at follow-up visits

Tests	Min.	X1st Qu.	Median	Mean	SD	X3rd Qu.	Max	NA
CBIss^#
Baseline	0	8	16	19.28	14.26	27	64	28
Follow-up1	0	8	17	20.28	14.96	30	69	166
Follow-up2^**	0	10	20.5	22.97	16.15	33.25	79	247
Follow-up3^***	0	12	22	24.42	15.99	35	83	377
CDR
Baseline	0	0.5	1	0.91	0.54	1	3	8
Follow-up1^**	0	0.5	1	1	0.62	1	3	157
Follow-up2^***	0	0.5	1	1.09	0.69	1	3	239
Follow-up3^**	0	0.5	1	1.29	0.78	2	3	372
CERAD-Plus
Baseline	–103.4	–13.4	–9.7	–10.23	7.29	–6.6	54	83
Follow-up1^***	–45.2	–14.4	–9.7	–10.49	6.12	–6.39	11.9	226
Follow-up2^***	–34.8	–15.14	–10.4	–11.21	6.48	–6.67	5.2	290
Follow-up3^***	–28.7	–17.08	–11.75	–12.22	6.80	–7.53	5.64	415
MMSE
Baseline	–9.91	–4.4	–3.3	–3.37	2.04	–2.1	16	69
Follow-up1^***	–10.4	–4.8	–3.6	–3.73	2	–2.4	4.2	204
Follow-up2^***	–11.1	–5.3	–3.8	–4.0	2.16	–2.49	2.1	276
Follow-up3^***	–11.48	–6.68	–4.2	–4.67	2.53	–2.8	0.8	400
NPI
Baseline	0	2	7	13.36	16.98	20	98	20
Follow-up1	0	2	7	12.97	15.62	20	88	158
Follow-up2	0	2	8	14.05	17.41	19	101	238
Follow-up3	0	3	8	15.45	19.14	22	103	372
DS
Baseline	0	4	6	6.07	3.31	8	15	27
Follow-up1^***	0	4	7	6.84	3.06	9	18	166
Follow-up2^***	0	4.25	7	7.28	3.02	10	16	247
Follow-up3^*	0	5	9	8.48	3.28	11	17	378

CBIss, Caregiver Burden Interview sum score; CDR, Clinical Dementia Rating scores; CERAD-Plus, Consortium on the Establishment of a Registry in Alzheimer’s Disease-Plus neuropsychological battery sum z scores; DS, Dependency Scale sum scores; Max, maximum; Min, minimum; MMSE, Mini-Mental State Examination z sum-scores; NA, not applicable; NPI, Neuropsychiatric Inventory total scores; SD, standard deviation; X1st Qu, first quartile; X3rd Qu, third quartile. Comparison of the scores of the indicated tests and inventories for differences between BL and the FU visits. Only significant differences are indicated. Significance levels of *p < 0.05, ^**p < 0.01 and ^***p < 0.0001. Threshold values used to test for significant transitions from BL to FU1, from BL to FU2, and from BL to FU3 (McNemar-test) are 1 for CDR, 8 for DS sum score and 20 for the CBI sum scores. Wilcoxon test for paired samples was applied for comparison of CERAD-Plus, MMSE z sum scores, and NPI total scores. ^#Wilcoxon test for paired samples showed qualitatively the same results for CBI sum scores as McNemar test (from BL to FU1 not significant (p > 0.05), BL to FU2 p < 0.0001, BL to FU3 p < 0.0001).

A CBIss of 20 was chosen as the parameter of interest to test for significant transitions from little to mild CB (McNemar test, Table 4). From BL to FU 1 the transition of the CBIss from little to mild was not significant (p-value = 0.8525). From BL to FU 2 and from BL to FU3 there was significant CBIss progression (p < 0.01 and <0.0001, respectively), with increasing proportions of participating caregivers reporting mild, moderate, and severe CB (Table 4, Fig. 1). Wilcoxon test for paired samples revealed no change of CBIss from BL to FU1 (p > 0.05), however, significant progression from BL to FU2 (p < 0.0001) and from BL to FU3 (p < 0.0001).

Disease severity (Clinical Dementia Rating), neuropsychological measures (CERAD-Plus, MMSE), neuropsychiatric symptoms (Neuropsychiatric Inventory) and dependency (Dependency Scale) at baseline and during follow-up

To find an explanation for the increase of the CBIss with duration of FU we analyzed the progression of disease-related parameters with duration of FU. CDR scores increased mildly from BL to FU 1, 2, and 3 (Table 4). A minimum of 75% of the patients were rated as having a CDR score not exceeding 1 from BL to FU2. At FU3, 35.7% of the patients had a score higher than 1. McNemar tests with a threshold of 1 show that CDR levels were significantly different between BL and all follow-ups (from BL to FU1 and to FU3 p < 0.01, from BL to FU2 p < 0.0001). CERAD-Plus and MMSE total scores (shown as z scores) deteriorated significantly from BL to FU1, BL to FU2 and BL to FU3 (Wilcoxon test for paired samples, all comparisons p < 0.0001, Table 4). NPI total scores increased insignificantly from BL to FU 1, 2, and 3 (Wilcoxon p > 0.05, Table 4). A DS of 8 was chosen as the threshold of transition for significant deterioration of DS from BL to FU1, 2 and 3 (McNemar test). The increase in DS sum scores from BL to FU1 (p < 0.0001), from BL to FU2 (p < 0.0001), and from BL to FU 3 (p < 0.05) was significant (Table 4).

Relationship of caregiver burden to demographic parameters, education, occupation and family relationship

The relation of CB to age (age groups ≤71; 72–77; 78–82, 83–96 years) and gender of the patients, age (age groups ≤50, 51–61, 62–72, and 73–93 years of age) and gender of the caregivers, education in years and longest occupation in life of the patients (occupation category), occupational status of caregivers, and relationship of caregiver to patient was examined at BL. No significant relationship was found between CB and these parameters using G-tests (patient’s sex: p = 0.0782, patient’s age (grouped) p = 0.067, caregiver’s age (grouped) p = 0.106, occupation category: p = 0.9866, education in years: p = 0.395, relation patient to caregiver: p = 0.3014).

Caregiver burden in relation to clinical dementia rating

In accordance with previous studies describing a relation between CB and dementia severity [3 –7], we tested whether CB was related to dementia severity. According to the performed G-test, CB correlated significantly with the CDR score (p value of G-test <0.0001; Fig. 2, Spearman’s ρ= 0.448, p < 0.0001).

Fig.2

Caregiver burden Interview sum-scores in relation to severity of disease (Clinical Dementia Rating), box plots. CBIss, Caregiver Burden interview sum-scores; CDR, Clinical Dementia Rating scores. G-test showed that caregiver burden (CBIss) correlated significantly with the CDR score (p < 0.0001). Spearman’s correlation coefficient (0.448) shows medium positive correlation between these two scores, p < 0.0001.

Dimensions of caregiver burden-factor analysis

We hypothesized that in agreement with previous studies [3 , 23] evaluation of the caregivers’ responses to the CBI questions could reveal clusters of stressors of caregiving. A factor analysis was performed that included questions 1 to 21. CBI question 22 asks for overall (global) CB and was therefore not included. The number of factors was determined using the Kaiser criterion and a scree plot. The Kaiser criterion as well as parallel analysis and optimal coordinates suggested that four factors should be selected (four factors explaining 50.7% and resulting also in a better assignment of items to factors and closer relationship to blocks provided in the literature) [16]. Three factors explained only 46.6% of the variance. Factor 1 captured limitations on personal needs and privacy and strain with regard to social activities, occupation and family. Factor 2 summarized feelings of loss of energy and control, decline in health, and uncertainty about caregiving activities, Factor 3, feelings of doubt about sufficient caregiving, and Factor 4 strong emotions, such as discomfort, embarrassment and strain. Generalized linear models showed a significant impact of the combined variables, representing the factors, on the dichotomous outcome of Question 22. However, the estimation showed that Factor 4 did not have a significant impact on this question. Using different link functions for the generalized linear model, i.e., binomial with logit and probit, as well as Poisson showed similar results.

Influence of various indices on caregiver burden: Logistic regression analysis

To address the question which patient or caregiver-related variables may cause CB [3 , 8], an ordered logistic regression model was calculated based on data available for 431 cases using the overall felt CB (Question 22 of the CBI), an ordinal variable, as the dependent variable. The indices MMSE z sum scores, CERAD-plus z sum scores, CDR scores, NPI total scores, DAD percentage scores, DS sum scores at BL, age and sex of patient and caregiver, patient education (years), relationship of the patient to the caregiver (caregiving married and unmarried partner versus other caregiver) and caregiver occupational status at BL were used as explanatory variables. CB increased with increasing NPI total scores, CDR score, years of education of the patient, and DS sum scores.

Further analysis suggested to dichotomize the relationship between caregiver and patient into partnership and other relationship. Model selection was based on minimizing AIC in a stepwise way. Ordered logistic regression showed that caregiving partners had a greater probability of more severe CB than did caregivers with other relationships to the patient (p = 0.04837). A significant effect of patient education was estimated (ANOVA, p = 0.0218, greater probability of greater CB with 17 compared to nine years of education). Higher DS scores and NPI total scores increased, whereas increasing caregiver age decreased the probability of greater CB. Greater probability of less CB was estimated for CDR values of 0.5, 1, 2, and of greater CB for a CDR value of 3. No significant effect was found for the other remaining variables.

Simultaneous analysis over all time points-linear mixed effects model

Out of 585 patients and caregivers, 58 had the required data available to carry out a simultaneous analysis on the CBIss using BL as well as the three FU time points. With these data we calculated a linear mixed effects model to explore time effects beyond the before described risk factors. Patient specific effects were incorporated as random intercepts. We also considered interaction terms of our covariates with time, but could not detect significant changes in covariate effects. We present the details of our chosen linear mixed effects model in Supplementary Table 1. Diagnostic plots of the residuals showed no signs of heteroscedasticity, or other model violations. The model reveals that time is an influential factor, increasing the burden felt by the caregiver beyond what can be explained by the overall severity of dementia (as measured by DAD, NPI, DS). In addition, caregivers suffer a stronger burden when DAD is more severe or NPI is higher. Moreover, for both female caregivers and patients, CB is larger compared to male caregivers and male patients, respectively. Compared to our BL analysis, fewer factors were significant. We attribute this to the smaller sample size with a mixed model. Indeed, only 58 cases had data for all four time points of analysis, compared to 431 patients available for our BL analysis.

DISCUSSION

This national multi-center longitudinal study included caregivers of patients living at home who for the most part suffered from mild or moderate probable or possible AD and exhibited on average mild neuropsychiatric symptoms (median NPI total score 7 at BL). The study was performed in 13 memory clinics in six of nine Austrian states (referral centers for urban and rural populations) and may therefore be considered representative for Austria. Informal caregiving prevailed (95.7%). Most patients were cared for by female family members and spouses played an important role in caregiving, but also children, mostly daughters, which corresponds to international findings [3–6 , 25–42].

Our primary hypothesis was that, in agreement with most other studies, CB is related to progressive dementia, expressed by loss of functions in activities of daily living, overall disease severity and need of time for caregiving [3 , 40–42]. This hypothesis was confirmed in the present study showing deterioration of CB (CBIss) in relation to dementia progression (CDR). At BL median CBIss was in the low range in most patients. The significant increase of the CBIss and of the proportions of caregivers with moderate or severe CB (according to our nomenclature) and elevated health risk (CBIss of 26 or higher [18]) during FU demonstrates that CB is an important issue in dementia care in Austria, which has so far not been comprehensively addressed. Logistic regression analysis found a relationship of severity of CB and CDR. Some studies demonstrated that CB may stabilize over time in response to support interventions and medical treatment [9 , 31]. A subgroup analysis of persons without progressive deterioration of CB and of potential effects of medical treatment, however, was not performed in this study. We hypothesized that CB might be related to deficits in specific neuropsychological tests [3 , 7]. Several studies found a correlation of neuropsychological deficits or global dementia severity with CB [8 , 42]. In agreement with other studies [5 , 41], logistic regression analysis did not reveal a relation between CBIss and CERAD-Plus or MMSE sum scores in our study. The most prevalent patient-related factor of CB was severity of neuropsychiatric symptoms. This finding is in agreement with numerous studies identifying neuropsychiatric symptoms including behavioral abnormalities as the primary patient-related determinants of CB [3 , 41–44]. Previous studies have shown that disability in activities of daily living and dependency are determinants of CB [5–7 , 45]. Disability may or may not result in dependency and need of caregiving, which might explain why in the present study dependency (DS) correlated with CB both in the logistic regression analysis and the linear mixed effects model, whereas DAD scores only in the linear mixed effects model.

Several studies revealed greater CB in children than spouses [8 , 36] or no correlation between CB and family relationship [28 , 33]. In other studies spouses suffered from more severe CB than caregiving children [5, 43]. Co-residency and overall duration of presence and care may explain larger CB in partners than in other caregivers in our study, which coincides with other studies [5 , 40]. In agreement with several publications [3 , 29] but in contrast to other studies [6 , 38] our study revealed an inverse relationship between CB and caregiver age. Caregiving-caused interference with occupation, family or leisure time activities might explain more severe CB in younger than older caregivers. The effect of the sex of the caregiver on CB has been viewed differently in the literature. Several publications reported similar CB severity in male and female caregivers [38, 39], other studies more severe CB in male than in female caregivers [5, 29] or larger CB in female than in male caregivers [23 , 43], which was also found in our study in the linear mixed effects model. In summarizing, family relationship, co-residency, and age and sex of the caregiver may or may not have an effect on CB, which might depend on differences in education, occupational status, traditions, social and economic factors and support measures. Further studies are needed to clarify this topic.

Most studies on CB in dementia include more female than male patients [28–33 , 43], which was also the case in our study. In most studies, male and older patients caused greater CB than did younger and female patients [5 , 35], or an inverse relationship [27] or no correlation between CB and sex and age of the patients was found [29 , 38]. In the present study, the linear mixed effects model revealed a larger CB in female patients and CB did not relate to the age of the patient. A low patient education level was described as a risk factor for CB [28 , 37]. Other studies did not find an effect of the education of the caregiver on CB [34, 38]. The present study found greater CB in patients with a high level of education. Explanations for this finding could not be derived from the existing data.

The factor analysis of CB performed in the present study according to the literature [23 , 46–49] revealed restrictions in social, occupational and family activities, personal needs and privacy [30] as an important factor of CB, followed by psychological and somatic exhaustion, feeling of uncertainty and guilt and strong negative emotions. Previous studies [23, 33] found a similar composition and hierarchical order of CB factors in three factor models. Other studies revealed factors capturing similar contents in different hierarchical order [17 , 46–49]. The present study suggests that absence of personal, medical and psychological support including positive feedback and esteem might be prevailing stressors for caregivers and contribute to negative emotions including frustrations [8 , 31].

Because of methodological differences tentative comparison of CB between countries result only in preliminary estimations. Recent European studies in persons with similar demography and slightly more advanced stages of dementia than in our patients reported higher CBIss than our study. Between European countries, however, there marked differences in CB were reported [4 , 50] (range of mean or median CBIss from 24.7 to 64.7). Markedly more severe CB was recently found in US studies concerning also Latin American caregivers [8, 23] (mean CBIss of 43.23 and 38.03), in studies from South Korea [38] (mean 36.3), China (mean 33–40) [43] and in a cross-national European study, where, again, differences between countries were observed [3] (range of mean CBIss 28 to 52). Finally, mean CB severity in our study was similar to that in recent studies from the US and Australia [27, 28] (mean CBIss 15.1. and 14.7, respectively) and larger than in a recent Japanese study (mean 7.8) [42].

Shortcomings of this study are that comorbidities of the patients, caregiver-related health problems, socioeconomic parameters, [28 , 37], personal, psychological, social, and medical support, cumulative duration of care, and reasons for premature study termination were not analyzed in this study. Patients with rapid clinical deterioration might have prematurely dropped out, so that overall reported CB might be less severe in this study than in real life.

Conclusion

CB was on average in the low range at BL, however, the proportion of caregivers reporting significant CB because of restrictions in time for other activities, psychological distress and health problems increased significantly during FU. Determinants of CB were identified, such as neuropsychiatric symptoms and behavioral abnormalities of the patients, dementia progression, dependency, disability in activities of daily living, younger caregiver age and female caregiver sex, and proximity between patient and caregiver (partners). These findings are applicable to identify caregivers at risk for CB in order to take targeted steps to alleviate CB, such as effective therapy of cognitive decline and neuropsychiatric symptoms of the client, personal and psychological support and medical care for the caregiver, presumably also better public funding of informal care, and increasing participation of male caregivers.

Footnotes

ACKNOWLEDGMENTS

We would like to thank Mrs. Mary Heaney-Margreiter for proof reading and language editing.

The Project is funded by the Austrian Alzheimer’s Disease Society, the Austrian Research Promotion Agency (FFG), project number 827462, and The Funds of the Austrian National Bank, project number 13240.

Authors’ disclosures available online ().

The supplementary material is available in the electronic version of this article: .

References

Winblad

, Amouyel

, Andrieu

, Ballard

, Brayne

, Brodaty

, Cedazo-Minguez

, Dubois

, Edvardsson

, Feldman

, Fratiglioni

, Frisoni

, Gauthier

, Georges

, Graff

, Iqbal

, Jessen

, Johansson

, Jönsson

, Kivipelto

, Knapp

, Mangialasche

, Melis

, Nordberg

, Rikkert

, Qiu

, Sakmar

, Scheltens

, Schneider

, Sperling

, Tjernberg

, Waldemar

, Wimo

, Zetterberg

(2013) Defeating Alzheimer’s disease and other dementias: A priority for European science and society. Lancet Neurol 15, 455–532.

George

, Gwyther

(1986) Caregiver well-being: A multidimensional examination of family caregivers of demented adults. Gerontologist 26, 253–259.

Schneider

, Murray

, Banerjee

, Mann

(1999) Eurocare: A cross-national study of the co-resident spouse carers for people with Alzheimer’s disease: I-Factors associated with carer burden. Int J Geriatr Psychiatry 14, 651–661.

Bleijlevens

MHC

, Stolt

, Stephan

, Zabalegui

, Saks

, Sutcliffe

, Lethin

, Soto

, Zwakhalen

SMG

, RightTimePlaceCare Consortium (2014) Changes in caregiver burden and health-related quality of life of informal caregivers of older people with dementia: Evidence from the European RightTimeplaceCare prospective cohort study. J Adv Nurs 71, 1378–1391.

Haro

, Kahle-Wrobleski

, Bruno

, Belger

, Dell’Agnello

, Dodel

, Jones

, Reed

, Vellas

, Wimo

, Argimon

(2014) Analysis of burden in caregivers of people with Alzheimer’s disease using self-report and supervision hours. J Nutr Health Aging 18, 677–684.

Stephan

, Afram

, Koskonniemi

, Verbeek

, Soto

, Bleijlevens

MHC

, Sutcliffe

, Lethin

, Risco

, Saks

, Hamers

JPH

, Meyer

, RightTimePlaceCare Consortium (2014) Older persons with dementia at risk for institutionalization in eight European countries: A cross-sectional study on the perceptions of informal caregivers and healthcare professionals. J Adv Nurs 71, 1392–1404.

Afram

, Stephan

, Verbeek

, Bleijlevens

, Suhonen

, Sutcliffe

, Raamat

, Cabrera

, Soto

, Hallberg

, Meyer

, Hamers

, RightTimePlaceCare Consortium (2014) Reasons for institutionalization of people with dementia: Informal caregiver reports from 8 European countries. J Am Med Dir Assoc 15, 108–116.

Luchsinger

, Tipiani

, Torres-Patiño

, Silver

, Eimicke

, Ramirez

, Teresi

, Mitelman

(2015) Characteristics and mental health of Hispanic dementia caregivers in New York City. Am J Alzheimers Dis Other Demen 30, 584–590.

Conde-Sala

, Turró-Garriga

, Calvó-Perxas

, Vilalta-Franch

, Lopez-Pousa

, Garre-Olmo

(2014) Three-year trajectories of caregiver burden in Alzheimer’s disease. J Alzheimers Dis 42, 623–633.

10.

Wimo

, Winblad

, Shah

, Chin

, Zhang

, McRae

(2004) Impact of donepezil treatment for Alzheimer‘s disease on caregiver time. Curr Med Res Opin 20, 1221–1225.

11.

Morris

(1993) The Clinical Dementia Rating (CDR): Current version and scoring rules. Neurology 43, 2412–2414.

12.

Schmid

, Ehrensperger

, Berres

, Beck

, Monsch

(2014) The extension if the German CERAD Neuropsychological Assessment Battery with tests assessing subcortical, executive and frontal functions improves accuracy in dementia diagnosis. Dement Geriatr Cogn Disord Extra 4, 322–334.

13.

Cummings

(1997) The Neuropsychiatric Inventory: Assessing psychopathology in dementia patients. Neurology 148(Suppl 6), S10–16.

14.

Gélinas

, Gauthier

, McIntyre

, Gauthier

(1999) Development of a functional measure for persons with Alzheimer’s disease: The disability assessment for dementia. Am J Occup Ther 53, 471–481.

15.

Stern

, Albert

, Sano

, Richards

, Miller

, Folstein

, Albert

, Bylsma

, Lafleche

(1994) Assessing patient dependence in Alzheimer’s disease. J Gerontol 49, M216–222.

16.

Zarit

, Reever

, Bach-Peterson

(1980) Relatives of the impaired elderly: Correlates of feelings of burden. Gerontologist 20, 649–655.

17.

Hébert

, Bravo

, Preville

(2000) Reliability, validity and reference values of the Zarit Burden Interview for assessing informal caregivers of community-dwelling older persons with dementia. Can J Aging 19, 494–507.

18.

Schreiner

, Morimoto

, Arai

, Zarit

(2006) Assessing family caregiver’s mental health using a statistically derived cut-off score for the Zarit Burden Interview. Aging Ment Health 10, 107–111.

19.

McKhann

, Drachman

, Folstein

, Katzman

, Price

, Stadlan

(1984) Clinical diagnosis of Alzheimer’s disease: Report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 34, 939–944.

20.

McKhann

, Albert

, Grossman

, Miller

, Dickson

, Trojanowski

, Work Group on Frontotemporal Dementia and Pick’s Disease (2001) Clinical and pathological diagnosis of frontotemporal dementia: Report of the Work Group on Frontotemporal Dementia and Pick’s Disease. Arch Neurol 58, 1803–1809.

21.

McKeith

, Dickson

, Lowe

, Emre

, O’Brien

, Feldman

, Cummings

, Duda

, Lippa

, Perry

, Aarsland

, Arai

, Ballard

, Boeve

, Burn

, Costa

, Del Ser

, Dubois

, Galasko

, Gauthier

, Goetz

, Gomez-Tortosa

, Halliday

, Hansen

, Hardy

, Iwatsubo

, Kalaria

, Kaufer

, Kenny

, Korczyn

, Kosaka

, Lee

, Lees

, Litvan

, Londos

, Lopez

, Minoshima

, Mizuno

, Molina

, Mukaetova-Ladinska

, Pasquier

, Perry

, Schulz

, Trojanowski

, Yamada

, Consortium on

DLB

(2005) Diagnosis and management of dementia with Lewy bodies: Third report of the DLB Consortium. Neurology 65, 1863–1872.

22.

Chui

, Victoroff

, Margolin

, Jagust

, Shankle

, Katzman

(1992) Criteria for the diagnosis of ischemic vascular dementia proposed by the State of California Alzheimer’s Disease Diagnostic and Treatment Centers. Neurology 42, 473–480.

23.

Springate

, Tremont

(2014) Dimensions of caregiver burden in dementia: Impact of demographic, mood, and care recipient variables. Am J Geriatr Psychiatry 22, 294–300.

24.

R Core Team (2015) R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna. Austria. https://www.r-project.org

25.

Dourado

, de Sousa

, Santos

, Simões Neto

, Nogueira

, Belfort

, Torres

, Dias

, Laks

(2016) Quality of life in mild dementia: Patterns of change in self and caregiver ratings over time. Rev Bras Psiquiatr 38, 294–300.

26.

Heru

, Ryan

(2006) Family functioning in the caregivers of patients with dementia: One-year follow-up. Bull Menninger Clin 70, 222–231.

27.

Miller

, Mioshi

, Savage

, Lah

, Hodges

, Piguet

(2013) Identifying cognitive and demographic variables that contribute to carer burden in dementia. Dement Geriatr Cogn Disord 36, 43–49.

28.

Hughes

, Black

, Albert

, Gitlin

, Johnson

, Lyketsos

, Samus

(2014) Correlates of objective and subjective measures of caregiver burden among dementia caregivers: Influence of unmet patient and caregiver dementia-related care needs. Int Psychogeriatr 26, 1875–1883.

29.

Kang

, Myung

, Na

, Kim

, Lee

J-H

, Han

S-H

, Choi

, Kim

(2014) Factors associated with caregiver burden in patients with Alzheimer’s disease. Psychiatry Investig 11, 152–159.

30.

Iavarone

, Ziello

, Pastore

, Fasanaro

, Poderico

(2014) Caregiver burden and coping strategies in caregivers of patients with Alzheimer’s disease. Neuropsychiatr Dis Treat 10, 1407–1413.

31.

Han

, Jeong

, Park

, Kim

, Lee

, Ryo

S-H

, Kim

, Yoon

, Jhoo

, Kim

, Lee

, Kwak

, Kim

, Park

, Kim

(2014) Effects of social supports on burden in caregivers of people with dementia. Int Psychogeriatr 26, 1639–1648.

32.

, Wang

, He

, Liang

, Zhou

(2015) Measuring the caregiver burden of caring for community-residing people with Alzheimer’s disease. PLoS One 10, e0132168.

33.

Ankri

, Andrieu

, Beaufils

, Grand

, Henrard

(2005) Beyond the global score of the Zarit Burden Interview: Useful dimensions for clinicians. Int J Geriatr Psychiatry 20, 254–260.

34.

Conde-Sala

, Garre-Olmo

, Turró-Garriga

, Vilalta-Franch

, López-Pousa

(2010) Differential features of burden between spouse and adult-child caregivers of patients with Alzheimer’s disease: An exploratory comparative design. Int J Nurs Stud 47, 1262–1273.

35.

Adelman

, Tmanova

, Delgado

, Dion

, Lachs

(2014) Caregiver burden. A clinical review. JAMA 311, 1052–1059.

36.

Lau

, Chong

, Ali

, Chan

, Chua

, Lim

(2015) Caregiver burden: Looking beyond the unidimensional total score. Alzheimer Dis Assoc Disord 29, 338–346.

37.

Chiao

, Wu

, Hsiao

(2015) Caregiver burden for informal caregivers of patients with dementia: A systematic review. Int Nurs Rev 62, 340–350.

38.

Shin

, Youn

, Kim

, Lee

J-Y

, Cho

JWC

(2012) Caregiver burden in Parkinson disease with dementia compared to Alzheimer disease in Korea. J Geriatr Psychiatry Neurol 25, 222–226.

39.

Nogueira

MML

, Neto

JPS

, Sousa

MFB

, Santos

, Rosa

RDL

, Belfort

, Torres

, Dourado

MCN

(2015) Spouse-caregivers’ quality of life in Alzheimer’s disease. Int Psychogeriatr 27, 837–845.

40.

D’Onofrio

, Sancarlo

, Addante

, Ciccone

, Cascavilla

, Paris

, Picoco

, Nuzzaci

, Elia

, Greco

, Chiarini

, Panza

, Pilotto

(2015) Caregiver burden characterization in patients with Alzheimer’s disease or vascular dementia. Int J Geriatr Psychiatry 30, 891–899.

41.

van der Lee

, Bakker

TJEM

, Duivenvoorden

, Dröes

R-M

(2014) Multivariate models of subjective caregiver burden in dementia: A systematic review. Ageing Res Rev 15, 76–93.

42.

Ikeda

, Terada

, Oshima

, Hayashi

, Okahisa

, Takaki

, Inagaki

, Yokota

, Uchitomi

(2015) Difference in determinants of caregiver burden between amnestic mild cognitive impairment and mild Alzheimer’s disease. Psychiatry Res 226, 242–246.

43.

Wang

, Xiao

, He

, Ullah

, De Bellis

(2014) Factors contributing to caregiver burden in dementia in a country without formal caregiver support. Aging Ment Health 18, 986–996.

44.

Lima-Silva

, Bahia

, Carvalho

, Guimarães

, Caramelli

, Balthazar

, Damasceno

, Bottino

, Brucki

, Nitrini

, Yassuda

(2015) Neuropsychiatric symptoms, caregiver burden and distress in behavioral-variant frontotemporal dementia and Alzheimer’s disease. Dement Geriatr Cogn Disord 40, 268–275.

45.

Jones

, Romeo

, Trigg

, Knapp

, Sato

, King

, Niecko

, Lacey

, DADE Investigator Group (2015) Dependence in Alzheimer’s disease and service use costs, quality of life, and caregiver burden: The DADE study. Alzheimers Dement 11, 280–290.

46.

Knight

, Fox

, Chou

C-P

(2000) Factor structure of the burden interview. J Clin Geropsychol 6, 249–258.

47.

Bédard

, Molloy

, Squire

, Dubois

, Lever

, O’Donnell

(2001) The Zarit Burden Interview: A new short version and screening version. Gerontologist 41, 652–657.

48.

O’Rourke

, Tuokko

(2003) Psychometric properties of an abridged version of the Zarit Burden Interview within a representative Canadian caregiver sample. Gerontologist 43, 121–127.

49.

Flynn Longmire

, Knight

(2011) Confirmatory factor analysis of a brief version of the Zarit Burden Interview in Black and White dementia caregivers. Gerontologist 51, 453–462.

50.

Froelich

, Andreasen

, Tsolaki

, Foucher

, Kavanagh

, Baelen

, Schwalen

(2009) Long-term treatment of patients with Alzheimer’s disease in primary and secondary care: Results from an international survey. Curr Med Res Opin 25, 3059–3068.