RESEARCH ARTICLE

Caregiver burden characterization in patients with Alzheimer’s disease or vascular dementia Grazia D’Onofrio1, Daniele Sancarlo1, Filomena Addante1, Filomena Ciccone1, Leandro Cascavilla1, Francesco Paris1, Michele Picoco1, Claudia Nuzzaci1, Anna Chiara Elia1, Antonio Greco1, Ramona Chiarini1,2, Francesco Panza1,3 and Alberto Pilotto1,2 Geriatric Unit and Laboratory of Gerontology and Geriatrics, Department of Medical Sciences, IRCCS “Casa Sollievo della Sofferenza”, San Giovanni Rotondo, Foggia, Italy 2 Geriatrics Unit, Azienda ULSS 16, Padova, Italy 3 Neurodegenerative Disease Unit, Department of Basic Medicine, Neuroscience, and Sense Organs, University of Bari Aldo Moro, Bari, Italy Correspondence to: Daniele Sancarlo, MD, E-mail: [email protected] 1

Objective: To characterize the differences of caregiver burden in patients with Alzheimer’s disease (AD) and vascular dementia (VaD) in order to improve the care counselling and management plan. Methods: We included 506 patients consecutively attending the Alzheimer’s Evaluation Unit of a Geriatric Unit, evaluated with Mini Mental State Examination (MMSE), Clinical Dementia Rating (CDR), Hamilton Rating Scale for Depression, and Neuropsychiatric Inventory. To all caregivers were administered the Caregiver Burden Inventory (CBI), a 24-item multidimensional questionnaire in which 5 subscales explore 5 dimensions of caregiver burden: (1) CBI-Objective; (2) CBI-Developmental; (3) CBI-Physical; (4) CBI-Social; and (5) CBI-Emotional. Results: The present study included, respectively, 253 AD patients and 253 VaD patients. AD patients at baseline showed a significantly higher instruction level (p < .0001), higher grade of cognitive impairment (MMSE, p < .0001), and increased severity stage of dementia (CDR, p < .0001) than VaD patients. AD caregivers, mainly females (p = 0.010), devoted significantly more length of time care (in months, p = 0.010) and time of daily care (in hours, p = 0.011) and showed a significantly higher burden level in CBI-Objective (p = 0.047), CBI-Physical (p < .0001), CBI-Social (p = 0.003), CBI-Emotional (p < .0001), and CBI-total score (p < .0001), than VaD caregivers. In both caregiver groups, a higher presence of spouses and sons (p < .0001) compared to other relatives was observed. AD caregiver burden showed a significant association with sex of caregivers and length of time care in months. Conclusions: AD caregivers showed a higher burden level than VaD caregivers, and this appeared to be associated with sex and length of time care. Copyright # 2014 John Wiley & Sons, Ltd. Key words: caregiver burden; Alzheimer’s disease; vascular dementia History: Received 14 March 2014; Revised 27 September 2014; Accepted 15 October 2014; Published online in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/gps.4232

Introduction Dementia is a term that describes disorders causing cognitive impairment severe enough to affect functional status and with devastating consequences for the entire familiar network. The most common forms of dementia are Alzheimer’s disease (AD) and vascular dementia (VaD). The global prevalence of dementia is rising and AD, which accounts for about 60% of all Copyright # 2014 John Wiley & Sons, Ltd.

cases of dementia, represents an increasing challenge for older adults, families, and health care systems worldwide (Ferri et al., 2005). One of the recurring themes in literature is the individual response to caregiving demands. Results are often different, with studies reporting that some caregivers are early overwhelmed by care responsibilities and others showing stability or even decreases in the burden over time (Gaugler et al., 2000). This variability Int J Geriatr Psychiatry 2014

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in caregiver response has often been explained in terms of the burden models. With this terms is indicated a subjective measure of the physical, economic, and psychosocial strain of caregiving, considered the product of a dynamic interaction among caregiver resources, vulnerabilities, and care demands (Vitaliano, 1990). Informal caregivers reported higher levels of depression and anxiety (Schulz et al., 1995; Mahoney et al., 2005), use of psychotropic medication more frequently (Clipp and George, 1990), engagement in fewer protective health behaviours, and increased risk of medical illness (Vitaliano et al., 2003; Son et al., 2007) and mortality (Schulz and Beach, 1999). Higher caregiver burden is also a predictor of early institutionalization of the patients (Luppa et al., 2008). Reviews of interventions on caregivers have reported small but significant effects upon burden and have underlined the need for increased understanding of the dynamics of caregiving toward the development of more targeted and effective practices (Pinquart and Sörensen, 2006). Patient variables that have been associated with increased caregiver burden included cognitive impairment, functional decline, and neuropsychiatric symptoms (NPS) (Coen et al., 1997; Black and Almeida, 2004; Machnicki et al., 2009). Equally, functional deficits have not been found to strongly predict caregiver burden with negative findings in several studies (Coen et al., 1997; Campbell et al., 2008). As pointed out by Berger et al. (2005), caregiver burden remained stable, and severe depression decreased over time suggesting the need of evaluating the relationship between dementia symptoms and caregiver perceived burden over time, in order to understand the changes in the adaptation to the various caregiving stressors. Moreover, large differences exist between data available on the consequences of caring for AD versus VaD patients. The aim of this study was to determine the differences in term of caregiver burden due to specific dementia subtypes in order to improve the treatment and counselling of the familiar network and of the patients. Methods Subjects

This study was conducted according to the World Medical Association’s 2008 Declaration of Helsinki and the guidelines for Good Clinical Practice and the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) (Von Elm et al., 2007) Copyright # 2014 John Wiley & Sons, Ltd.

and was approved by the local ethics committee. Written informed consent for research was obtained from each patient or from relatives or a legal guardian. Patients consecutively evaluated from April 2009 to January 2012 at the Alzheimer’s Evaluation Unit of the Geriatric Unit of the IRCCS “Casa Sollievo della Sofferenza”, San Giovanni Rotondo, Foggia, Italy were screened for eligibility. Inclusion criteria were: (1) age ≥65 years; (2) ability to provide an informed consent or availability of a relatives or a legal guardian in the case of severe demented patients; (3) diagnosis of AD or VaD; and (4) a complete neuropsychiatric assessment. Exclusion criteria were: presence of serious comorbidity, tumours and other diseases that could be causally related to cognitive impairment (ascertained blood infections, vitamin B12 deficiency, anemia, disorders of the thyroid, kidneys or liver), history of alcohol or drug abuse, head trauma, and other causes that can cause memory impairment. No specific inclusion/exclusion criteria for caregivers were used. Cognitive evaluation and diagnosis of dementia

In all patients, cognitive status was screened by means of the Mini-Mental State Examination (MMSE) (Folstein et al., 1975) and the Clinical Dementia Rating scale (CDR) (Hughes et al., 1982; Morris, 1993). The MMSE was used to assess the orientation, memory, attention and calculation, language, ability to follow commands, reading comprehension, ability to write a sentence, and ability to copy a drawing. The CDR was a scale designed to grade subjects from normal function through various stages of dementia. It is composed of several domains assessing cognition and function and rated according to the degree of cognitive loss as follows: 0 (no dementia), 0.5 (uncertain or deferred diagnosis), 1 (mild dementia), 2 (moderate dementia), and 3 (severe dementia). Dementia was diagnosed following the Diagnostic and Statistical Manual of Mental Disorders—Fourth Edition (DMS-IV) (APA, 1994). Diagnoses of possible/probable AD were made according to the criteria of the National Institute of Neurological and Communicative Disorders and Stroke—Alzheimer’s Disease and Related Disorders Association Work Group (NINCDS-ADRDA) (McKhann et al., 1984). Diagnoses of possible/probable VaD were made according to the criteria of the National Institute of Neurological Disorders and Stroke—Association Internationale pour la Recherche et l’Enseignement en Neurosciences Work Group (NINDS-AIREN) (Roman et al., 1993). In uncertain cases, differential diagnosis between AD Int J Geriatr Psychiatry 2014

Caregiver burden in Alzheimer or vascular dementia

and VaD was based also on the Hachinski Ischemic Score (Hachinski et al., 1975): scores ≤4 were considered as probable AD, scores ≥7 were diagnosed as VaD. Diagnosis of AD, and VaD was always supported by neuroimaging evidence (CT scan and/or NMR). In particular, the presence of multiple cortical/subcortical infarcts or an infarct in a strategic area such as the thalamus or temporal lobe and/or lesions of the white matter indicated probable VaD; the absence of the above-mentioned cerebrovascular lesions indicated AD. Affective and neuropsychiatric evaluation

Depressive symptoms were evaluated using the Hamilton Rating Scale for Depression (HDRS) (Hamilton, 1967) comprising 21 items. The following cut-offs for the HDRS score were used: ≥25: severe depression; 18–24: moderate depression; 8–17: mild depression; and ≤7: absence of depression (Hamilton, 1967). NPS were evaluated with the Neuropsychiatric Inventory (NPI) (Cummings et al., 1994) including the following 12 domains: delusions, hallucinations, agitation/aggression, depression mood, anxiety, euphoria, apathy, disinhibition, irritability/lability, aberrant motor activity, sleep disturbance, and eating disorder. For each domain the severity and frequency of the behaviours are determined according to the criteria provided for each domain. Frequency is rated from 1 to 4 and severity is scored from 1 to 3. The product (severity frequency) is calculated for each behavioural change present during the previous month or since the last evaluation. Caregiving assessment

The following parameters were collected by a systematic interview about the caregivers: gender, relationship with the patient, length of time care (in months), and time of daily care (in hours). To all caregivers were administered the Caregiver Burden Inventory (CBI) (Novak and Guest, 1989; Zanetti et al., 1999). The CBI is a 24-item multidimensional questionnaire in which 5 subscales explore 5 different dimensions of caregiver burden: (1) CBI-Objective: the burden on the caregiver due to shortage of time (items 1–5); (2) CBI-Developmental: the caregiver’s sense of being left behind, unable to enjoy the same expectations and opportunities as his or her peers (items 6–10); (3) CBI-Physical: feelings of fatigue and chronic health problems (items 11–14); (4) CBI-Social, which results from a perceived conflict of roles (items 15–19); and (5) CBI-Emotional, which originates from awareness of negative feelings towards the patient that can be Copyright # 2014 John Wiley & Sons, Ltd.

induced by the patient’s bizarre and unpredictable behaviour (items 20–24). Scores for each item are evaluated using a 5-point Likert scale ranging from 0 (not at all disruptive) to 4 (very disruptive) for a total ranging from 0 to 20 for each subscale, with the exception of the CBIPhysical which is composed 4-item: is then applied a correction factor 1.25. The range of the total score ranges from 0 to 96: a score >36 indicate a risk of “burning out” whereas scores near or slightly above 24 indicate a need to seek some form of respite care. The time to administer is approximately 10–15 min. Statistical analyses

For dichotomous variables, hypotheses regarding differences between the groups were tested using Fisher’s exact test. This analysis was made using the 2-Way Contingency Table Analysis available at the Interactive Statistical Calculation Pages (The R Project for Statistical Computing; available at URL http://www.r-project. org/). For continuous variables, normal distribution was verified by the Shapiro–Wilk normality test and the one-sample Kolgomorov–Smirnov test. For normally distributed variables, hypotheses regarding differences among the groups were compared by means of the Welch two sample t-test or by means of the analysis of variance (ANOVA) under general linear model. For non-normally distributed variables, hypotheses regarding differences among the groups were compared by means of the Wilcoxon rank sum test with continuity correction or by means of the Kruskal–Wallis rank sum test. Finally, AD diagnosis as independent predictor of caregiver burden was assessed using univariate multinomial logistic regression analysis (ANCOVA) including into the model gender, length of time care (in months), and time of day care (in hours). Risks will be reported as odds ratios (OR) along with their 95% confidence interval (CI). All the statistical analyses were made with the R Ver. 2.8.1 statistical software package (The R Project for Statistical Computing; available at URL http://www.r-project.org/). Tests in which the p value was smaller than the Type I error rate α = 0.05 were declared significant. Results Clinical and functional characteristics of patients

During the enrolment period, 570 elderly patients were screened for the inclusion in the study. Of these, 12 patients were excluded because they were younger Int J Geriatr Psychiatry 2014

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than 65 years, 31 patients had an incomplete examination, and 21 patients had severe comorbidity associated with cognitive impairment. Thus, the final population included 506 patients, 183 men (36.2%), and 323 women (63.8%) with a mean age of 78.04 years ± 5.70 and a range from 65 to 95 years. 253 patients had a diagnosis of AD and 253 of VaD. Demo-

graphic and clinical characteristics of AD patients and VaD patients are summarized in Table 1. The two groups of patients did not differ in age (p = 0.108), gender distribution (p = 0.165), HDRS (p = 0.856), and number of medications (p = 0.157). AD patients had a significantly higher instruction level (6.62 vs. 5.13, p < 0.0001), higher grade of cognitive impairment in MMSE (18.48 vs. 20.46, p < 0.0001), and increased severity stage of dementia in CDR (1.32 vs. 1.15, p < .0001) than VaD patients. Conversely, AD patients showed a significant lower impairment in NPI (18.76 vs. 40.52, p < 0.0001) than VaD patients. Caregiver burden level

The general characteristics of AD and VaD caregivers are summarized in Table 2. AD caregivers showed a significantly higher prevalence of females (54.9% vs. 43.5%, p = 0.010), more length of time care (16.28 vs. 14.35, p = 0.011), and more time of daily care

(8.15 vs. 5.72, p < 0.0001). Both groups of caregivers showed a higher presence of spouses and sons (p < 0.0001) compared to other relatives. Caregiver burden level in AD caregivers and VaD caregivers are summarized in Table 3. Caregivers of AD patients showed a significantly higher burden level in CBI-Objective (12.04 vs. 11.48, p = 0.047), CBIPhysical (14.64 vs. 13.44, p < 0.0001), CBI-Social (12.90 vs. 12.21, p = 0.003), CBI-Emotional (12.50 vs. 11.24, p < 0.0001), and total score of CBI (64.71 vs. 60.83, p < 0.0001), than caregivers of VaD patients. The two groups of caregivers did not differ in CBIDevelopmental (12.63 vs. 12.46, p = 0.468). Univariate multinomial logistic regression analysis was performed as shown in Table 4. In this analysis, AD caregiver burden showed a significant association with sex of caregivers and length of time care in months. Discussion In the present study, using a relatively large sample of newly diagnosed dementia patients and their caregivers, we investigated whether subtype of dementia is related to reported caregiver burden. At the first evaluation, AD patients showed a worst MMSE than patients with VaD. AD caregivers spend more time in caring and showed a significantly higher burden level in CBIObjective, CBI-Physical, CBI-Social, CBI-Emotional,

Table 1 Demographic and clinical characteristics of Alzheimer’s disease (AD) and vascular dementia (VaD) patients AD

VaD

(n = 253)

(n = 253)

78.44 ± 5.15 65–90 99/154 60.9% 6.62 ± 5.11 0–18 18.48 ± 3.83 11–23 1.32 ± 0.51 1–2 18.08 ± 4.93 0–24 18.76 ± 16.35 0–67 2.40 ± 1.68 0–6

77.60 ± 6.23 65–95 84/169 66.8% 5.13 ± 4.04 0–18 20.46 ± 3.20 10–23 1.15 ± 0.50 1–2 18.00 ± 4.86 0–22 40.52 ± 18.48 0–108 2.08 ± 1.41 0–7

p

Age (years)* Range Sex (M/F) Female Instruction level (years)* Range MMSE (score)* Range CDR* Range HDRS (score)* Range NPI (score)* Range N of medications* Range

0.108 0.165