Costs of care of agitation associated to dementia in 8 European countries:

results from the RightTimePlaceCare study

ABSTRACT

Objective: To estimate the additional societal costs for People living with Dementia (PwD)

with agitation in Home Care (HC) and Institutional Long-Term Care (ILTC) settings in eight

European countries.

Design: Cross sectional data from the RightTimePlaceCare cohort

Setting: HC and ILTC settings from eight European countries (Estonia, Finland, France,

Germany, Netherlands, Spain, Sweden and England).

Participants: One thousand nine hundred and ninety-seven PwD (1217 in HC group and 780

lived in an ILTC) and their caregivers.

Main outcome measures: Medical care, community care and informal care were recorded

using the Resource Utilization in Dementia (RUD) questionnaire. Agitation was assessed

based on the agitation symptoms cluster defined by the presence of agitation and/or irritability

and/or deshinibition and/or aberrant motor behavior items of the Neuropsychiatric Inventory-

Questionnaire (NPI-Q).

Results: Total monthly mean costs difference due to agitation were 445€ in the HC setting

and 561€ in the ILTC setting (p=0.01 and 0.02, respectively). Informal care costs were the

main driver in the HC group (73% of total costs) and institutional care costs were the main

driver in the ILTC group (53% of total costs). After adjustments, the log link generalized

linear mixed model showed an association between agitation symptoms and an increase of

informal care costs by 17% per month in HC setting (p <0.05).

Conclusion: This study found that agitation symptoms have a substantial impact on informal

care costs in community care setting. Future research is needed to evaluate which strategies

may be efficient by improving the cost-effectiveness ratio and reducing the burden associated

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to informal care in the management of agitation in people living with dementia.

Key words: dementia, long-term care, informal care, costs, Europe, Agitation

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Introduction

More than 46.8 million people in the world are currently affected by dementia, most of them

living with Alzheimer’s disease (AD). In 2015, the yearly societal costs of dementia were

estimated up to US $ 818 billion worldwide 1. As numbers of People living with Dementia

(PwD) are expected to almost double every 20 years, there will be nearly 131 million in

20501. Hence, all countries need to anticipate a substantial care demand and to provide

comprehensive data about the different cost components of caring for PwD and planning

healthcare services for policy development 2.

In dementia, Neuropsychiatric Symptoms (NPS) are frequent and are associated with

greater caregiver burden 3, earlier institutionalization and death 4, poorer functioning 5, more

acute hospitalizations 6 and finally, with increased informal care 7 and greater cost of care 8-10.

Agitation encompasses a range of affective, verbal and motor disturbances such as

restlessness, cursing, aggression, hyperactivity, combativeness, wandering, repetitive calling

out or irritability. These agitation symptoms are among the most frequent and disruptive NPS

affecting 40% and 60% of PwD, respectively in both, community-dwelling and institutional

long-term care living settings 11, 12. However, there is very little evidence on the costs of

agitation in PwD; a recent report only covered a small national sample of community

dwelling AD patients, but informal care costs were not estimated 13. Currently the cost

components, and separate estimates in different settings, of agitation in PwD are unknown in

Europe. The aim of this paper is to estimate the additional societal costs for patients living

with dementia with agitation in home care (HC) and institutional long-term care (ILTC)

settings in eight European countries.

Methods

Recruitment and Participants

The current study uses data collected within the RightTimePlaceCare (RTPC)

project14. The RTPC survey is a longitudinal prospective study, conducted in eight European

countries (Estonia, Finland, France, Germany, Netherlands, Spain, Sweden and England). The

sample comprised two groups of PwD who either: a) were recently admitted to an ILTC (if

they lived at least 1 month in the institution and no longer than 3 months); or b) were living in

the community receiving professional home care but judged at risk by a healthcare

professional of admission to a ILTC within the following six months. These data were

collected at a baseline and at a three-month follow-up assessment. For the purpose of this

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study, only the baseline data were used to avoid problems of non-response to panel

recruitment and panel attrition. Participants were included between November 2010 and

December 2011.

Participants were PwD and their informal caregivers who were consecutively recruited

in ILTC or at home. Eligible participants (PwD and their informal caregivers) were asked if

they agreed to be contacted by researchers. PwD were included if: they were aged 65 and

over, they had a formal diagnosis of dementia as diagnosed by an expert assessment (i.e.

psychiatrist, neurologist, geriatrician or general practitioner depending on countries’ specific

diagnostic procedures) and recorded in the medical record, a Mini Mental State Examination

(MMSE) score of 24 or below 15, and the presence of an informal caregiver (who visits at least

twice a month). PwD with a primary psychiatric diagnosis or Korsakoff’s syndrome were

excluded.

Local ethics committees of all participating countries approved the study protocol. Country-

specific research permission and consent procedures were applied. PwD and their informal

caregivers participated on a voluntary basis and their informed consent was given by their

legal representatives or next of kin (according to each country regulation) and, when possible,

by PwD themselves.

Measures

Data collection was performed by professionals in health or social care or

medical/nursing/social care students with practical experience and at least a Bachelor’s

degree. Data was collected during face-to-face interviews. In order to standardize and

facilitate data collection, the work package survey leading centre (Maastricht University, the

Netherlands) had prepared a manual as a standardized operating procedure. The interviewers

were trained by the same protocol.

Neuropsychiatric symptoms (NPS) were measured by total and individual items of the

Neuropsychiatric Inventory Questionnaire (NPI- Q) scale 16. NPI-Q surveys 12 domains:

Agitation and aggression, delusions, hallucinations, depression, euphoria, aberrant motor

behaviour, apathy, irritability, disinhibition, anxiety, sleep, and eating. It is administered as a

structured interview with a knowledgeable informant who can report the patient’s NPS. NPI-

Q is a simplified clinical version of the NPI, with two scores reported for each domain: 1)

presence of symptoms and 2) severity on a 0-3 scale (0 = none, 1 = mild, 2 = moderate, 3 =

severe). We reported the presence (yes/no) for each NPI-Q symptom domain and further

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calculated the sum of the individual severity symptom referred later as NPI-Q Total. The total

score ranges from 0 to 36, with higher scores indicating the presence of more (severe) NPS.

Unlike the NPI, the frequency of symptoms is not assessed on NPI-Q. Agitation was defined

as the cluster of the NPI-Q following items: agitation/aggression, irritability, disinhibition and

aberrant motor behavior. The agitation cluster was assessed if at least one of the four items

(agitation/aggression and/or irritability and/or deshinibition and/or aberrant motor behavior)

were present at baseline. Therefore, the “agitation cluster” variable was coded as a

dichotomous variable (yes/no) for the presence of the symptoms. The choice of these items

was based on recent criteria for agitation in dementia 17.

Cognitive impairment was based on standardised MMSE and the disease severity was

defined as mild (MMSE>21), moderate (10-21) and severe (<10) 15. Diagnosis of dementia

was coded in three categories: 1) Alzheimer’s disease (AD) and mixed disease (AD with

vascular disease component), 2) vascular disease and 3) other types of dementia. Physical

impairment was based on Katz’s activities of daily living (ADL) scale and was defined as

mild (ADL 5-6), moderate (2-4) and severe (<2) 18. Medical history of past and current

clinical conditions were recorded and based on the Charlson index for comorbidities 19.

Resource use and costing methods

Assessment and data collection procedures as well as costing methods are described in a

previous RTPC report 20.

Healthcare resources consumed by PwD were assessed with the Resource Utilization in

Dementia (RUD) instrument 21. Information about medical resources (inpatient stays,

outpatient visits and medication), community care services (district nurse, home help, day

care, transportation, meals on wheels) and time spent by the caregiver on ADL and

Instrumental ADL, were collected.

The societal perspective, including direct medical and non-medical costs and informal care

costs was used in the basic study 22. Costs were estimated by multiplying the number of units

used for each relevant resource with the corresponding unit cost. In the absence of valid and

comparable unit costs for all participating countries, a common price vector based mainly on

Swedish sources was used for all countries 10, 20, 22.

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Time spent to care for ADL and IADL was valued from the opportunity cost approach at

9€/hour in the base case analysis and different values were used in a sensitivity analysis (e.g.

3€, 6€, 15€, 20€) to test the impact of informal care unit cost on the total cost of care. Costs of

nursing homes were derived from previous reports 20, 21, 24.

All costs were inflated to a 2014 level using Consumer Prices Indicators (CPI) available on

the OECD.stat website (OECD-CPI, 2015) 25. Costs were subsequently converted to 2014

€PPP (i.e. Purchasing Power Parity) with the corresponding rate available on the OECD. stat

website (OECD. PPPs and exchange rates, 2015) 26.

Statistical analysis

Informal caregiver and PwD characteristics are described using means and standard deviation

for continuous variables and using numbers and percentages for categorical variables. The

results are shown for overall pooled data (i.e. all countries). Agitation was divided into 2

groups according to the score reported for the NPI-Q “agitation cluster” variable at baseline.

Patients were classified in the agitation group (A+) when if at least one of the baseline scores

of the following NPI-Q items (agitation/aggression and/or irritability and/or deshinibition

and/or aberrant motor behavior) were ≥1. Patients were classified in the non-agitated group

(A-) when their baseline scores to the NPI-Q agitation cluster items were 0. Differences in

means between PwD with and without agitation symptoms in both settings for overall pooled

data were tested using independent sample t-tests (for continuous variables) or Chi-2 test (for

nominal or ordinal variables). The same method was applied to test differences in means by

country.

For the pooled mean cost of care per month, confidence intervals were estimated using non

parametric bootstrapping with 1000 replication 27.

A deterministic sensitivity analysis was performed to assess the impact of the informal care

unit costs variation (e.g. extreme values from the replacement cost approach, 3€, 6€, 15€, 20€;

and the opportunity cost approach, 19.18€ and 3.15€) on total cost difference between PwD

with and without agitation symptoms in HC setting 20, 23, 24.

A log link generalized linear mixed model (GLMM) assuming a gamma distribution of costs

was implemented to estimate main predictors of total and informal costs in the HC group

taking into account the contextual effect of the country if it is necessary. The predictor of

interest was the agitation cluster, but other covariates were also included (i.e. MMSE, ADL

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score, Zarit caregiver burden, PwD and caregiver age, gender and marital status,). Countries

were taken into account as random effect in the GLMM.

Informal care costs may represent more than 50% of total cost in dementia 28. That is why we

choose to implement a GLMM specifically on this type of costs.

All statistical analysis was performed using the R software (version 3.1.2).

Ethical approval

Local ethics committees of all participating countries approved the study protocol. Country-

specific research permission and consent procedures were applied. PwD and their informal

caregivers participated on a voluntary basis and their informed consent was given by their

legal representatives or next of kin (according to each country regulation) and, when possible,

by PwD themselves.

Results

Characteristics of the studied population

Table 1 shows the characteristics of the 1997 PwD and their caregivers included in this

study, for which the agitation item on the NPI-Q at baseline was completed. Among these,

1217 were in the home care group (HC) and 780 lived in an institutional long-term care

(ILTC). Seventy five percent of the population in the HC group (n=917) presented agitation

symptoms and 68% (n=529) in the ILTC group. The highest proportions of their samples with

agitation were UK and Germany (p<0.001).

PwD had a mean age of 82 years (SD±7) in the HC group and 84 years in ILTC

(SD±7). Most people were women in both settings. PwD living in HC were more likely to be

married than in ILTC, where more were widowed. In both settings, AD was the most

common dementia and PwD were mostly at a moderate stage of the disease. In ILTC setting,

AD type of dementia and severity discriminated between PwD with and without agitation.

There are more PwD with agitation than without whom present at least 4 other NPI items in

both settings (p=0.00 in both settings).

Among the HC population, patients with agitation were younger (p=0.03), with than patients

without agitation. These differences were not observed in the ILTC setting. However, PwD

with agitation were more physically disabled in both settings than PwD without agitation

(p=0.02, p=0.01).

In the whole sample caregivers were predominantly women with the oldest were in HC at 66

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years (SD±14). The majority of the caregivers were married in both settings.

Among the HC sample, the relation between the PwD and the informal caregiver as spouse

type was more frequent in the agitation group (p=0.04). In the HC sample, caregiver burden

was higher in the agitation group (p=0.00).

Costs differences by setting and by agitation symptoms

Comparative analysis

Table 2 shows the monthly mean costs and costs differences by setting and by

agitation symptoms. Total cost difference due to agitation were 445€ in the HC setting and

561€ in the ILTC setting (p=0.01 and 0.02, respectively). In HC the main driver of cost

difference was informal care cost covering 73% of total cost. In ILTC, the main driver of cost

difference was unsurprisingly institutional care cost covering 53% of total additional cost.

In both HC and ILTC settings, medical care (i.e. inpatient, outpatient, medication) was

the second main driver of cost difference among PwD with agitation with higher inpatient

cost (i.e. hospitalizations) in HC, and higher outpatient cost (i.e. medical consultations and

acts) in ILTC.

In the HC setting, day care was the main component of cost difference in community

care.

Appendix I shows the monthly costs and costs differences by setting, by agitation

symptoms and by countries (material on line).

Drivers of costs differences varied considerably according to countries. In the presence

of agitation symptoms, medical care costs, and particularly outpatient costs, from ILTC were

the main driver of cost difference in England, France and Spain. Informal care costs from HC

were the main driver of cost difference for UK, Estonia, Finland, France, Germany and the

Netherlands. They were led by IADL for UK, Estonia and the Netherlands and by ADL for

Finland, France and Germany. Community care in HC was the main driver of cost difference

in Spain.

Figure 1 shows the impact of varying informal unit costs on total costs in the HC

group. Mean cost difference between PwD with and without agitation symptoms in the HC

group varied from 105€ to 919 € per month according to the costing approach used to value

informal care.

Multivariate analysis

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Table 3 shows the results of the adjusted GLMM. Model 1, which focused on total

costs, showed no association between the presence of agitation symptoms and total cost when

country is taken into account as random effect and when adjusted by gender and age of PwD

and dementia type. Moderate (p <0.05) and severe (p <0.01) cognitive decline and moderate

to severe physical disability (p <0.01) were however predictors of higher total cost.

Nevertheless, when we put an interaction term between patients with at least 4 other NPI-Q

items and the agitation cluster symptoms, we show an additional cost of 37% compared to

patients with at least 4 other NPI-Q symptoms and no agitation symptoms (p=0.013).

Model 2, which focused on informal costs, shows the presence of agitation symptoms as an

independent predictor of higher informal care costs (p <0.05) after adjustments on PwD age,

PwD gender, marital status of caregiver, and a random effect on countries. Both moderate to

severe cognitive decline and physical disability (p <0.01) were also independent predictors of

higher informal care costs.

Discussion

The principal findings of this study show that among people living with dementia (PwD), the

monthly cost difference associated to the presence of agitation were 445€ in the home care

group and 561€ in ILTC group. Informal care costs were the main driver in the HC group

(73% of total costs) and institutional care costs were the main driver in the ILTC group (53%

of total costs). Medical care costs were the second main cost driver (i.e. inpatient costs in HC

group and outpatient costs in ILTC group). By country, medical care costs were the

commonest cost driver. After adjustments, no association was found between agitation

symptoms and total costs in the HC setting while agitation was an independent predictor of an

increase of informal care costs by 17%.

The large collection of data and sample size are main strengths of the current study.

Resource utilization, socio demographics characteristics and disease severity have been

described for over 2000 PwD, living at home with an identified caregiver or in an ILTC

facility, across eight countries in Europe.

The costs were measured from a broad societal perspective including medical care,

community care and informal care. Because of growing evidence that informal care costs

represent a considerable part of the total costs in AD 29, 30, this study adjudged it using several

alternative methods frequently used in the literature 23.

Neuropsychiatric symptoms increase total costs in AD but less is known specifically about the

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relationship between agitation symptoms and additional costs 8, 10. To our knowledge, only

two studies recently addressed the impact of agitation symptoms upon health resources

utilization among PwD 13, 31. However, these studies did not assess costs comprehensively

from a societal perspective. Morris and colleagues found that the presence of agitation

increases the costs in both HC and ILTC settings 13. Among 224 people with AD health and

costs varied from £29 000 over a 1 year period with no agitation symptoms to £57 000 at the

most severe agitation symptoms. Authors found after adjusting for covariates that a one-unit

increase in NPI agitation score was associated with a £1064 increase in costs per patient over

a 12-month period. However, this study took into account only direct costs and not informal

care costs, which may underestimate the additional costs due to agitation. Recently, the

presence of agitation was described as one of the main determinants of healthcare resource

utilization in urban China among people with moderate and severe AD 31. Once again, authors

highlighted the limitation of the lack of informal care cost evaluation in their report. On the

other hand, only two recent reports addressed the relation between informal care costs and

global NPS symptoms 7, 32. Thus, to authors’ knowledge our study is the first to assess

specifically the impact of agitation on total societal costs, on a large sample collected in both

community dwelling and institutional care facilities, and addressing the role of informal care

costs in community dwelling.

In our study, after adjusting for covariates, agitation was associated with an increase in total

care costs only in the group of patients with agitation and the presence of at least 4 other NPI-

Q items. Agitation is significantly associated with an increase in informal care costs. As

disabilities in dementia are still mainly supported by non-professional caregivers (relatives,

friends or neighbors) in community dwelling 33, many studies confirm the preponderance of

informal care in total costs 32, 34, 28. According to the method employed for informal care

costing, informal care ranges from 45% to 60% of the total costs 5, 29, 35, 36. Similarly, in the

current study informal care costs accounted for 73% of the total additional costs for

community dwelling A/A patient.

In the presence of agitation symptoms medical care cost was the second main cost

driver in both settings. In the HC group, there was an increase in inpatient costs (i.e.

hospitalisations), while in the ILTC outpatient costs (i.e. visits) increased. These results are in

line with previous reports, which showed an increase of health resources utilizations along

with rising informal care costs in home care 36.

However, the comparative analysis by country showed high variability for the main

driver of cost difference. These results might reflect different national strategies for the

10

management of PwD, possibly influenced by different economic policies and cultural

background. In the context of informal caregiving, there is known to be a significant north

south gradient within Europe: intra-generational support seems to be more pronounced in

southern European countries, whereas institutionalization is more common in Nordic

countries and Central Europe.

Our study contains some limitations. Firstly, given specific inclusion criteria, namely

those on the margin between community dwelling and institutional patients, our sample is

necessarily not representative of the general population of PwD, which might challenge the

external validity. Furthermore, the sample was collected on eight European countries with

different recruiting strategies across countries, which might influence the internal validity of

the results. Secondary, as discussed by Wübker et al., there is a lack of readily available

country specific unit cost data for different countries, and adjustment of relative price effect

by labor cost variation is a limited control 20. Thirdly, the study collected self-reported data on

resource utilization. As with all self-reported data, this might be subject to inaccuracies,

although studies that validated the RUD-instrument are encouraging 21.

When considering the presence of agitation, we found that cost difference due to

agitation was higher in institution than in home care. These results might suggest that

providing more resources in community care might be a good economic strategy. Indeed,

currently ‘aging in place’ (i.e., aiming at postponing admission to long-term institutional care

for older adults as long as possible) is increasingly common in countries facing the demands

of an ageing society on the healthcare system 37. However, providing informal care seems to

be associated with poorer mental and physical health and more health care use for the

informal caregiver 38, 39. Agitation symptoms in PwD are one of the most distressing

symptoms for the caregiver11 and caregiver burden is a strong predictor of

institutionalization40. Compared to non-caregivers, presence of caregivers increases outpatient

care costs with more visits to the general practitioner 41. On the other hand, recent reports for

the management of agitation symptoms emphasize the impact of non-pharmacological

approaches especially psychosocial interventions and training for caregivers and PwD 42. A

recent systematic review assessing the clinical effectiveness and cost-effectiveness of non-

pharmacological interventions for managing agitation in PwD in ILTC showed that training

paid caregivers in person-centered care or communication skills, were interventions which

significantly impacted on agitation 43. In this study, less was known about both the clinical

and the costs effectiveness of these interventions in community dwelling.

In our study, agitation symptoms increased outpatient costs (medical consultations and

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acts) in ILTC. Little work has been done with NPS in dementia and telemedicine 44.

Telemedicine may facilitate management of agitation symptoms in institutionalized PwD. It

would be interesting if this type of intervention could show a reduction of inappropriate

hospitalisations and other costs such transportations in the presence of NPS.

Finally, further data is needed to assess global additional costs in people with AD and

particularly the cost of caregiver time (i.e. both by professional staff and informal caregivers).

This time, in relation to agitation and other NPS, could be of interest specifically in nursing

homes.

Conclusion

The results of the current study highlight that agitation symptoms have a substantial impact on

informal care costs in community care setting. Future research is needed to evaluate which

strategies may be efficient by improving the cost-effectiveness ratio and reducing the burden

associated to informal care in the management of agitation in people living with dementia.

Acknowledgements

The RightTimePlaceCare Consortium partners are as follows:

Coordinator:

University of Witten/Herdecke (DE): Gabriele Meyer PhD, RN, professor (scientific

coordinator, WP 1 leader), Astrid Stephan MScN, RN, Anna Renom Guiteras, geriatrician,

Dirk Sauerland Dr.rer.pol., professor (WP 4 & 6 leader), Dr Ansgar Wübker, Patrick Bremer.

Consortium Members:

Maastricht University (NL): Jan P.H. Hamers PhD, RN, professor (WP 3 leader); Basema

Afram MSc, Hanneke C. Beerens MSc, RN, Michel H.C. Bleijlevens, PhD, PT; Hilde

Verbeek, PhD; Sandra M.G. Zwakhalen, PhD, RN; Dirk Ruwaard, MD, professor.

Lund University (SE): Ingalill Rahm Hallberg, professor (WP 2 leader); Ulla Melin Emilsson,

professor; Staffan Karlsson, PhD

University of Manchester (UK): David Challis, professor; Caroline Sutcliffe; Dr David Jolley;

Sue Tucker; Ian Bowns; Brenda Roe, professor; Alistair Burns, professor

University of Turku (FI): Helena Leino-Kilpi, PhD, RN, professor; Jaana Koskenniemi,

MNSc, RN, researcher; Riitta Suhonen, PhD, RN, professor; Matti Viitanen, MD, PhD,

professor; Seija Arve, PhD, RN, adj professor; Minna Stolt, MNSc; Maija Hupli, PhD, RN.

12

University of Tartu (EE): Kai Saks, MD, PhD, professor (WP 5 leader); Ene-Margit Tiit,

PhD, professor; Jelena Leibur, MD, MBA; Katrin Raamat, MA; Angelika Armolik, MA;

Teija Tuula Marjatta Toivari, RN;

Fundació Privada Clinic per la Recerca Biomedica, Hospital Clinic of Barcelona (ES):

Adelaida Zabalegui PhD, RN (WP 5 leader); Montserrat Navarro PhD, RN; Esther Cabrera

PhD, RN (Tecnocampus Mataró), Ester Risco MNSc, RN.

Gerontôpole, University of Toulouse (FR): Pr Maria Soto; Agathe Milhet; Dr Sandrine

Sourdet; Sophie Gillette; Bruno Vellas, professor.

Funding

The RightTimePlaceCare study is supported by a grant from the European Commission within the 7th

framework programme (project 242153).

Conflicts of interest

No conflicts of interest

Role of sponsor

None

Competing interests

All authors have completed the ICMJE uniform disclosure form at

http://www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author)

and declare: no support from any organisation for the submitted work; no financial

relationships with any organisations that might have an interest in the submitted work in the

previous three years; no other relationships or activities that could appear to have influenced

the submitted work.

Data sharing

RightTimePlacecare data, protocols, and other metadata are available to the scientific

community

13

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Table 1. Population characteristics at baseline by settings and by agitation symptoms*Home care ILTC

N=1217 N=780A- A+

pA- A+

pN=300 N=917 N=251 N=529

PwD Age (SD) 82.88 (0.36) 82.02(0.22) 0.04 84.48(0.39) 83.88(0.28) 0.24PwD Women % 68 62 0.08 76 73 0.38PwD Charlson index (SD)0 [0-2] 74 69

0.0560 62

0.851 [3-4] 19 26 30 282 [≥5] 7 5 10 10PwD Marital status %Married 48 51

0.5329 32

0.39Not married 52 49 71 67PwD Dementia type %Alzheimer disease 54 54

0.9735 47

0.01Vascular dementia 17 16 40 35Others 28 29 25 18PwD MMSE %Mild 31 27

0.1718 11

0.00Moderate 39 38 41 36Severe 18 21 24 28

NPI-Q Total score (SD)

1 [0-1] 44 14

0.00

55 24

0.002[2-3] 41 38 37 393 [4-5] 12 34 7 274 [6-8] 3 14 1 10Physical disability %No or mild [0-1-2] 41 32

0.0220 11

0.01Moderate [3-4] 26 30 19 24Severe [5-6] 33 37 61 65PwD Country %England 2 8

0.00

9 64

0.00

Estonia 17 13 57 58Finland 13 16 40 81France 21 12 15 31Germany 6 10 29 88The Netherlands 11 16 36 77Spain 18 13 32 79Sweden 14 11 33 51Caregiver Women % 66 69 0.31 70 63 0.06Caregiver Age (SD) 65.92 (0.77) 64.35 (0.44) 0.10 61.16(0.73) 61.24(0.48) 0.95Marital status Caregiver %Married 73 79

0.0473 75

0.58Not Married 27 21 27 25

20

Zarit %Mild 30 17

0.00

36 33

0.60Mild to Moderate 47 47 37 41Moderate to Severe 16 28 16 17Severe 7 8 11 9

*Agitation symptoms: the presence of agitation and/or irritability and/or deshinibition and/or aberrant motor behavior

Abbreviations: ILTC: Institutional Long Term Care; A: agitation symptoms; PwD: People living with Dementia; SD: Standard Deviation; NPI-Q: Neuropsychiatry Inventory- Questionnaire; MMSE: Mini Mental State Examination;

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Table 3. Predictors of total and informal costs in Home Care settingTotal costs (1) Informal costs (2)

Coeff CI - 95% Coeff CI - 95%Agitation symptoms§ 1,00 [0,89-1,12] 1,17* [1,01-1,36]Others NPI-Q items without agitation|| 0,87 [0,69-1,09] - -Others NPI-Q items with agitation|| 1,37* [1.07-1.76] - -Dementia severity (MMSE)Mild 1Moderate 1,13* [1,02-1,24] 1,23† [1,06-1,43]Severe 1,18* [1,03-1,34] 1,43‡ [1,18-1,73]Physical disability (ADL)No or mild 1Moderate 1,24‡ [1,12-1,38] 1,36‡ [1,16-1,58]Severe 1,64‡ [1,47-1,84] 1,83‡ [1,55-2,18]Caregiver Burden (Zarit)Mild 1 1Mild to moderate 0,99 [0,89-1,11] 1.19* [1.00-1.40]Moderate to severe 1,06 [0,93-1,21] 1.57‡ [1.29-1.91]Severe 1,27† [1,06-1,53] 1.48† [1.13-1.95]*:<0,10; †: <0,05; ‡:<0,01; (1) GLMM (General linear mixed model) adjusted on countries, gender and age of PwD and dementia type; (2) Model adjusted on countries, PwD and informal caregiver ages, PwD gender and marital status of informal caregiver;

§Agitation symptoms: the presence of agitation and/or irritability and/or deshinibition and/or aberrant motor behavior

|| Others NPI-Q items with agitation: the interaction term between presenting 4 or more NPI-Q items with no agitation symptoms and presenting 4 or more NPI-Q items with agitation symptoms.

Abbreviations: NPI-Q= Neuropsychiatry Inventory-Questionnaire; MMSE= Mini Mental State Examination; CI= Confidential interval; ADL= Activity Daily Living;

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Figure 1. Costs Differences according to the informal care costing approach

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Annexe 1. Monthly mean costs and costs differences by setting, by agitation symptoms and by countries (€PPP, 2014)

Home careN=1217

ILTCN= 780

A-N= 300

A+N= 917

Mean Costs Differences p A-

N= 251A+

N= 529Mean Costs Differences p

N Mean N Mean N Mean N MeanEngland (N=153) 5 75 9 64Informal care 777 1983 1206 0.09 0 0 0 -ADL 360 893 533 0.39 0 0 0 -IADL 417 1090 673 0.05 0 0 0 -Medical care 232 611 379 0.52 114 231 117 0.27Inpatient 127 471 344 0.60 35 64 29 0.76Outpatient 61 94 33 0.85 42 130 88 0.14Medication 45 47 2 0.78 37 36 -1 0.86Community care 862 621 -241 0.17 3 1 -2 0.16Day care 287 258 -29 1.00 0 0 0 -District nurse 0 12 12 0.39 0 0 0 -Home help 563 276 -287 0.15 0 0 0 -Transportation 0 66 66 0.10 3 1 -2 0.16Meals on wheel 11 9 -2 0.02 0 0 0 -Institutional care 0 0 0 - 4477 4477 0 -Total costs 5 1871 75 3216 1345 0.14 4594 4709 115 0.31Estonia (N=286) 50 121 57 58Informal care 487 621 134 0.09 0 0 0 -ADL 245 311 66 0.16 0 0 0 -IADL 242 310 68 0.06 0 0 0 -Medical care 80 122 42 0.86 125 88 -37 0.09Inpatient 61 91 30 0.88 66 5 -61 0.54Outpatient 15 26 11 0.28 58 82 24 0.07

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Medication 5 5 0 0.74 1 1 0 1.00

Annexe 1. Continued (part 2)

Community care 169 162 -7 0.45 0 0 0 0.08Day care 26 41 15 0.11 0 0 0 -District nurse 16 34 18 0.23 0 0 0 -Home help 124 83 -41 0.39 0 0 0 -Transportation 3 2 -1 0.56 0 0 0 0.08Meals on wheel 2 0 -2 0.34 0 0 0 -Institutional care 0 0 0 - 1431 1431 0 -Total costs 50 736 121 905 169 0.14 57 1556 58 1519 -37 0.10Finland (N=303) 38 144 40 81

Informal care 745 1029 284 0.08 0 0 0 -ADL 266 452 186 0.06 0 0 0 -IADL 478 577 99 0.16 0 0 0 -Medical care 1134 1298 164 0.93 315 547 232 0.80Inpatient 761 909 148 0.92 19 185 166 0.51Outpatient 147 162 15 0.91 175 209 34 0.26Medication 1134 228 -906 0.93 120 152 32 0.19Community care 639 522 -117 0.87 8 7 -1 0.77Day care 32 74 42 0.25 0 0 0 -District nurse 237 129 -108 0.70 0 0 0 -Home help 306 240 -66 0.89 0 0 0 -Transportation 18 18 0 0.54 8 7 -1 0.77Meals on wheel 46 60 14 0.92 0 0 0 -Institutional care - - - - 5443 5443 0 -Total costs 38 2517 144 2849 332 0.63 40 5766 81 5996 230 0.10

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Annexe1. Continued (part 3)France (N=221) 62 111 15 31

Informal care 779 1042 263 0.23 0 0 0 -

ADL 214 373 159 0.06 0 0 0 -IADL 565 669 104 0.60 0 0 0 -Medical care 1119 1191 72 0.35 301 1058 757 0.59Inpatient 652 746 94 0.86 0 125 125 0.49Outpatient 369 346 -23 0.36 223 849 626 0.52Medication 98 99 1 0.95 77 84 7 0.80Community care 1303 1557 254 0.44 5 1 -4 0.20Day care 59 36 -23 0.90 0 0 0 -District nurse 502 570 68 0.36 0 0 0 -Home help 706 934 228 0.36 0 0 0 -Transportation 2 1 -1 0.92 5 1 -4 0.20Meals on wheel 33 16 -17 0.08 0 0 0Institutional care 0 0 0 - 5706 5706 0 -Total costs 62 3200 111 3790 590 0.04 15 6012 31 6765 753 0.61Germany (N=232) 19 96 29 88

Informal care 972 1730 758 0.01 0 0 0 -ADL 376 797 421 0.00 0 0 0 -IADL 597 933 336 0.07 0 0 0 -Medical care 134 545 411 0.01 250 814 564 0.00Inpatient 0 284 284 0.19 0 313 313 0.09Outpatient 98 199 101 0.07 196 444 248 0.00Medication 37 62 25 0.25 54 57 3 0.82Community care 1298 1089 -209 0.05 0 10 10 0.25Day care 182 289 107 0.11 0 0 0 -District nurse 991 487 -504 0.01 0 0 0 -Home help 64 249 185 0.70 0 0 0 -Transportation 6 33 27 0,01 0 10 10 0.25

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Annexe 1. Continued (part 4)Meals on wheel 53 30 -23 0.28 0 0 0 -Institutional care 0 0 0 - 5041 5041 0 -Total costs 19 2405 96 3364 959 0.08 29 5291 88 5865 574 0.00Netherland (N=290) 32 145 36 77

Informal care 605 846 241 0.03 0 0 0 -ADL 239 285 46 0.30 0 0 0 -IADL 367 561 194 0.02 0 0 0 -Medical care 240 310 70 0.53 356 327 -29 0.52Inpatient 54 49 -5 0.72 0 0 0 -Outpatient 143 200 57 0.40 316 297 -19 0.85Medication 43 61 18 0.37 40 30 -10 0.31Community care 1624 1625 1 0.93 2 0 -2 0.19Day care 381 460 79 0.19 0 0 0 -District nurse 99 56 -43 0.10 0 0 0 -Home help 1026 932 -94 0.52 0 0 0 -Transportation 96 138 42 0.35 2 0 -2 0.19Meals on wheel 23 39 16 0.75 0 0 0Institutional care 0 0 0 - 4891 4891 0 -Total costs 32 2470 145 2781 311 0.34 36 5248 77 5218 -30 0.49Spain (N=285) 53 121 32 79Informal care 1202 1342 140 0.29 0 0 0 -ADL 532 613 81 0.32 0 0 0 -IADL 670 729 59 0.32 0 0 0 -Medical care 284 300 16 0.64 408 996 588 0.02Inpatient 127 127 0 0.99 0 251 251 0.20Outpatient 44 76 32 0.06 347 700 353 0.01Medication 113 97 -16 0.28 61 45 -16 0.69Community care 278 629 351 0.14 0 1 1 0.14Day care 150 206 56 0.16 0 0 0 -District nurse 5 15 10 0.31 0 0 0 -

27

Annexe 1. Continued (part 5)Home help 123 403 280 0.38 0 0 0 -Transportation 0 5 5 0.10 0 1 1 0.14Meals on wheel 0 0 0 - 0 0 0 -Institutional care 0 0 0 - 2980 2980 0 -Total costs 53 1764 121 2271 507 0.05 32 3388 79 3977 589 0.02Sweden (N=229) 41 104 33 51

Informal care 956 1055 99 0.33 0 0 0 -ADL 308 311 3 0.60 0 0 0 -IADL 647 744 97 0.27 0 0 0 -Medical care 137 223 86 0.91 293 179 -114 0.77Inpatient 20 82 62 0.99 163 16 -147 0.31Outpatient 27 46 19 0.27 82 124 42 0.80Medication 90 94 4 0.86 47 39 -8 0.43Community care 1309 972 -337 0.18 5 5 0 0.62Day care 271 334 63 0.30 0 0 0 -District nurse 20 22 2 0.96 0 0 0 -Home help 916 497 -419 0.03 0 0 0 -Transportation 67 65 -2 0.86 5 5 0 0.62Meals on wheel 36 53 17 0.90 0 0 0 -Institutional care 0 0 0 - 5872 5872 0 -Total costs 41 2402 104 2249 -153 0.35 33 6170 51 6056 -114 0. 76

Abbreviation: ILTC= Institutional long term care ; A = agitation cluster symptoms; PPP: Purchasing Power Parity; ADL: Activity of Daily Living; IADL: Instrumental Activity of Daily Living

28