V. Dauphinot1, A. Garnier-Crussard1, C. Moutet1, F. Delphin-Combe1, H.-M. Späth2, P. Krolak-Salmon1,3,4
1. Clinical and Research Memory Center of Lyon, Lyon Institute For Elderly, University hospital of Lyon, Lyon, France; 2. EA 4129 “Parcours Santé Systémique”, University Lyon 1, Lyon, France; 3. Clinical Research Centre CRC – VCF (Vieillissement – Cerveau – Fragilité), Hospital of Charpennes, University Hospital of Lyon, Lyon, France; 4. Neuroscience Research Centre of Lyon, Inserm 1048, CNRS 5292, Lyon, France
Corresponding Author: Dr Virginie Dauphinot, Hôpital des Charpennes, 27 rue Gabriel Péri, 69100 Villeurbanne, France, Tel: +33 (0) 472433114. Fax: +33 (0) 472432054, E-mail address: email@example.com
J Prev Alz Dis 2021;
Published online April 10, 2021, http://dx.doi.org/10.14283/jpad.2021.16
Background: Alzheimer’s disease and related diseases (ADRD) are a major cause of health-related cost increase.
Objectives: This study aimed to estimate the real medical direct costs of care of patients followed at a memory center, and to investigate potential associations between patients’ characteristics and costs.
Design: Cross-sectional analyses conducted on matched data between clinical data of a cohort of patients and the claims database of the French Primary Health Insurance Fund.
Setting: Memory center in France
Participants: Patients attending a memory center with subjective cognitive complaint
Measurements: Medical or nonmedical direct costs (transportation) reimbursed by the French health insurance during the one year after the first memory visit, and socio-demographic, clinical, cognitive, functional, and behavioral characteristics were analyzed.
Results: Among 2,746 patients (mean ± SD age 79.9 ± 8 years, 42.4% of patients with dementia), the total direct cost was on average € 9,885 per patient during the year after the first memory visit: € 7,897 for patients with subjective cognitive complaint, € 9,600 for patients with MCI, and € 11,505 for patients with dementia. A higher functional and cognitive impairment, greater behavioral disorders, and a higher caregiver burden were independently associated with a higher total direct cost. A one-point decrease in the Instrumental Activities of Daily Living score was associated with a € 1,211 cost increase. The cost was higher in patients with Parkinson’s disease, and Lewy body disease compared to patients with AD. Diabetes mellitus, anxiety disorders and number of drugs were also significantly associated with greater costs.
Conclusions: Higher real medical direct costs were independently associated with cognitive, functional, and behavioral impairment, diabetes mellitus, anxiety disorders, number of drugs, etiologies as well as caregiver burden in patients attending a memory center. The identification of factors associated to higher direct costs of care offers additional direct targets to evaluate how interventions conducted in patients with NCD impact direct costs of care.
Key words: Costs of care, dependence, cognitive status, economics, Alzheimer’s disease.
Alzheimer’s disease and related diseases (ADRD) are considered as the main cause of health-related cost increase in developed countries (1, 2). Dementia represented a total cost of € 105.2 billion in Europe in 2010 (3). In France, the prevalence of dementia has been estimated to 7.9% among people aged 65 and over, and it is expected to reach 9.6% by 2050 (4). To anticipate and optimize interventions targeting patients developing neurocognitive disorders (NCD)(5), it is of crucial importance to evaluate the cost of resources associated with the main characteristics of NCD. Cost-of-illness studies for ADRD appear essential to anticipate future resource needs, nevertheless they remain difficult to conduct as aging is related to various health conditions and comorbidities, and it is unclear whether comorbidities should be directly linked to ADRD (6, 7). In cost-of-illness studies, costs of care have been mainly estimated from self-reported resource utilization by patients and/or their informal caregivers (8-10). The use of real costs associated to patients’ care (estimated from claims data) offers an objective evaluation of costs related to patient care, independently of the possible recall bias that self-report might induce (11). Most previous studies have estimated the average cost per patient selected with a specific diagnosis (12-14), and costs of care in patients with ADRD were generally related to symptoms severity such as cognitive, functional and behavioral impairment (6, 12-23). These costs were presented with different amplitudes depending on the study population characteristics, the perspective of the study (payer, societal), the components of the costs (direct, indirect, informal), and the time of evaluation, which makes difficult any comparisons (12, 24, 25). Analyses of economic data of patients suffering from neurocognitive disorders with real-world data are scare in France while they are needed to evaluate the economic impact of interventions and for policy makers (26). The present study aimed at estimating the real medical direct costs of care of patients of a memory center at all stages of cognitive impairment during the one year after their first memory visit, and at investigating the potential associations between patient socio demographic and clinical characteristics and the average real medical and non-medical direct costs. Furthermore, these associations were assessed in the sub-group of patients with Alzheimer’s disease (AD).
Study design and setting
The present study was a cross-sectional analysis conducted on matched data between the MEMORA cohort including patient clinical data and the claims database of the French Primary Health Insurance Fund (PHIF). The protocol of the MEMORA cohort has been published previously (27). The match between the two databases was performed using the date of the 1st visit at a memory center. The claims database includes real medical and nonmedical direct costs of care for patients. Claims data were analyzed for one year after the first visit at a memory center. The present study was conducted at the University Clinical and Research Memory Centre of Lyon (University Hospital of Lyon, France), in collaboration with the regional PHIF of Rhône (Lyon, France). Around 90% of the French population is covered by the PHIF (28).
The study population included consecutive patients who underwent a medical examination in a memory center with a neurologist, geriatrician, or psychiatrist between 2014 and 2017. The inclusion criteria of patients were: to attend a memory visit, to have an evaluation of the functional autonomy level, not to live in a nursing home, and to be covered by the PHIF. Patients under legal protection were excluded from the study. The ethics Committee for the Protection of Persons Lyon Sud-Est IV was consulted on the 21st June 2013, and as the study was not classified as an interventional study, no written consent was required for participation. Written information regarding collection of individual data was provided to the patients and their informal caregivers and they were given the possibility to decline participation. Authorization for handling these data has been granted by the French Data Protection Authority (CNIL: Commission Nationale de l’Informatique et Libertés).
Real medical and nonmedical direct costs of cares
Source of cost data
This study was carried out from the perspective of the main payer of cares in France: the PHIF. The PHIF collects for each patient the real costs in Euros (€) of each care, act, and treatment that are reimbursed to patients. The costs included all the medical direct costs supported by the PHIF and one nonmedical direct cost (medical transportation). The others nonmedical direct costs such as home support and the indirect costs were not included since they are not covered by the PHIF.
Collected items of costs
The collected items of costs were grouped as medical direct costs ((1) outpatient cares, i.e. consultations and cares provided by general practitioners or specialists, surgical procedures in private practice, ophthalmological and hearing devices, dental cares, laboratory analyses, radiology examinations (radiology, scanners, MRI, PET, echography, bone densitometry), immunization, home dialysis, at-home hospitalizations, and health cures, (2) paramedical cares, i.e. nursing, physiotherapist, speech therapist, orthoptist, (3) pharmaceutical treatment in retail pharmacies, (4) public hospital stays, and (5) private hospital stays) and nonmedical direct costs (the medical transportations).
Valorization of the costs
The total cost per patient was estimated by adding all the costs of care, act, and treatment that occurred during the first year after the first memory center visit. The costs were presented as constant costs after adjustment using the value of Euro in 2017 as a reference, this value was available from the French national institute for statistical and economic studies (INSEE: Institut National de la Statistique et des Etudes Economiques) (https://www.insee.fr/fr/information/2417794). For each care, act, and treatment, the PHIF applies a specific reimbursement level, which is similar nationally.
Socio-demographic and clinical data at the memory center
Socio-demographic and clinical data were collected from the MEMORA cohort database, upon the first visit to the memory center (27). Socio-demographic data were: gender, age, marital status, and educational level.
Diagnosis etiologies and stages were determined by the specialist physician (neurologist, geriatrician, or psychiatrist) in charge of the patient (29-33). Patients with a cognitive complaint and normal neuropsychological performances were considered as having subjective cognitive complaint. A time to death variable was considered and calculated as the number of months between the first visit to the memory center and either the occurrence of the death or the last time the patient was known to be alive (corresponding to the end of the study period).
The following comorbidities information was collected: hypertension, hypercholesterolemia, diabetes mellitus, anxiety disorders and depressive disorders using medical report, as well as the number of drugs. The functional autonomy level was assessed during the interview with the primary caregiver with the Instrumental Activities of Daily Living (IADL) scale, including 8 activities (34). The IADL score ranges from 0 (dependent) to 8 (independent). Overall cognitive performances were assessed using the Mini Mental State Examination (MMSE), which ranges from 0 to 30 (35). The behavioral and psychological symptoms of dementia were assessed using the Neuropsychiatric Inventory (NPI) (36). A higher overall NPI score (maximum 144) is indicative of more severe behavioral disorders. The caregiver burden was assessed using the mini-Zarit scale, ranging from 0 to 7 (37). MMSE, IADL, NPI, and mini-Zarit scores were considered as continuous scores and as tertiles. MMSE scores were also considered using categories i.e. <10 (severe), 10-20 (moderate), >20 (mild).
The study population characteristics were described using the mean value ± standard deviation (SD) or the percentage, as appropriate. The costs per patient were expressed in euros and decomposed according to the origin of the costs, using means and their 95% confidence intervals (CI), medians, the 25th and 75th percentiles, and the minimum and maximum values. As the nonmedical direct costs of medical transport did not represent a large amount of the total cost, they were added, after description, to the medical direct costs to obtain a global cost per patient for further analyses.
As the distribution of the global cost was skewed, the relationship between each patient’s characteristics and the global cost was studied using generalized linear model (GLM) with log link and gamma distribution (38, 39). All significant variables associated with the total cost were then modeled together in multivariate GLM. Due to missing values for NPI and mini-Zarit scores, two different multivariate models were performed: the model 1 did not take into account the NPI and mini-Zarit scores, the model 2 did. The same multivariate models were performed within the sub-group of patients with AD. Results were summarized and presented as unadjusted and adjusted mean total cost, 95% CI, and p value. Additionally, the adjusted cost per 1 unit of IADL decrease was estimated and represented graphically.
A sensitivity analysis was conducted to examine the effect of potential “outliers” on the results. The “outliers” were identified as individual total cost greater than 3SD from the mean. The characteristics of the patients with outlier costs were compared to the characteristics of other patients, using Student t test or Pearson’s chi-square test. A new model was then performed after excluding the costs from the patients with outliers to verify whether the associations remained similar. P values below 0.05 were considered as statistically significant. Analyses were performed using STATA version 13 for Windows (StataCorp. 2013. Stata Statistical Software: Release 13. College Station, TX: StataCorp LP), and SPSS (Statistical Package for the Social Sciences) version 19.0 for Windows (SPSS Inc., Chicago, Illinois, USA).
Study population characteristics
The study population included 2,746 patients (Table 1). Overall, 62.8% of patients were female; the mean age was 79.9 ± 8 years. The mean MMSE score was 19.7 ± 7, the mean IADL score was 4.2 ± 2, and the mean NPI score was 19.8 ± 17. In terms of etiology, 27.6% of patients had probable AD with or without cerebrovascular component, 6.4% had vascular encephalopathy (with no AD), 1.5% had Lewy body disease, and 0.4% had fronto temporal dementia. For 53.5% of the patients, the diagnosis etiology could not be established at the 1st visit at the memory center.
* Time to death was the number of months from the first visit to the memory center until either the occurrence of the death or the last time the patient was known to be alive; IADL: Instrumental Activities of Daily Living; MMSE: Mini-Mental State Examination; NPI: Neuropsychiatric Inventory
Real direct costs of care
The total direct cost of cares was on average € 9,885 [9,175; 10,594] per patient during the year after the first memory center visit (including € 9,647 [8,946; 10,350] for medical direct costs and € 238 [213; 263] for the medical transport considered as nonmedical cost (Table 2). Most of the direct medical cost was attributable to the hospital care in public hospital (€ 6,158 [5,492; 6,824]), representing 62% of the total direct cost, followed by the cost of paramedical care (€ 1,933 [1,816; 2,050]), to the pharmaceutical treatment in retail pharmacies (€ 725 [671; 779]), to the ambulatory medicine (€ 595 [553; 637]), and finally to the care in private hospital (€ 238 [177; 299]).
* It includes consultations and cares provided by general practitioners or specialists, surgical procedures in private practice, ophthalmological and hearing devices, dental cares, biological analyses, radiology examinations (radiology, scanners, MRI, PET, echography, bone densitometry), vaccinations, home dialysis, at-home hospitalizations, and SPA treatments; † It includes nursing, physiotherapy, speech therapy, orthoptist.
Unadjusted associations between patient characteristics and the mean total cost of cares
The mean total cost was significantly higher with increasing age (p<0.0001), whereas no difference was found between genders (p=0.53; Table 3). The mean total cost was significantly higher when the educational level was lower (p<0.0001) e.g. € 10,782 [9,850; 11,714] for patients with primary educational level vs. € 6,938 [5,909; 7,967] for patients with tertiary educational level. The mean total cost was also significantly associated with the marital status (p<0.0001) and it was higher for patients with diabetes mellitus (€ 12,042 [10,580; 13,505], p<0.0001) or anxiety disorders (€ 12,557 [11,388; 13,725], p<0.0001) compared to those without (€ 9,491 [8,963; 10,018] and € 8,844 [8,314; 9,375] respectively). The mean total cost was higher when the number of drugs increased (p<0.0001). The mean total cost varied depending on the diagnosis etiology (p<0.0001): € 10,444 [9,444; 11,444] for patients with AD, while it was the highest for patients with Parkinson’s disease (€ 21,155 [11,443; 30,866]) and Lewy body disease (€ 20,433 [11,913; 28,951]). The mean total cost increased with the diagnosis severity (p<0.0001): the mean total cost was € 7,897 [7,142; 8,651] for patients with subjective cognitive complaint, € 9,600 for patients with MCI [8,714; 10,487], and € 11,505 [10,614; 12,396] for patients with dementia. The mean total cost was higher when the cognitive performance was lower (based on the MMSE score, p<0.0001); a one-point decrease of the MMSE score was associated with an increase cost of € 288 [170; 408]. The mean total cost was higher when the functional autonomy level was lower (based on the IADL score, p<0.0001), and a one-point decrease of the IADL score was associated with an increase cost of € 1,359 [1,069; 1,648]. The mean total was higher when the behavioral disturbances were higher (based on the NPI score, p=0.0001).
* Generalized linear model with log-normal link and gamma distribution; † Time to death was the number of months from the first visit to the memory center until either the occurrence of the death or the last time the patient was known to be alive; IADL: Instrumental Activities of Daily Living; MMSE: Mini-Mental State Examination; NPI: Neuropsychiatric Inventory
Adjusted associations between patient characteristics and the mean total cost of care
When all the variables that were significantly associated with the mean total cost in the unadjusted models were modeled together, all the variables still contributed significantly to the model, and the adjusted mean total cost was 13,057 [10,957; 15,168] per patient (Table 4). More precisely, the IADL score was negatively correlated to the mean cost, and a one-point decrease in the IADL score corresponded to an increase of the cost of € 1,211 [890; 1,532], after adjustment for age, educational level, diabetes mellitus, anxiety disorders, number of drugs, marital status, diagnosis etiology, time to death variable and MMSE score (Figure 1).
*Adjusted for age, educational level, diabetes mellitus, anxiety disorders, number of drugs, marital status, diagnosis etiology, MMSE score and time to death; IADL: Instrumental Activities of Daily Living
* Model 1: Generalized linear model (GLM) with log-normal link and gamma distribution including age, educational level, marital status, diabetes mellitus, anxiety disorders, number of drugs, etiology, time to death, IADL score and MMSE score tertiles; † Model 2: GLM with log-normal link and gamma distribution including the variables of the model 1, and NPI score and mini-Zarit score tertiles; IADL: Instrumental Activities of Daily Living; MMSE: Mini-Mental State Examination; NPI: Neuropsychiatric Inventory
In the sub-group of patients with AD (n=758), the adjusted mean total cost was 11,421 [9,982; 12,859]; a higher age (p=0.002), the presence of hypercholesterolemia (p=0.045), the presence of anxiety disorders (p<0.0001), a higher number of drugs (p<0.0001), and a lower IADL score (p<0.0001) were independently associated with higher costs of care (Supplement Table 1). The multivariate model found higher costs for patients with a MMSE score between 13 and 18 (€ 11,918 [9,687; 14,149]) compared to patients with lower and higher MMSE score: € 7,913 [6,425; 9,401] (MMSE≤13), and € 8,400 [7,165; 9,636] (MMSE>18). When including the NPI score and the mini-Zarit score tertiles in the model (Model 2), higher behavioral disorders (p=0.003) and higher caregiver burden (p<0.0001) were significantly associated with higher cost of cares. For patients with AD, the IADL score was negatively correlated to the mean cost, and a one-point decrease in the IADL score corresponded to a cost increase of € 1,096 [372; 1,820], after adjustment for age, number of drugs, time to death variable, anxiety, hypercholesterolemia, and MMSE score (Supplement Figure 1).
Among the 2,746 patients included in the present study, 88 were identified as having outlier costs (Supplementary Table 2). These patients were characterized by a slightly older age (81.9 ± 7.5 years vs. 79.9 ± 7.9 years, p=0.02), a higher number of drugs (13.4 ± 5.8 vs. 11 ± 5.5, p<0.0001), a worse functional impairment (IADL≤3 in 69.4% vs. 40.8% patients, p<0.0001), a lower MMSE score (MMSE≤17 in 52.3 vs. 33.1% patients, p<0.0001) compared to the group of patients without outlier costs. Among these patients, the proportion of dementia was higher (56.8% vs. 41.9% patients, p=0.02). Caregiver burden was higher in the group with outliers compared to the group without (Mini-Zarit>4: 43.1% vs. 29.4%). The multivariate model without outliers found similar associations between characteristics and total costs (Supplementary Table 3) as obtained with the complete set of patient data, excepted for the educational level and the diabetes mellitus for which the statistical significance was not reached anymore.
The present study provides an estimation of real medical and non-medical (transportation) direct costs of cares occurring during one year after the first memory center visit, for a large sample of outpatients at all stages of cognitive impairment, from the perspective of the main health insurance: annual medical direct cost of € 9,885 per patient varying from € 7,897 in patients cognitively normal but with subjective cognitive complaint, to € 9,600 in patients with MCI and € 11,505 in patients with dementia. The main part of direct costs of cares in our study was related to cares provided in public hospitals. Also, higher direct costs were independently associated with functional, cognitive and behavioral impairments, diabetes mellitus, anxiety disorders, higher number of drugs as well as with higher caregiver burden. The costs also varied across NCD etiologies, in particular they were higher in patients with Parkinson’s disease, and Lewy body disease compared to patients with AD. The associations between higher direct costs and functional, cognitive and behavioral impairments, anxiety disorders, number of drugs as well as with higher caregiver burden remained significant in the sub-group of patients with AD and in the sensitivity analyses restricted to individuals for whom the cost was not considered as outlier.
These results are consistent with the study of Leibson et al. conducted in a US population-based sample, showing that 70% of the direct costs of care was related to public hospitals cares, and which found an annual medical direct cost at $ 11,678 for patients with prevalent dementia, $ 9,431 for patients with newly discovered dementia, $ 6,784 for patients with MCI, and $ 6,042 for patients considered as cognitively normal (11). Besides, one can note that these results are surprisingly close in terms of level of costs, given than healthcare systems differ between countries.
The present study also confirmed and extended findings of others studies conducted in different contexts and from different economic perspectives, showing that the functional abilities was a main cost driver (2, 9, 20, 25, 40-42). In Zhu et al., a decrease of one-point in functional capacities measured with the Blessed Dementia Rating Scale (score out of 22) was associated with an increase of $ 1,406 in medical direct costs among community-dwelling patients with probable AD (15), whereas a decrease of one-point in functional capacities measured with the IADL scale (score out of 8) was associated with an increase of € 1,096 for one-point decrease of IADL in the sub-group of AD patients in the present study.
In the present study, direct medical costs were higher in patients with Lewy body disease or Parkinson’s disease compared to others NCD etiologies such as AD. While sample sizes in these sub-groups were limited, this observation is sustained by previous studies showing that Lewy body dementia was the costliest compared to others dementia’s etiologies (43), explained in part by cost of cares related to falls, urinary incontinence or infection, depression, anxiety, dehydration, and delirium. Another study also showed that Parkinson’s disease was associated with higher direct health care cost per patient compared to dementia without providing possible explanations (3).
Additional evidences of the association between costs and the MMSE were provided herein, in accordance with others studies (12, 25). However, in the study of Lindholm et al., the MMSE was not associated with the costs after adjustment for functional abilities (40). In the latter study, the characteristics of the population (community-dwelling population-based with a mean MMSE score of 26.6 ± 6) differed from the characteristics of the population studied here (patients of a memory center with a mean MMSE score of 19.7 ± 7), and the sample size was smaller, which may partially explain this discrepancy. Interestingly, in adjusted models, higher direct costs were found in patients with a MMSE score in the second tertile in the whole population study as well as in the AD sub-group (i.e. 13-18), whereas costs were lower in patients with lower or higher MMSE. In particular, patients with a MMSE score at 13-18 were found to have higher costs related to hospital stays for surgery and geriatric cares, higher costs for ambulatory cares in linked with visits to physicians, hearing device, radiology, and laboratory evaluations, and higher costs linked with medical transportation compared to patients with lower or higher MMSE score (detailed results not shown). A possible explanation for this finding is that patients at a more advanced stage of NCD may undergo less elective surgery due to higher risks of complications and higher mortality rates following surgical procedures in patients with dementia (44), and they might have lower health care consumption since the diagnosis has been previously made and less exploratory examinations are needed.
Similarly, higher direct costs were significantly associated with behavioral disorders in accordance with some studies (20, 21), but not all (23, 45). The use of reimbursement data from claims database in the present study instead of self-report use of care reinforces the objectivity of the analysis and strengthens the conclusion that behavioral disorders are associated with a significant increase of cost independently of other patient characteristics.
Also, higher costs were associated with higher caregiver burden, as observed in a previous study conducted from a societal point of view (23). Since the association remained significant after adjustment for others characteristics, we hypothesize that higher costs could directly contribute to the higher burden carried by the informal caregiver, independently of the patients’ impairments. This hypothesis is supported by a previous study showing an association between the financial stress and the higher caregiver burden (46). Even though the costs were estimated from the perspective of the national health insurance in the present study, the insurance may not cover the entire cost borne by patients and their caregivers. Nevertheless, further evidences are needed to confirm this hypothesis.
An original result of the present study was that among the comorbidities considered in the present study, diabetes mellitus and anxiety disorders were independently related to higher costs, while hypertension and hypercholesterolemia were not in the whole sample. In patients with AD, diabetes mellitus was not associated with costs, whereas a slight association was observed with hypercholesterolemia. The results are controversial in the literature concerning the link between comorbidities and costs in patients with NCD, e.g. Jutkowitz et al did not find significant link between comorbidities and costs (42), whereas Hill et al did (47).
Strengths and limits of the study
The present study included a large sample of outpatients attending a memory center with matched patient clinical data and costs. Real costs of care were estimated from claims database from the PHIF that is the main insurance in France and covers 90% of the French population (28), this limited the introduction of selection biases in the population other than the ones considered for the study. The study included patients at all stages of cognitive impairment, which allowed to conduct study between stage groups and to have a global overview of the medical direct costs (plus the medical transport) of patients visiting a memory center. According to a previous study based on the French National Alzheimer Database (48), 118,776 patients with AD attended a memory center in 2010, based on the results of the present study, the total direct cost covered by the PHIF for patients with AD one year after the first visit would be estimated to €370,337,356.
Limitations should nevertheless be considered when interpreting the results herein. This study had a cross-sectional design which does not allow causal relationships between the associations to be determined. The study did not include the societal perspective: this cost analysis did not include the indirect costs (e.g. indirect consequences of the disease such as lost work productivity or earning and informal costs), and the others nonmedical direct costs (e.g expenditures linked with the disease but not associated with medical services such as home services, nonmedical transport), except medical transportation, which led to an underestimation of the costs related to NCD, nevertheless it was specified that this study is not a cost-of-illness study. Previous studies have shown that a major part of the cost related to patients with cognitive impairment was supported by informal caregivers (informal care costs), especially when the patients were living at home, and costs estimation required specific surveys, often based on self-reported caregiving time allowed to patient and an extrapolation of the caregiver’s loss of earnings (21). In addition, the interpretation of these results should take into account the fact that a part of the direct medical costs can also be covered by private insurance that the patients can contract, the present study is from the point of view of the main French public health insurance. This study should also be interpreted in regards of the setting since all patients with cognitive impairment are not managed in memory centers and a part are followed by community practitioners, the care and then the costs may differ. Finally, mean costs should be interpreted with caution as the distribution of costs was skewed, nevertheless the statistical models took into account this data distribution.
This large study showed that functional and cognitive impairment, behavioral disorders, caregiver burden, diabetes mellitus, anxiety disorders, and the number of drugs were independently associated with higher direct cost of care for patients attending a memory center, from the payer perspective (French health insurance). The identification of these factors associated to higher direct costs of care offers additional direct targets to evaluate how interventions conducted in patients with NCD impact direct costs of care. Further researches are needed to broaden the economic perspective to the societal one and verify whether societal costs remain driven by the same factors.
Funding: The MEMORA study has received funding supports from MSD Avenir Fund, and Biogen Inc. These sponsors enabled the funding of nurses to carry out the research and questionnaires; they had no role in the design, conduct, collection, analysis and interpretation of the data, as well as in the preparation of the manuscript, its review and approval.
Acknowledgements: We thank Mrs. Pascale Gauthier-Robino and Mr. Laurent Colas from the Primary Health Insurance Fund of the Rhône (CPAM Rhône, France) for their collaboration during this research, Dr Michele Potasham for her advice, Mrs. Hélène Boyer (Direction de la Recherche Clinique et Innovation, Hospices Civils de Lyon, Lyon, France) for her help in the manuscript preparation and Mrs. Sarah Achi for her help in data management. We are grateful to the participants and the hospital staff.
Conflict of interest: The authors declare that they have no competing interests.
Study registration: ClinicalTrials.gov Identifier: NCT02302482. Registered: 27th November 2014, https://clinicaltrials.gov/ct2/show/NCT02302482.
Ethical standards: Written information regarding collection of individual data was provided to the patients and their informal caregivers and they were given the possibility to decline participation. This research conducted in routine care was considered as non-interventional by the local ethics committee CPP Lyon Sud-Est IV (Comité de Protection des Personnes / committee for the protection of people). Authorization for handling these data has been granted by the French Data Protection Authority (CNIL: Commission Nationale de l’Informatique et Libertés).
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