Impact of modifications to antidementia drug reimbursement in France: Analysis of the FRA-DEM cohort.

AIMS: Alzheimer's disease and related diseases (ADRD) is a progressive and inexorable disease. In France, acetylcholinesterase inhibitors and memantine were reimbursed for subjects with ADRD, until 2 modifications of their reimbursement rate (2012, 2018). We aimed to study the consequences of these measures on ADRD subjects' healthcare use. METHODS: We analysed data from the FRA-DEM cohort, including subjects with presumed incident ADRD identified since 2011 in the French health insurance system. We studied the healthcare use of subjects identified with incident ADRD in 2011, 2013, 2015, 2017 and 2019, notably the annual number of defined daily doses of various psychotropic groups. We performed 2 multivariate multinomial logistic regressions with the subcohort year as the dependent variable. RESULTS: In total, 165 120 subjects were included. A progressive decrease in exposure to antidementia drugs was observed between 2011 and 2019. Consultations with private neurologists or psychiatrists, and exposure to risperidone, antidepressants and benzodiazepines increased in the 2019 subcohort, following the 2018 reimbursement withdrawal. Meanwhile, the use of nursing/allied healthcare and emergency care increased over the subcohort years, whereas we observed a decrease in general practitioner consultations. CONCLUSION: These results suggest increases in private neurologist or psychiatrist consultations and exposure to recommended drugs after the reimbursement withdrawal, contrary to the fears expressed. However, antidementia drug exposure decreased long before the reimbursement modifications, probably due to the growing evidence of the modest effect of these drugs, and exposure to benzodiazepines increased after the reimbursement withdrawal.

Healthcare use according to deprivation among French Alzheimer's Disease and Related Diseases subjects: a national cross-sectional descriptive study based on the FRA-DEM cohort.

Introduction: Pluriprofessional and coordinated healthcare use is recommended for Alzheimer's Disease and Related Diseases (ADRD). Despite a protective health system, France is characterized by persistent and significant social inequalities in health. Although social health inequalities are well documented, less is known about social disparities in healthcare use in ADRD, especially in France. Therefore, this study aimed to describe healthcare use according to socioeconomic deprivation among ADRD subjects and the possible potentiating role of deprivation by age. Methods: We studied subjects identified with incident ADRD in 2017 in the French health insurance database (SNDS). We described a large extent of their healthcare use during the year following their ADRD identification. Deprivation was assessed through French deprivation index (Fdep), measured at the municipality level, and categorized into quintiles. We compared healthcare use according to the Fdep quintiles through chi-square tests. We stratified the description of certain healthcare uses by age groups (40-64 years, 65-74 years, 75-84 years, 85 years, and older), number of comorbidities (0, 1, 2-3, 4 comorbidities and more), or the presence of psychiatric comorbidity. Results: In total, 124,441 subjects were included. The most deprived subjects had less use of physiotherapy (28.56% vs. 38.24%), ambulatory specialists (27.24% vs. 34.07%), ambulatory speech therapy (6.35% vs. 16.64%), preventive consultations (62.34% vs. 69.65%), and were less institutionalized (28.09% vs. 31.33%) than the less deprived ones. Conversely, they were more exposed to antipsychotics (11.16% vs. 8.43%), benzodiazepines (24.34% vs. 19.07%), hospital emergency care (63.84% vs. 57.57%), and potentially avoidable hospitalizations (12.04% vs. 10.95%) than the less deprived ones. Discussion and conclusion: The healthcare use of subjects with ADRD in France differed according to the deprivation index, suggesting potential health renunciation as in other diseases. These social inequalities may be driven by financial barriers and lower education levels, which contribute to health literacy (especially for preventive care). Further studies may explore them.

Which factors preceding dementia identification impact future healthcare use trajectories: multilevel analyses in administrative data.

BACKGROUND: Healthcare use patterns preceding a diagnosis of Alzheimer's Disease and Related Diseases (ADRD) may be associated with the quality of healthcare use trajectories (HUTs) after diagnosis. We aimed to identify determinants of future favorable HUTs, notably healthcare use preceding ADRD identification. METHODS: This nationwide retrospective observational study was conducted on subjects with incident ADRD identified in 2012 in the French health insurance database. We studied the 12-month healthcare use ranging between 18 and 6 months preceding ADRD identification. The five-year HUTs after ADRD identification were qualified by experts as favorable or not. In order to take into account geographical differences in healthcare supply, we performed mixed random effects multilevel multivariable logistic regression model to identify determinants of future favorable HUTs. Analyses were stratified by age group (65-74, 75-84, ≥ 85). RESULTS: Being a woman, and preventive and specialist care preceding ADRD identification increased the probability of future favorable HUT, whereas institutionalization, comorbidities, medical transportation and no reimbursed drug during [-18;-6] months decreased it. Besides, some specificities appeared according to age groups. Among the 65-74 years subjects, anxiolytic dispensing preceding ADRD identification decreased the probability of future favorable HUT. In the 75-84 years group, unplanned hospitalization and emergency room visit preceding ADRD identification decreased this probability. Among subjects aged 85 and older, short hospitalization preceding ADRD identification increased the probability of future favorable HUTs. CONCLUSION: Regular healthcare use with preventive and specialist care preceding ADRD identification increased the probability of future favorable HUTs whereas dependency decreased it.

Healthcare use patterns before Alzheimer's disease and related diseases identification and future healthcare trajectory.

OBJECTIVES: A frequent late Alzheimer's Disease and Related Diseases (ADRD) identification is described and may induce erratic health resource use. We aimed to describe healthcare use patterns preceding ADRD identification. METHODS: We studied persons aged 65 or older, identified with incident ADRD in 2012 in the French health insurance database. Healthcare use covering a wide range of care in ambulatory and hospital settings during the period ranging from 18 to six months before ADRD identification was studied. The main dimensions of healthcare use patterns before ADRD identification were investigated in three age groups (65-74, 75-84, ≥85) through a multiple correspondence analysis. These dimensions were secondarily interpreted according to the 5-year healthcare trajectory following ADRD identification, qualified as favorable (or not) by experts in the field. RESULTS: This research studied 36,990 subjects. Four dimensions raised in each age group. Two dimensions' interpretations were retrieved in all age groups: intensity of healthcare use, functional dependency. However, their rank differed along with the qualification of the future healthcare trajectory. Some specificities appeared in some age group. In the 65-74 and 75-84 years groups, there were dimensions reflecting healthcare use related to psychiatric or psycho-behavioral disorders. In the ≥85 group, two dimensions reflected dependency related to other comorbidities, and organised medical follow-up. CONCLUSION: Several dimensions emerged in line with erratic trajectories before ADRD identification. They underlined the need for actions towards ADRD identification.

Development and Validation of a Model to Identify Alzheimer's Disease and Related Syndromes in Administrative Data.

BACKGROUND: Administrative data are used in the field of Alzheimer's Disease and Related Syndromes (ADRS), however their performance to identify ADRS is unknown. OBJECTIVE: i) To develop and validate a model to identify ADRS prevalent cases in French administrative data (SNDS), ii) to identify factors associated with false negatives. METHODS: Retrospective cohort of subjects ≥ 65 years, living in South-Western France, who attended a memory clinic between April and December 2013. Gold standard for ADRS diagnosis was the memory clinic specialized diagnosis. Memory clinics' data were matched to administrative data (drug reimbursements, diagnoses during hospitalizations, registration with costly chronic conditions). Prediction models were developed for 1-year and 3-year periods of administrative data using multivariable logistic regression models. Overall model performance, discrimination, and calibration were estimated and corrected for optimism by resampling. Youden index was used to define ADRS positivity and to estimate sensitivity, specificity, positive predictive and negative probabilities. Factors associated with false negatives were identified using multivariable logistic regressions. RESULTS: 3360 subjects were studied, 52% diagnosed with ADRS by memory clinics. Prediction model based on age, all-cause hospitalization, registration with ADRS as a chronic condition, number of anti-dementia drugs, mention of ADRS during hospitalizations had good discriminative performance (c-statistic: 0.814, sensitivity: 76.0%, specificity: 74.2% for 2013 data). 419 false negatives (24.0%) were younger, had more often ADRS types other than Alzheimer's disease, moderate forms of ADRS, recent diagnosis, and suffered from other comorbidities than true positives. CONCLUSION: Administrative data presented acceptable performance for detecting ADRS. External validation studies should be encouraged.

Benzodiazepine exposure in subjects with incident Alzheimer's disease and related syndromes in France: a longitudinal study 2011-2017.

Benzodiazepines are commonly used for behavioral and psychiatric symptoms of dementia, despite their numerous adverse effects and the lack of evidence regarding their efficacy in this context. We studied longitudinal benzodiazepines exposure in incident cases of Alzheimer's disease and related syndromes (ADRS) in France. We used a cohort of incident ADRS patients identified in 2012 within the national health data system. Benzodiazepines exposure was measured 1 year before, to 5 years after ADRS identification. Quarterly benzodiazepines prevalence and incidence were computed. We identified factors associated with long half-life benzodiazepines initiation. A total of 106 508 subjects were included. Quarterly benzodiazepines prevalence was stable (around 25%) but we saw an important decrease in long half-life benzodiazepines compensated by an increase in short half-life benzodiazepines. In most benzodiazepine initiations, the first episode lasted less than 3 months. Factors associated with initiating a long half-life benzodiazepine were young age, male gender, no registration with ADRS as a long-term disease, having consulted an ADRS specialist, antipsychotic reimbursement before the index date, no admission in nursing home. Prevalence of benzodiazepines use remains high in subjects with ADRS despite guidelines for their avoidance. However, indicators regarding benzodiazepine initiations (duration, benzodiazepine type) suggest some caution in their use.

Benzodiazepine Dispensing to Persons With Dementia in France, 2011-2016: A Nationwide Study.

OBJECTIVE: To study temporal trends of benzodiazepine exposure among incident Alzheimer's disease and related dementia (ADRD) cohorts between 2011 and 2016. DESIGN: Repeated cross-sectional study. SETTING AND PARTICIPANTS: Three nationwide incident ADRD cohorts (community-dwelling and institutionalized subjects) were identified in 2011, 2013, and 2016 through the French health insurance database. Subjects were followed 4 semesters around ADRD identification [Semester -2 (S-2) to Semester 2 (S2)]. MEASURES: Odds ratios (ORs) for semestrial prevalent exposure, initiation, and adherence to benzodiazepine prescription recommendations (prescription duration <3 months, single reimbursement) were computed using multivariate logistic regressions for each cohort and according to benzodiazepine half-life. RESULTS: Among 262,024 community-dwelling subjects, as compared to 2011, overall benzodiazepine prevalence risk decreased slightly immediately after ADRD identification [S1: aOR2013 = 0.93 (0.91-0.95), aOR2016 = 0.95 (0.93-0.97)] and did not differ during S2. Among 72,013 institutionalized subjects, it increased over time [S2: aOR2013 = 1.16 (1.11-1.21), aOR2016 = 1.26 (1.21-1.32)]. Long half-life benzodiazepine prevalence risk decreased in the 4 semesters among recent cohorts, for both populations [S2: community-dwelling: aOR2013 = 0.77 (0.74-0.79), aOR2016 = 0.61 (0.59-0.64); institutionalized: aOR2013 = 0.74 (0.68-0.80), aOR2016 = 0.58 (0.54-0.63)]. Short half-life benzodiazepine prevalence risk increased [S2: community-dwelling: aOR2013 = 1.13 (1.10-1.16), aOR2016 = 1.22 (1.20-1.25); institutionalized: aOR2013 = 1.26 (1.21-1.32), aOR2016 = 1.44 (1.38-1.50)]. The same patterns were observed for benzodiazepine initiation. Adherence to benzodiazepine prescription recommendations (based on French prescription duration) worsened over years [prescription duration <3 months: aOR2013 = 0.90 (0.86-0.95), aOR2016 = 0.90 (0.85-0.95), single reimbursement: aOR2013 = 0.95 (0.91-1.00), aOR2016 = 0.94 (0.90-0.99)]. CONCLUSIONS AND IMPLICATIONS: Long half-life benzodiazepine exposure was reduced whereas short half-life benzodiazepine exposure increased, and adherence to recommendations worsened (prescription duration longer than 3 months and more than a single reimbursement in recent cohorts). Efforts from prescribers and authorities are required in order to restrict psychotropic exposure among the ADRD population. Further research among institutionalized ADRD subjects could provide useful data to disentangle the effects of changes in prescribing practices and in patients' characteristics.