Medication exposure of the dyad patient-caregiver in Alzheimer's disease and related dementias: a cross-sectional study.

BACKGROUND: Patients with Alzheimer's disease and related dementias and their caregivers can be defined as people with higher risk of developing medication-related problems due to aging and polypharmacy. AIM: To assess the medication exposure of patient with Alzheimer's disease and related dementias and their caregivers. METHOD: Ancillary cross-sectional study based on baseline medication data of the PHARMAID RCT. The PHARMAID study was a multi-center RCT assessing an integrated pharmaceutical care at a psychosocial program. Older outpatients with Alzheimer's disease and related dementias and their older caregivers were eligible for inclusion. Baseline medication data were used to assess the medication exposure, illustrated by the number of medications, the prevalence of potentially inappropriate medications (PIMs) using the EU(7)-PIM list and the Medication Regimen Complexity Index (MRCI). RESULTS: Seventy-three dyads were included in this ancillary study. The mean numbers (SD) of medications used by patients was 6.8 (2.6) and by caregivers was 4.7 (3.7). Overall, 60.3% of patients used at least one PIM and 47.9% of caregivers. Regarding the medication regimen complexity, the mean MRCI was 16.3(8.1) for patients and 11.3(10.5) for caregivers. CONCLUSION: The results of this study confirm the relevance of carrying out medication review with patients, but also with their caregivers who can be considered as hidden patients.

Impact of pharmaceutical care integrated at a psychosocial intervention to reduce caregiver's burden in Alzheimer's disease or related dementias: Negative results at 18 months and difficulties to conduct PHARMAID RCT.

Background: Psychosocial interventions for caregivers of patients with Alzheimer disease and relative dementias (ADRD) reported a caregiver burden improvement. Multicomponent intervention integrating pharmaceutical care has not yet been evaluated while ADRD patients and their caregivers are exposed to high risk of drug-related problems. The PHARMAID study aimed to assess the impact of personalized pharmaceutical care integrated to a psychosocial program on the burden of ADRD caregivers at 18 months. Methods: The PHARMAID RCT was conducted between September 2016 and June 2020 [ClinicalTrials.gov: NCT02802371]. PHARMAID study planned to enroll 240 dyads, i.e. ADRD patients and caregivers, whose inclusion criteria were: outpatient with mild or major neurocognitive disorders due to ADRD, living at home, receiving support from a family caregiver. Three parallel groups compared a control group with two interventional groups: psychosocial intervention and integrated pharmaceutical care at a psychosocial intervention. The main outcome was the caregiver burden assessed by the Zarit Burden Index (ZBI, score range 0-88) at 18 months. Results: Overall, 77 dyads were included (32% of the expected sample size). At 18 months, the mean ZBI scores were 36.7 ± 16.8 in the control group, 30.3 ± 16.3 for the group with psychosocial intervention, and 28.8 ± 14.1 in group with integrated pharmaceutical care at psychosocial intervention. No significant difference was demonstrated between the three groups (p = 0.326). Conclusions: The findings suggest that PHARMAID program had no significant impact on caregiver burden at 18 months. Several limitations have been highlighted and discussed by the authors in order to formulate recommendations for further research.

Brain Volume Predicts Behavioral and Psychological Symptoms in Alzheimer's Disease.

BACKGROUND: Behavioral and psychological symptoms of dementia (BPSD) are frequent and troublesome for patients and caregivers. Considering possible preventive approaches, a better understanding of underlying neural correlates of BPSD is crucial. OBJECTIVE: The aim is to assess whether brain regional volume predicts behavioral changes in mild AD. METHODS: This work took part from the PACO study, a multicenter and prospective study that included 252 patients with mild AD from 2009 to 2014. Fifty-three patients were retained. Forty healthy matched control subjects from the ADNI cohort were included as controls. Voxel-based morphometry analysis was conducted to assess regional brain volume using baseline MRI scans as a predictor of future behavioral changes over a period of 18 months. Behavior was assessed at baseline and longitudinally at 6-month intervals using the shortened form of the Neuropsychiatric Inventory (NPI). RESULTS: The volume of 23 brain structures in frontal, temporal, parietal, occipital, subcortical regions and cerebellum predicted the evolution of NPI scores. Frontal volume was the most powerful predictor with frontal gyri, anterior cingulate cortex, and orbital gyri being particularly involved. CONCLUSION: To our knowledge, this is the first study assessing regional brain volumes as predictors of behavioral changes considered at earlier stages of AD. Up to 23 brain structures were associated with an increased risk of developing BPSD. Frontal lobe volume was the strongest predictor of future evolution of NPI. The involvement of multiple structures in the prediction of behavior suggests a role of the main large-scale networks involved in cognition.

Study protocol on Alzheimer's disease and related disorders: focus on clinical and imaging predictive markers in co-existing lesions.

BACKGROUND: One of the crucial challenges for the future of therapeutic approaches to Alzheimer's disease (AD) is to target the main pathological processes responsible for disability and dependency. However, a progressive cognitive impairment occurring after the age of 70, the main population affected by dementia, is often related to mixed lesions of neurodegenerative and vascular origins. Whereas young patients are mostly affected by pure lesions, ageing favours the occurrence of co-lesions of AD, cerebrovascular disease (CVD) and Lewy body dementia (LBD). Most of clinical studies report on functional and clinical disabilities in patients with presumed pure pathologies. But, the weight of co-morbid processes involved in the transition from an independent functional status to disability in the elderly with co-lesions still remains to be elucidated. Neuropathological examination often performed at late stages cannot answer this question at mild or moderate stages of cognitive disorders. Brain MRI, Single Photon Emission Computed Tomography (SPECT) with DaTscan®, amyloid Positron Emission Tomography (PET) and CerebroSpinal Fluid (CSF) AD biomarkers routinely help in performing the diagnosis of underlying lesions. The combination of these measures seems to be of incremental value for the diagnosis of mixed profiles of AD, CVD and LBD. The aim is to determine the clinical, neuropsychological, neuroradiological and biological features the most predictive of cognitive, behavioral and functional impairment at 2 years in patients with co-existing lesions. METHODS: A multicentre and prospective cohort study with clinical, neuro-imaging and biological markers assessment will recruit 214 patients over 70 years old with a cognitive disorder of AD, cerebrovascular and Lewy body type or with coexisting lesions of two or three of these pathologies and fulfilling the diagnostic criteria for dementia at a mild to moderate stage. Patients will be followed every 6 months (clinical, neuropsychological and imaging examination and collection of cognitive, behavioural and functional impairment) for 24 months. DISCUSSION: This study aims at identifying the best combination of markers (clinical, neuropsychological, MRI, SPECT-DaTscan®, PET and CSF) to predict disability progression in elderly patients presenting coexisting patterns. TRIAL REGISTRATION: NCT02052947 .

Predictors of Discharge Destinations and Three-Month Evolution of Patients Initially Hospitalized in a Cognitive Behavioral Unit.

BACKGROUND: Previous studies showed that a third of patients living at home entered an institution after hospitalization in Cognitive and Behavioral Units (CBUs). OBJECTIVE: The main objective of this study was to identify predictors of discharge destination for these patients. The secondary objective was to estimate whether institutionalization can have an impact on a patient's long-term prognosis. METHODS: The study population was selected from the EVITAL study and included 140 participants living at home before hospitalization in CBUs. Factors favoring nursing-home admission were investigated and the impact of discharge destinations (i.e., home or nursing home) on patients' prognosis was examined. RESULTS: Institutionalized patients were more likely to be women (F = 4.7; p = 0.03), with a higher dementia severity (F = 9.82; p = 0.007), often living alone (F = 19.69; p = 0.001), with a caregiver other than spouse (F = 8.93; p = 0.003), and with a higher patient quality of life (QoL) according to the caregiver (F = 11.73; p = 0.001). When using multivariate logistic linear regressions, we showed a relationship between marital status (OR = 0.19, 95% CI: 0.08-0.43, p < 0.001), dementia severity (OR = 0.15, 95% CI: 0.03-0.79, p = 0.03), QoL (OR = 0.88, 95% CI: 0.79-0.98, p = 0.017), and institutionalization. At three months, a higher overall rate of rehospitalization (F = 12.21; p < 0.001) and rehospitalization for behavioral and psychological symptoms of dementia (F = 6.76; p = 0.006) were observed for patients staying at home after CBU discharge. CONCLUSION: Our study allows for a better understanding of the institutionalization risk factors of the patients hospitalized in CBUs. Identification of these factors could help clinicians to better support patients and to help the transition to be smoother. Moreover, our results suggest that prognosis of institutionalized patients is not unfavorable when compared with patients staying at home.

One-Year Evolution of Behavioral and Psychological Symptoms of Dementia in Patients Initially Hospitalized in Cognitive Behavioral Units: The EVITAL Prospective Cohort.

BACKGROUND: The 2008-2012 French Alzheimer's Plan has provided hospital Cognitive and Behavioral Units (CBU) to improve the management of patients with productive behavioral and psychological symptoms of dementia (BPSD). Little is known concerning the behavioral outcome of these patients after discharge. OBJECTIVE: The present study investigated the long-term evolution of BPSD over one year after CBU discharge. METHODS: The EVITAL cohort included 221 participants admitted to the CBUs of 3 French hospitals. BPSD were collected using the Neuropsychiatric Inventory (NPI) at admission and 3, 6, and 12 months after hospitalization. The global NPI score evolution was assessed using a linear mixed-effect model. A four-factor model of the NPI including behavioral dyscontrol, psychosis, mood, and agitation subscores was also analyzed. RESULTS: Our analysis focused on 148 patients followed up during 12 months and evaluated at each visit. The global NPI score was 48.5 (SD 21.7) at baseline, 28.8 (SD 18.7) at 3-month, 23.2 (SD 16.4) at 6-month and 20.9 (SD 15.9) at 12-month follow-up. The score significantly decreased from baseline to follow-up (F = 109.3 p < 0.0001). Moreover, the decrease was observed for each NPI subscores. The Clinical Dementia Rating (CDR) scale score was significantly linked to the baseline NPI score (t = 2.76, p = 0.009). Conversely, the NPI decline was observed whatever the CDR level. CONCLUSION: The present study showed a decrease in the global NPI score and all its subscores during the year following the CBU hospitalization, regardless of the initial CDR score.

Initial and long-term evaluation of patients with Alzheimer's after hospitalization in cognitive and behavioural units: the EVITAL study design.

BACKGROUND: Alzheimer's disease and related disorders are characterized by cognitive impairment associated with behavioral and psychological symptoms of dementia. These symptoms have significant consequences for both the patient and his family environment. While risk factors for behavioral disorders have been identified in several studies, few studies have focused on the evolution of these disorders. Moreover, it is important to identify factors linked to the long-term evolution of behavioral disorders, as well as patients' and caregivers' quality of life. Our purpose is to present the methodology of the EVITAL study, which primary objective is to determine the factors associated with the evolution of behavioral disorders among patients with Alzheimer's disease and related disorders during the year following their hospitalization in cognitive and behavioral units. Secondary objectives were 1) to assess the factors related to the evolution of behavioral disorders during hospitalization in cognitive and behavioral units; 2) to identify the factors linked to patients' and caregivers' quality of life, as well as caregivers' burden; 3) to assess the factors associated with rehospitalization of the patients for behavioral disorders in the year following their hospitalization in cognitive and behavioral units. METHOD/DESIGN: A multicenter, prospective cohort of patients with Alzheimer's disease and related disorders as well as behavioral disorders who are hospitalized in cognitive and behavioral units. The patients will be included in the study for a period of 24 months and followed-up for 12 months. Socio-demographic and environmental data, behavioral disorders, medications, patients and caregivers quality of life as well as caregivers burden will be assessed throughout hospitalization in cognitive and behavioral units. Follow-up will be performed at months 3, 6 and 12 after hospitalization. Socio-demographic and environmental data, behavioral disorders, medications, patients and caregivers quality of life, unplanned rehospitalization as well as caregivers burden will also be assessed at each follow-up interview. DISCUSSION: The present study should help better identify the factors associated with reduction or stabilization of the behavioral and psychological symptoms of dementia in patients with Alzheimer's disease. It could therefore help clinicians to better manage these symptoms. TRIAL REGISTRATION: Clinical Trials NCT01901263. Registered July 9, 2013.

Personality, Alzheimer's disease and behavioural and cognitive symptoms of dementia: the PACO prospective cohort study protocol.

BACKGROUND: Alzheimer's disease is characterised by a loss of cognitive function and behavioural problems as set out in the term "Behavioural and Psychological Symptoms of Dementia". These behavioural symptoms have heavy consequences for the patients and their families. A greater understanding of behavioural symptoms risk factors would allow better detection of those patients, a better understanding of crisis situations and better management of these patients. Some retrospective studies or simple observations suggested that personality could play a role in the occurrence of behavioural symptoms. Finally, performance in social cognition like facial recognition and perspective taking could be linked to certain personality traits and the subsequent risks of behavioural symptoms. We propose to clarify this through a prospective, multicentre, multidisciplinary study. Main Objective: -To assess the effect of personality and life events on the risk of developing behavioural symptoms. Secondary Objectives: -To evaluate, at the time of inclusion, the connection between personality and performance in social cognition tests; -To evaluate the correlation between performance in social cognition at inclusion and the risks of occurrence of behavioural symptoms; -To evaluate the correlation between regional cerebral atrophy, using brain Magnetic Resonance Imaging at baseline, and the risk of behavioural symptoms. METHODS/DESIGN: Study type and Population: Prospective multicentre cohort study with 252 patients with Alzheimer's disease at prodromal or mild dementia stage. The inclusion period will be of 18 months and the patients will be followed during 18 months. The initial evaluation will include: a clinical and neuropsychological examination, collection of behavioural symptoms data (Neuropsychiatric-Inventory scale) and their risk factors, a personality study using both a dimensional (personality traits) and categorical approach, an inventory of life events, social cognition tests and an Magnetic Resonance Imaging. Patients will be followed every 6 months (clinical examination and collection of behavioural symptoms data and risk factors) during 18 months. DISCUSSION: This study aims at better identifying the patients with Alzheimer's disease at high risk of developing behavioural symptoms, to anticipate, detect and quickly treat these disorders and so, prevent serious consequences for the patient and his caregivers. TRIAL REGISTRATION: ClincalTrials.gov: NCT01297140.

[Role of personality, familial environment, and severity of the disease on the behavioral and psychological symptoms of dementia]. / Particularités sémiologiques des symptômes comportementaux et psychologiques de la démence en fonction de la personnalité antérieure, de l'environnement familial et de la sévérité de la démence.

The phenomenology of Behavioral and Psychological Symptoms of Dementia (BPSD) occurring in the Alzheimer's disease and related syndromes remains not well known. The goal of this study was to assess the role of disorders of personality, psychiatric disorders and home environment in the occurence of the BPSD; 99 inpatients from a short-term Alzheimer unit were included in the study. BPSD were assessed by the NeuroPsychiatric Inventory, the severity of dementia by the MMSE. Previous somatic, psychiatric and personality disorders were evaluated by a semi-structured interview of the family, and classified according to the A, B and C groups from the DSM-IV. Eighty eight percent of the patients presented at least one BPSD. The patients whose the main caregiver was a spouse appeared to be more aggressive. Sixty seven per cent of the patients presented with former disorders of personality; they were more delirious, more anxious, more irritable and suffered more disorders of appetite. Each type of personality disorder modified the phenomenology of the BPSD. The severity of dementia does not seem sufficient to explain the occurrence of BPSD. Other factors seem to play a dominating part such as the previous disorders of personality and psychiatric antecedents. However, the exact links between disorders of personality, psychiatric antecedents and BPSD remain difficult to specify.