Proposition of a corrected measure of the Lawton instrumental activities of daily living score.

BACKGROUND: We aimed to propose a correction of the Lawton instrumental activity of daily living (IADL) score to take into account the possibility to have never done some activities, and measured its agreement and reliability with the usual IADL score. METHODS: A cross-sectional study was conducted in outpatients attending French memory clinics between 2014 and 2017. Lawton IADL, cognitive performance, diagnosis, neuropsychiatric symptoms, and sociodemographics characteristics were collected. A corrected IADL was calculated and its agreement with the usual IADL was assessed. RESULTS: The study included of 2391 patients (79.9 years old, 61.7% female). Based on the usual IADL, 36.9% of patients had never carried out at least one of the activities. This proportion reached 68.8% for men and 17.7% for women. Women had a mean IADL higher than men: 4.72 vs 3.49, this difference decreased when considering the corrected IADL: 4.82 vs 4.26 respectively. Based on Bland-Altman method, 93.5% of observations lied within the limits agreement. The ICC between the 2 scores was 0.98. The relationships between patients' characteristics and the IADL scores were similar, regardless the usual or corrected version. CONCLUSIONS: This corrected IADL score had an excellent degree of agreement with the usual version based the ICC. This simple correction could benefit both for the clinical practice by providing a more accurate description of the real clinical state of the patients allowing to manage them more precisely, and for research involving the evaluation of the functional abilities of patients.

A multicenter cohort study to investigate the factors associated with functional autonomy change in patients with cognitive complaint or neurocognitive disorders: the MEMORA study protocol.

BACKGROUND: The identification of factors associated with functional impairment, in particular those which are potentially modifiable, may help to delay the advanced stages of functional dependence in patients with neurocognitive disorders such as Alzheimer's disease and related disorders. The objectives of the MEMORA cohort are to investigate the factors associated, first with functional autonomy change over time, and secondarily with the cognitive performance and behavioral disorders changes over time. METHODS: The MEMORA study is a multicenter prospective cohort study carried out throughout the patient's care pathway, in Memory centers of Lyon (France). The study will include 6780 patients at all stages of memory disorders in 6 years. The follow-up for each patient is planned for 3 years. The main outcome is the functional autonomy level change as assessed by the instrumental abilities of daily living (IADL) score. Patient characteristics include sociodemographic and clinical features, neuropsychological performance, pharmaceutical and non-pharmaceutical therapy. DISCUSSION: This study conducted in a context of routine care may help to identify the factors associated with functional impairment related to progressive neurocognitive disorders. Subsequently, interventions on potentially modifiable factors could be proposed to the patients to improve their management and delay functional dependence. TRIAL REGISTRATION: NCT02302482 , registered 27 November 2014.

Reliability of the assessment of the clinical dementia rating scale from the analysis of medical records in comparison with the reference method.

BACKGROUND: The Clinical Dementia Rating (CDR) scale allows to detect the presence of dementia and to assess its severity, however its evaluation requires a significant time (45 min). We evaluated the agreement between two methods of collection of the CDR: face-to-face interview or based on the information available in the patient's medical record. METHODS: The CLIMER study was conducted among patients attending a memory center. The CDR scale was evaluated during face-to-face interviews between neuropsychologists and patients and their caregivers and based on blind analysis of the information of the patients' medical record by neuropsychologists. The agreement of the CDR sum of boxes (CDR-SB), the 5-point scale CDR and the different domains of the CDR evaluated between the different methods was measured using intraclass correlation (ICC) coefficient, Bland and Altman method, and linearly weighted Kappa. RESULTS: The study included 139 patients (means ± SD age 80.1 ± 6, 58.3% women, 71.9% with dementia). The ICC for the CDR-SB score assessed by face-to-face and with all the information available in the patient's medical record was 0.95 (95% CI: 0.93-0.97). The mean difference between the CDR-SB score assessed by face-to-face and with the medical record was 0.098 ± 1.036, and 92.4% of the patients lay within the 95% limits of agreement. The ICC for the 5-point scale CDR assessed by face-to-face and with the patient's medical record was 0.92 (95% CI: 0.88-0.95) when all the available information of the patient's medical record was used. The linear weighted Kappa coefficients was 0.79 (95% CI: 0.68-0.91) for the 5-point scale CDR comparison between the two evaluation methods. The analysis by domain of the CDR showed ICC ranging from 0.65 to 0.91 depending of the domains and the methods of evaluation. CONCLUSION: This study showed an excellent level of agreement of the evaluation of the CDR- SB and the 5-point scale CDR when using all the information of the patient's medical record compared to the face-to-face interview. TRIAL REGISTRATION: https//clinicaltrials.gov/ct2/show/NCT04763941 Registration Date 02/17/2021.

Impact of cumulative exposure to anticholinergic and sedative drugs on cognition in older adults: a memory clinic cohort study.

BACKGROUND: Long-term exposure to anticholinergic and sedative drugs could be a modifiable risk factor for cognitive decline. The objective of this study was to measure the association between previous cumulative anticholinergic and sedative drug exposure (Drug Burden Index) and cognitive decline. METHODS: A cohort study (MEMORA cohort) was conducted in a French memory clinic for patients attending a consultation between November 2014 and December 2020, with at least 2 Mini-Mental State Examination (MMSE) measurements (≥ 6 months apart) and available medication data from the local Primary Health Insurance Fund database (n = 1,970). Drug Burden Index was linearly cumulated until each MMSE measurement and was used to categorise patients according to their level of exposure (no exposure, moderate, or high). The longitudinal association between Drug Burden Index and MMSE was assessed using a multivariate linear mixed model, adjusted for age, education level, anxiety disorders, depressive disorders, functional autonomy, and behavioural disorders. RESULTS: Overall, 1,970 patients were included with a mean follow-up duration of 2.78 years (± 1.54) and 2.99 visits per patients (5,900 MMSE + Drug Burden Index measurements collected). At baseline, 68.0% of patients had moderate cumulative anticholinergic and sedative drug exposure and a mean MMSE of 21.1. MMSE decrease was steeper in patients with moderate and high Drug Burden Index ( -1.74 and -1.70/year, respectively) than in patients with no exposure (-1.26/year) after adjusting for age, education, anxiety and depressive disorders, functional autonomy, and behavioural disorders (p < 0.01). CONCLUSIONS: Long-term exposure to anticholinergic and sedative drugs is associated with steeper cognitive decline. Medication review focusing on de-prescribing these drugs could be implemented early to reduce cognitive impairment.

Identification of profiles associated with conversions between the Alzheimer's disease stages, using a machine learning approach.

BACKGROUND: The identification of factors involved in the conversion across the different Alzheimer's disease (AD) stages is crucial to prevent or slow the disease progression. We aimed to assess the factors and their combination associated with the conversion across the AD stages, from mild cognitive impairment to dementia, at a mild, moderate or severe stage and to identify profiles associated with earliest/latest conversion across the AD stages. METHODS: In this study conducted on the real-life MEMORA cohort data collected from January 1, 2013, and December 31, 2019, three cohorts were selected depending on the baseline neurocognitive stage from a consecutive sample of patients attending a memory center, aged between 50 and 90 years old, with a diagnosis of AD during the follow-up, and with at least 2 visits at 6 months to 1 year of interval. A machine learning approach was used to assess the relationship between factors including socio-demographic characteristics, comorbidities and history of diseases, prescription of drugs, and geriatric hospitalizations, and the censored time to conversion from mild cognitive impairment to AD dementia, from the mild stage of dementia to the moderate or severe stages of AD dementia, and from the moderate stage of AD dementia to the severe stage. Profiles of earliest/latest conversion compared to median time to conversion across stages were identified. The median time to conversion was estimated with a Kaplan-Meier estimator. RESULTS: Overall, 2891 patients were included (mean age 77±9 years old, 65% women). The median time of follow-up was 28 months for mild cognitive impairment (MCI) patients, 33 months for mild AD dementia and 30 months for moderate AD dementia. Among the 1264 patients at MCI stage, 61% converted to AD dementia (median time to conversion: 25 months). Among the 1142 patients with mild AD dementia, 59% converted to moderate/severe stage (median time: 23 months) and among the 1332 patients with moderate AD dementia, 23% converted to severe stage (Q3 time to conversion: 22 months). Among the studied factors, cardiovascular comorbidities, anxiety, social isolation, osteoporosis, and hearing disorders were identified as being associated with earlier conversion across stages. Symptomatic treatment i.e. cholinesterase inhibitors for AD was associated with later conversion from mild stage of dementia to moderate/severe stages. CONCLUSION: This study based on a machine learning approach allowed to identify potentially modifiable factors associated with conversion across AD stages for which timely interventions may be implemented to delay disease progression.

Comparison of Instrumental Activities of Daily Living assessment by face-to-face or telephone interviews: a randomized, crossover study.

BACKGROUND: The functional autonomy assessment is essential to manage patients with a neurodegenerative disease, but its evaluation is not always possible during a consultation. To optimize ambulatory autonomy assessment, we compared the Lawton Instrumental Activities of Daily Living (IADL) questionnaire collected by telephone and face-to-face interviews. METHODS: A randomized, crossover study was carried out among patients attending a memory clinic (MC). The IADL questionnaire was collected for patients during telephone and face-to-face interviews between nurses and patients' caregivers. The agreement between the two methods was measured using the proportion of participants giving the same response, Cohen's kappa, intraclass correlation (ICC) coefficient, and Bland and Altman method. The associations between patients' characteristics, events occurring between the two assessments, and agreement were assessed. RESULTS: Among the 292 patients (means ± SD age 81.5 ± 7, MMSE 19.6 ± 6, 39.7% with major neurocognitive disorders) analyzed, the proportion of agreement between the two modes was 89.4% for the total IADL score. Weighted kappa coefficient was 0.66 and ICC score was 0.91 for total IADL score. The mean difference between the IADL score by telephone or face-to-face was 0.32. Overall, 96.9% of measures lay within the 95% limits of agreement. The occurrence of fall was less likely associated with the probability to lie within the 95% limits of agreement (OR = 0.07 [0.02-0.27]). CONCLUSION: The administration of IADL by telephone with the caregiver appears to be an acceptable method of assessment for MC patients compared to face-to-face interview. The events such as falls which could occur in a time close to the evaluation should be reported. STUDY REGISTRATION: ClinicalTrials.gov, NCT02654574. Retrospectively registered: 13 January 2016.

Impact of Cognitive, Functional, Behavioral Disorders, and Caregiver Burden on the Risk of Nursing Home Placement.

OBJECTIVES: To estimate the attributable fraction of nursing home placement associated with cognitive impairment, neuropsychiatric symptoms, behavioral disorders, functional limitations, and caregiver burden. DESIGN: Longitudinal study conducted on the "MEMORA cohort" linked with both regional public health insurance and hospital discharge databases. SETTING: Memory center at the University Hospital of Lyon, France. PARTICIPANTS: A sample of 2456 outpatients attending the memory center between 2012 and 2017. MEASURES: Cognitive impairment, functional limitations, neuropsychiatric symptoms/behavioral disorders, and caregiver burden were measured with the Mini-Mental State Examination, the Instrumental Activities of Daily Living scale, the Neuropsychiatric Inventory (NPI), and a short version of the Zarit Burden Inventory, respectively. Sociodemographics characteristics were collected during the first visit. Comorbidities were gathered from the hospital discharge database. Dates of nursing home placement were obtained from the public health insurance database. RESULTS: More than 38% of nursing home placements were attributable to caregiver burden, and the attributable fraction associated with functional limitations exceeded 35%. Between 20% and 25% of nursing home placements were due to cognitive impairment whereas less than 16% were attributable to neuropsychiatric symptoms or behavioral disorders. The associations between anxiety or agitation and nursing home placement were mediated by caregiver burden. Apathy or aberrant motor behaviors were associated with a higher risk of nursing home placement independently of caregiver burden. CONCLUSIONS/IMPLICATIONS: Our findings suggest that a high proportion of nursing home placements are attributable to caregiver burden and functional limitations in outpatients attending a memory center. Cognitive impairment and neuropsychiatric symptoms or behavioral disorders contribute less to nursing home placements. Interventions directed to delay nursing home placement should emphasize actions toward reducing caregiver burden and functional limitations of patients.

Perception of Benefits and Risks of Neurocognitive Disorders Diagnosis: A French National Survey.

BACKGROUND: Neurocognitive disorders (NCD) are underdiagnosed in primary care, mainly because of the misunderstanding of benefits associated with timely diagnosis. OBJECTIVE: The aim of this study was to explore the benefits and risks of diagnosis in a population of general practitioners (GPs), specialized physicians (SPs), other healthcare professionals (HPs), and informal caregivers (ICs). METHODS: A questionnaire was submitted to GPs, SPs, HPs. and ICs. It aimed at evaluating benefits and risks related to NCD diagnosis associated with four prototypical clinical cases at different stages: isolated cognitive complaint/mild NCD, major NCD at mild/moderate stage, moderate stage with behavioral and psychotic symptoms, and severe stage. The concepts of early, timely, and personalized diagnosis were evaluated. RESULTS: A total of 719 completed surveys were collected from 183 GPs, 176 SPs, 281 HPs, and 79 ICs. More than 90% of the participants considered initiating a diagnosis as relevant except at the severe stage. Benefits were superior to risks for all groups and all four cases alike (p < 0.001). Benefits were lower according to GPs and higher for SPs than the other groups at the first two stages (p < 0.001). At the moderate stage, there were few differences between groups. At the severe stage, GPs and SPs claimed it was less relevant to carry out a diagnosis than the other groups (p < 0.001). Risks were higher for ICs and lower for SPs (p < 0.001). The best diagnosis concept was the personalized diagnosis. CONCLUSION: Benefits appeared more relevant than risks with differences according to the stage of the disease and type of respondents.

The Scale of instantaneous wellbeing: validity in a population with major neurocognitive disorders.

The quality of life (QoL) of people with a neurodegenerative pathology is a major issue in the absence of curative treatment. However, validated tools, suitable for patients with major neurocognitive disorders at a severe stage are rare and time-consuming in routine. The aim of this study is to analyze the validity of convergence and the reliability over time of a visual analog scale of well-being named EVIBE (Échelle d'évaluation instantanée de bien-être). The correlation between the EVIBE and another quality of life scale, the Qol-Ad was studied. The correlation with other scales expected to vary with QoL was also studied with the EQ-5D for the measurement of the state of health felt and the NPI-ES for the measurement of behavioral disorders. The EVIBE was administered twice, a few minutes apart, to measure its reliability over time. One hundred and thirty-five patients with Alzheimer's disease or a related disorder were recruited. The results indicated a significant correlation with Qol-AD (r=0.54, p< 0.001). The correlation remained significant when the Mini mental state examination was less than 10 (r=0.39, p=0.05). Correlations between EVIBE and EQ-5D and NPI-ES indicated more mixed results with significant correlation only for the analog part of the EQ-5D (r=0.34, p=0.007). The comparison between the two EVIBEs a few minutes apart showed a satisfactory agreement (r=0.52, p> 0.001). This study shows that EVIBE present a good convergence validity and a good reliability over time to measure the QoL of patients with neurodegenerative pathology even at severe stages of the disease. The scale allows a direct and rapid assessment of the QoL of patients in routine.

Exposure to anticholinergic and sedative medicines as indicators of high-risk prescriptions in the elderly.

Background There are several assessment scales to evaluate the risk of falls or the adverse drug reaction risk. Few are sufficiently specific to assess the impact of drug prescriptions on falls in geriatric populations. Objective To define the risk of anticholinergic and sedation-related ADRs in an elderly hospitalized patient population using the Drug Burden Index (DBI), Anticholinergic Drug Scale (ADS), and Sedative Load Model (SLM). Setting Five geriatric university hospital centers in France. Method Multicenter prospective cohort study from 2011 to 2013. Drug prescriptions were compiled to estimate anticholinergic and sedative exposure. Any associations between the drug scales and falls were assessed. Main outcome measure Drug exposure estimated with the DBI, ADS, and SLM scales. Results 315 patients, with a mean age of 87 years and 117 documented falls, were included from 5 geriatric hospitals. Sixty-one percent of these patients had a DBI > 0, 20.3% had an ADS ≥ 3, 56.2% a SLM > 0. No association was detected between the scores and the risk of a fall (p > 0.05). Factors significantly associated with a risk of a fall were: a prior history of a fall in the previous 12 months (adjusted odds ratio [aOR] = 7.24, 4.06-12.89), orthostatic hypotension ([aOR] = 2.84; 1.39-5.79), or prescription of antidepressants ([aOR] = 2.12; 1.17-3.84). Conclusion A specific scale to identify high-risk prescriptions would help clinicians and pharmacists to optimize therapeutic treatments for the elderly. In light of the multifactorial characteristics of falls, predicting their risk should be based on a well-defined set of factors.

Relationship Between Comorbidities in Patients With Cognitive Complaint and Caregiver Burden: A Cross-Sectional Study.

BACKGROUND/OBJECTIVES: Informal caregivers of patients with a cognitive impairment may face exhaustion while taking care of their relatives, and are themselves at higher risk of disease. The objective was to assess the relationship between patients' comorbidities evaluated with the Charlson index, and the caregiver burden, independently of health disorders related to cognitive impairment. DESIGN: Cross-sectional observational study. SETTING: Memory clinic at the University Hospital of Lyon. PARTICIPANTS: Outpatients with cognitive complaint and consulting a Clinical and Research Memory Centre of Lyon (n = 1300). MEASUREMENTS: Comorbidity was measured using the Charlson Comorbidity Index related to age (CCI). The caregiver burden was measured with the short version of the Zarit Burden Interview (ZBI). The relationship was assessed between the CCI and the mini-Zarit and other patients' characteristics: behavior, cognition, autonomy as assessed respectively by the Neuropsychiatric Inventory (NPI), Mini Mental State Examination (MMSE), Instrumental Activities of Daily Living (IADL), etiology, and stage of the cognitive impairment. RESULTS: The study included 1300 outpatients: mean age: 80.8 ± 7 years. The mean CCI was 4.8 ± 1.7. The mini-Zarit score: 3.1 ± 2.0. The caregiver burden increased by 0.22 per unit of CCI (95% confidence interval 0.15-0.28, P < .001) in unadjusted analysis. The caregiver burden remained significantly associated with CCI, after adjustment for the MMSE, IADL, and NPI. CONCLUSION: The caregiver burden is higher when patients' comorbidities increase, independently of behavioral and psychological symptoms, level of functional autonomy, and the stage of the cognitive disease. However, dementia may be the comorbidity that contributes the most to caregiver burden.