Cholinergic Antagonists and Behavioral Disturbances in Neurodegenerative Diseases.

Cholinergic antagonists interfere with synaptic transmission in the central nervous system and are involved in pathological processes in patients with neurocognitive disorders (NCD), such as behavioral and psychological symptoms of dementia (BPSD). In this commentary, we will briefly review the current knowledge on the impact of cholinergic burden on BPSD in persons with NCD, including the main pathophysiological mechanisms. Given the lack of clear consensus regarding symptomatic management of BPSD, special attention must be paid to this preventable, iatrogenic condition in patients with NCD, and de-prescription of cholinergic antagonists should be considered in patients with BPSD.

Threshold for a Reduction in Anticholinergic Burden to Decrease Behavioral and Psychological Symptoms of Dementia.

BACKGROUND: A high anticholinergic burden (AB) is associated with the occurrence of behavioral and psychological symptoms (BPSDs), which are frequent in dementia. OBJECTIVES: Our aim was to determine the threshold for a reduction in AB that would lead to a clinically significant improvement in BPSDs (in terms of frequency, severity, and disruptiveness). DESIGN: A single-center prospective study. SETTINGS: Dedicated geriatric care unit specializing in the management of patients with dementia. PARTICIPANTS: The study involved older patients with dementia, hospitalized for management of BPSDs. METHODS: One hundred forty-seven patients were included (mean age = 84.1 ± 5.2 years). The AB was assessed using 3 scales, namely, the Anticholinergic Drug Scale (ADS), the Anticholinergic Cognitive Burden scale (ACB), and the Anticholinergic Risk Scale (ARS). A clinically significant improvement in BPSDs was defined as a reduction of 4 points in the frequency × severity (F×S) score of the Neuropsychiatric Inventory-Nursing Home (NPI-NH) questionnaire. The threshold for a reduction in AB that corresponded to a clinically significant improvement in BPSDs was determined by multiple linear regression. RESULTS: One hundred forty-seven patients were included (mean age = 84.1 ± 5.2 years). Using the ADS, a reduction of 2 points in AB in patients with moderate-intensity BPSDs was associated with a clinically significant improvement in the F×S score of the NPI-NH [6.34, 95% confidence interval (CI) 4.54-8.14], and a reduction of 3 points was associated with a clinically significant improvement in the occupational disruptiveness score (4.26, 95% CI 3.11-5.41). CONCLUSIONS/IMPLICATIONS: In older patients with dementia presenting BPSDs, the risk-benefit ratio of anticholinergic drugs is debatable and, where possible, drugs with a lower AB would be preferable. Because BPSDs are a frequent cause of hospitalization, a standardized approach to analysis and reduction of AB is warranted in this population. Depending on the scale used to assess anticholinergic burden (AB), a small reduction in AB is associated with a decrease in frequency, severity, and disruptiveness of moderate-intensity BPSDs. Drugs with a high AB should be avoided where possible in older patients with dementia, and drugs with a lower AB would be preferable. Heterogeneity between the assessment scales for AB precludes generalization of the impact of a reduction in AB on BPSDs.

Brief aerobic exercise immediately enhances visual attentional control and perceptual speed. Testing the mediating role of feelings of energy.

While the effects of acute exercise on mood and cognitive functions have been separately documented over the last decade, recent findings have pointed to a possible connection between affective responses to exercise and cognitive performance. The main objective of this study was to test whether the effects of acute exercise on cognition were mediated by changes in feelings of energy. One-hundred-and-one undergraduate students were randomized into one of two experimental conditions: 15 min of jogging at "moderate" intensity, or 15 min of relaxation/concentration (control condition). Perceptual speed, visual attentional control, working memory, and cognitive flexibility were assessed pre- and post-intervention in both groups via the Trail Making Test. Self-rated feelings of energy were also recorded pre- and post-intervention. Only completion time for the TMT-A significantly improved from pre- to post-intervention in participants who exercised compared with participants who practiced relaxation/concentration. No Group × Time interaction was found with regard to the other TMT variables. Finally, changes in feelings of energy were found to fully mediate the relationship between exercise and perceptual speed/visual attentional control. Taken together, our data suggest that a brief bout of moderate intensity exercise can improve the efficiency of certain cognitive processes through increases in feelings of energy, but further research is required to evaluate the duration of benefits and to determine whether these apply to other populations.

Factors associated with quality of life in patients with Alzheimer's disease.

BACKGROUND: Evaluation of health-related quality of life (HRQoL) in patients with Alzheimer's disease (AD) is necessary to ensure optimal management. Several scales for assessing HRQoL of patients with AD exist, in particular the Quality of Life in Alzheimer's Disease (QoL-AD), which includes an evaluation by the caregiver of the patient's HRQoL. The aim of this study was to identify factors associated with patient, caregiver and overall HRQoL as assessed by the QoL-AD. METHODS: Cross-sectional multicenter study in subjects aged 65 years and older, with mild to moderate AD. HRQoL scores from the QoL-AD were recorded (3 scores, corresponding to patient, caregiver and overall), as well as sociodemographic variables for the patient and the caregiver, and data from the geriatric cognitive assessment (cognitive, psycho-behavioral, functional evaluations). Caregiver burden was evaluated using the Zarit caregiver burden scale. Factors associated with each QoL-AD score were identified by multivariate linear regression using t-tests and ß estimations. Study was registered in Clinical Trial.gov (NCT02814773). RESULTS: In total, 123 patients with AD were included. For the patient QoL-AD evaluation, depression was significantly associated with lower HRQoL (ß = - 2.56 ± 1.28, p = 0.04), while polypharmacy (ß = - 1.80 ± 0.99, p = 0.07) and anxiety (ß = - 1.70 ± 1.01, p = 0.09) tended to be associated with lower HRQoL scores. In terms of caregiver evaluations, depression (ß = - 3.46 ± 1.09, p = 0.002), polypharmacy (ß = - 1.91 ± 0.92, p = 0.04) and the presence of caregiver burden (ß = - 3.50 ± 0.91, p = 0.0002) were associated with lower HRQoL. For the overall evaluation, depression (ß = - 3.26 ± 1.02, p = 0.002) and polypharmacy (ß = - 1.85 ± 0.81, p = 0.03) were significantly related to lower HRQoL. CONCLUSIONS: Depression and polypharmacy were two factors influencing HRQoL in patients with AD, both by patient self-report and on the caregiver report. Thus, despite the discrepancies between HRQoL as assessed by patients with AD and HRQoL as assessed by their caregiver, the caregiver's assessment may be used to guide patient management when the patient can no longer complete QoL evaluations. Moreover, the association between caregiver burden and the caregiver's QoL-AD score underlines the need to take caregivers into consideration in the overall management of the AD patient.

Naturalistic Driving Study Investigating Self-Regulation Behavior in Early Alzheimer's Disease: A Pilot Study.

BACKGROUND: Because cognitive processes decline in the earliest stages of Alzheimer's disease (AD), the driving abilities are often affected. The naturalistic driving approach is relevant to study the driving habits and behaviors in normal or critical situations in a familiar environment of participants. OBJECTIVE: This pilot study analyzed in-car video recordings of naturalistic driving in patients with early-stage AD and in healthy controls, with a special focus on tactical self-regulation behavior. METHODS: Twenty patients with early-stage AD (Diagnosis and Statistical Manual of Mental Disorders, Fourth Edition [DSM-IV] criteria), and 21 healthy older adults were included in the study. Data collection equipment was installed in their personal vehicles. Two expert psychologists assessed driving performance using a specially designed Naturalistic Driving Assessment Scale (NaDAS), paying particular attention to tactical self-regulation behavior, and they recorded all critical safety events. RESULTS: Poorer driving performance was observed among AD drivers: their tactical self-regulation behavior was of lower quality. AD patients had also twice as many critical events as healthy drivers and three times more "unaware" critical events. CONCLUSION: This pilot study used a naturalistic approach to accurately show that AD drivers have poorer tactical self-regulation behavior than healthy older drivers. Future deployment of assistance systems in vehicles should specifically target tactical self-regulation components.

Exploring quality of life in people with slowly-progressive neuromuscular disease.

PURPOSE: A qualitative work is conducted to enable later the construction of a health-related quality of life (HRQL) questionnaire for patients with slowly-progressive neuromuscular disease (NMD) such as myopathies and muscular dystrophies. METHODS: The formation of focus groups is an efficient method to perform an in-depth exploration of the aspects of HRQL potentially impaired by NMD. Patients were recruited in France by 4 NMD reference centers. To ensure adequate representativeness in terms of severity, three types of focus groups were formed: (1) Patients able to walk (WP). (2) Patients using a wheelchair (WCP). (3) Patients using a wheelchair and requiring continuous mechanical ventilation (WCMVP). All verbal interactions among group participants were recorded. A qualitative analysis of the verbatim was performed using the framework of the International Classification of Functioning, Disability and Health model (ICF). RESULTS: A total of 41 patients distributed across five focus groups were interviewed. The verbatim provided 2424 ICF categories. The percentages of mentions of the different ICF categories were calculated and graphically displayed. CONCLUSION: The results enabled to identify and quantify the aspects of life that are altered by NMD according to patients. This qualitative work was the first phase of a more ambitious project to develop a new NMD-specific HRQL questionnaire. Implication of rehabilitation Patients with NMD have more to say about the quality of their environment, their social relationships and their psychological state than about their physical symptoms. This observation should be compared to clinician perceptions which often focus mainly on the physical symptoms, overlooking those elements that they cannot assess directly. Many patients reported relationship issues with various people from their surrounding (e.g., health professionals, acquaintances, colleagues, and strangers). In particular, it is essential that health professionals are careful not to make adult patients with NMD feel infantilized. This issue can be addressed by making all relevant medical information available and asking for the patient's opinion on any important change in their medical care.

Predictive Factors of Rapid Cognitive Decline in Patients with Alzheimer Disease.

AIM: To determine predictive factors associated with rapid cognitive decline (RCD) in elderly patients suffering from Alzheimer disease (AD). METHODS: Patients suffering from mild to moderate AD were included. RCD was defined as the loss of at least 3 points on the Mini-Mental State Examination (MMSE) over 12 months. Factors associated with RCD were identified by logistic regression. RESULTS: Among 123 patients included, 61 were followed up until 12 months. RCD occurred in 46% of patients (n = 28). Polymedication (p < 0.0001), the fact that the caregiver was the child or spouse of the patient (p < 0.0001) and autonomy for washing (p < 0.0001) were protective factors against RCD, while the presence of caregiver burden (p < 0.0001) was shown to be a risk factor for RCD. CONCLUSION: Early detection of the RCD risk in AD patients could make it possible to anticipate the patient's medical needs and adjust the care plan for caregiver burden.

Construction of a Quality of Life Questionnaire for slowly progressive neuromuscular disease.

PURPOSE: To build a questionnaire to assess health-related quality of life (HRQL) in patients suffering from slowly progressive neuromuscular disease (NMD) using item response theory (IRT). METHODS: A pool of 64 items and a validated questionnaire (WHOQOL-BREF) were administered to 159 patients recruited in eight NMD referral centers. Exploratory statistical analysis included methods derived from both IRT and classical test theory. RESULTS: We constructed a questionnaire named QoL-NMD which is composed of two general items and 24 items classified in three domains: (1) "Impact of Physical Symptoms," (2) "Self-perception" and (3) "Activities and Social Participation." Each domain has good psychometric properties (Cronbach's alpha > 0.77, test-retest ICC > 0.81, Loevinger's H > 0.41) and meets IRT assumptions. Comparison with the WHOQOL-BREF enabled assessing similarities and discrepancies with a generic questionnaire. CONCLUSION: This study enabled the development of a new HRQL questionnaire specifically designed for slowly progressive NMD patients. The QoL-NMD is short enough to be used in clinical practice (26 items). The next steps will be to validate QoL-NMD by re-assessing psychometrics in an independent sample of patients and calibrate the IRT scoring system.

Comparison of QoL-AD and DQoL in elderly with Alzheimer's disease.

OBJECTIVE: The Dementia Quality of Life (DQoL) and the Quality of Life in Alzheimer's Disease (QoL-AD) are the two most widely used dementia-specific QoL instruments in the world. We aimed to compare the psychometric properties of these two instruments and identify which is most adapted to use in geriatric consultations. METHODS: To evaluate the psychometric properties of the French language validation of DQoL and QoL-AD, 123 patients aged 65 years and over suffering from AD (Mini Mental State Examination score ≥10) were recruited in seven French hospitals and one Switzerland hospital. The DQoL comprises 29 items, ranked on a five-point Likert scale and measuring five QoL domains: self-esteem, positive affect, negative affect, feeling of belonging and sense of aesthetics. The QoL-AD contains 13 items giving an overall score ranging from 13 to 52 and evaluating the domains of interpersonal relationships, financial difficulties, physical condition, memory, mood and overall health. RESULTS: Both questionnaires showed adequate reproducibility at 2 weeks interval (intra-class correlation coefficient >0.80), good internal consistency (Cronbach's alpha coefficient >0.70) and good convergent validity with the general health dimension of the Duke Health Profile. The time required to complete the QoL-AD was significantly shorter (p < 0.0001). DQoL had better discriminant capacity (with at least one dimension significant for each subgroup of severity of cognitive decline, dependency, presence of depression or behavioural disorders). CONCLUSIONS: For quick evaluation of QoL during consultations in geriatric care, the QoL-AD is preferable, whereas for the purposes of research and more in-depth evaluation, the DQoL is more suitable.

[Quality of life in dementia: state of the knowledge]. / Qualité de vie et démence : état des connaissances.

BACKGROUND: Dementia is a chronic and evolutive disease, for which no curative treatment exists. Evaluating the quality of life of patients suffering from dementia is therefore an important component of management. AIMS: To summarise existing literature regarding quality of life instruments specific to dementia, and to identify factors associated with quality of life. METHODS: We analysed studies published between November 1996 and December 2010 and referenced in PubMed, and focusing on the development and/or validation of quality of life instruments specific to dementia, or studies having used any such instrument to evaluate a therapeutic intervention. RESULTS: Nine quality of life instruments were identified. Place of residence and level of education do not appear to play any significant role. Results were conflicting for age and sex. There appears to be a relation, albeit a weak one, with cognitive function. The factors most frequently associated with lower quality of life were behavioural disorders, dependence, and caregiver burden. Quality of life of patients under pharmacological treatment is poorly documented, while occupational therapy and cognitive stimulation appear to have moderate positive effects.

[Identification and memorisation of emotions in Alzheimer's disease: a critical review of litterature]. / Identification et mémorisation des émotions dans la démence de type Alzheimer : revue critique de la littérature.

Although the first signs of Alzheimer's disease (AD) mainly affect episodic memory and executive functions, emotional disturbances also have a considerable impact on the mental and relational capacities of AD patients. In AD, the early impairment of amygdala structures, whose central role in the recognition and memorisation of emotions has previously been demonstrated, has led researchers to focus on the possible implications of such impairment in generating cognitive disturbances or behavioural troubles in these subjects. Several studies have shown that emotional processes are altered in AD, and can contribute to varying degrees to deficits in terms of social cognition, and to the generation of behavioural troubles. This review will detail the main avenues of research into the capacity to identify and memorise emotions in AD, and summarise the often conflicting results that have, to date, prevented the emergence of a general consensus concerning the emotional processes. It seems thereby legitimate to question about different elements that can explain these conflicting results, such as the existence of various theories, divergences about the definition of emotions and important methodological differences.

Aging and inhibition processes: the case of metaphor treatment.

The inhibitory deficit hypothesis has often been cited as a possible explanation for cognitive changes related to age. The aim of this study was to develop a new procedure for evaluating effortful inhibition on the basis of the comprehension of metaphors. Our experiment was carried out on younger and older adults, in whom we also measured inhibitory capacity, working memory, and processing speed. The results show that older participants required a longer time and made more frequent errors in rejecting metaphors versus literally false statements. The interference effect was predicted by the psychometric tests designed to evaluate inhibition.

Transcultural adaptation and psychometric validation of a French-language version of the QoL-AD.

OBJECTIVES: The aim of this study was to assess the psychometric properties and the transcultural adaptation into French of the quality-of-life in Alzheimer's disease (QoL-AD). METHODS: A total of 120 patient-proxy pairs were recruited in six French hospitals and one French-speaking Swiss hospital to take part in the study. The patients presented mild to moderate AD (MMSE > or = 10). The QoL-AD was administered by an interviewer for patients and was self-administered for caregiver proxies. Thus, the psychometric validation enabled the study of feasibility, acceptability, reliability and convergent and discriminant validity of the instrument. RESULTS: The French version of the QoL-AD showed good internal consistency (Cronbach's alpha coefficient > or = 0.70) and good reliability (Intra-class correlation > 0.80) at a 2-week interval, for patient and caregiver questionnaires. Convergent validity, as indicated by correlation between the QoL-AD (disease-specific instrument) and the dimensions of the Duke Health Profile (generic instrument), was also good for eight dimensions in the Duke profile (p < 0.05). Discriminant validity showed a significant difference for depression (p = 0.0025) and did not show significant difference for two groups of dementia (p = 0.11). CONCLUSION: There is now a validated French version of the QoL-AD available, following transcultural adaptation according to international recommendations, which possesses good psychometric qualities.

Predictors of rapid cognitive decline among demented subjects aged 75 or more: ('Sujet Agé Fragile--Evaluation et Suivi' Cohort-SAFES).

OBJECTIVE: To identify factors predictive of rapid cognitive decline (RCD) among elderly subjects aged 75 or over suffering from dementia. METHODS: The analysis concerned 250 patients drawn from the 'Sujet Agé Fragile--Evaluation et Suivi' (SAFES) cohort, presenting a dementia syndrome at inclusion and followed-up for at least 1 year. RCD was defined as the loss of at least 3 points on the Mini-Mental State Examination (MMSE) in the follow-up period of 12 months. All patients underwent a standardised geriatric evaluation. Logistic regression was used to identify factors predictive of RCD. RESULTS: In the study sample, 84 patients (33.6%) presented RCD. The factors identified in multivariate analysis as predictive of RCD were: high level of education (OR = 7.8, 95% CI = [1.9-31.2], p = 0.004), risk of depression (OR = 1.8, 95% CI = [1.02-3.18], p = 0.048, and the initial MMSE score (OR = 1.1, 95% CI = [1.0-1.2], p = 0.002). Among subjects with a main caregiver (n = 177), the predictive factors were malnutrition or risk thereof (OR = 4.2, 95% CI = [1.3-14.1], p = 0.02), risk of a fall (OR = 2.6, 95% CI = [1.1-6.1], p = 0.03, caregiver burden (OR = 2.6, 95% CI = [1.1-6.4], p = 0.04) and initial MMSE score (OR = 1.1, 95% CI = [1.0-1.3], p = 0.004). CONCLUSIONS: As soon as dementia is diagnosed in elderly subjects, information should be collected about the subject's socioeconomic status, nutritional status, risk of falling, mood state, and caregiver burden. This would enable the provision of appropriate therapeutic care, and make it possible to adapt follow-up in case of a risk of accelerated cognitive deterioration.

Factors relating to carer burden for families of persons with muscular dystrophy.

OBJECTIVE: To assess the burden on family carers of persons with muscular dystrophy living in their homes and to determine factors contributing to carer burden. METHODS: The study included 56 dyads of people with muscular dystrophy and their family carers. The variables for carer burden were compared by logistic regression in 2 carer groups (burden + /burden-). RESULTS: The mean age of the patients with muscular dystrophy was 32.7 years (median 26.7, range 15-65 years) and that of the carers 51 years (median 48, range 30-80 years). The carers reported the care burden using the Zarit Burden Inventory (median score 23, range 0-57/88). Multivariate analysis produced 3 adjusted explicative factors: carer characteristics related to risk of perceived burden are self-report of poor social functioning on the SF-36 (OR = 26.6 (2.6-278); p=0.006), self report of anxiety on the Hospital Anxiety Scale (OR = 7.1 (1.4-36); p=0.02) and being a carer under 48 years of age (OR = 7.8 (1.7-34.5); p=0.007). However, it was difficult to dissociate the different health variables of the carers from each other. CONCLUSION: This approach should lead to better decision-making by medical teams, patients and their carers.

[Ethical approach to severe dementia]. / Pour une approche éthique dans la démence sévère.

General principles of medical ethics are discussed in the context of care for patients with severe dementia.