Renaud David

Striatal dopamine transporter levels correlate with apathy in neurodegenerative diseases: A SPECT study with partial volume effect correction

OBJECTIVES The aim of the present study was to stress the relationship between neuropsychiatric symptoms and most particularly apathy and striatal dopamine uptake in patients with Alzheimers disease (AD) or dementia with Lewy body (DLB). PATIENTS AND METHODS Twenty-two patients (AD n=14; DLB n=8) were included. All patients had neuropsychological and behavioral examination including Mini Mental Test Examination (MMSE), Neuropsychiatric Inventory (NPI), and UPDRS for the motor activity assessment. Apathy dimensions, emotional blunting, lack of initiative and lack of interest were assessed using the Apathy Inventory (AI). Dopamine transporter (DAT) striatal uptake was assessed using (123)I-FP-CIT (DaTSCAN) SPECT. Quantitative measurements were obtained in 3D using a method which compensates for physical detection biases including partial volume effect. RESULTS We observed a correlation between DAT uptake and NPIs domains only for apathy. More specifically using the AI, lack of initiative significantly correlated with bilateral putamen DAT uptake. Using partial correlation coefficients controlling for the UPDRS score, the correlation remained significant between lack of initiative and right and left putamen DAT uptake. CONCLUSION These results demonstrate a relationship between apathy and DAT levels independent from motor activity. They suggest that the patients with neurodegenerative diseases presenting with apathy are characterized by some degree of dopaminergic neuronal loss.

Apathy Diagnosis, Assessment, and Treatment in Alzheimer's Disease

Apathy is defined as a disorder of motivation. There is wide acknowledgement that apathy is an important behavioral syndrome in Alzheimers disease and in various neuropsychiatric disorders. In light of recent research and the renewed interest in the correlates and impacts of apathy and in its treatments, it is important to develop criteria for apathy that will be widely accepted, have clear operational steps, and be easy to apply in clinical practice and in research settings. Meeting these needs was the focus for a task force that included members of the European Psychiatric Association, the European Alzheimers Disease Consortium and experts from Europe, Australia and North America.

'Kitchen and cooking,' a serious game for mild cognitive impairment and Alzheimer's disease: a pilot study.

Recently there has been a growing interest in employing serious games (SGs) for the assessment and rehabilitation of elderly people with mild cognitive impairment (MCI), Alzheimer’s disease (AD), and related disorders. In the present study we examined the acceptability of ‘Kitchen and cooking’ – a SG developed in the context of the EU project VERVE (http://www.verveconsortium.eu/) – in these populations. In this game a cooking plot is employed to assess and stimulate executive functions (such as planning abilities) and praxis. The game is installed on a tablet, to be flexibly employed at home and in nursing homes. Twenty one elderly participants (9 MCI and 12 AD, including 14 outpatients and 7 patients living in nursing homes, as well as 11 apathetic and 10 non-apathetic) took part in a 1-month trail, including a clinical and neuropsychological assessment, and 4-week training where the participants were free to play as long as they wanted on a personal tablet. During the training, participants met once a week with a clinician in order to fill in self-report questionnaires assessing their overall game experience (including acceptability, motivation, and perceived emotions). The results of the self reports and of the data concerning game performance (e.g., time spent playing, number of errors, etc) confirm the overall acceptability of Kitchen and cooking for both patients with MCI and patients with AD and related disorders, and the utility to employ it for training purposes. Interestingly, the results confirm that the game is adapted also to apathetic patients.

Detection of activities of daily living impairment in Alzheimer's disease and mild cognitive impairment using information and communication technology

Background One of the key clinical features of Alzheimer’s disease (AD) is impairment in daily functioning. Patients with mild cognitive impairment (MCI) also commonly have mild problems performing complex tasks. Information and communication technology (ICT), particularly techniques involving imaging and video processing, is of interest in order to improve assessment. The overall aim of this study is to demonstrate that it is possible using a video monitoring system to obtain a quantifiable assessment of instrumental activities of daily living (IADLs) in AD and in MCI. Methods The aim of the study is to propose a daily activity scenario (DAS) score that detects functional impairment using ICTs in AD and MCI compared with normal control group (NC). Sixty-four participants over 65 years old were included: 16 AD matched with 10 NC for protocol 1 (P1) and 19 MCI matched with 19 NC for protocol 2 (P2). Each participant was asked to undertake a set of daily tasks in the setting of a “smart home” equipped with two video cameras and everyday objects for use in activities of daily living (8 IADLs for P1 and 11 for P2, plus 4 temporal execution constraints). The DAS score was then computed from quantitative and qualitative parameters collected from video recordings. Results In P1, the DAS score differentiated AD (DASAD,P1 = 0.47, 95% confidence interval [CI] 0.38–0.56) from NC (DASNC,P1 = 0.71, 95% CI 0.68–0.74). In P2, the DAS score differentiated MCI (DASMCI,P2 = 0.11, 95% CI 0.05–0.16) and NC (DASNC,P2 = 0.36, 95% CI 0.26–0.45). Conclusion In conclusion, this study outlines the interest of a novel tool coming from the ICT world for the assessment of functional impairment in AD and MCI. The derived DAS scores provide a pragmatic, ecological, objective measurement which may improve the prediction of future dementia, be used as an outcome measurement in clinical trials and lead to earlier therapeutic intervention.

Decreased Daytime Motor Activity Associated With Apathy in Alzheimer Disease: An Actigraphic Study

OBJECTIVE Across all stages of Alzheimer disease (AD), apathy is the most common neuropsychiatric symptom. Studies using the Neuropsychiatric Inventory (NPI) have found that apathy is present in up to 70% of individuals with Alzheimer disease. One of the main difficulties in assessing apathy and other neuropsychiatric symptoms is the absence of reliable, objective measures. Motor activity assessment using ambulatory actigraphy could provide an indirect, objective evaluation of apathy. The aim of our study was to assess the relationship between apathy and daytime motor activity in AD, using ambulatory actigraphy. METHODS One hundred seven AD outpatients wore a wrist actigraph (Motionlogger) during seven consecutive 24-hour periods to evaluate motor activity. Participants were divided into two subgroups according to their apathy subscores on the NPI: individuals with apathy (NPI-apathy subscores >4) and those without. Daytime mean motor activity scores were compared between the two subgroups. RESULTS Individuals with AD who had symptoms of apathy (n = 43; age = 79 ± 4.7 years; Mini-Mental State Examination = 20.9 ± 4.8) had significantly lower daytime mean motor activity than AD patients without apathy (n = 64; age = 76.3 ± 7.7; Mini-Mental State Examination = 21.5 ± 4.7), while nighttime mean motor activity did not significantly differ between the two subgroups. CONCLUSIONS Ambulatory actigraphy could be added to currently used questionnaires as a simple, objective technique for assessing apathy in the routine assessment of AD patients.

Management of apathy in nursing homes using a teaching program for care staff: the STIM-EHPAD study.

This study aimed to evaluate the effectiveness of a nursing home (NH) staff education to manage apathy in older individuals with a diagnosis of dementia.

Relationship between Apathy and Sleep Disturbance in Mild and Moderate Alzheimer's Disease: An Actigraphic Study

Apathy is the most frequently reported neuropsychiatric symptom across all stages of Alzheimers disease (AD). Both apathy and sleep disorders are known to have independent negative effects on the quality of life in individuals with AD. The aim of this study was to assess the relationship between apathy and sleep/wake patterns in individuals with AD using ambulatory actigraphy. One hundred and three non-institutionalized individuals with AD wore a wrist actigraph continuously over seven consecutive 24-h periods. Apathy was assessed using the Neuropsychiatric Inventory. Daytime mean motor activity (dMMA) was calculated from daytime wrist actigraphy data. Actigraphic parameters of sleep included total sleep time (TST), wake after sleep onset (WASO), time in bed (TIB), WASO normalized by TIB, sleep latency, and nighttime mean motor activity (nMMA). Among the 103 individuals with AD (aged 76.9 ± 7.2 years; MMSE = 21.4 ± 4.3), those with apathy had significantly lower dMMA, higher WASO (both raw and normalized), and spent more time in bed during the night than those without apathy. Sleep latency, nMMA and TST did not differ significantly between the two subgroups. To our knowledge, this study is the first to identify a relationship between apathy and sleep disturbance in those with mild or moderate AD: apathy was associated with increased TIB during the night and more WASO. These results suggest that AD patients with apathy have less consolidated nocturnal sleep than those without apathy.

Automatic speech analysis for the assessment of patients with predementia and Alzheimer's disease

To evaluate the interest of using automatic speech analyses for the assessment of mild cognitive impairment (MCI) and early‐stage Alzheimers disease (AD).

Circadian Clock Gene Polymorphisms and Sleep–Wake Disturbance in Alzheimer Disease

OBJECTIVES One of the hypothesized causes of the breakdown in sleep-wake consolidation often occurring in individuals with Alzheimer disease (AD) is the dysfunction of the circadian clock. The goal of this study is to report indices of sleep-wake function collected from individuals with AD in relation to relevant polymorphisms in circadian clock-related genes. DESIGN One week of ad libitum ambulatory sleep data collection. SETTING At-home collection of sleep data and in-laboratory questionnaire. PARTICIPANTS Two cohorts of AD participants. Cohort 1 (N = 124): individuals with probable AD recruited from the Stanford/Veterans Affairs, National Institute on Aging Alzheimers Disease Core Center (N = 81), and the Memory Disorders Clinic at the University of Nice School of Medicine (N = 43). Cohort 2 (N = 176): individuals with probable AD derived from the Alzheimers Disease Neuroimaging Initiative data set. MEASUREMENTS Determination of sleep-wake state was obtained by wrist actigraphy data for 7 days in Cohort 1 and by the Neuropsychiatric Inventory questionnaire for Cohort 2. Both cohorts were genotyped by using an Illumina Beadstation (Illumina, San Diego, CA), and 122 circadian-related single-nucleotide polymorphisms (SNPs) were examined. In Cohort 1, an additional polymorphism (variable-number tandem repeat in per3) was also determined. RESULTS Adjusting for multiple tests, none of the candidate gene SNPs were significantly associated with the amount of wake time after sleep onset (WASO), a marker of sleep consolidation. Although the study was powered sufficiently to identify moderate-sized correlations, we found no relationships likely to be of clinical relevance. CONCLUSIONS It is unlikely that a relationship with a clinically meaningful correlation exists between the circadian rhythm-associated SNPs and WASO in individuals with AD.

Validation of an Automatic Video Monitoring System for the Detection of Instrumental Activities of Daily Living in Dementia Patients

Over the last few years, the use of new technologies for the support of elderly people and in particular dementia patients received increasing interest. We investigated the use of a video monitoring system for automatic event recognition for the assessment of instrumental activities of daily living (IADL) in dementia patients. Participants (19 healthy subjects (HC) and 19 mild cognitive impairment (MCI) patients) had to carry out a standardized scenario consisting of several IADLs such as making a phone call while they were recorded by 2D video cameras. After the recording session, data was processed by a platform of video signal analysis in order to extract kinematic parameters detecting activities undertaken by the participant. We compared our automated activity quality prediction as well as cognitive health prediction with direct observation annotation and neuropsychological assessment scores. With a sensitivity of 85.31% and a precision of 75.90%, the overall activities were correctly automatically detected. Activity frequency differed significantly between MCI and HC participants (p < 0.05). In all activities, differences in the execution time could be identified in the manually and automatically extracted data. We obtained statistically significant correlations between manually as automatically extracted parameters and neuropsychological test scores (p < 0.05). However, no significant differences were found between the groups according to the IADL scale. The results suggest that it is possible to assess IADL functioning with the help of an automatic video monitoring system and that even based on the extracted data, significant group differences can be obtained.