Can the Ability to Recognize Facial Emotions in Individuals With Neurodegenerative Disease be Improved? A Systematic Review and Meta-analysis.

BACKGROUND: Facial emotion recognition (FER) is commonly impaired in individuals with neurodegenerative disease (NDD). This impairment has been linked to an increase in behavioral disorders and caregiver burden. OBJECTIVE: To identify interventions targeting the improvement of FER ability in individuals with NDD and investigate the magnitude of the efficacy of the interventions. We also wanted to explore the duration of the effects of the intervention and their possible impacts on behavioral and psychological symptoms of dementia and caregiver burden. METHOD: We included 15 studies with 604 individuals who had been diagnosed with NDD. The identified interventions were categorized into three types of approach (cognitive, neurostimulation, and pharmacological) as well as a combined approach (neurostimulation with pharmacological). RESULTS: The three types of approaches pooled together had a significant large effect size for FER ability improvement (standard mean difference: 1.21, 95% CI = 0.11, 2.31, z = 2.15, P = 0.03). The improvement lasted post intervention, in tandem with a decrease in behavioral disorders and caregiver burden. CONCLUSION: A combination of different approaches for FER ability improvement may be beneficial for individuals with NDD and their caregivers.

Facial emotion impairment in multiple sclerosis is linked to modifying observation strategies of emotional faces.

BACKGROUND: Facial emotion recognition (FER) may be impaired in patients with multiple sclerosis (MS). Nevertheless, the literature is heterogeneous, with studies not highlighting this kind of impairment. Moreover, most studies have not explored differences between MS spectrum disorders (radiologically isolated syndrome (RIS), clinically-isolated syndrome (CIS), relapsing-remitting (RRMS), and progressive (primary - (PPMS) and secondary - (SPMS)). One hypothesis would be that FER impairment results from an alteration of eye-gaze strategies while observing emotional faces. Consequently, a FER deficit would be found in MS patients for whom these observation strategies would be disturbed and more frequent in the progressive forms. METHODS: We prospectively enroled 52 patients (10 RIS, 10 CIS, 12RRMS, 10 SPMS, 10 PPMS) and 23 healthy controls (HC) to assess FER using Ekman Faces Test. Eye movements (number and duration of fixations) were recorded with an eye-tracking device. RESULTS: 21% of the MS participants had significant FER impairment. This impairment was observed in all phenotypes. In progressive forms, FER impairment was more frequent, more severe, and associated with modified emotional face observation strategies. MS participants with significant FER impairment had significantly more modification of eye-gaze strategies during observation of expressive faces than MS participants without FER impairment. CONCLUSION: FER impairment seems to be linked to a deficit of attention orientation in MS. Remediation of eye-gaze strategies during observation of emotional faces could be beneficial, as observed in other neurological diseases.

Reliability of mobile video-oculography in multiple sclerosis patients using an iPad: A prospective validation study.

BACKGROUND: Video-oculography (VOG) could be useful for monitoring neurodegenerative diseases and multiple sclerosis (MS), as a high prevalence of subclinical eye movements abnormalities (EMA) has been previously reported, with a potential prognostic value regarding disease evolution. However, access to VOG is limited in clinical practice. OBJECTIVE: To evaluate the reliability of VOG recordings performed using eVOG, a mobile application developed on an iPad. METHOD: Patients with MS or related disease without clinically detectable EMA were enrolled in a cross-sectional study during which two VOG exams (classical VOG and eVOG) were performed on the same day. We examined reflex saccades, antisaccades, smooth pursuit and fixation. The total number of deficits, saccadic latencies and velocities, qualitative smooth pursuit were compared. RESULTS: 30 patients were included. The mean number of EMA per patient on classical VOG was 4.1 and 2.3 on eVOG. We found a statistical association between the number of EMA for each exam (r = 0.66, p < 0.0001). Saccades latencies (r = 0.57, p < 0.0001) and velocities (r = 0.45, p < 0.0001) were also well correlated. Assessing eVOG accuracy, we found a sensitivity ranging from 44% to 100% and a specificity ranging from 71% to 88.9% depending on the considered abnormality. CONCLUSION: eVOG could be an easily accessible solution to screen MS patients for the presence of EMA. We plan to use eVOG on a larger cohort of patients, in a prospective study to assess the prognostic value of subclinical EMA in MS. We also plan to investigate the use of eVOG in other neurological conditions.

Eye-gaze Strategies During Facial Emotion Recognition in Neurodegenerative Diseases and Links With Neuropsychiatric Disorders.

BACKGROUND: Facial emotion recognition (FER) is primarily and severely impaired in individuals with the behavioral variant of frontotemporal dementia (bvFTD) and is often mildy impaired in individuals with Alzheimer disease (AD) or Parkinson disease (PD). Such impairment is associated with inappropriate social behaviors. OBJECTIVE: To determine whether FER impairment is linked to the use of inappropriate eye-gaze strategies to decode facial emotions, leading to misinterpretation of others' intentions and then to behavioral disorders. METHOD: We assessed FER in 9 individuals with bvFTD, 23 with AD, and 20 with PD, as well as 22 healthy controls (HC), using the Reading the Mind in the Eyes (RME) Test and the Ekman Faces Test. Eye movements (number and duration of fixations) were recorded with an eye-tracking device. Behavior was assessed using the Neuropsychiatric Inventory. RESULTS: FER was mildly impaired in the AD and PD groups and severely impaired in the bvFTD group. FER impairment was accompanied by an increase in the number of fixations and a more attracted gaze toward the lower part of one's face. FER impairment and an increase in the number of fixations were positively correlated with behavioral disorders. CONCLUSION: Our study demonstrated a link between FER impairment, modification of eye-gaze strategies during the observation of emotional faces, and behavioral disorders in individuals with bvFTD and those with AD or PD. These results suggest that an eye-gaze strategy rehabilitation program could have beneficial effects on emotion recognition and behavioral disorders in individuals with these diseases.

Theory of mind, empathy and eye gaze strategies during observation of a work of art: neurodegenerative pathologies.

OBJECTIVE: Theory of mind (ToM) and empathy are severely impaired in the behavioural variant of frontotemporal dementia (bvFTD) and more mildly in Alzheimer's (AD) and Parkinson's diseases (PD). Such impairments are associated with behavioural disorders. Modification of visual scanning strategies of complex visual scenes is also found in these pathologies. We hypothesised that these patients applied atypical gaze strategies when observing social events, which does not allow them to properly process social cues and results in the production of erroneous inferences and lack of empathy towards others. METHODS: Fifty-five participants were divided into four groups: five bvFTD subjects, 19 AD subjects, 17 PD subjects and 14 matched control subjects. ToM and empathy were assessed by eye movement recording (eye-tracking) and by a questionnaire during a painting observation. Scores obtained were compared between each group and to social cognition reference tests and correlated to the NeuroPsychiatric Inventory. RESULTS: Our paradigm was suitable for assessing cognitive ToM while it lacked sensitivity for empathy assessment. Severe ToM impairment was highlighted in bvFTD, while milder difficulties were observed in AD and for PD. Subjects with bvFTD and AD produced erroneous inferences from cognitive mental states. ToM performances were linked to visual exploration strategies of the painting. Atypical visual observation was highlighted in the bvFTD and AD groups causing a time delay in taking the perspective of the other person. Finally, we highlighted that social cognition performances, gaze strategies and behavioural disorders were correlated. CONCLUSION: Observing a painting in association with eye-tracking technology can be a good support for social cognition assessment. We highlighted a link between atypical visual scanning strategies, ToM impairment and behavioural disorders in these pathologies. ToM skills could be improved by training in the search for visual social cues. Therefore, this kind of remediation could have positive effects on behavioural disorders.

[Theory of mind, empathy and eye gaze strategies during an artwork observation in neurodegenerative pathologies]. / Théorie de l'esprit, empathie et stratégies de regard durant l'observation d'une œuvre d'art dans les pathologies neurodégénératives.

OBJECTIVE: Theory of mind (ToM) and empathy are severely impaired in the behavioral-variant of frontotemporal dementia (bvFTD) and more mildly in Alzheimer's (AD) and Parkinson's diseases (PD). Such impairments are associated with behavioral disorders (BD). Modification of visual scanning strategies of complex visual scenes is also found in these pathologies. We hypothesized that these patients applied atypical gaze strategies when observing social events, which would not allow to properly process social cues and would result in the production of erroneous inferences and lack of empathy towards others. METHODS: Fifty-five participants were divided into four groups: five bvFTD, 19 AD, 17 PD and 14 matched controls subjects. ToM and empathy were assessed by eye movements recording (eye-tracking) and by a questionnaire during a painting observation. Scores obtained were compared between each group and to social cognition reference tests, and correlated to the NeuroPsychiatric Inventory. RESULTS: Our paradigm was suitable for assessing cognitive ToM while it lacked sensitivity for empathy assessment. Severe ToM impairment was highlighted in bvFTD while milder difficulties were observed in AD and for PD. bvFTD and AD groups produced erroneous inferences from cognitive mental states. ToM performances were linked to visual exploration strategies of the painting. Atypical visual observation was highlighted in bvFTD and AD groups causing a time shift in perspective taking of the character. Finally, we have highlighted that social cognition performances, gaze strategies and BD were correlated. CONCLUSION: The observation of a painting in association with eye-tracking technology can be a good support for social cognition assessment. We highlighted a link between atypical visual scanning strategies, ToM impairment and BD in these pathologies. ToM skills could be improved by training in the search for visual social cues. Therefore, this kind of remediation could have positive effects on BD.

National survey on the management of heart failure in individuals over 80 years of age in French geriatric care units.

BACKGROUND: To evaluate the prevalence and management of heart failure (HF) in very old patients in geriatric settings. METHODS: Members of the French Society of Geriatrics and Gerontology throughout France were invited to participate in a point prevalence survey and to include all patients ≥80 years old, hospitalized in geriatric settings, with HF (stable or decompensated) on June 18, 2012. General characteristics, presence of comorbidities, blood tests and medications were recorded. RESULTS: Among 7,197 patients in geriatric institution, prevalence of HF was 20.5% (n = 1,478): (27% in acute care, 24.2% in rehabilitation care and 18% in nursing home). Mean age was 88.2 (SD = 5.2) and Charlson co morbidity score was high (8.49 (SD = 2.21)). Left ventricular ejection fraction (LVEF) was available in 770 (52%) patients: 536 (69.6%) had a preserved LVEF (≥ 50%), 120 (15.6%) a reduced LVEF (< 40%), and 114 (14.8%) a midrange LVEF (40-49%). Prescription of recommended HF drugs was low: 42.6% (629) used Angiotensin Converting Enzyme Inhibitors (ACEI) or Angiotensin Receptor Blockers (ARBs), 48.0% (709) ß-blockers, and 21.9% (324) ACEI or ARB with ß-blockers, even in reduced LVEF. In multivariate analysis ACEI or ARBs were more often used in patients with myocardial infarction (1.36 (1.04-1.78)), stroke (1.42 (1.06-1.91)), and diabetes (1.54 (1.14-2.06)). ß blockers were more likely used in patients with myocardial infarction (2.06 (1.54-2.76)) and atrial fibrillation (1.70 (1.28-2.28)). CONCLUSION: In this large very old population, prevalence of HF was high. Recommended HF drugs were underused even in reduced LVEF. These results indicate that management of HF in geriatric settings can still be improved.

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 .

Effect of long-term omega 3 polyunsaturated fatty acid supplementation with or without multidomain intervention on cognitive function in elderly adults with memory complaints (MAPT): a randomised, placebo-controlled trial.

BACKGROUND: No large trials have been done to investigate the efficacy of an intervention combining a specific compound and several lifestyle interventions compared with placebo for the prevention of cognitive decline. We tested the effect of omega 3 polyunsaturated fatty acid supplementation and a multidomain intervention (physical activity, cognitive training, and nutritional advice), alone or in combination, compared with placebo, on cognitive decline. METHODS: The Multidomain Alzheimer Preventive Trial was a 3-year, multicentre, randomised, placebo-controlled superiority trial with four parallel groups at 13 memory centres in France and Monaco. Participants were non-demented, aged 70 years or older, and community-dwelling, and had either relayed a spontaneous memory complaint to their physician, limitations in one instrumental activity of daily living, or slow gait speed. They were randomly assigned (1:1:1:1) to either the multidomain intervention (43 group sessions integrating cognitive training, physical activity, and nutrition, and three preventive consultations) plus omega 3 polyunsaturated fatty acids (ie, two capsules a day providing a total daily dose of 800 mg docosahexaenoic acid and 225 mg eicosapentaenoic acid), the multidomain intervention plus placebo, omega 3 polyunsaturated fatty acids alone, or placebo alone. A computer-generated randomisation procedure was used to stratify patients by centre. All participants and study staff were blinded to polyunsaturated fatty acid or placebo assignment, but were unblinded to the multidomain intervention component. Assessment of cognitive outcomes was done by independent neuropsychologists blinded to group assignment. The primary outcome was change from baseline to 36 months on a composite Z score combining four cognitive tests (free and total recall of the Free and Cued Selective Reminding test, ten Mini-Mental State Examination orientation items, Digit Symbol Substitution Test, and Category Naming Test) in the modified intention-to-treat population. The trial was registered with ClinicalTrials.gov (NCT00672685). FINDINGS: 1680 participants were enrolled and randomly allocated between May 30, 2008, and Feb 24, 2011. In the modified intention-to-treat population (n=1525), there were no significant differences in 3-year cognitive decline between any of the three intervention groups and the placebo group. Between-group differences compared with placebo were 0·093 (95% CI 0·001 to 0·184; adjusted p=0·142) for the combined intervention group, 0·079 (-0·012 to 0·170; 0·179) for the multidomain intervention plus placebo group, and 0·011 (-0·081 to 0·103; 0·812) for the omega 3 polyunsaturated fatty acids group. 146 (36%) participants in the multidomain plus polyunsaturated fatty acids group, 142 (34%) in the multidomain plus placebo group, 134 (33%) in the polyunsaturated fatty acids group, and 133 (32%) in the placebo group had at least one serious emerging adverse event. Four treatment-related deaths were recorded (two in the multidomain plus placebo group and two in the placebo group). The interventions did not raise any safety concerns and there were no differences between groups in serious or other adverse events. INTERPRETATION: The multidomain intervention and polyunsaturated fatty acids, either alone or in combination, had no significant effects on cognitive decline over 3 years in elderly people with memory complaints. An effective multidomain intervention strategy to prevent or delay cognitive impairment and the target population remain to be determined, particularly in real-world settings. FUNDING: French Ministry of Health, Pierre Fabre Research Institute, Gerontopole, Exhonit Therapeutics, Avid Radiopharmaceuticals.

AMPA workshop on challenges faced by investigators conducting Alzheimer's disease clinical trials.

The recruitment and retention of patients are among the greatest challenges currently being faced by researchers who conduct Alzheimer's disease (AD) clinical trials. To discuss these challenges and other major issues associated with clinical research in AD, an international workshop was organized by the Association Monégasque pour la recherche sur la Maladie d'Alzheimer at Monte Carlo, Monaco, in February 2010, with the participation of leading research experts in the field of Alzheimer's. Key topics discussed were as follows: (1) the selection, recruitment, and retention of clinical trial subjects; (2) international co-operation among researchers; and (3) patient rights and informed consent for participants in clinical trials. This article highlights some of the challenges faced by investigators when conducting clinical trials in AD, and it also offers some recommendations aimed at overcoming these challenges.

Apoptosis of naive CD4+ T-cells from HIV-infected patients with poor immune response to HAART is enhanced in vitro by steroid.

OBJECTIVE: Because the absence of immune restoration in HIV-infected patients efficiently treated by highly active antiretroviral therapy (HAART) may be due to excessive immune activation, we prospectively studied the effect of hydrocortisone on T-cell apoptosis in a cohort of patients with satisfactory virologic response. METHODS: Apoptosis of T-cell subsets including naïve CD45RA(+)CD4+ T-cells was determined at baseline and at months 1 and 3 after initiation of HAART. A satisfactory immune response was defined as an increase >100/microL CD4+ T-cells at month 3 compared to baseline. RESULTS: Twenty out of 63 patients showed undetectable viral load at month 3, among whom eight exhibited a satisfactory immune response. Down-regulation spontaneous CD4+T-cell apoptosis was significant in the group of patients with a satisfactory immune response compared to the other patients. However, hydrocortisone up-regulated apoptosis of naïve CD4+ CD45RA+ T-cells, specifically in group of patients with poor immune response, whatever the time point considered: percentage of apoptotic CD4 T-cells was 16+/-16% without hydrocortisone and 22+/-22% with hydrocortisone at month 1, and respectively, 10+/-9 and 17+/-15% at month 3 (P < 0.05) Hydrocortisone had no impact on CD8+ T-cell apoptosis, whatever the considered group. CONCLUSION: Our results suggest to not use steroid therapy as adjuvant immunotherapy in patients with less than optimal immunologic response to HAART.

Efficacy of an educational and counseling intervention on adherence to highly active antiretroviral therapy: French prospective controlled study.

PURPOSE: The objective was to evaluate the impact of an intervention for improving adherence to antiretroviral therapies (HAART) in HIV-infected patients. METHOD: We designed a prospective, controlled, randomized trial to assess the impact of an educational and counseling intervention in addition to standard of care. At M0, the study enrolled 244 HAART-treated patients who attended a medical consultation between September and December 1999 who were not included in another protocol. Patients in the intervention group (IG) were offered three individual sessions by trained nurses. The proportions of adherent patients at 6 months followup (M6) and the change in HIV RNA between M0 and M6 were measured. RESULTS: Between M0 and M6, HIV RNA significantly decreased in the 123 patients of the IG (mean difference = -0.22 log [+/-0.86], p =.013), while it increased (+0.12 log [+/-0.90], p =.14) in the 121 patients of the control group. However, the proportion of patients with HIV RNA <40 copies/mL remained similar in both groups. In an intent-to-treat analysis, the only significant predictor of 100% adherence at M6 was the intervention group (p =.05) after adjustment for baseline adherence (p =.001). Among the 202 patients with available data on adherence, the proportion of adherent patients was similar in both groups at M0 (58% vs. 63%, p =.59) but became higher in the IG at M6 (75% vs. 61%, p =.04). CONCLUSION: The educational and counseling intervention was efficient for increasing adherence to HAART and could be implemented in most clinical settings.

Early CD4(+) T cell recovery in human immunodeficiency virus-infected patients receiving effective therapy is related to a down-regulation of apoptosis and not to proliferation.

This prospective study investigated the contributions of apoptosis and proliferation of CD4(+) T cells obtained by the introduction of a new antiretroviral treatment for human immunodeficiency virus infection. Virus load; T cell counts; apoptosis of T cell subsets, including naive cells; and proliferation were determined from treatment initiation to the third month in a cohort of patients. An increase in CD4(+) T cell count > or = 100 cells/microL over baseline was considered to be a satisfactory immune reconstitution. Sixty-nine patients completed the protocol, 22 of whom met our definition of a satisfactory immune reconstitution, showing a significantly more pronounced reduction in spontaneous CD4(+) T cell apoptosis at month 1 as well as month 3, compared with the other patients. In contrast, neither Fas-induced apoptosis down-regulation nor Fas-induced increased proliferation capacity was associated with a satisfactory immune reconstitution. Down-regulation of CD4(+) T cell apoptosis by antiretroviral treatment is the main mechanism associated with early CD4(+) T cell increase.