Connectivity patterns of the core resting-state networks associated with apathy in late-life depression.

BACKGROUND: Apathy is associated with reduced antidepressant response and dementia in late-life depression (LLD). However, the functional cerebral basis of apathy is understudied in LLD. We investigated the functional connectivity of 5 resting-state networks (RSN) hypothesized to underlie apathy in LLD. METHODS: Resting-state functional MRI data were collected from individuals with LLD who did not have dementia as well as healthy older adults between October 2019 and April 2022. Apathy was evaluated using the diagnostic criteria for apathy (DCA), the Apathy Evaluation Scale (AES) and the Apathy Motivation Index (AMI). Subnetworks whose connectivity was significantly associated with each apathy measure were identified via the threshold-free network-based statistics. Regions that were consistently associated with apathy across the measures were reported as robust findings. RESULTS: Our sample included 39 individuals with LLD who did not have dementia and 26 healthy older adults. Compared with healthy controls, individuals with LLD had an altered intra-RSN and inter-RNS connectivity in the default mode, the cingulo-opercular and the frontoparietal networks. All 3 apathy measurements showed associations with modified intra-RSN connectivity in these networks, except for the DCA in the cingulo-opercular network. The AMI scores showed stronger associations with the cingulo-opercular and frontoparietal networks, whereas the AES had stronger associations with the default mode network and the goal-oriented behaviour network. LIMITATIONS: The study was limited by the small number of participants without apathy according to the DCA, which may have reduced the statistical power of between-group comparisons. Additionally, the reliance on specific apathy measures may have influenced the observed overlap in brain regions. CONCLUSION: Our findings indicate that apathy in LLD is consistently associated with changes in both intra-RSN and inter-RSN connectivity of brain regions implicated in goal-oriented behaviours. These results corroborate previous findings of altered functional RSN connectivity in severe LLD.

Physical activity, biomarkers of brain pathologies and dementia risk: Results from the Memento clinical cohort.

INTRODUCTION: This study aims to examine whether physical activity moderates the association between biomarkers of brain pathologies and dementia risk. METHODS: From the Memento cohort, we analyzed 1044 patients with mild cognitive impairment, aged 60 and older. Self-reported physical activity was assessed using the International Physical Activity Questionnaire. Biomarkers of brain pathologies comprised medial temporal lobe atrophy (MTA), white matter lesions, and plasma amyloid beta (Aß)42/40 and phosphorylated tau181. Association between physical activity and risk of developing dementia over 5 years of follow-up, and interactions with biomarkers of brain pathologies were tested. RESULTS: Physical activity moderated the association between MTA and plasma Aß42/40 level and increased dementia risk. Compared to participants with low physical activity, associations of both MTA and plasma Aß42/40 on dementia risk were attenuated in participants with high physical activity. DISCUSSION: Although reverse causality cannot be excluded, this work suggests that physical activity may contribute to cognitive reserve. HIGHLIGHTS: Physical activity is an interesting modifiable target for dementia prevention. Physical activity may moderate the impact of brain pathology on dementia risk. Medial temporal lobe atrophy and plasma amyloid beta 42/40 ratio were associated with increased dementia risk especially in those with low level of physical activity.

Assessing the pool activity level (PAL) checklist for use with people with hearing and vision loss.

BACKGROUND: The PAL is a career-completed assessment that indexes cognitive functional ability to inform individualised support. As hearing and vision loss are prevalent, we assessed the PAL for potential bias with hearing or vision impairment. METHODS: We collected PAL responses for 333 adults aged over 60 years in the UK, France, Canada, Greece and Cyprus. All participants had normal cognition based on self-reported status and normal range scores on a cognitive screening test. Using a Kruskal-Wallis test, we compared PAL item response distributions for people with assessed hearing or vision loss compared to those with normal sensory function. RESULTS: There were no differences in response distributions between hearing or vision impaired groups versus those with normal sensory function on any PAL item. CONCLUSION: The PAL reliably indexes cognitive functional ability and may be used to inform support tailored to individual cognitive level amongst older adults with prevalent hearing and vision impairments.

Recommendations for the Nonpharmacological Treatment of Apathy in Brain Disorders.

Apathy is a common neuropsychiatric syndrome observed across many neurocognitive and psychiatric disorders. Although there are currently no definitive standard therapies for the treatment of apathy, nonpharmacological treatment (NPT) is often considered to be at the forefront of clinical management. However, guidelines on how to select, prescribe, and administer NPT in clinical practice are lacking. Furthermore, although new Information and Communication Technologies (ICT) are beginning to be employed in NPT, their role is still unclear. The objective of the present work is to provide recommendations for the use of NPT for apathy, and to discuss the role of ICT in this domain, based on opinions gathered from experts in the field. The expert panel included 20 researchers and healthcare professionals working on brain disorders and apathy. Following a standard Delphi methodology, experts answered questions via several rounds of web-surveys, and then discussed the results in a plenary meeting. The experts suggested that NPT are useful to consider as therapy for people presenting with different neurocognitive and psychiatric diseases at all stages, with evidence of apathy across domains. The presence of a therapist and/or a caregiver is important in delivering NPT effectively, but parts of the treatment may be performed by the patient alone. NPT can be delivered both in clinical settings and at home. However, while remote treatment delivery may be cost and time-effective, it should be considered with caution, and tailored based on the patient's cognitive and physical profile and living conditions.

Pathways to care for people with dementia: An international multicentre study.

OBJECTIVE: The aim of the present study was to characterize the clinical pathways that people with dementia (PwD) in different countries follow to reach specialized dementia care. METHODS: We recruited 548 consecutive clinical attendees with a standardized diagnosis of dementia, in 19 specialized public centres for dementia care in 15 countries. The WHO "encounter form," a standardized schedule that enables data concerning basic socio-demographic, clinical, and pathways data to be gathered, was completed for each participant. RESULTS: The median time from the appearance of the first symptoms to the first contact with specialist dementia care was 56 weeks. The primary point of access to care was the general practitioners (55.8%). Psychiatrists, geriatricians, and neurologists represented the most important second point of access. In about a third of cases, PwD were prescribed psychotropic drugs (mostly antidepressants and tranquillizers). Psychosocial interventions (such as psychological counselling, psychotherapy, and practical advice) were delivered in less than 3% of situations. The analyses of the "pathways diagram" revealed that the path of PwD to receiving care is complex and diverse across countries and that there are important barriers to clinical care. CONCLUSIONS: The study of pathways followed by PwD to reach specialized care has implications for the subsequent course and the outcome of dementia. Insights into local differences in the clinical presentations and the implementation of currently available dementia care are essential to develop more tailored strategies for these patients, locally, nationally, and internationally.

[Mindfulness meditation for family caregivers]. / La méditation de pleine conscience pour les aidants familiaux.

A significant proportion of elderly people suffering from neurodegenerative pathologies are cared for by an informal caregiver. From the earliest stages of the disease, the psychological and behavioural disorders of patients constitute stress and anxiety factors for their caregivers. Mindfulness meditation has proven its usefulness in the management of anxiety. A study proposes caregiver management based on a mindfulness meditation program.

Objective measurement of gait parameters in healthy and cognitively impaired elderly using the dual-task paradigm.

OBJECTIVES: The present study explores the differences in gait parameters in elderly subjects with or without cognitive impairment measured by means of ambulatory actigraphy while performing a single and a dual task. METHODS: Sixty-nine participants of which 23 individuals were diagnosed with Alzheimer's disease (AD), 24 individuals with mild cognitive impairment (MCI), and 22 healthy controls performed a single and dual walking task while wearing a wrist-worn accelerometer. Objective measures of gait features such as walking speed, cadence (i.e., number of steps per minute), and step variance (i.e., variance in time between two consecutive steps) were derived and analyzed. RESULTS: While differences in several gait parameters, namely walking speed, were found between MCI and AD patients, no differences between healthy elderly and MCI patients were found. CONCLUSION: Walking speed seems to be a gait-related feature that differs significantly between MCI and AD patients and thus could be used as an additional measurement in clinical assessment. However, differences in gait may not be salient enough in the early stages of dementia to be detected by actigraphy. More research comparing different methods to measure gait in early stages of dementia under different dual task conditions is neccessary.

[Robotics and improvement of the quality of geriatric care]. / Robotique et amélioration de la qualité des soins en gériatrie.

New technologies offer innovations to improve the care of the elderly with Alzheimer's or and other forms of dementia. Robots, endowed with features such as monitoring of physiological parameters, cognitive training or occupational therapy, have appeared. They are not, however, intended to replace humans. Still underutilized, these robots are in development, much like the digital literacy of the elderly.

[Serious game, a link between institution and home]. / Le serious game, un lien entre institution et domicile.

Serious game is a personal innovative technology to facilitate learning and social interaction. It can be used in a patient's home or in an institution. This training tool can also be developed for health professionals, especially accommodation facilities for the elderly. The objective is to integrate knowledge and know-how.

[Neuropsychiatric disorders and technological solutions]. / Troubles neuropsychiatriques et solutions technologiques.

Innovative new tools today allow better clinical evaluation. Indeed, new information and communication technology is particularly interesting for the screening, monitoring and management of neuropsychiatric disorders of the elderly. A personalised approach to patients can further enhance their adherence and involvement.

[Frequency and coding of psychiatric care of short-stay patients]. / Fréquence et codage des prises en charge psychiques des patients hospitalisés en court séjour.

INTRODUCTION: The objective of this study was to describe the frequency and coding of the psychiatric management of short-stay patients admitted to Nice University Hospital in 2013. METHODS: Various parameters were measured : percentage of outpatient psychiatric procedures or psychiatric diagnosis codes ; coding practice differences between the Programme de médicalisation des systèmes d'information (Medical Information System Programme) for medicine, surgery and obstetrics and psychiatric medical data records, and the impact of coding on diagnosis-related groups. RESULTS: Twenty-four per cent of hospitalised patients received psychiatric management (either outpatient care or a psychiatric diagnosis) and 3.9% received both psychiatric management and a psychiatric diagnosis. Liaison psychiatrists more commonly used codes for neurotic and psychosomatic disorders (28% vs 16%), while somatic physicians more commonly used codes for psychoactive substance use-related disorders (26% vs 16%).The presence of psychiatric comorbidity had an impact on the DRG classification or the level of severity for 0.5% of standardized discharge summaries. CONCLUSION: This study illustrates the importance of the active involvement of psychiatry personnel in the management of short-stay patients. The importance of psychosomatic medicine in a short-stay institution could be improved by establishing a clearer definition of coding rules for these diseases and revising and identifying wards or beds devoted to psychosomatic disorders.

[Alzheimer's disease and the organization of visits to cultural sites]. / Maladie d'Alzheimer et aménagement de visites dans les lieux culturels.

In the framework of a policy to open up cultural sites within the city to the specific disability of Alzheimer's disease, the Resource and Research Memory Centre at Nice general hospital in partnership with Nice's city hall, has developed a cultural programme. The aim of this project is to assess the therapeutic aspects of this programme and notably the perception of the disease by the family carers.

A review of current information and communication technologies: can they be used to assess apathy?

BACKGROUND: Neuropsychiatric symptoms, such as apathy, have an important impact on the quality of life of both patients diagnosed with dementia and their caregivers and represent a strong predictor of progression of the illness. Current clinical assessment methods risk bias resulting from the assessor's subjectivity, pointing to a need for additional objective and systematic assessment tools. Therefore, the use of information and communication technologies (ICT) such as actigraphy and automatized video monitoring are of interest in addition to current assessment methods. AIM: The goal of this study is to give an overview of current assessment tools for apathy in clinical practice and new approaches to assessment methods with the help ICT. METHODS: This study was conducted with the use of narrative literature overview. RESULTS: There is evidence that apart from the currently used assessment methods for apathy, new ICT approaches could provide clinicians with valuable additional information for an earlier detection and therefore more accurate diagnosis of apathy. CONCLUSIONS: There are no ICT techniques specifically designed for the assessment of apathy, but nevertheless several techniques seem to be promising and deserve more study.

Quantifying Apathy in Late-Life Depression: Unraveling Neurobehavioral Links Through Daily Activity Patterns and Brain Connectivity Analysis.

BACKGROUND: Better understanding apathy in late-life depression would help improve prediction of poor prognosis of diseases such as dementia. Actimetry provides an objective and ecological measure of apathy from patients' daily motor activity. We aimed to determine whether patterns of motor activity were associated with apathy and brain connectivity in networks that underlie goal-directed behaviors. METHODS: Resting-state functional magnetic resonance imaging and diffusion magnetic resonance imaging were collected from 38 nondemented participants with late-life depression. Apathy was evaluated using the diagnostic criteria for apathy, Apathy Evaluation Scale, and Apathy Motivation Index. Functional principal components (fPCs) of motor activity were derived from actimetry recordings taken for 72 hours. Associations between fPCs and apathy were estimated by linear regression. Subnetworks whose connectivity was significantly associated with fPCs were identified via threshold-free network-based statistics. The relationship between apathy and microstructure metrics was estimated along fibers by diffusion tensor imaging and a multicompartment model called neurite orientation dispersion and density imaging via tractometry. RESULTS: We found 2 fPCs associated with apathy: mean diurnal activity, negatively associated with Apathy Evaluation Scale scores, and an early chronotype, negatively associated with Apathy Motivation Index scores. Mean diurnal activity was associated with increased connectivity in the default mode, cingulo-opercular, and frontoparietal networks, while chronotype was associated with a more heterogeneous connectivity pattern in the same networks. We did not find significant associations between microstructural metrics and fPCs. CONCLUSIONS: Our findings suggest that mean diurnal activity and chronotype could provide indirect ambulatory measures of apathy in late-life depression, associated with modified functional connectivity of brain networks that underlie goal-directed behaviors.

A cross-cultural study of the Montreal Cognitive Assessment for people with hearing impairment.

BACKGROUND: Cognitive screening tools enable the detection of cognitive impairment, facilitate timely intervention, inform clinical care, and allow long-term planning. The Montreal Cognitive Assessment for people with hearing impairment (MoCA-H) was developed as a reliable cognitive screening tool for people with hearing loss. Using the same methodology across four languages, this study examined whether cultural or linguistic factors affect the performance of the MoCA-H. METHODS: The current study investigated the performance of the MoCA-H across English, German, French, and Greek language groups (n = 385) controlling for demographic factors known to affect the performance of the MoCA-H. RESULTS: In a multiple regression model accounting for age, sex, and education, cultural-linguistic group accounted for 6.89% of variance in the total MoCA-H score. Differences between languages in mean score of up to 2.6 points were observed. CONCLUSIONS: Cultural or linguistic factors have a clinically significant impact on the performance of the MoCA-H such that optimal performance cut points for identification of cognitive impairment derived in English-speaking populations are likely inappropriate for use in non-English speaking populations. To ensure reliable identification of cognitive impairment, it is essential that locally appropriate performance cut points are established for each translation of the MoCA-H.

Phenotyping apathy in individuals with Alzheimer disease using functional principal component analysis.

OBJECTIVES: To determine if there is a specific pattern of gross motor activity associated with apathy in individuals with Alzheimer disease (AD). DESIGN: Examination of ad libitum 24-hour ambulatory gross motor activity patterns. SETTING: Community-dwelling, outpatient. PARTICIPANTS: Ninety-two individuals with AD, 35 of whom had apathy. MEASUREMENTS: Wrist actigraphy data were collected and examined using functional principal component analysis (fPCA). RESULTS: Individuals with apathy have a different pattern of gross motor activity than those without apathy (first fPCA component, p <0.0001, t = 5.73, df = 90, t test) such that there is a pronounced decline in early afternoon activity in those with apathy. This change in activity is independent of depression (p = 0.68, F[1, 89] = 0.05, analysis of variance). The decline in activity is consistent with an increase in napping. Those with apathy also have an early wake and bedtime (second fPCA component, t = 2.53, df = 90, p <0.05, t test). CONCLUSIONS: There is a signature activity pattern in individuals with apathy and AD that is distinct from those without apathy and those with depression. Actigraphy may be a useful adjunctive measurement in the clinical diagnosis of apathy in the context of AD.

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

OBJECTIVE: 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. METHODS: Sixteen NHs agreed to participate, and 230 demented apathetic residents were randomly assigned to the reference group (RG) or the intervention group (IG). IG received a month of weekly 4-h training. Qualitative evaluation was performed through interviews and questionnaires regarding work practices and knowledge about dementia. Quantitative evaluation was at baseline, at the end of the training program (week 4), and 3 months after the end of it with the use of the Neuropsychiatric Inventory (NPI), the Apathy Inventory, and two observation scales. RESULTS: In the qualitative evaluation, very few staff responded to the questionnaire. Concerning the difficulty that managing residents' behavioral symptoms presented, aggressiveness was ranked as the most difficult behavior to manage and apathy as the least difficult. In the quantitative evaluation, the results are as follows. NPI: the IG scores increased from baseline to week 4 more than the RG for symptoms belonging to the affective and the psychotic NPI item subgroup. Apathy Inventory: there was a significant decrease of the emotional blunting score dimension in the IG. Group Observation Scale: significant improvement was observed for the emotional blunting dimension in the IG only. CONCLUSIONS: Apathy is rarely identified as a problem in NH. Emotional blunting was the only dimension sensitive to change. Failure to improve residents' level of interest could be explained by the difficulties encountered in accessing information regarding the subjects' personal interests. But it remains possible to modify residents' emotional reactivity and staff's perceptions of residents' behaviors and emotions.

[Alzheimer's disease, amyloid-b peptides and ubiquitin-proteasome system: Therapeutic perspectives]. / Maladie d'Alzheimer, peptides ß-amyloïdes et système ubiquitine-protéasome - Perspectives thérapeutiques.

The Alzheimer's disease - an age-related neurodegenerative disorder leading to a progressive cognitive impairment - is characterized by an intracerebral accumulation of soluble ß-amyloid (Aß) oligomers, followed by the appearance of abnormally ubiquitinylated neurofibrillary tangles - a process associated with a chronic inflammation. The systematic presence of ubiquitinylated inclusions reflects a decrease in the proteasome activity due to (and contributing to) the presence of Aß oligomers - a central dysfunction in the etiology of the disease. The involvement of the ubiquitin-proteasome system opens new therapeutic perspectives for both prevention and treatment.

Title: Maladie d'Alzheimer, peptides ß-amyloïdes et système ubiquitine-protéasome - Perspectives thérapeutiques. Abstract: La maladie d'Alzheimer ­ une maladie neurodégénérative liée à l'âge entraînant une altération progressive des fonctions cognitives ­ se caractérise par une accumulation intracérébrale d'oligomères ß-amyloïdes (Aß) solubles, suivie d'une apparition d'enchevêtrements neurofibrillaires anormalement ubiquitinylés ­ un processus associé à une inflammation chronique. La présence systématique d'inclusions ubiquitinylées traduit une baisse d'activité du protéasome due (et concourant) à la présence d'oligomères Aß ­ un dysfonctionnement central dans l'étiologie de la maladie. L'implication du système ubiquitine-protéasome ouvre de nouvelles perspectives thérapeutiques tant préventives que curatives.

Development and validation of the Montreal cognitive assessment for people with hearing impairment (MoCA-H).

BACKGROUND: Hearing impairment is common among older adults and affects cognitive assessments for identification of dementia which rely on good hearing function. We developed and validated a version of the Montreal Cognitive Assessment (MoCA) for people with hearing impairment. METHODS: We adapted existing MoCA 8.1 items for people with hearing impairment by presenting instructions and stimuli in written rather than spoken format. One Attention domain and two Language domain items required substitution by alternative items. Three and four candidate items respectively were constructed and field-tested along with the items adapted to written form. We used a combination of individual item analysis and item substitution to select the set of alternative items to be included in the final form of the MoCA-H in place of the excluded original items. We then evaluated the performance and reliability of the final tool, including making any required adjustments for demographic factors. RESULTS: One hundred and fifty-nine hearing-impaired participants, including 76 with normal cognition and 83 with dementia, completed the adapted version of the MoCA. A further 97 participants with normal hearing completed the standard MoCA as well as the novel items developed for the MoCA-H to assess score equivalence between the existing and alternative MoCA items and for independence from hearing impairment. Twenty-eight participants were retested between 2-4 weeks after initial testing. After the selection of optimal item set, the final MoCA-H had an area under the curve of 0.973 (95% CI 0.952-0.994). At a cut-point of 24 points or less sensitivity and specificity for dementia was 92.8% and 90.8%, respectively. The intraclass correlation for test-retest reliability was 0.92 (95%CI 0.78-0.97). CONCLUSION: The MoCA-H is a sensitive and reliable means of identifying dementia among adults with acquired hearing impairment.

Different Trajectories of Apathy and Depression Among Subjective Cognitive Impairment Individuals with or without Conversion to Dementia: Results from the Memento Cohort in France.

BACKGROUND: Apathy and depression are two early behavioral symptoms in Alzheimer's disease (AD) and related disorders that often occur prior to the onset of cognitive decline and memory disturbances. Both have been associated with an increased risk of conversion to dementia, with a distinct neuropathology. OBJECTIVE: The assessment of the trajectories of apathy and depression and their independent impact on dementia conversion. METHODS: Apathy and Depression were measured using the Neuropsychiatric Inventory for caregiver (NPI) and clinician (NPI-C), among the nondemented individuals reporting subjective cognitive decline (SCD) at baseline. They were followed up over a 60-month period. Some converted to dementia, according to the methodology carried out by the French Memento Cohort. RESULTS: Among individuals with SCD (n = 2,323), the levels of apathy and depression were low and did not evolve significantly over the 60-month period, despite a trend in apathy increasing as of month 24. Regarding SCD individuals who converted to dementia within the 60-month period (n = 27), the prevalence of depression remained globally steady, while the levels of apathy increased over time. CONCLUSION: Apathy and depression have different trajectories among individuals with SCD and apathy alone is more likely-compared to depression-to be associated with conversion to dementia.