Severe worry is a transdiagnostic syndrome associated with significant morbidity in older adults. In this study, we aim to infer worry-related mental states though brain activity timeseries. We acquired fMRI on two cohorts (N=116 and N=88), using an in-scanner worry induction and reappraisal task. We trained a recurrent long short-term memory (LSTM) neural network, using the first cohort as the train/validation and the second cohort as an independent test set. We predicted worry induction, reappraisal, and neutral states (area under the curve 0.89, 0.77, 0.91 for the test set and 0.78, 0.63, 0.81 for the independent set). The model was most accurate when participants reported high worry during the induction state. Dorsal attention network, and networks seeded on the anterior hippocampus, and supplementary motor area were most important for predicting worry states. The LSTM approach may have critical translational implications for identifying and treating severe worry in older adults.

Background:Late-life depression with inadequate antidepressant response is a pressing clinical issue with limited proven therapies. Nitrous oxide (N2O) may offer a new therapeutic avenue with rapid and safe antidepressant effects in late-life depression with inadequate antidepressant response. Methods:We conducted a double-blind, randomised, placebo-controlled, single-dose trial (November 2021-December 2024) in three old-age psychiatry departments at French university hospitals. Eligible participants were aged 60-90 years with a current major depressive episode, a Montgomery-Åsberg Depression Rating Scale (MADRS) score >20 and documented non-response to ≥1 adequate antidepressant trial. Participants were randomly assigned (1:1) to a single 60-min inhalation of either 50% N2O/50% O2 (N2O group) or medical air (placebo group). The primary outcome was change in MADRS score from baseline to 2 weeks, analysed under the intention-to-treat principle with a linear mixed-effects model using all available data. Secondary outcomes included clinician- and self-rated depressive symptom scales and safety. The study is complete and registered in ClinicalTrials.gov (NCT05007028). Findings:Among the 60 participants enrolled in the study, those who received N2O experienced a significant and sustained reduction in depressive symptoms compared to the placebo group. The antidepressant effect was rapid, with significant improvements noted as early as 24 h and at one week. At the two-week endpoint, the N2O group showed a significantly greater reduction in MADRS scores (-6.2 points; 95% CI: -9.1 to -3.4; P < 0.001). These positive findings were supported by both clinician- and self-rated questionnaires, and all reported adverse events were mild and transient. Interpretation:While further studies are needed to confirm its long-term efficacy and safety, our findings suggest that N2O offers a new therapeutic strategy with rapid, sustained and safe antidepressant effects in late-life depression with inadequate antidepressant response. Funding:This study was supported by a grant from the French Ministry of Health and Prevention.

Introduction La musique est une forme d’expression universelle aux multiples fonctions. Si de nombreux travaux ont étudié ses effets sur les structures cérébrales, l’impact comparatif de différents styles musicaux d’une même époque sur les réseaux neuronaux reste peu exploré. L’objectif de cette étude était d’identifier les régions cérébrales et réseaux fonctionnels co-activés en IRMf lors de l’écoute de quatre extraits d’œuvres classiques de styles différents. Matériel et méthodes Vingt-cinq sujets sains ont été inclus dans cette étude prospective. Le statut de musicien et les résultats d'échelles psychométriques étaient évalués. Une IRM 3T (séquence BOLD) a permis l’analyse fonctionnelle de quatre extraits musicaux d’une minute présentés aléatoirement : Guillaume Tell (Rossini), La Bayadère (Minkus), Gymnopédie n°1 (Satie/Debussy) et Le Sacre du Printemps (Stravinsky). Les données ont été traitées sous MatLab® et CONN Toolbox afin d’examiner les co-activations significatives et leur relation avec les caractéristiques musicales (rythme, harmonie, mode). Résultats L’analyse ROI-to-ROI et par réseaux montre des profils de connectivité distincts pour chaque œuvre. La Bayadère sollicite surtout les régions temporales médiales, occipitales et cérébelleuses, reflétant l’interaction entre réseaux mnésiques, attentionnels et visuo-associatifs. La Gymnopédie implique principalement les circuits thalamo-insulaires, orbitofrontaux et occipitaux, liés à l’intégration attentionnelle, exécutive et sensorielle. Guillaume Tell active les régions frontales inférieures, temporales et cérébelleuses, mobilisant les réseaux attentionnels ventral, émotionnel et cérébelleux. Enfin, Stravinsky montre une forte co-activation fronto-orbitale et temporale bilatérale, traduisant l’engagement des réseaux limbique, attentionnel ventral et visuel. Aucune influence du sexe ou du statut de musicien n’a été observée. Conclusion Les œuvres relaxantes (Bayadère, Gymnopédie) favorisent une connectivité introspective, tandis que les œuvres entraînantes (Guillaume Tell, Stravinsky) mobilisent davantage les réseaux attentionnels, émotionnels et cérébelleux. Ces résultats illustrent la sensibilité cérébrale aux propriétés rythmiques et harmoniques et ouvrent la voie à une musicothérapie personnalisée fondée sur l’activation ciblée de réseaux neuronaux.

Neurofilament light chain (NFL) is a structural axonal protein released into extracellular fluids following neuroaxonal injury. Blood-based NfL measurement has emerged as a marker of neurodegeneration, but its relevance in geriatric psychiatry remains insufficiently defined. We conducted a narrative review of peer-reviewed studies reporting serum or plasma NfL concentrations in older adults with neurodegenerative diseases or major psychiatric disorders. In MEDLINE/PubMed, were searched up to 31 October 2025. We synthesised data on normative values and biological determinants, compared NfL levels across diagnostic categories, examined evidence from mild behavioral impairment and late-onset psychiatric presentations, and developed a clinically oriented interpretative framework. Across studies, blood NfL concentrations increased with age and were influenced by medical comorbidities, particularly renal function. Neurodegenerative disorders were associated with higher NfL levels than primary psychiatric disorders, whereas most psychiatric conditions overlapped with age-adjusted normative ranges. Meta-analytic evidence showed no significant elevation in major depressive disorder and modest, heterogeneous increases in bipolar disorder, while schizophrenia spectrum disorders largely overlapped with physiological ageing. In transdiagnostic contexts, including mild behavioral impairment and late-onset psychiatric syndromes, higher baseline NfL levels and steeper longitudinal increases were associated with greater risk of underlying neurodegeneration. These findings support a stepwise interpretation strategy integrating age, comorbidities, clinical context and longitudinal trajectories. Age- and comorbidity-adjusted interpretation of blood NfL can support risk stratification in geriatric psychiatry. Used as an adjunctive biomarker, NfL may help identify patients requiring monitoring or additional neurological assessment.

BACKGROUND:Frailty is a prevalent condition among older adults with neurocognitive disorders. OBJECTIVES:To ascertain whether frailty contributes to the severity of cognitive impairment and neuropsychiatric symptoms, and its association with cerebral pathology measured in vivo by fluid and imaging biomarkers. DESIGN:We conducted cross-sectional and longitudinal analyses based on CLEM Study, a multicentre memory-clinic cohort that recruited participants between 2014 and 2018. SETTING:CLEM Study occurred in eight memory centres in France (Lyon, Paris, Strasbourg, Poitiers, Tours, Grenoble) and Monaco. PARTICIPANTS:A total of 168 participants (mean age 80.5 ± 4.8 years) with mild to moderate dementia due to at least one aetiological diagnosis between Alzheimer's disease, dementia with Lewy bodies or vascular dementia were included in the study. MEASUREMENTS:The participants were evaluated at baseline and followed up for two years. The concept of frailty was operationalised using a 45-item Frailty Index. Cognition was assessed using the ADAS-cog scale, while neuropsychiatric symptoms were evaluated with the Neuropsychiatric Inventory. The cerebral pathological score, a proxy for brain pathologies, was a composite score based on the presence of several in vivo biomarkers: presynaptic dopaminergic denervation on 123I-FP-CIT SPECT (DaTscan®), vascular lesions on MRI, elevated blood-based pTau181, neurofilaments light-chain or glial fibrillary acid protein. Linear and mixed regression analyses were conducted to model the relationships between cognitive or neuropsychiatric symptoms, frailty and cerebral pathologic score, adjusted for age, sex and education. RESULTS:The findings indicate an impact of both frailty (β = 0.28, 95 % CI [0.14-0.43], p < 0.001) and cerebral pathological score (β = 0.30, 95 % CI [0.13-0.47], p = 0.002) on cognitive impairment. However, only frailty was associated with neuropsychiatric symptoms (β = 0.28, 95 % CI [0.14-0.43], p < 0.001), particularly with apathy (β = 0.40, 95 % CI [0.26-0.53], p < 0.001). We found an association between cerebral pathological score and longitudinal cognitive decline (β = 0.36, 95 % CI [0.19-0.53], p < 0.001) in exploratory analyses with available longitudinal data at 24 months (n = 74). CONCLUSIONS:Neurocognitive disorders are complex entities, where cognitive and neuropsychiatric symptoms are not fully influenced by the same factors. When cognitive symptoms seem more driven by cerebral pathology than frailty, neuropsychiatric symptoms appear to be more influenced by general state of frailty. Measuring and treating frailty might be a key factor in dealing with neuropsychiatric symptoms and their consequences.

INTRODUCTION:The "I-Learn Cognition and Behavior" program, integrating e-learning and simulation, aims to equip long-term care facility staff with non-pharmacological approaches for managing agitation in residents with neurocognitive disorders. This study evaluated the program's effectiveness. METHOD:In this multicenter cluster-randomized trial, long-term care facilities served as the randomization units for a population of residents with neurocognitive disorders and agitation who underwent blinded assessments at baseline, 3, 6, and 10 months. Assessments included the Cohen-Mansfield Agitation Inventory (CMAI) as the primary outcome, the Neuropsychiatric Inventory-Nursing Home (NPI-NH), the Quality of Life in Alzheimer's Disease questionnaire, the Maslach Burnout Inventory (MBI), psychotropic use, and hospitalizations. Mixed-effects models analyzed changes in outcomes. RESULTS:Twelve long-term care facilities were randomized to receive the I-Learn program (intervention) or usual care (control). One hundred sixty-nine residents were enrolled. There were no significant differences in total CMAI score changes between groups. The intervention group demonstrated significant reduced CMAI non-aggressive verbal agitation, MBI depersonalization, and psychotropic medication use (higher withdrawal rates and lower dosage increases) compared to the control group. NPI-NH scores decreased less in the intervention group. DISCUSSION:The I-Learn program demonstrated potential for improving specific aspects of agitation in residents and well-being in caregivers while significantly reducing psychotropic medication use. "I-Learn Cognition and Behavior" is an easily accessible program with the potential for widespread distribution, contributing to improved well-being and quality of care in long-term care facilities for managing agitation in residents with neurocognitive disorders.

Abnormal brain accumulation of amyloid-β peptides, represents one of the earliest biological indicators of Alzheimer’s disease (AD) risk. Estimation on amyloid positivity (A+) prevalence among older adults without dementia are needed to assess the epidemiological impact of AD diagnosis solely through biological markers. We combined data from the French MEMENTO clinical cohort, where amyloid status was assessed through reference procedures, with the nationally representative SHARE-HCAP survey. Using stabilized inverse odds of selection weights, we adjusted the MEMENTO sample to estimate the prevalence of A+ in the French population aged 65–85 without dementia and their five-year risk of developing AD dementia. A+ prevalence was 21.4% (95% CI: 18.4–24.7) in French adults aged 65–85 without dementia i.e. approximately 2.5 million individuals, reaching 27.5% in the 80–85 age group. Over five years of follow-up, the cumulative incidence of AD dementia was 22.7% among A+ individuals, 8.0% among cognitively normal A+ adults and 62.3% among those with mild cognitive impairment. While A+ is common in older adults without dementia, most do not develop dementia within five years. Defining AD by A+ could substantially increase diagnoses, raising major public health, ethical, and health system challenges, especially as new anti-amyloid therapies emerge.

Background:White matter hyperintensities (WMH) are prevalent in dementia, but lesion volume does not capture their microstructural heterogeneity. The T1-weighted to fluid-attenuated inversion recovery (T1w/T2w-FLAIR) ratio is sensitive to myelin, gliosis, and tissue water. We tested whether lesion-specific T1w/T2w-FLAIR ratio, referenced to each participanťs normal-appearing white matter (NAWM), differs by diagnosis and reflects distinct amyloid and vascular mechanisms in Alzheimer's disease (AD) and vascular dementia (VD). Methods:We analyzed 576 participants from the multicentre BICWALZS cohort (seven South Korean sites), spanning subjective cognitive impairment (SCI, n=71), mild cognitive impairment (n=270), AD (n=125) and VD (n=88). WMH T1w/T2w-FLAIR ratio was regressed on NAWM ratio, yielding standardized residuals as the outcome. Regression and mediation models tested diagnosis, plasma biomarkers, APOE genotype, amyloid PET and vascular risk burden, adjusting for age, sex, education and site. We conducted regression and mediation analyses after multiple imputation for missing variables. We adjusted for hierarchical models using Bonferroni correction. We tested for insensitivity to site effects by applying ComBat harmonization. Results:Older age, AD, VD, and high vascular risk burden were associated with higher residualized T1w/T2w-FLAIR ratios relative to SCI. Lower plasma amyloid-beta 42 (greater amyloid burden) was associated with lower T1w/T2w-FLAIR ratios. Greater vascular burden was associated with greater T1w/T2w-FLAIR ratios, which partially mediated the VD association with T1w/T2w-FLAIR. Lower amyloid-beta 42 (greater amyloid) was associated with lower T1w/T2w-FLAIR, which partially mediated the effect between AD and T1w/T2w-FLAIR ratio. Findings were robust to harmonization. Conclusions:Residualized WMH T1w/T2w-FLAIR ratio captures lesion-specific microstructural variation missed by volumetric measures, consistent with vascular-gliotic injury in VD and coexisting amyloid-linked demyelination in AD. Limitations include the cross-sectional design, no cognitively normal comparison group, and a predominantly Korean sample.

This study aims to determine if the six different types of communication (Directive, Imaginative, Reflective, Persuasive, Harmonizing, Promoting), as presented in the Process Communication Model, correlate with a respective neural pathway. Participants were 30 medical students with no past medical history. They underwent functional magnetic resonance imaging (fMRI) while watching videos typical of each communication type. By comparing each of the six experimental conditions with all the other ones, common activations were detected in the core memory network. Assertive communication styles (Directive, Imaginative) generated activations in conflict detection and resolution related areas, with a predominance in the frontal lobe. Emotive communication (Harmonizing, Promoting) highlighted activations associated with the interpretation of social and emotional cues, with a temporo-occipital predominance. There were no significant activations for the Reflective and Persuasive channel, the two channels that were most coherent with the subjects’ base patterns and communication. This study indicated that out of the six communication types that were analyzed, four have a specific and congruous underlying cerebral process. This shows that neural response patterns vary across different communication styles, reflecting differences in cognitive and emotional processing.

OBJECTIVES:The ASAP study investigated whether amyloid load in the brain would be associated with poor antidepressant response in the short term (8 weeks) and worse clinical outcomes (remission status) in the long term (2 years). METHODS:Nondemented older adults with non-treatment-resistant depression were enrolled in an 8-week observational study to assess the relationship between amyloid load and antidepressant response and subsequently followed for 2 years. Amyloid load was measured using 18F-Florbetapir Positron Emission Tomography scans, and treatment response was evaluated using the Montgomery-Åsberg Depression Rating Scale. The primary analysis compared amyloid load in responders versus nonresponders at week 8 and in remitters versus non-remitters at year 1 and year 2, employing logistic regressions controlled for potential confounders. RESULTS:A total of 73 (among which 56% were responders and 30% were remitters), 63 (48% remitters) and 56 (54% remitters) participants were included in the analysis at week 8, year 1 and year 2, respectively. We found no significant association between amyloid load and treatment response at week 8. However, remission status at year 2 was positively associated with higher total amyloid load at baseline, independent of confounders (OR = 1.28, 95% CI [1.02-1.60]). CONCLUSIONS:In this observational cohort of nondemented depressed older adults, amyloid load does not appear to modify response status in the short term. Conversely, greater amyloid load was associated with better clinical outcomes in the long term. Amyloid may influence the long-term course of depressive symptoms by altering the serotoninergic system and/or modifying the clinical presentation of depression.

Initially restricted to the absence of negative emotion and respect for the needs of animals, animal welfare is defined as resulting from a positive mental state. This paradigm shift has placed mental states at the centre of animal welfare research. However, it is still difficult to understand and assess them, two objectives that we aim to achieve in this article. After mentioning a few historical and scientific elements that we consider fundamental, we propose defining mental states as all the processes involved in affective states, social cognition, physical cognition, and embodied cognition. This definition is consistent with the definition and methods used to assess animal welfare, which initially focused on affective states such as emotions. We will review several experimental approaches to understanding the affective states of farm animals and some approaches used to assess them in livestock farming. To access other mental states such as the different forms of cognition, we propose to explore the approaches used to diagnose and manage the mental health of animals and humans. In particular, we are interested in the Research Domain of Criteria (RDoC) project, which provides a relevant framework for investigating and assessing the mental states of animals. We will discuss its benefits and look ahead to the implementation of such a project to explore the biological substrates of mental states, identify new indicators of welfare, and initiate an approach integrating both welfare and health.

Introduction Mild worry is a relatively common, spontaneous and evolutionary adaptative phenomenon. By contrast, severe, pathologic worry is defined as a complex affective and cognitive process, negative-affect laden and relatively uncontrollable. Severe worry is frequently encountered transdiagnostic symptom in late-life mood and anxiety disorders. We have previously mapped neural correlates of severe, pathological worry by using functional magnetic resonance imaging (fMRI). However, much of this work has focused on traditional statistical approaches that can miss the inherent fluctuations of worry-related mental states. In this analysis, we used a long short-term memory (LSTM) approach, a type of deep recurrent neural network, to predict worry-related mental states using regional timeseries brain activity. Methods We recruited older adults into two studies using 3T MRI (FINA, n=116, R01MH108509) and 7T (RAW, n=88, R01MH108509, 06-07) who were recruited along a spectrum of worry. Through a clinical interview, we identified participant-specific worry induction and reappraisal statements. These were shown to the participants (along with neutral statements) in a block design fMRI task. We trained the model using the FINA dataset, which we divided into training (80%) and validation (20%). The RAW dataset was retained as an independent test set. Data were preprocessed and normalized in MNI space. We extracted fMRI timeseries for 481 cortical, subcortical, and cerebellar regions, which were Z-scored. We trained the model to predict the convolved blocks of worry, reappraisal, and neutral conditions. The model is composed of LSTM blocks with residual connections. We used a bidirectional LSTM with 2 LSTM layers, 20 seconds sequence length, MAE loss, 32 samples batch size, trained with an AdamW optimizer over 250 epochs. We conducted a Bayesian optimization procedure. Best MAE were computed by 0.1113 using validation data. We used SHAP scores to understand what regions were most important to predict worry states. Results We found that we were able to accurately predict worry, reappraisal, and neutral states with validation AUC of 0.82, 0.70, and 0.91, respectively. This prediction was reliable in the independent test set with AUC of 0.71, 0.60, and 0.77, respectively. The model was best at predicting states when the reported worry rating was concordant with the block (e.g., worry blocks with high worry and neutral blocks with low worry). The following networks were most important (in order) for predicting worry: dorsal attention, anterior hippocampus, cerebellum, left executive control and basal ganglia networks compared to neutral: supplementary motor, motor, left executive control, posterior default mode and secondary visual networks. Conclusions We were able to accurately predict worry-related mental states in older adults using an LSTM and identified brain networks that predicted these states. Validated on larger cohorts, this model may be used to identify natural worry-related mental states occurring during resting states, and consequently may serve as a neural marker of treatment response for severe worry.

Understanding the pulsing dynamics of tissue and fluids in the intracranial environment is an evolving research theme aimed at gaining new insights into brain physiology and disease progression. This article provides an overview of related research in magnetic resonance imaging, ultrasound medical diagnostics and mathematical modelling of biological tissues and fluids. It highlights recent developments, illustrates current research goals and emphasizes the importance of collaboration between these fields.

Excessive brain tissue pulsations (BTP), measured by ultrasound, have been associated with depression and are hypothesized to contribute to brain damage in this population at risk for cerebrovascular lesions. However, previous research has been limited by small sample sizes. To address this issue, our study pooled data from three separate investigations, resulting in the largest cohort of depressed participants with BTP measurements to date. We analysed 123 participants (74 individuals with depression and 49 healthy controls) using ultrasound tissue pulsatility imaging (TPI) to assess resting BTP. Results showed that both MeanBTP and MaxBTP were significantly associated with depression, as determined by multiple linear regression models that included age, sex and blood pressure as covariates. Additionally, we found that age, sex and diastolic blood pressure were significant predictors of BTP. Specifically, BTP decreased with age, was higher in men, and was more strongly predicted by diastolic blood pressure than by systolic blood pressure. In this large cohort, we replicated the association between depression and increased BTP, supporting the notion that elevated BTP may be a potential mechanism underlying brain damage over time. Our findings suggest that TPI could serve as a valuable surrogate marker for brain health in clinical practice.

Late-life depression (LLD) is both common and disabling and doubles the risk of dementia onset. Apathy might constitute an additional risk of cognitive decline but clear understanding of its pathophysiology is lacking. While white matter (WM) alterations have been assessed using diffusion tensor imaging (DTI), this model cannot accurately represent WM microstructure. We hypothesized that a more complex multi-compartment model would provide new biomarkers of LLD and apathy. Fifty-six individuals (LLD n = 35, 26 females, 75.2 ± 6.4 years, apathy evaluation scale scores (41.8 ± 8.7) and Healthy controls, n = 21, 16 females, 74.7 ± 5.2 years) were included. In this article, a tract-based approach was conducted to investigate novel diffusion model biomarkers of LLD and apathy by interpolating microstructural metrics directly along the fiber bundle. We performed multivariate statistical analysis, combined with principal component analysis for dimensional data reduction. We then tested the utility of our framework by demonstrating classically reported from the literature modifications in LDD while reporting new results of biological-basis of apathy in LLD. Finally, we aimed to investigate the relationship between apathy and microstructure in different fiber bundles. Our study suggests that new fiber bundles, such as the striato-premotor tracts, may be involved in LLD and apathy, which bring new light of apathy mechanisms in major depression. We also identified statistical changes in diffusion MRI metrics in 5 different tracts, previously reported in major cognitive disorders dementia, suggesting that these alterations among these tracts are both involved in motivation and cognition and might explain how apathy is a prodromal phase of degenerative disorders.

Objective: We sought to examine the association between chronic Benzodiazepine (BZD) use and brain metabolism obtained from 2-deoxy-2-fluoro-D-glucose (FDG) positron emission tomography (PET) in the MEMENTO clinical cohort of nondemented older adults with an isolated memory complaint or mild cognitive impairment at baseline. Methods: Our analysis focused on 3 levels: (1) the global mean brain standardized uptake value (SUVR), (2) the Alzheimer's disease (AD)-specific regions of interest (ROIs), and (3) the ratio of total SUVR on the brain and different anatomical ROIs. Cerebral metabolism was obtained from 2-deoxy-2-fluoro-D-glucose-FDG-PET and compared between chronic BZD users and nonusers using multiple linear regressions adjusted for age, sex, education, APOE e 4 copy number, cognitive and neuropsychiatric assessments, history of major depressive episodes and antidepressant use. Results: We found that the SUVR was significantly higher in chronic BZD users (n = 192) than in nonusers (n = 1,122) in the whole brain (beta = 0.03; p = 0.038) and in the right amygdala (beta = 0.32; p = 0.012). Trends were observed for the half-lives of BZDs (short- and long -acting BZDs) (p = 0.051) and Z -drug hypnotic treatments (p = 0.060) on the SUVR of the right amygdala. We found no significant association in the other ROIs. Conclusion: Our study is the first to find a greater global metabolism in chronic BZD users and a specific greater metabolism in the right amygdala. Because the acute administration of BZDs tends to reduce brain metabolism, these findings may correspond to a compensatory mechanism while the brain adapts with global metabolism upregulation, with a specific focus on the right amygdala.

Training novice ophthalmology residents on the EyeSi® simulator increases cataract surgery safety. However, there is no consensus regarding how much training residents should perform before their first time on patients. We evaluated the French national training program through the analysis of the learning curves of novice residents. This prospective multicentric pedagogic study was conducted with French novice residents. Each resident completed the recommended four two-hour training sessions and performed a standardized assessment simulating standard cataract surgery before the first session (A0), at the end of the first (A1), second (A2), third (A3) and fourth (A4) sessions. For each surgical step of each attempt, the following data were collected: score, odometer, completion time, posterior capsular rupture and cumulative energy delivered (ultrasounds) during phacoemulsification. A performance threshold was set at a score of 80/100 for each surgical step, 400/500 for the overall procedure. Only descriptive statistics were employed. Sixteen newly nominated ophthalmology residents were included. Median score progressively increased from 95 [IQR 53; 147]) at A0 to 425 [IQR 411; 451] at A4. Despite a significant progression, the “emulsification” step had the lowest A4 scores 86 [IQR 60; 94] without reduction in completion time, odometer or ultrasounds delivered. The rate of posterior capsular rupture decreased linearly from 75

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.