Working alliance in treating staff and patients with Schizophrenia Spectrum Disorder living in Residential Facilities.

OBJECTIVES: Working Alliance (WA) is important in the care of patients with Schizophrenia Spectrum Disorders (SSD). This study aims to determine which sociodemographic and clinical factors are associated with WA, as assessed by patients and staff members in Residential Facilities (RFs), and may predict WA dyads' discrepancies. METHODS: Three hundred and three SSD patients and 165 healthcare workers were recruited from 98 RFs and characterized for sociodemographic features. WA was rated by the Working Alliance Inventory (WAI) for patients (WAI-P) and staff members (WAI-T). SSD patients were assessed for the severity of psychopathology and psychosocial functioning. RESULTS: Pearson's correlation revealed a positive correlation (ρ = .314; p < .001) between WAI-P and WAI-T ratings. Linear regression showed that patients with higher education reported lower WAI-P ratings (ß = -.50, p = .044), while not being engaged in work or study was associated with lower WAI-T scores (ß = -4.17, p = .015). A shorter lifetime hospitalization was associated with higher WAI-P ratings (ß = 5.90, p = .008), while higher psychopathology severity negatively predicted WAI-T (ß = -.10, p = .002) and WAI-P ratings (ß = -.19, p < .001). Better functioning level positively foresaw WAI-T (ß = .14, p < .001) and WAI-P ratings (ß = .12, p < .001). Regarding discrepancies, staff members' age was associated with higher dyads discrepancy in Total scale and Agreement subscale scores, which were also associated with more severe negative symptoms, while patients' age was negatively correlated to Relationship subscale discrepancy. CONCLUSIONS: This study provides insight into the factors that influence WA in SSD patients and health workers in RFs. The findings address interventions to improve WA and ultimately patient outcomes.

Time will tell: Associations between unbalanced time perspectives and symptom severity in individuals with schizophrenia spectrum disorders.

Patients with schizophrenia spectrum disorder (SSD) experience disrupted temporality on the immediate timescale. However, insufficient information is available for longer time frames, and the interaction of temporal perspectives with the clinical manifestations of SSD is unknown. We explored the association between unbalanced time perspectives and symptom severity. Thirty-seven Italian mental health services participating in the DiAPAson project recruited 620 patients with DSM-5 SSD (68 % males, mean age = 41.3 ± 9.5 years). Time perspective biases were measured using the Deviation from the Balanced Time Perspective-revisited (DBTP-r) indicator, based on Zimbardo Time Perspective Inventory (ZTPI) scores. Psychiatric symptoms were assessed using the Brief Psychiatric Rating Scale (BPRS) and Brief Negative Symptoms Scale (BNSS). Preliminary analyses examined the associations between ZTPI/DBTP-r and BPRS/BNSS total scores. In secondary analyses, we first tested the associations between the ZTPI/DBTP-r and BPRS/BNSS subscales and then compared ZTPI differences between patients with and without hallucinations, delusions, and conceptual disorganisation. Statistical significance was set at Holm-Bonferroni corrected p < 0.05. Low-to-moderate positive correlations were found between the DBTP-r and BPRS/BNSS total scores (r = 0.29/0.22). The strongest associations were between DBTP-r/ZTPI_Past-Negative and anxiety/depression (r = 0.34/0.36), followed by DBTP-r/ZTPI_Present-Fatalistic with thought disturbances (r = 0.22/0.20). DBTP-r was associated with BNSS anhedonia and avolition (r = 0.21/0.24). DBTP-r was higher in patients with hallucinations (ES = 0.391) and conceptual disorganisation (ES = 0.397) than in those without these symptoms. Unbalanced time perspective was positively associated with the severity of primary and secondary SSD features. These findings provide a rationale for empirical tests focused on balancing time perspectives in patients with SSD.

Ecological monitoring of emotional intensity, variability, and instability in individuals with schizophrenia spectrum disorders: Results of a multicentre study.

BACKGROUND: Evaluating emotional experiences in the life of people with Schizophrenia Spectrum Disorder (SSD) is fundamental for developing interventions aimed at promoting well-being in specific times and contexts. However, little is known about emotional variability in this population. In DiAPAson project, we evaluated between- and within-person differences in emotional intensity, variability, and instability between people with SSD and healthy controls, and the association with psychiatric severity and levels of functioning. METHODS: 102 individuals diagnosed with SSD (57 residential patients, 46 outpatients) and 112 healthy controls were thoroughly evaluated. Daily emotions were prospectively assessed with Experience Sampling Method eight times a day for a week. Statistical analyses included ANOVA, correlations, and generalized linear models. RESULTS: Participants with SSD, and especially residential patients, had a higher intensity of negative emotions when compared to controls. Moreover, all people with SSD reported a greater between-person-variability of both positive and negative emotions and greater intra-variability of negative emotions than healthy controls. In addition, the emotion variability in people with SSD does not follow a linear or quadratic trend but is more "chaotic" if compared to controls. CONCLUSIONS: Adequate assessments of positive and negative emotional experiences and their time course in people with SSD can assist mental health professionals with well-being assessment, implementing targeted interventions through the identification of patterns, triggers, and potential predictors of emotional states.

Daily time use among individuals with schizophrenia spectrum disorders and unaffected controls: Results from the DiAPAson multicentric project.

OBJECTIVE: In the framework of daily time use, physical activity, and interpersonal relationships in patients with schizophrenia project, we aimed to investigate (a) within and between-group differences in daily time use of individuals with schizophrenia spectrum disorders (SSDs) and unaffected controls, stratifying them by age, sex, and employment status; (b) the associations between daily time use, the severity of psychiatric symptoms, and psychosocial functioning amongst those with SSD. METHOD: From October 2020 to October 2021, 306 outpatients and 312 individuals living in residential facilities (RFs) with SSD were recruited from 37 centers across Italy and compared on a measure of daily time use with 113 people unaffected by mental health problems. Statistical analyses included chi-squared tests, analysis of variance tests, t tests, Pearson's correlations, and nonparametric corresponding tests. RESULTS: Individuals with SSD spent significantly more time in sedentary activities, leisure, and religious activities than unaffected controls, independent of age, sex, and employment status. Unaffected controls and outpatients spent more time engaged in productive activities than patients in RFs. Among the latter group, time spent in productive activities decreased significantly after 45 years of age, while time spent in self-care activities increased. Spending time engaged in sedentary activities was associated with greater severity of psychiatric symptoms and lower levels of functioning. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: This study provides a deep understanding of how individuals with SSD spend their time and how this is associated with the severity of their mental health problems. These findings highlight the need for proactive rehabilitation programs to promote productive occupation and social inclusion of people with SSD. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Comparing Adherence to the Experience Sampling Method Among Patients With Schizophrenia Spectrum Disorder and Unaffected Individuals: Observational Study From the Multicentric DiAPAson Project.

BACKGROUND: The Experience Sampling Method (ESM) is a valid method of remotely recording activities and mood, but the predictors of adherence to ESM in patients with Schizophrenia Spectrum Disorder (SSD) are not known. Studies on adherence are significant as they highlight the strengths and weaknesses of ESM-based study designs and allow the development of recommendations and practical guidelines for implementing future studies or treatment plans. OBJECTIVE: The aim of this study was to compare the adherence to ESM in patients with SSD and unaffected control individuals, investigate their patterns, and report the predictors of adherence. METHODS: In total, 131 patients with SSD (74 in residential facilities and 57 outpatients) and 115 unaffected control individuals were recruited at 10 different centers in Italy as part of the DiAPAson project. Demographic information, symptom severity, disability level, and level of function were recorded for the clinical sample. Participants were evaluated for daily time use and mood through a smartphone-based ESM 8 times a day for 7 consecutive days. Adherence was measured by the response rate to ESM notifications. Results were analyzed using the chi-square test, ANOVA, Kruskal-Wallis test, and Friedman test, and a logistic regression model. RESULTS: The overall adherence rate in this study was 50% for residents, 59% for outpatients, and 78% for unaffected control individuals. Indeed, patients with SSD had a lower rate of adherence to ESM than the unaffected control group (P≤.001), independent of time slot, day of monitoring, or day of the week. No differences in adherence rates between weekdays and weekends were found among the 3 groups. The adherence rate was the lowest in the late evening time slot (8 PM to 12 AM) and days 6-7 of the study for both patients with SSD and unaffected control individuals. The adherence rate among patients with SSD was not predicted by sociodemographic characteristics, cognitive function, or other clinical features. A higher adherence rate (ie, ≥70%) among patients with SSD was predicted by higher collaboration skills (odds ratio [OR] 2.952; P=.046) and self-esteem (OR 3.394; P=.03), and lower positive symptom severity (OR 0.835; P=.04). CONCLUSIONS: Adherence to ESM prompts for both patients with SSD and unaffected control individuals decreased during late evening and after 6 days of monitoring. Higher self-esteem and collaboration skills predicted higher adherence to ESM among patients with SSD, while higher positive symptom scores predicted lower adherence rates. This study provides important information to guide protocols for future studies using ESM. Future clinical or research studies should set ESM monitoring to waking hours, limit the number of days of monitoring, select patients with more collaborative skills and avoid those with marked positive symptoms, provide intensive training sessions, and improve participants' self-confidence with technologies. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s12888-020-02588-y.

Shared and distinct abnormalities in sleep-wake patterns and their relationship with the negative symptoms of Schizophrenia Spectrum Disorder patients.

Sleep and rest-activity-rhythm (RAR) abnormalities are commonly reported in schizophrenia spectrum disorder (SSD) patients. However, an in-depth characterization of sleep/RAR alterations in SSD, including patients in different treatment settings, and the relationship between these alterations and SSD clinical features (e.g., negative symptoms) is lacking. SSD (N = 137 altogether, N = 79 residential and N = 58 outpatients) and healthy control (HC) subjects (N = 113) were recruited for the DiAPAson project. Participants wore an ActiGraph for seven consecutive days to monitor habitual sleep-RAR patterns. Sleep/rest duration, activity (i.e., M10, calculated on the 10 most active hours), rhythm fragmentation within days (i.e., intra-daily variability, IV; beta, steepness of rest-active changes), and rhythm regularity across days (i.e., inter-daily stability, IS) were computed in each study participant. Negative symptoms were assessed in SSD patients with the Brief Negative Symptom Scale (BNSS). Both SSD groups showed lower M10 and longer sleep/rest duration vs. HC, while only residential patients had more fragmented and irregular rhythms than HC. Compared to outpatients, residential patients had lower M10 and higher beta, IV and IS. Furthermore, residential patients had worse BNSS scores relative to outpatients, and higher IS contributed to between-group differences in BNSS score severity. Altogether, residentials and outpatients SSD had both shared and unique abnormalities in Sleep/RAR measures vs. HC and relative to one another, which also contributed to the patients' negative symptom severity. Future work will help establish whether improving some of these measures may ameliorate the quality of life and clinical symptoms of SSD patients.

Needs for care of residents with schizophrenia spectrum disorders and association with daily activities and mood monitored with experience sampling method: the DIAPASON study.

AIMS: Care needs represent an essential paradigm in planning residential facility (RF) interventions. However, possible disagreements between users and staff are critical issues in service delivery. The Experience Sampling Method (ESM) tracks experiences in the real world and real time. This study aimed to evaluate the care needs of patients with schizophrenia spectrum disorder (SSD) in RFs and its association with daily activities and mood monitored using the ESM. METHODS: As part of the DIAPASON project, 313 residents with SSD were recruited from 99 Italian RFs. Sociodemographic and clinical characteristics were recorded. Care needs, the severity of symptomatology and negative symptoms were assessed. Fifty-six residents were also assessed for 7 consecutive days using the mobile ESM. Descriptive, agreement, predictor and moderator analyses were conducted. RESULTS: The staff rated a higher number of total and met needs than service users (p < 0.001). Only a slight agreement between users and staff on unmet needs was found in self-care (k = 0.106) and information (k = 0.100) needs, while a moderate agreement was found in accommodation (k = 0.484), food (k = 0.406), childcare (k = 0.530), physical health (k = 0.470), telephone (k = 0.458) and transport (k = 0.425) needs. Older age (-0.15; p < 0.01), longer SSD diagnosis (-0.16; p < 0.01), higher collaboration (-0.16; p < 0.01) and lower symptomatology (-0.16; p < 0.01) decreased the number of unmet needs, while being a female (0.27; p < 0.05) and a shorter length of stay in an RF (0.54; p < 0.001) increased the number of unmet needs. A higher number of unmet needs was associated with a lower amount of time spent in leisure activities or reporting a positive mood: on the contrary, more unmet needs were associated with a greater amount of time spent in religious or non-productive activities. The associations between unmet needs rated by staff and users and momentary mood as assessed using the ESM were not moderated by the severity of symptomatology. CONCLUSIONS: Although care needs are fundamental in planning residential activities aimed at recovery-oriented rehabilitation, RF interventions did not fully meet users' needs, and some disagreements on unmet needs between users and staff were reported. Further efforts are necessary to overcome Italian RF limits in delivering rehabilitative interventions defined by real users' needs to facilitate users' productivity and progress towards personal recovery.

Time perspective affects daily time use and daily functioning in individuals with Schizophrenia Spectrum Disorders: Results from the multicentric DiAPAson study.

Time perspective (TP) influences various aspects of human life. We aimed to explore the associations between TP, daily time use, and levels of functioning among 620 patients (313 residential patients and 307 outpatients) with a diagnosis of Schizophrenia Spectrum Disorders (SSD) recruited from 37 different centres in Italy. The Brief Psychiatric Rating Scale and the Specific Levels of Functioning (SLOF) were used to assess psychiatric symptoms severity and levels of functioning. Daily time use was assessed using an ad hoc paper and pencil Time Use Survey. The Zimbardo Time Perspective Inventory (ZTPI) was used to assess TP. Deviation from Balanced Time Perspective (DBTP-r) was used as an indicator of temporal imbalance. Results showed that the amount of time spent on non-productive activities (NPA) was positively predicted by DBTP-r (Exp(ß): 1.36; p .003), and negatively predicted by the Past-Positive (Exp(ß): 0.80; p .022), Present-Hedonistic (Exp(ß): 0.77; p .008), and Future (Exp(ß): 0.78; p .012) subscales. DBTP-r significantly negatively predicted SLOF outcomes (p .002), and daily time use, in particular the amount of time spent in NPA and Productive Activities (PA), mediated their association. Results suggested that rehabilitative programs for individuals with SSD should consider fostering a balanced time perspective to reduce inactivity, increase physical activity, and promote healthy daily functioning and autonomy.

Patterns of antipsychotic prescription and accelerometer-based physical activity levels in people with schizophrenia spectrum disorders: a multicenter, prospective study.

Antipsychotic polypharmacy (APP) in patients with schizophrenia spectrum disorders (SSDs) is usually not recommended, though it is very common in clinical practice. Both APP and SSDs have been linked to worse health outcomes and decreased levels of physical activity, which in turn is an important risk factor for cardiovascular diseases and premature mortality. This real-world, observational study aimed to investigate antipsychotic prescribing patterns and physical activity in residential patients and outpatients with SSDs. A total of 620 patients and 114 healthy controls were recruited in 37 centers across Italy. Each participant underwent a comprehensive sociodemographic and clinical evaluation. Physical activity was monitored for seven consecutive days through accelerometer-based biosensors. High rates of APP were found in all patients, with residential patients receiving more APP than outpatients, probably because of greater psychopathological severity. Physical activity was lower in patients compared to controls. However, patients on APP showed trends of reduced sedentariness and higher levels of light physical activity than those in monopharmacy. Rehabilitation efforts in psychiatric residential treatment facilities were likely to result in improved physical activity performances in residential patients. Our findings may have important public health implications, as they indicate the importance of reducing APP and encouraging physical activity.

Quality of residential facilities in Italy: satisfaction and quality of life of residents with schizophrenia spectrum disorders.

BACKGROUND: Recovery and human rights promotion for people with Schizophrenia Spectrum Disorders (SSDs) is fundamental to provide good care in Residential Facilities (RFs). However, there is a concern about rehabilitation ethos in RFs. This study aimed to investigate the care quality of Italian RFs, the quality of life (QoL) and care experience of residents with SSD. METHODS: Fourty-eight RFs were assessed using a quality assessment tool (QuIRC-SA) and 161 residents with SSD were enrolled. Seventeen RFs provided high intensity rehabilitation (SRP1), 15 medium intensity (SRP2), and 16 medium-low level support (SRP3). Staff-rated tools measured psychiatric symptoms and psychosocial functioning; user-rated tools assessed QoL and satisfaction with services. RFs comparisons were made using ANOVA and Chi-squared. RESULTS: Over two-thirds patients (41.5 y.o., SD 9.7) were male. Seventy-six were recruited from SRP1 services, 48 from SRP2, and 27 from SRP3. The lowest QuIRC-SA scoring was Recovery Based Practice (45.8%), and the highest was promotion of Human Rights (58.4%). SRP2 had the lowest QuIRC-SA ratings and SRP3 the highest. Residents had similar psychopathology (p = 0.140) and functioning (p = 0.537). SRP3 residents were more employed (18.9%) than SRP1 (7.9%) or SRP2 (2.2%) ones, and had less severe negative symptoms (p = 0.016) and better QoL (p = 0.020) than SRP2 residents. There were no differences in the RF therapeutic milieu and their satisfaction with care. CONCLUSIONS: Residents of the lowest supported RFs in Italy had less severe negative symptoms, better QoL and more employment than others. The lowest ratings for Recovery Based Practice across all RFs suggest more work is needed to improve recovery.

Assessing adherence to and usability of Experience Sampling Method (ESM) and actigraph in patients with Schizophrenia Spectrum Disorder: A mixed-method study.

The application of innovative technologies in psychiatry is promising, but the debate about its feasibility is not settled. Our aim was to investigate and compare adherence to and usability of 7-day monitoring with an Experience Sampling Method (ESM) and Actigraphy among a sample of individuals with a diagnosis of Schizophrenia Spectrum Disorders (SSD) and paired healthy controls. Twenty-two patients living in residential facilities (RFs), 20 outpatients and 26 controls were enrolled in this study as part of the DiAPAson project. Participants wore an actigraph and were evaluated for daily time use and mood with a smartphone-based ESM. Then, they completed questionnaires to assess the usability of the devices and were interviewed. Adherence was assessed as the percentage of time spent wearing actigraph and answering ESM notifications. Residential patients, compared to controls, showed significantly higher usability of the actigraph and lower adherence to both the actigraph and ESM. From the qualitative interviews, four high-order themes emerged: effects of monitoring, adherence and usability, emotions and mental states, and advice. Findings are promising for the application of these methodologies in such populations. The role of multidisciplinary staff in RFs is crucial for guaranteeing the realization of such projects.

DAily time use, Physical Activity, quality of care and interpersonal relationships in patients with Schizophrenia spectrum disorders (DiAPASon): an Italian multicentre study.

BACKGROUND: Schizophrenia spectrum disorders (SSD) are ranked among the leading causes of disabilities worldwide. Many people with SSD spend most of their daily time being inactive, and this is related to the severity of negative symptoms. Here, we present the 3-year DiAPAson project aimed at (1) evaluating the daily time use among patients with SSD living in Residential Facilities (RFs) compared to outpatients with SSD and to the general population (Study 1); (2) evaluating the quality of staff-patient relationships, its association with specific patient outcomes and the quality of care provided in RFs (Study 2); and (3) assessing daily activity patterns in residential patients, outpatients with SSD and healthy controls using real-time methodologies (Study 3). METHODS: Study 1 will include 300 patients with SSD living in RFs and 300 outpatients; data obtained in these clinical populations will be compared with normative data obtained by the National Institute of Statistics (ISTAT) in the national survey on daily time use. Time use assessments will consist of daily diaries asking participants to retrospectively report time spent in different activities. In Study 2, a series of questionnaires will be administered to 300 residential patients (recruited for Study 1) to evaluate the quality of care and staff-patient relationships, level of well-being and burnout of RFs' staff, and quality of RFs using a European standardized questionnaire (QuIRC-SA). In Study 3, the daily time use will be evaluated in a subgroup of 50 residential patients, 50 outpatients and 50 healthy controls using the Experience Sampling Method approach (participants will complete a brief questionnaire -about time use, mood and perceived energy- on a smartphone 8 times a day for 1 week) to compare retrospective and real-time reports. Moreover, their level of physical activity, sleep patterns, and energy expenditure will be monitored through a multi-sensor device. DISCUSSION: This project is highly innovative because it combines different types of assessments (i.e., retrospective and real-time reports; multi-sensor monitoring) to trace an accurate picture of daily time use and levels of physical activity that will help identify the best therapeutic options promoting daily activities and physical exercise in patients with SSD. TRIAL REGISTRATION: ISRCTN registry ID ISRCTN21141466.

I See Your Effort: Force-Related BOLD Effects in an Extended Action Execution-Observation Network Involving the Cerebellum.

Action observation (AO) is crucial for motor planning, imitation learning, and social interaction, but it is not clear whether and how an action execution-observation network (AEON) processes the effort of others engaged in performing actions. In this functional magnetic resonance imaging (fMRI) study, we used a "squeeze ball" task involving different grip forces to investigate whether AEON activation showed similar patterns when executing the task or observing others performing it. Both in action execution, AE (subjects performed the visuomotor task) and action observation, AO (subjects watched a video of the task being performed by someone else), the fMRI signal was detected in cerebral and cerebellar regions. These responses showed various relationships with force mapping onto specific areas of the sensorimotor and cognitive systems. Conjunction analysis of AE and AO was repeated for the "0th" order and linear and nonlinear responses, and revealed multiple AEON nodes remapping the detection of actions, and also effort, of another person onto the observer's own cerebrocerebellar system. This result implies that the AEON exploits the cerebellum, which is known to process sensorimotor predictions and simulations, performing an internal assessment of forces and integrating information into high-level schemes, providing a crucial substrate for action imitation.

Prominent Changes in Cerebro-Cerebellar Functional Connectivity During Continuous Cognitive Processing.

While task-dependent responses of specific brain areas during cognitive tasks are well established, much less is known about the changes occurring in resting state networks (RSNs) in relation to continuous cognitive processing. In particular, the functional involvement of cerebro-cerebellar loops connecting the posterior cerebellum to associative cortices, remains unclear. In this study, 22 healthy volunteers underwent a multi-session functional magnetic resonance imaging (fMRI) protocol composed of four consecutive 8-min resting state fMRI (rs-fMRI) scans. After a first control scan, participants listened to a narrated story for the entire duration of the second rs-fMRI scan; two further rs-fMRI scans followed the end of story listening. The story plot was purposely designed to stimulate specific cognitive processes that are known to involve the cerebro-cerebellar loops. Almost all of the identified 15 RSNs showed changes in functional connectivity (FC) during and for several minutes after the story. The FC changes mainly occurred in the frontal and prefrontal cortices and in the posterior cerebellum, especially in Crus I-II and lobule VI. The FC changes occurred in cerebellar clusters belonging to different RSNs, including the cerebellar network (CBLN), sensory networks (lateral visual network, LVN; medial visual network, MVN) and cognitive networks (default mode network, DMN; executive control network, ECN; right and left ventral attention networks, RVAN and LVAN; salience network, SN; language network, LN; and working memory network, WMN). Interestingly, a k-means analysis of FC changes revealed clustering of FCN, ECN, and WMN, which are all involved in working memory functions, CBLN, DMN, and SN, which play a key-role in attention switching, and RSNs involved in visual imagery. These results show that the cerebellum is deeply entrained in well-structured network clusters, which reflect multiple aspects of cognitive processing, during and beyond the conclusion of auditory stimulation.

Specific Patterns of White Matter Alterations Help Distinguishing Alzheimer's and Vascular Dementia.

Alzheimer disease (AD) and vascular dementia (VaD) together represent the majority of dementia cases. Since their neuropsychological profiles often overlap and white matter lesions are observed in elderly subjects including AD, differentiating between VaD and AD can be difficult. Characterization of these different forms of dementia would benefit by identification of quantitative imaging biomarkers specifically sensitive to AD or VaD. Parameters of microstructural abnormalities derived from diffusion tensor imaging (DTI) have been reported to be helpful in differentiating between dementias, but only few studies have used them to compare AD and VaD with a voxelwise approach. Therefore, in this study a whole brain statistical analysis was performed on DTI data of 93 subjects (31 AD, 27 VaD, and 35 healthy controls-HC) to identify specific white matter patterns of alteration in patients affected by VaD and AD with respect to HC. Parahippocampal tracts were found to be mainly affected in AD, while VaD showed more spread white matter damages associated with thalamic radiations involvement. The genu of the corpus callosum was predominantly affected in VaD, while the splenium was predominantly affected in AD revealing the existence of specific patterns of alteration useful in distinguishing between VaD and AD. Therefore, DTI parameters of these regions could be informative to understand the pathogenesis and support the etiological diagnosis of dementia. Further studies on larger cohorts of subjects, characterized for brain amyloidosis, will allow to confirm and to integrate the present findings and, furthermore, to elucidate the mechanisms of mixed dementia. These steps will be essential to translate these advances to clinical practice.

Exploring Patterns of Alteration in Alzheimer's Disease Brain Networks: A Combined Structural and Functional Connectomics Analysis.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a severe derangement of cognitive functions, primarily memory, in elderly subjects. As far as the functional impairment is concerned, growing evidence supports the "disconnection syndrome" hypothesis. Recent investigations using fMRI have revealed a generalized alteration of resting state networks (RSNs) in patients affected by AD and mild cognitive impairment (MCI). However, it was unclear whether the changes in functional connectivity were accompanied by corresponding structural network changes. In this work, we have developed a novel structural/functional connectomic approach: resting state fMRI was used to identify the functional cortical network nodes and diffusion MRI to reconstruct the fiber tracts to give a weight to internodal subcortical connections. Then, local and global efficiency were determined for different networks, exploring specific alterations of integration and segregation patterns in AD and MCI patients compared to healthy controls (HC). In the default mode network (DMN), that was the most affected, axonal loss, and reduced axonal integrity appeared to compromise both local and global efficiency along posterior-anterior connections. In the basal ganglia network (BGN), disruption of white matter integrity implied that main alterations occurred in local microstructure. In the anterior insular network (AIN), neuronal loss probably subtended a compromised communication with the insular cortex. Cognitive performance, evaluated by neuropsychological examinations, revealed a dependency on integration and segregation of brain networks. These findings are indicative of the fact that cognitive deficits in AD could be associated not only with cortical alterations (revealed by fMRI) but also with subcortical alterations (revealed by diffusion MRI) that extend beyond the areas primarily damaged by neurodegeneration, toward the support of an emerging concept of AD as a "disconnection syndrome." Since only AD but not MCI patients were characterized by a significant decrease in structural connectivity, integrated structural/functional connectomics could provide a useful tool for assessing disease progression from MCI to AD.