Clinical course of SARS-CoV-2 infection in patients with severe acquired brain injury and a disorder of consciousness: an observational study.

Purpose: SARS-CoV-2 infection can cause the coronavirus disease (COVID), ranging from flu-like symptoms to interstitial pneumonia. Mortality is high in COVID pneumonia and it is the highest among the frailest. COVID could be particularly serious in patients with severe acquired brain injury (SABI), such as those with a disorder of consciousness. We here describe a cohort of patients with a disorder of consciousness exposed to SARS-CoV-2 early after their SABI.Materials and methods: The full cohort of 11 patients with SABI hospitalized in March 2020 in the IRCCS Fondazione Don Gnocchi rehabilitation (Milan, Italy) was recruited. Participants received SARS-CoV-2 testing and different clinical and laboratory data were collected.Results: Six patients contracted SARS-CoV-2 and four of them developed the COVID. Of these, one patient had ground-glass opacities on the chest CT scan, while the remaining three developed consolidations. No patient died and the overall respiratory involvement was mild, requiring in the worst cases low-flow oxygen.Conclusions: Here we report the clinical course of a cohort of patients with SABI exposed to SARS-CoV-2. The infection spread among patients and caused COVID in some of them. Unexpectedly, COVID was moderate, caused at most mild respiratory distress and did not result in fatalities.

Misidentification Delusions: Prevalence in Different Types of Dementia and Validation of a Structured Questionnaire.

Misidentification delusions (MDs) are considered relatively rare psychopathologic phenomena that may occur within the context of psychiatric or neurological conditions. The purpose of this study was to assess the prevalence of MD in different types of dementia, correlate the presence of MD with demographic and clinical variables, and validate a specific questionnaire. We examined 146 subjects with Alzheimer disease, 21 with Lewy body dementia, 6 with frontotemporal dementia, and 13 with vascular dementia (subcortical type), who were consecutively enrolled in the study from 2 Memory Clinics. Patients had a mean age of 78.7±6.4 years and an Mini-Mental State Examination average score of 16.9±6.1. The Neuropsychiatric Inventory delusion subscale and a new Misidentification Delusion Questionnaire aimed at specific assessment of 11 delusional misidentification syndromes were administrated to the caregivers. On the basis of the Neuropsychiatric Inventory, MDs were present in 33.3% of the subjects, whereas according to the Misidentification Delusion Questionnaire they were present in 36.0% of the subjects. Specifically, 34.2% of Alzheimer disease, 52.4% of Lewy body dementia, and 46.1% of vascular dementia patients experienced at least 1 MD. None of the patients with frontotemporal dementia developed MD. The most frequent MD was house misidentification, followed by splitting of people and reduplicative paramnesia. Our self-administered questionnaire proved to be an accurate and specific tool for the detection of MD.

A digital health home intervention for people within the Alzheimer's disease continuum: results from the Ability-TelerehABILITation pilot randomized controlled trial.

PURPOSE: This study tested the efficacy of digital-health home intervention for people within the Alzheimer's disease (AD)-continuum. METHODS: Thirty people within the AD continuum were randomly assigned to a telerehabilitation (ABILITY; 6 males, Mage=78.2 ± 3.95) or treatment as usual (TAU; 8 males, Mage=77.13 ± 6.38), performing cognitive and physical activities at home for six weeks. The ABILITY intervention additionally included a digital platform enabling communication between the hospital and the patient's home. Efficiency, such as adherence, perceived fit of demands and skills, usability, and effectiveness measures, including neuropsychological level, neuropsychiatric symptoms, and autonomy in daily living, were collected before (T0), after the treatment (T1), and at the 1-year-follow-up (T2). RESULTS: The ABILITY program was efficient, with a higher adherence (81% vs. 62%), a higher perceived fit of demands and skills than TAU (p<.05), and a good level of technology usability. In terms of effectiveness, a treatment effect (ABILITY > TAU) emerged on the global cognitive level, especially in language, executive functions, and memory domains. Moreover, a treatment carry-over effect (1-year follow-up) was observed in global cognitive functions (especially language) (ABILITY > TAU), behavioral symptoms, and caregiver distress (TAU > ABILITY). CONCLUSIONS: Our preliminary findings suggest that ABILITY is a promising eHealth intervention to improve at-home treatment adherence and to preserve cognitive and behavioral abilities.

People in the Alzheimer's Disease continuum facing chronic cognitive disabilities represent an emergency for the healthcare system given the substantial need for long-term rehabilitation;This study evaluates a new model of rehabilitation in the continuity of care for people with cognitive disabilities, adopting an asynchronous approach;The asynchronous telerehabilitation model may be considered a new frontier for continuity of care, capable of answering the unmet need of scaling up rehabilitation services to the broad population.

Increased activity of Th-17 and Th-9 lymphocytes and a skewing of the post-thymic differentiation pathway are seen in Alzheimer's disease.

Inflammatory mediators are responsible for the neuroinflammation observed in Alzheimer's disease (AD), a phenomenon that might be the culprit of disease or, possibly, a reaction to pathology. To better investigate inflammation in AD we performed an extensive immunophenotypic and functional analysis of amyloid-beta (Aß) stimulated T lymphocytes in patients with a diagnosis of AD comparing data to those obtained in individuals with mild cognitive impairment (MCI) or aged-matched healthy individuals (HC). Results showed that IL-21- and IL-9-producing Aß stimulated CD4(+) T cells, as well as IL-23- and IL-6-producing monocytes and CD4(+) T cells expressing the RORγ and NFATc1 transcriptional factors (TF), were significantly increased, whereas IL-10-producing monocytes were decreased in AD. Notably, GATA-3 TF-expressing CD4(+) T lymphocytes were significantly increased in MCI alone. Analysis of the post-thymic differentiation pathway indicated that Aß specific naïve and central memory CD4(+) T lymphocytes were diminished whereas effector memory and terminally differentiated CD4(+) T lymphocytes were increased in AD and MCI compared to HC. Data herein indicate that cytokines (IL-21, IL-6, IL-23) and TF (RORγ) involved in the differentiation of Th-17 cells), as well as cytokines (IL-21, IL-22) generated by such cells, and IL-9, produced by Th-9 cells, are significantly increased in AD. This is accompanied by a shift of post-thymic differentiation pathways favoring the accumulation of differentiated, effector T lymphocytes. These data shed light on the nature of AD-associated neuroinflammation. A better understanding of the complexity of this phenomenon could facilitate the search for novel therapeutic strategies.

Mapping levels of theory of mind in Alzheimer's disease: a preliminary study.

BACKGROUND: Research on Theory of Mind (ToM), the ability to understand behaviour based on mental state representation, has shifted towards a life span perspective in typical and atypical conditions (dementia). OBJECTIVES: The aim of this study is to investigate the presence and the features of ToM decay in early Alzheimer's disease (AD) patients compared to healthy controls adopting a neurodevelopmental stance. METHOD: Sixteen AD patients and 16 healthy controls were submitted to an increasing complexity ToM battery, tapping ToM precursors, standard first- and second-order false beliefs and advanced ToM tasks (Eyes Test and strange stories). RESULTS: The results underline a similar pattern of increasing difficulty of the tasks that explore ToM abilities in both the groups. They also confirm the presence of a strong gap in performance between the CTR and the AD groups, especially in the more complex ToM tasks, whereas there is no significant difference between the two groups in the first level of reasoning about beliefs (first-order false belief). The impairment in specific cognitive functions (i.e. memory and executive functions) seems to correlate with the decline in the most complex mentalistic abilities. CONCLUSION: This study identifies a specific pattern of deterioration in ToM abilities in AD patients, following backwards developmental steps typical of the acquisition of mentalizing abilities, where the most complex ToM levels are impaired, whereas the intermediate and the simplest ones are preserved.

Neuroimaging Biomarkers Predicting the Efficacy of Multimodal Rehabilitative Intervention in the Alzheimer's Dementia Continuum Pathology.

In this work we aimed to identify neural predictors of the efficacy of multimodal rehabilitative interventions in AD-continuum patients in the attempt to identify ideal candidates to improve the treatment outcome. Subjects in the AD continuum who participated in a multimodal rehabilitative treatment were included in the analysis [n = 82, 38 Males, mean age = 76 ± 5.30, mean education years = 9.09 ± 3.81, Mini Mental State Examination (MMSE) mean score = 23.31 ± 3.81]. All subjects underwent an MRI acquisition (1.5T) at baseline (T0) and a neuropsychological evaluation before (T0) and after intervention (T1). All subjects underwent an intensive multimodal cognitive rehabilitation (8-10 weeks). The MMSE and Neuropsychiatric Inventory (NPI) scores were considered as the main cognitive and behavioral outcome measures, and Delta change scores (T1-T0) were categorized in Improved (ΔMMSE > 0; ΔNPI < 0) and Not Improved (ΔMMSE ≤ 0; ΔNPI ≥ 0). Logistic Regression (LR) and Random Forest classification models were performed including neural markers (Medial Temporal Brain; Posterior Brain (PB); Frontal Brain (FB), Subcortical Brain indexes), neuropsychological (MMSE, NPI, verbal fluencies), and demographical variables (sex, age, education) at baseline. More than 50% of patients showed a positive effect of the treatment (ΔMMSE > 0: 51%, ΔNPI < 0: 52%). LR model on ΔMMSE (Improved vs. Not Improved) indicate a predictive role for MMSE score (p = 0.003) and PB index (p = 0.005), especially the right PB (p = 0.002) at baseline. The Random Forest analysis correctly classified 77% of cognitively improved and not improved AD patients. Concerning the NPI, LR model on ΔNPI (Improved vs. Not Improved) showed a predictive role of sex (p = 0.002), NPI (p = 0.005), PB index (p = 0.006), and FB index (p = 0.039) at baseline. The Random Forest reported a classification accuracy of 86%. Our data indicate that cognitive and behavioral status alone are not sufficient to identify best responders to a multidomain rehabilitation treatment. Increased neural reserve, especially in the parietal areas, is also relevant for the compensatory mechanisms activated by rehabilitative treatment. These data are relevant to support clinical decision by identifying target patients with high probability of success after rehabilitative programs on cognitive and behavioral functioning.

EEG evidence of posterior cortical disconnection in PD and related dementias.

Electroencephalogram (EEG) reactivity to eyes opening and 12-Hz photic stimulation was investigated in 14 healthy elderly subjects, 21 parkinsonian patients (PD), 7 demented parkinsonian patients (PDD), and 10 patients with Lewy body dementia (LBD) using global field synchronization (GFS). During eyes closed Theta GFS was increased in Parkinson's disease and patients and alpha1 GFS was decreased in LBD subjects. During 12-Hz intermittent photic stimulation (IPS), reactivity of posterior electrodes was decreased in PD and LBD patients. No reactivity was observed in PDD. Results are consistent with a graded posterior cortical disconnection in parkinsonian syndromes and with a model of dopamine-modulated thalamocortical interplay in visual processing.

Social Cognition in Rehabilitation Context: Different Evolution of Affective and Cognitive Theory of Mind in Mild Cognitive Impairment.

Maintaining social skills such as Theory of Mind (ToM) competences is important to counteract the conversion into dementia in Mild Cognitive Impairment (MCI). Multidimensional nonpharmacological interventions demonstrated their potential in improving cognitive and behavioral abilities; however, little is known about the long-term effect of such interventions on social skills in people with MCI. The aim of this longitudinal study was to monitor ToM competences considering both cognitive and affective domains in an amnestic MCI (aMCI) sample involved in a home-based multistimulation treatment (MST@H). 30 aMCI subjects (M : F = 15 : 15; mean age ± SD = 77.00 ± 4.60) were enrolled, and three steps of evaluation with neuropsychological tests and ToM tasks have been implemented. 21 healthy controls (HC) were also included (M : F = 9 : 12; mean age ± SD = 74.95 ± 3.88) to characterize the aMCI sample regarding differences in ToM performance compared to HC at the baseline evaluation. Our results show that the aMCI group statistically significantly underperformed the HC group only in the advanced ToM tasks, confirming an initial decline of high-level ToM competences in this population. The longitudinal evaluation revealed time changes not only in some subcognitive domains of MoCA (memory and executive functions) but also in cognitive and affective ToM dimensions in aMCI subjects. Our findings suggest that cognitive and affective ToM can be considered useful outcome measures to test the long-term effect of treatment over time.

"Art, Colors, and Emotions" Treatment (ACE-t): A Pilot Study on the Efficacy of an Art-Based Intervention for People With Alzheimer's Disease.

Increasing evidence suggests that non-pharmacological therapies impact on neuropsychiatric symptoms and quality of life in people with Alzheimer's disease. Among these, art-based interventions seem particularly suitable for elders' rehabilitation as they act both on cognitive functions and quality of life. However, their benefits are not yet appropriately explored. The main aim of this quasi-experimental study was to test the feasibility and the likely efficacy of a novel multi-dimensional visual art intervention for people with Alzheimer's disease (PWAD), named Art, Colors, and Emotions treatment (ACE-t). A group of PWAD (N = 10) was recruited from the Memory Clinic of Don Gnocchi Foundation to take part in the ACE-t. A historical control group that followed a usual care program (N = 10) was used for comparison. We considered both feasibility output (adherence and acceptability) and efficacy outcome measures (neuropsychological and neurobehavioral scales). We observed a good adherence to and acceptability of the ACE-t. The following significant intervention-related changes were also observed in ACE-t with respect to usual care: improvement in general cognition, as assessed with the Alzheimer's Disease Assessment Scale-Cognitive, amelioration in language, and in executive functions, and reduction in Neuropsychiatric Inventory Scale score. In conclusion, ACE-t could be considered as a suitable intervention for the rehabilitation of PWAD, with positive effects on the cognitive and the behavioral status. ACE is a promising new art-based intervention that merits further research, including confirmatory trials of our preliminary results.

The Use of a Virtual Reality Platform for the Assessment of the Memory Decline and the Hippocampal Neural Injury in Subjects with Mild Cognitive Impairment: The Validity of Smart Aging Serious Game (SASG).

Due to the lack of pharmacological treatment for dementia, timely detection of subjects at risk can be of seminal importance for preemptive rehabilitation interventions. The aim of the study was to determine the usability of the smart aging serious game (SASG), a virtual reality platform, in assessing the cognitive profile of an amnestic mild cognitive impairment (aMCI) population, its validity in discriminating aMCI from healthy controls (HC), and in detecting hippocampal degeneration, a biomarker of clinical progression towards dementia. Thirty-six aMCI and 107 HC subjects were recruited and administered the SASG together with a neuropsychological evaluation. All aMCI and 30 HC subjects performed also an MRI for hippocampal volume measurement. Results showed good usability of the SASG despite the low familiarity with technology in both groups. ROC curve analyses showed similar discriminating abilities for SASG and gold standard tests, and a greater discrimination ability compared to non-specific neuropsychological tests. Finally, linear regression analysis revealed that the SASG outperformed the Montreal cognitive assessment test (MoCA) in the ability to detect neuronal degeneration in the hippocampus on the right side. These data show that SASG is an ecological task, that can be considered a digital biomarker providing objective and clinically meaningful data about the cognitive profile of aMCI subjects.

Cognitive and Affective Theory of Mind in Mild Cognitive Impairment and Parkinson's Disease: Preliminary Evidence from the Italian Version of the Yoni Task.

The aim of the study was to explore cognitive and affective dimensions of ToM using the computerized Yoni task in participants with amnestic Mild Cognitive Impairment (aMCI=16), early stage of Parkinson's Disease (PD=14), and healthy controls (HC=18) Results demonstrated that the Yoni task was effective in discriminating between groups in 1th order cognitive dimension (MCI

A global immune deficit in Alzheimer's disease and mild cognitive impairment disclosed by a novel data mining process.

Alzheimer's disease (AD) is the most common form of dementia, while mild cognitive impairment (MCI) causes a slight but measurable decline in cognitive abilities. A person with MCI has an increased risk of developing AD or another dementia. Thus, it is of medical interest to develop predictive tools to assess this risk. A growing awareness exists that pro-oxidative state and neuro-inflammation are both involved in AD. However, the extent of this relationship is still a matter of debate. Due to the expected non-linear correlations between oxidative and inflammatory markers, traditional statistics is unsuitable to dissect their relationship with the disease. Artificial neural networks (ANNs) are computational models inspired by central nervous system networks, capable of machine learning and pattern recognition. The aim of this work was to disclose the relationship between immunological and oxidative stress markers in AD and MCI by the application of ANNs. Through a machine learning approach, we were able to construct an algorithm to classify MCI and AD with high accuracy. Such an instrument, requiring a small amount of immunological and oxidative-stress parameters, would be useful in the clinical practice. Moreover, applying an innovative non-linear mathematical technique, a global immune deficit was shown to be associated with cognitive impairment. Surprisingly, both adaptive and innate immunity were peripherally defective in AD and MCI patients. From this study, new pathogenetic aspects of these diseases could emerge.

Multistimulation group therapy in Alzheimer's disease promotes changes in brain functioning.

Background. The growing social emergency represented by Alzheimer's disease (AD) and the lack of medical treatments able to modify the disease course have kindled the interest in nonpharmacological therapies. Objective. We introduced a novel nonpharmacological approach for people with AD (PWA) named Multidimensional Stimulation group Therapy (MST) to improve PWA condition in different disease domains: cognition, behavior, and motor functioning. Methods. Enrolling 60 PWA in a mild to moderate stage of the disease, we evaluated the efficacy of MST with a randomized-controlled study. Neuropsychological and neurobehavioral measures and functional magnetic resonance imaging (fMRI) data were considered as outcome measures. Results. The following significant intervention-related changes were observed: reduction in Neuropsychiatric Inventory scale score, improvement in language and memory subscales of Alzheimer's Disease Assessment Scale-Cognitive subscale, and increased fMRI activations in temporal brain areas, right insular cortex, and thalamus. Conclusions. Cognitive-behavioral and fMRI results support the notion that MST has significant effects in improving PWA cognitive-behavioral status by restoring neural functioning.

Direction and position factors in performance of line extension task by unilateral neglect subjects.

In this study was investigated the influence of direction and position in the performance of a line extension task by patients with unilateral neglect, with the aim of exploring the role of perceptual and premotor factors in this task. Twenty-three right brain damaged patients (14 patients with left unilateral neglect) were asked to extend horizontal lines both leftward and rightward; lines were presented in three different positions (left, right and central). Patients with neglect significantly overextended the lines in all conditions, but particularly toward the sagittal mid plane of the body and leftward when the line was presented on the right. The global overextension seem to be related to concomitant hemianopsia. A crucial finding in neglect group was that left extensions reduced progressively on passing from right through central to left presentation, particularly in patients with lesions involving frontal regions or the basal ganglia. The last finding supports the hypothesis that left overextension does not exclude the coexistence of both perceptual and premotor factors (causing directional hypometria) in left unilateral neglect.

A complex proinflammatory role for peripheral monocytes in Alzheimer's disease.

An impairment of the microglial catabolic mechanisms allows amyloid-ß (Aß) accumulation in plaques within the brain in Alzheimer's disease (AD). Monocytes/macrophages (M/M) are activated in AD and migrate thorough the blood-brain barrier (BBB) trying to improve Aß clearing. In the attempt to shed light on the role of M/M in AD, these cells were analyzed in patients with AD or mild cognitive impairment (MCI) and in age-matched healthy controls. Results obtained in Aß42-stimulated cell cultures showed that significantly higher percentages of inflammatory M/M (CD14+ CD16-CCR2++CX3CR1low) expressing toll like receptors (TLR) 2 and 4, as well as IL-6 and CCR2, a chemokine favoring M/M migration through the BBB, are seen in AD. Confocal microscopy suggested the presence of MHC-II/Aß42 complexes on AD M/M alone. Finally, TRL3- and TLR8-expressing and IL-23-producing M/M were increased in both AD and MCI compared to HC. These data indicate that M/M in AD are characterized by an inflammatory profile and are involved in the induction of both innate immune responses via TLR stimulation and of acquired immunity possibly secondarily to the presentation of Aß peptides in an MHC-restricted fashion. Therapeutic approaches designed to interrupt these mechanism might prove beneficial.

A potential role for the PD1/PD-L1 pathway in the neuroinflammation of Alzheimer's disease.

The interaction between PD1 on T lymphocytes and PD-L1 on antigen presenting cells (APC) modulates the balance between inflammation and tolerance by inducing IL-10 production and apoptosis of antigen-specific cells. We analyzed the PD1/PD-L1 pathway, annexin V (AV)-expression, and proliferation in amyloid-beta (Aß)-stimulated PBMC of patients with Alzheimer's disease (AD) (N = 35) or mild cognitive impairment (MCI) (N = 30) and of age-matched healthy controls (HC; N = 30). Results showed that PD1-expressing CD4(+) T cells, density of PD-L1 on CD14(+) APC, IL-10 production, and PD-L1-expressing/IL-10-producing CD14(+) APC were significantly reduced in AD and MCI patients compared to HC. Aß-stimulated PD1/AV-expressing (apoptotic) CD4(+) T cells were also diminished, whereas proliferation was augmented in AD and MCI patients compared to controls. Finally, incubation of cells with PD-L1-neutralizing antibodies significantly decreased apoptosis of Aß-specific CD4(+) T lymphocytes. An impairment of the PD-L1/PD1 pathway is present in AD and MCI. Such alteration results in reduced IL-10 production and diminished apoptosis of Aß-specific CD4(+) T lymphocytes; these phenomena could play a role in the neuroinflammation accompanying AD.

Theory of mind in amnestic mild cognitive impairment: an FMRI study.

Theory of Mind (ToM) undergoes changes at the behavioral level in pathological aging (Alzheimer's disease (AD)) and at the neural level in physiological aging. The aim was to determine if there are changes in ToM in the behavioral and neural domains in old subjects with high risk of switching from successful to unsuccessful neurocognitive aging. Patients with amnestic mild cognitive impairment (aMCI) syndrome were studied, since aMCI was proposed to fill the gap between normal aging and dementia. Sixteen aMCI patients (mean age 71 years) and fifteen healthy controls (mean age 67 years) with no differences in age or education were subjected to increasingly complex ToM tasks and to fMRI scanning while performing the Reading the Mind in the Eyes test (RME), which attributes mental states by focusing on eye-gaze. aMCI subjects had worse performances in two second order false belief tasks, confirming the decay of ToM on the behavioral level. Despite a minor activation of some components (posterior end of the superior temporal sulcus and temporal pole) of the ToM neural circuit, no significant differences in the behavioral performances to the RME was found in aMCI compared to controls. Probably the preservation of the mirror neuron system (precentral gyrus-BA 6; Broca area - BA 44) and the stronger involvement of frontal areas (middle and medial frontal cortex and anterior cingulate cortex) supplemented the decay of part of the mentalizing neural circuit, preserving task performance.

Spatio-temporal features of visual exploration in unilaterally brain-damaged subjects with or without neglect: results from a touchscreen test.

Cognitive assessment in a clinical setting is generally made by pencil-and-paper tests, while computer-based tests enable the measurement and the extraction of additional performance indexes. Previous studies have demonstrated that in a research context exploration deficits occur also in patients without evidence of unilateral neglect at pencil-and-paper tests. The objective of this study is to apply a touchscreen-based cancellation test, feasible also in a clinical context, to large groups of control subjects and unilaterally brain-damaged patients, with and without unilateral spatial neglect (USN), in order to assess disturbances of the exploratory skills. A computerized cancellation test on a touchscreen interface was used for assessing the performance of 119 neurologically unimpaired control subjects and 193 patients with unilateral right or left hemispheric brain damage, either with or without USN. A set of performance indexes were defined including Latency, Proximity, Crossings and their spatial lateral gradients, and Preferred Search Direction. Classic outcome scores were computed as well. Results show statistically significant differences among groups (assumed p<0.05). Right-brain-damaged patients with USN were significantly slower (median latency per detected item was 1.18 s) and less efficient (about 13 search-path crossings) in the search than controls (median latency 0.64 s; about 3 crossings). Their preferred search direction (53.6% downward, 36.7% leftward) was different from the one in control patients (88.2% downward, 2.1% leftward). Right-brain-damaged patients without USN showed a significantly abnormal behavior (median latency 0.84 s, about 5 crossings, 83.3% downward and 9.1% leftward direction) situated half way between controls and right-brain-damaged patients with USN. Left-brain-damaged patients without USN were significantly slower and less efficient than controls (latency 1.19 s, about 7 crossings), preserving a normal preferred search direction (93.7% downward). Therefore, the proposed touchscreen-based assessment had evidenced disorders in spatial exploration also in patients without clinically diagnosed USN.

Effects of aging on mindreading ability through the eyes: an fMRI study.

Theory of Mind--ToM, the capacity to understand one's own and other people's mental states and to refer to them to foresee and explain the behaviour--relies upon a circumscribed neural system: the posterior end of the superior temporal sulcus (pSTS), the adjacent temporo-parietal junction (TPJ), the temporal pole (TP), the medial prefrontal cortex (mPFC) and the adjacent paracingulate cortex. To our knowledge, the neural basis of mentalizing has not yet been studied in a developmental perspective covering old age, so the aim of this work is to compare the neural basis of a specific aspect of ToM, the mindreading ability through the eyes, in healthy young and old subjects. Two groups of healthy adults (young: 25.2 years; old: 65.2 years) were submitted to an fMRI scanning while performing the Reading the Mind in the Eyes test, which requires the attribution of a mental state to the other person focussing only on the eye-gaze. There was no difference in the behavioural performances between young and old and both groups of subjects activated the pSTS and the TP, thus indicating that old people show no impairment of mentalizing circuits. However, a relevant shifting of the neural circuit implied in each group to solve the task emerged. Old subjects showed a more bilateral activation of frontal areas and a stronger involvement of the linguistic components of the mirror neuron system (i.e. area 44), as compared to young. Both young and old participants activated the non-linguistic components of the mirror neuron system, such as area 6. These findings are discussed taking into account the recent literature dealing with cognitive functions during normal aging.

Efficacy of recreational and occupational activities associated to psychologic support in mild to moderate Alzheimer disease: a multicenter controlled study.

We evaluated the efficacy of a stimulation program mainly based on recreational and occupational activities, associated with a brief cycle of support psychotherapy for patients and caregivers, in mild to moderate Alzheimer Disease (AD) associated or not with cerebrovascular lesions. Sixty-seven patients and 31 controls from 2 Italian towns entered the study. The control group was comprised of AD subjects who voluntarily declined to participate in the program for practical reasons. Patients were divided in groups of 4 subjects: treatment was delivered for 6 weeks. Multidimensional efficacy assessment of functional, behavioral, and neuropsychologic aspects was performed. When comparing baseline with posttraining condition, patients displayed a substantial reduction in disruptive behavior, and a tendency to a general reduction of behavioral symptoms compared with controls (Revised Memory and Behavior Problems Checklist--RMBPC--symptoms frequency-total P=0.07; frequency of disruptive behavior P=0.008). This reduction was mirrored by a significant reduction of caregiver reaction to behavioral disturbances (RMBPC caregiver reaction-total P=0.035; reaction to disruptive behavior, P=0.011). At 3 months follow-up, the reduction of caregiver reaction to behavioral symptoms results was confirmed (RMBPC caregiver reaction-total P=0.014, caregiver reaction to disruptive behavior P=0.028). No other significant difference was detected. These results partially confirm findings of previous studies, showing that AD patients treated with similar techniques demonstrated an improvement in behavioral disturbances.