Hypofractionated Stereotactic Re-irradiation and Anti-PDL1 Durvalumab Combination in Recurrent Glioblastoma: STERIMGLI Phase I Results.

BACKGROUND: Hypofractionated stereotactic radiotherapy (hFSRT) is a salvage option for recurrent glioblastoma (GB) which may synergize anti-PDL1 treatment. This phase I study evaluated the safety and the recommended phase II dose of anti-PDL1 durvalumab combined with hFSRT in patients with recurrent GB. METHODS: Patients were treated with 24 Gy, 8 Gy per fraction on days 1, 3, and 5 combined with the first 1500 mg Durvalumab dose on day 5, followed by infusions q4weeks until progression or for a maximum of 12 months. A standard 3 + 3 Durvalumab dose de-escalation design was used. Longitudinal lymphocytes count, cytokines analyses on plasma samples, and magnetic resonance imaging (MRI) were collected. RESULTS: Six patients were included. One dose limiting toxicity, an immune-related grade 3 vestibular neuritis related to Durvalumab, was reported. Median progression-free interval (PFI) and overall survival (OS) were 2.3 and 16.7 months, respectively. Multi-modal deep learning-based analysis including MRI, cytokines, and lymphocytes/neutrophil ratio isolated the patients presenting pseudoprogression, the longest PFI and those with the longest OS, but statistical significance cannot be established considering phase I data only. CONCLUSION: Combination of hFSRT and Durvalumab in recurrent GB was well tolerated in this phase I study. These encouraging results led to an ongoing randomized phase II. (ClinicalTrials.gov Identifier: NCT02866747).

A mid-term follow-up with a lung ultrasonographic score correlates with the severity of COVID-19 acute phase.

Lung ultrasound (LUS) has rapidly emerged in COVID-19 diagnosis and for the follow-up during the acute phase. LUS is not yet used routinely in lung damage follow-up after COVID-19 infection. We investigated the correlation between LUS score, and clinical and laboratory parameters of severity of SARS-COV-2 damage during hospitalization and at follow-up visit. Observational retrospective study including all the patients discharged from the COVID-19 wards, who attended the post-COVID outpatient clinic of the IRCCS Policlinico San Matteo in April-June 2020. 115 patients were enrolled. Follow-up visits with LUS score measurements were at a median of 38 days (IQR 28-48) after discharge. LUS scores were associated with the length of hospitalization (p < 0.001), patients' age (p = 0.036), use of non-invasive ventilation (CPAP p < 0.001 or HFNC p = 0.018), administration of corticosteroids therapy (p = 0.030), and laboratory parameters during the acute phase (WBC p < 0.001, LDH p < 0.001, CRP p < 0.001, D-dimer p = 0.008, IL-6 p = 0.045), and inversely correlated with lymphocyte count (p = 0.007). We found correlation between LUS score and both LDH (p = 0.001) and the antibody anti-SARS-CoV-2 titers (p value = 0.008). Most of these finding were confirmed by dichothomizing the LUS score (≤ 9 or > 9 points). We found a significantly higher LUS score at the follow-up in the patients with persistent dyspnea (7.00, IQR 3.00-11.00) when compared to eupnoeic patients (3.00, IQR 0-7.00 p < 0.001). LUS score at follow-up visit correlates with more severe lung disease. These findings support the hypothesis that ultrasound could be a valid tool in the follow-up medium-term COVID-19 lung damage.

Mid-term follow-up chest CT findings in recovered COVID-19 patients with residual symptoms.

OBJECTIVES: More than a year has passed since the initial outbreak of SARS-CoV-2, which caused many hospitalizations worldwide due to COVID-19 pneumonia and its complications. However, there is still a lack of information detailing short- and long-term outcomes of previously hospitalized patients. The purpose of this study is to analyze the most frequent lung CT findings in recovered COVID-19 patients at mid-term follow-ups. METHODS: A total of 407 consecutive COVID-19 patients who were admitted to the Fondazione IRCCS Policlinico San Matteo, Pavia and discharged between February 27, 2020, and June 26, 2020 were recruited into this study. Out of these patients, a subset of 108 patients who presented with residual asthenia and dyspnea at discharge, altered spirometric data, positive lung ultrasound and positive chest X-ray was subsequently selected, and was scheduled to undergo a mid-term chest CT study, which was evaluated for specific lung alterations and morphological patterns. RESULTS: The most frequently observed lung CT alterations, in order of frequency, were ground-glass opacities (81%), linear opacities (74%), bronchiolectases (64.81%), and reticular opacities (63.88%). The most common morphological pattern was the non-specific interstitial pneumonia pattern (63.88%). Features consistent with pulmonary fibrosis were observed in 32 patients (29.62%). CONCLUSIONS: Our work showed that recovered COVID-19 patients who were hospitalized and who exhibited residual symptoms after discharge had a slow radiological recovery with persistent residual lung alterations. ADVANCES IN KNOWLEDGE: This slow recovery process should be kept in mind when determining the follow-up phases in order to improve the long-term management of patients affected by COVID-19.

Hydroxychloroquine Blood Concentrations Can Be Clinically Relevant Also After Drug Discontinuation.

BACKGROUND AND OBJECTIVE: Hydroxychloroquine was widely used during the severe acute respiratory syndrome coronavirus 2 pandemic as an antiviral drug. Most previous pharmacokinetic/pharmacodynamic studies on hydroxychloroquine were conducted on healthy volunteers or patients receiving long-term therapy. There are no studies on the elimination of hydroxychloroquine after short-term treatments. Hydroxychloroquine is known to have a pro-arrhythmic effect through QT interval prolongation, but data in this setting are not conclusive. Our aims were to estimate the time needed for hydroxychloroquine concentrations (CHCQ) to drop to a safe concentration (500 ng/mL) after a short-term therapeutic cycle and to correlate the corrected QT interval with CHCQ. METHODS: We collected blood samples and electrocardiograms of patients who underwent short-term therapy with hydroxychloroquine during drug intake and after discontinuation. Hydroxychloroquine concentrations were determined by high-performance liquid chromatography-tandem mass spectrometry and analysed with a linear regression model to estimate the elimination time of the drug after its discontinuation. We conducted a multivariate analysis of the corrected QT interval correlation with CHCQ. RESULTS: Our data suggest that short-term hydroxychloroquine courses can generate significant CHCQ persisting above 500 ng/mL up to 16 days after discontinuation of treatment. Corrected QT interval prolongation significantly correlates with CHCQ. CONCLUSIONS: The study confirms the long half-life of hydroxychloroquine and its effect on the corrected QT interval even after short-term courses of the drug. This can inform the clinician using hydroxychloroquine treatments that it would be safer to start or re-initiate treatments with corrected QT interval-prolonging potential 16 days after hydroxychloroquine discontinuation.

Radiomics-Based Detection of Radionecrosis Using Harmonized Multiparametric MRI.

In this study, a radiomics analysis was conducted to provide insights into the differentiation of radionecrosis and tumor progression in multiparametric MRI in the context of a multicentric clinical trial. First, the sensitivity of radiomic features to the unwanted variability caused by different protocol settings was assessed for each modality. Then, the ability of image normalization and ComBat-based harmonization to reduce the scanner-related variability was evaluated. Finally, the performances of several radiomic models dedicated to the classification of MRI examinations were measured. Our results showed that using radiomic models trained on harmonized data achieved better predictive performance for the investigated clinical outcome (balanced accuracy of 0.61 with the model based on raw data and 0.72 with ComBat harmonization). A comparison of several models based on information extracted from different MR modalities showed that the best classification accuracy was achieved with a model based on MR perfusion features in conjunction with clinical observation (balanced accuracy of 0.76 using LASSO feature selection and a Random Forest classifier). Although multimodality did not provide additional benefit in predictive power, the model based on T1-weighted MRI before injection provided an accuracy close to the performance achieved with perfusion.

"Spazio Huntington": Tracing the Early Motor, Cognitive and Behavioral Profiles of Kids with Proven Pediatric Huntington Disease and Expanded Mutations > 80 CAG Repeats.

The "Spazio Huntington-A Place for Children" program was launched in 2019. The aim was to contact at risk kids within Huntington disease (HD) families, to provide counseling to their parents and to start a prospective follow-up of kids suspicious to manifest pediatric HD (PHD). We met 25 at risk kids in two years, four of whom with PHD and highly expanded (HE) mutations beyond 80 CAG repeats. We rated motor, neuropsychological and behavioral changes in all PHD kids by the Unified HD Rating Scale (UHDRS)-total motor score (TMS) and additional measures of (1) cognitive level (Leiter International Performance Scale), (2) adaptive functioning (Adaptive Behavior Assessment Systems), (3) receptive language (Peabody Picture Vocabulary Test) and (4) behavioral abnormalities (Child Behavior Check List and Children's Yale-Brown Obsessive Compulsive Scale). All PHD kids showed a severe progression of neurological and psychiatric manifestations including motor, cognitive and behavioral changes. The magnetic resonance imaging contributed to confirm the suspicious clinical observation by highlighting very initial striatum abnormalities in PHD. Spazio Huntington is a program to prospectively study PHD, the most atypical face of HD, and may represent the basis to recruit PHD patients in future clinical trials.

Lung Ultrasound in COVID-19 and Post-COVID-19 Patients, an Evidence-Based Approach.

OBJECTIVES: Worldwide, lung ultrasound (LUS) was utilized to assess coronavirus disease 2019 (COVID-19) patients. Often, imaging protocols were however defined arbitrarily and not following an evidence-based approach. Moreover, extensive studies on LUS in post-COVID-19 patients are currently lacking. This study analyses the impact of different LUS imaging protocols on the evaluation of COVID-19 and post-COVID-19 LUS data. METHODS: LUS data from 220 patients were collected, 100 COVID-19 positive and 120 post-COVID-19. A validated and standardized imaging protocol based on 14 scanning areas and a 4-level scoring system was implemented. We utilized this dataset to compare the capability of 5 imaging protocols, respectively based on 4, 8, 10, 12, and 14 scanning areas, to intercept the most important LUS findings. This to evaluate the optimal trade-off between a time-efficient imaging protocol and an accurate LUS examination. We also performed a longitudinal study, aimed at investigating how to eventually simplify the protocol during follow-up. Additionally, we present results on the agreement between AI models and LUS experts with respect to LUS data evaluation. RESULTS: A 12-areas protocol emerges as the optimal trade-off, for both COVID-19 and post-COVID-19 patients. For what concerns follow-up studies, it appears not to be possible to reduce the number of scanning areas. Finally, COVID-19 and post-COVID-19 LUS data seem to show differences capable to confuse AI models that were not trained on post-COVID-19 data, supporting the hypothesis of the existence of LUS patterns specific to post-COVID-19 patients. CONCLUSIONS: A 12-areas acquisition protocol is recommended for both COVID-19 and post-COVID-19 patients, also during follow-up.

Machine Learning-based Voice Assessment for the Detection of Positive and Recovered COVID-19 Patients.

Many virological tests have been implemented during the Coronavirus Disease 2019 (COVID-19) pandemic for diagnostic purposes, but they appear unsuitable for screening purposes. Furthermore, current screening strategies are not accurate enough to effectively curb the spread of the disease. Therefore, the present study was conducted within a controlled clinical environment to determine eventual detectable variations in the voice of COVID-19 patients, recovered and healthy subjects, and also to determine whether machine learning-based voice assessment (MLVA) can accurately discriminate between them, thus potentially serving as a more effective mass-screening tool. Three different subpopulations were consecutively recruited: positive COVID-19 patients, recovered COVID-19 patients and healthy individuals as controls. Positive patients were recruited within 10 days from nasal swab positivity. Recovery from COVID-19 was established clinically, virologically and radiologically. Healthy individuals reported no COVID-19 symptoms and yielded negative results at serological testing. All study participants provided three trials for multiple vocal tasks (sustained vowel phonation, speech, cough). All recordings were initially divided into three different binary classifications with a feature selection, ranking and cross-validated RBF-SVM pipeline. This brough a mean accuracy of 90.24%, a mean sensitivity of 91.15%, a mean specificity of 89.13% and a mean AUC of 0.94 across all tasks and all comparisons, and outlined the sustained vowel as the most effective vocal task for COVID discrimination. Moreover, a three-way classification was carried out on an external test set comprised of 30 subjects, 10 per class, with a mean accuracy of 80% and an accuracy of 100% for the detection of positive subjects. Within this assessment, recovered individuals proved to be the most difficult class to identify, and all the misclassified subjects were declared positive; this might be related to mid and short-term vocal traces of COVID-19, even after the clinical resolution of the infection. In conclusion, MLVA may accurately discriminate between positive COVID-19 patients, recovered COVID-19 patients and healthy individuals. Further studies should test MLVA among larger populations and asymptomatic positive COVID-19 patients to validate this novel screening technology and test its potential application as a potentially more effective surveillance strategy for COVID-19.

Pilocytic Astrocytoma-Derived Cells in Peripheral Blood: A Case Report.

Imaging limitations, invasive tissue biopsies and poor information over the course of treatment to evaluate 'real-time' tumor dynamics justify the emerging use of liquid biopsies in the field of brain tumors. Circulating tumor cells (CTCs) from high-grade astrocytomas might reach the circulation by crossing the blood-brain barrier. Here, for the first time, CTCs cytology in a case of pylocitic astrocytoma is described. An obstructive hydrocephalous due to a lateral mesencephalic tectum mass occluding the Silvio Aqueduct was diagnosed in a young, 18 years old, male. Considering the location of the tumor and the rapid deterioration of the neurological status, it has been decided to urgency treat the patient with ventriculoperitoneal shunting. Magnetic resonance imaging showed a nodular shaped lesion localized within the left lateral mesencephalic tectum. Stereotactic biopsy was not approachable due significant risk of neurological consequences. The diagnosis was performed by blood sampling, a non-invasive procedure for the patient, in order to provide tumor information. Cytopathological features on detected circulating atypical GFAP positive cells led to pilocytic diagnosis confirmed by the patient's 68 months outcome.

Effects of Ballroom Dance on Physical Fitness and Reaction Time in Experienced Middle-Aged Adults of Both Genders.

Ballroom dance practice might play a pivotal role for successful aging, but its effects could differ depending on dancers' experience level. The aim of this study was to investigate the effects of six months of ballroom dance (three times/w) on physical fitness and reaction time (RT) in 24 middle-aged adults who are experienced dancers (age: 59.4 ± 11.6 years). Body composition, handgrip test (HG), standing long-jump test (SLJ), step test (ST), one-legged stance balance test (OLSB), and RT were assessed before (T0) and after six months (T6) of dance practice. RT was re-evaluated four months later (T10). RT was significantly (p < 0.05) lower at T6 (221.2 ± 20.3 ms) and T10 (212.0 ± 21.9 ms) than T0 (239.1 ± 40,7 ms); no significant differences were found between T6 and T10. No significant differences were observed for all the other parameters between T0 and T6: weight and muscle mass were significantly lower (p < 0.01) in females than in males, and percentage of fat mass was significantly higher (p < 0.01) in females than in males. HG was significantly higher in males than females (p < 0.01). Results suggest that in experienced middle-aged adults of both genders, ballroom dance may positively influence RT, and this result could be maintained for four months.

A New Lung Ultrasound Protocol Able to Predict Worsening in Patients Affected by Severe Acute Respiratory Syndrome Coronavirus 2 Pneumonia.

OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can generate severe pneumonia associated with high mortality. A bedside lung ultrasound (LUS) examination has been shown to have a potential role in this setting. The purpose of this study was to evaluate the potential prognostic value of a new LUS protocol (evaluation of 14 anatomic landmarks, with graded scores of 0-3) in patients with SARS-CoV-2 pneumonia and the association of LUS patterns with clinical or laboratory findings. METHODS: A cohort of 52 consecutive patients with laboratory-confirmed SARS-CoV-2 underwent LUS examinations on admission in an internal medicine ward and before their discharge. A total LUS score as the sum of the scores at each explored area was computed. We investigated the association between the LUS score and clinical worsening, defined as a combination of high-flow oxygen support, intensive care unit admission, or 30-day mortality as the primary end point. RESULTS: Twenty (39%) patients showed a worse outcome during the observation period; the mean LUS scores ± SDs were 20.4 ± 8.5 and 29.2 ± 7.3 in patients without and with worsening, respectively (P < .001). In a multivariable analysis, adjusted for comorbidities (>2), age (>65 years), sex (male), and body mass index (≥25 kg/m2 ), the association between the LUS score and worsening (odds ratio, 1.17; 95% confidence interval, 1.05 to 1.29; P = .003) was confirmed, with good discrimination of the model (area under the receiver operating characteristic curve, 0.82). A median LUS score higher than 24 was associated with an almost 6-fold increase in the odds of worsening (odds ratio, 5.67; 95% confidence interval, 1.29 to 24.8; P = .021). CONCLUSIONS: Lung ultrasound can represent an effective tool for monitoring and stratifying the prognosis of patients with SARS-CoV-2 pulmonary involvement.

Depletion of circulating IgM memory B cells predicts unfavourable outcome in COVID-19.

Impaired immune responses have been hypothesised to be a possible trigger of unfavourable outcomes in coronavirus disease 2019 (COVID-19). We aimed to characterise IgM memory B cells in patients with COVID-19 admitted to an internal medicine ward in Northern Italy. Overall, 66 COVID-19 patients (mean age 74 ± 16.6 years; 29 females) were enrolled. Three patients (4.5%; 1 female) had been splenectomised and were excluded from further analyses. Fifty-five patients (87.3%) had IgM memory B cell depletion, and 18 (28.6%) died during hospitalisation (cumulative incidence rate 9.26/100 person-week; 5.8-14.7 95% CI). All patients who died had IgM memory B cell depletion. A superimposed infection was found in 6 patients (9.5%), all of them having IgM memory B cell depletion (cumulative incidence rate 3.08/100 person-week; 1.3-6.8 95% CI). At bivariable analyses, older age, sex, number of comorbidities, and peripheral blood lymphocyte count < 1500/µl were not correlated with IgM memory B cell depletion. A discrete-to-marked reduction of the B-cell compartment was also noticed in autoptic spleen specimens of two COVID-19 patients. We conclude that IgM memory B cells are commonly depleted in COVID-19 patients and this correlates with increased mortality and superimposed infections.

A Phase 1 Randomized Trial of Specific Active α-Synuclein Immunotherapies PD01A and PD03A in Multiple System Atrophy.

Multiple system atrophy (MSA) is a rare and fatal neurodegenerative disease with limited symptomatic treatment options. Aggregation of α-synuclein in oligodendrocytes is believed to be a central mechanism of the neurodegenerative process. PD01A and PD03A are 2 novel therapeutic vaccine candidates containing short peptides as antigenic moieties that are designed to induce a sustained antibody response, specifically targeting pathogenic assemblies of α-synuclein. The objectives of the current study were to evaluate primarily the safety and tolerability of PD01A and PD03A in patients with early MSA. Thirty patients (11 women) were randomized to receive 5 subcutaneous injections of either PD01A (n = 12), PD03A (n = 12), or placebo (n = 6) in this patient- and examiner-blinded, placebo-controlled, 52-week phase 1 clinical trial (ClinicalTrial.gov identifier: NCT02270489). Immunogenicity and clinical scores were assessed as secondary objectives. Twenty-nine patients reported a total of 595 treatment-emergent adverse events (mild or moderate, n = 555; severe, n = 40). Treatment-related adverse events included 190 injection-site reactions typically observed in vaccination trials with similar per-subject incidence in the treatment groups over time. Sustained IgG titers were observed in the PD01A-treated group, and 89% of treated patients developed a PD01-specific antibody response after receiving all injections. Induced antibodies displayed clear reactivity to the α-synuclein target epitope. Titers and antibody responder rate (58%) were lower in the PD03A-treated group. In conclusion, both PD01A and PD03A were safe and well tolerated. PD01A triggered a rapid and long-lasting antibody response that specifically targeted the α-synuclein epitope. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Tracing the mutated HTT and haplotype of the African ancestor who spread Huntington disease into the Middle East.

PURPOSE: We aimed to determine the origin and genetic characteristics of Huntington disease (HD) in the Middle East. METHODS: We performed genetic and genealogical analyses to establish the ancestral origin of the HTT pathgenic variant from a large kindred from Oman (hereafter called the OM-HD-01 pedigree) by single-nucleotide polymorphism and dense haplotype analysis genotyping. RESULTS: We traced the oldest ancestry of the largest, eight-generation, OM-HD-01 pedigree (n = 302 subjects, with 54 showing manifest HD) back to sub-Saharan Africa and identified a unique HD haplotype carried by all pedigree members, which consisted of portions of the C6 and C9 haplotypes and was carried by all affected members. Such a unique HD haplotype was of African origin and appeared to be associated with large CAG repeat expansions on average and high frequency of juvenile-onset HD. Three other families from the same area were also identified and found carrying a Caucasian HD haplotype A, also shared by most families of Arab ancestry. CONCLUSION: Mutated HTT spread into Middle East with a unique haplotype of African origin, appeared to be associated with juvenile-onset, a HD condition frequently occurring in Black Africans, and may have a significant impact on further development of novel targeted genetic therapies.

Neuroplasticity and brain reorganization associated with positive outcomes of multidisciplinary rehabilitation in progressive multiple sclerosis: A fMRI study.

BACKGROUND: Multiple sclerosis (MS) is characterized by a range of symptoms, including motor, sensorimotor and cognitive impairments, that limit the quality of life. A multidisciplinary rehabilitation approach in people affected by multiple sclerosis was recently reported to improve the functional abilities of MS patients in daily activities. The purpose of the study was to assess the effect of multidisciplinary rehabilitation on the whole brain of MS patients by means of functional magnetic resonance imaging (fMRI). METHODS: Thirty individuals affected by MS (49.9 ± 12.1 years; disease duration: 16.0 ± 8.5 years) with a medium-high severity of disease were enrolled. The fMRI examination assessed a range of action-related tasks involving passive movement, mental simulation of action and miming of action triggered by external stimuli, such as object photography. The three tasks were performed using each arm separately. The fMRI acquisitions were performed at T1 (inclusion in the study), T2 (3 months later, at the start of rehabilitation) and T3 (after 3 months of multidisciplinary rehabilitation). RESULTS: The fMRI results revealed a significant reduction in the activity of brain areas related to task-specific networks as well as the activation of cerebral regions not usually involved in task-specific related network, such as the medial prefrontal area. CONCLUSIONS: The effectiveness of multidisciplinary rehabilitation on activity and participation has been established in previous studies. Our study sheds new light on the effect of such treatment on brain reorganization.

Impact of [64Cu][Cu(ATSM)] PET/CT in the evaluation of hypoxia in a patient with Glioblastoma: a case report.

BACKGROUND: Glioblastoma multiform (GBM), a malignant brain tumour, has a very often poor prognosis. The therapeutic approach is represented by surgery followed by radiotherapy and chemotherapy. Hypoxia is a factor that causes a reduction of both radiotherapy and chemotherapy effectiveness in GBM and other cancers. Through the use of [64Cu][Cu(ATSM)], a hypoxia-targeting positron emission tomography (PET) radiotracer, is possible to identify the presence of hypoxic areas within a lesion and therefore modulate the therapeutic approach according to the findings. CASE PRESENTATION: In this case report, we observed an increase of radiotracer uptake from early acquisition to late acquisition in hypoxia sites and high correlation between [64Cu][Cu(ATSM) PET/CT results and expression of the hypoxia marker HIF-1α. CONCLUSIONS: [64Cu][Cu(ATSM) PET/CT represents a valid opportunity to reveal in vivo hypoxic areas in GBM lesion which can guide clinicians on selecting GMB patient's therapeutic scheme.

Neuroimaging and Neurolaw: Drawing the Future of Aging.

Human brain-aging is a complex, multidimensional phenomenon. Knowledge of the numerous aspects that revolve around it is therefore essential if not only the medical issues, but also the social, psychological, and legal issues related to this phenomenon are to be managed correctly. In the coming decades, it will be necessary to find solutions to the management of the progressive aging of the population so as to increase the number of individuals that achieve successful aging. The aim of this article is to provide a current overview of the physiopathology of brain aging and of the role and perspectives of neuroimaging in this context. The progressive development of neuroimaging has opened new perspectives in clinical and basic research and it has modified the concept of brain aging. Neuroimaging will play an increasingly important role in the definition of the individual's brain aging in every phase of the physiological and pathological process. However, when the process involved in age-related brain cognitive diseases is being investigated, factors that might affect this process on a clinical and behavioral level (genetic susceptibility, risks factors, endocrine changes) cannot be ignored but must, on the contrary, be integrated into a neuroimaging evaluation to ensure a correct and global management, and they are therefore discussed in this article. Neuroimaging appears important to the correct management of age-related brain cognitive diseases not only within a medical perspective, but also legal, according to a wider approach based on development of relationship between neuroscience and law. The term neurolaw, the neologism born from the relationship between these two disciplines, is an emerging field of study, that deals with various issues in the impact of neurosciences on individual rights. Neuroimaging, enhancing the detection of physiological and pathological brain aging, could give an important contribution to the field of neurolaw in elderly where the full control of cognitive and volitional functions is necessary to maintain a whole series of rights linked to legal capacity. For this reason, in order to provide the clinician and researcher with a broad view of the brain-aging process, the role of neurolaw will be introduced into the brain-aging context.