Development and Preclinical Evaluation of a Copper-64-Labeled Antibody Targeting Glycine-Alanine Dipeptides for PET Imaging of C9orf72-Associated Amyotrophic Lateral Sclerosis/Frontotemporal Dementia.

Aggregating poly(glycine-alanine) (poly-GA) is derived from the unconventional translation of the pathogenic intronic hexanucleotide repeat expansion in the C9orf72 gene, which is the most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Poly-GA accumulates predominantly in neuronal cytoplasmic inclusions unique to C9orf72 ALS/FTD patients. Poly-GA is, therefore, a promising target for PET/CT imaging of FTD/ALS to monitor disease progression and therapeutic interventions. A novel 64Cu-labeled anti-GA antibody (mAb1A12) targeting the poly-GA protein was developed and evaluated in a transgenic mouse model. It was obtained with high radiochemical purity (RCP), radiochemical yield (RCY), and specific activity, and showed high stability in vitro and ex vivo and specifically bound to poly-GA. The affinity of NODAGA-mAb1A12 for poly-GA was not affected by this modification. [64Cu]Cu-NODAGA-mAb1A12 was injected into transgenic mice expressing GFP-(GA)175 in excitatory neurons driven by Camk2a-Cre and in control littermates. PET/CT imaging was performed at 2, 20, and 40 h post-injection (p.i.) and revealed a higher accumulation in the cortex in transgenic mice than in wild-type mice, as reflected by higher standardized uptake value ratios (SUVR) using the cerebellum as the reference region. The organs were isolated for biodistribution and ex vivo autoradiography. Autoradiography revealed a higher cortex-to-cerebellum ratio in the transgenic mice than in the controls. Results from autoradiography were validated by immunohistochemistry and poly-GA immunoassays. Moreover, we confirmed antibody uptake in the CNS in a pharmacokinetic study of the perfused tissues. In summary, [64Cu]Cu-NODAGA-mAb1A12 demonstrated favorable in vitro characteristics and an increased relative binding in poly-GA transgenic mice compared to wild-type mice in vivo. Our results with this first-in-class radiotracer suggested that targeting poly-GA is a promising approach for PET/CT imaging in FTD/ALS.

Urinary sFlt-1 and PlGF as preeclampsia predictors: sFlt-1/creatinine ratio improves the prediction value.

OBJECTIVES: To evaluate the correlation between maternal serum and urinary soluble Fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) levels and to assess their potential value in preeclampsia and fetal growth restriction. STUDY DESIGN: This case-control longitudinal prospective study was performed in 49 singleton pregnant women, divided into two clinical groups, low risk pregnancy (n = 23) and pregnancy complicated by preeclampsia (n = 26). Maternal serum and urinary sFlt-1 and PlGF levels were quantified by electrochemiluminescence. Every patient underwent an ultrasound for fetal biometry. Doppler assessment was done when estimated fetal weight was under the 10th centile. ROC curves were used to evaluate the predictive capability of serum and urinary angiogenic biomarkers and their ratios on preeclampsia. Linear regression was used to compare the values of serum and urinary sFlt-1 and PlGF and their ratios. RESULTS: Urine biomarkers were positively associated with their serum values, being the best associated urinary PlGF (R2 = 0.73), which also showed the highest predictive capability of preeclampsia of urine biomarkers (AUC 0.866). The predictive capability of urinary sFlt-1 was much lower (AUC 0.640), but increased when adjusting by serum creatinine, a more precise parameter (AUC 0.863). CONCLUSIONS: Urinary PlGF could be a lesser invasive alternative to circulating biomarkers to monitor pregnancies complicated with preeclampsia that need repeated controls of their pregnancy complication. Urinary sFlt-1 values need adjustment by serum creatinine to be reliable.

Real-practice management and treatment of idiopathic multicentric Castleman disease with siltuximab: a collection of clinical experiences.

Castleman disease (CD) is a group of lymphoproliferative disorders that share common histopathological features yet have widely different aetiologies, clinical features and grades of severity as well as treatments and outcomes. Siltuximab is currently the only therapy approved by the FDA and EMA for idiopathic multicentric CD and is recommended as first-line therapy in treatment guidelines. Despite the extensive characterization of siltuximab treatment in clinical trials, available evidence from real-world practice is still scant. This collection of clinical experiences focuses on patients treated with siltuximab therapy, particularly regarding the idiopathic multicentric CD diagnostic work-up, and on treatment administration in patients with complex disease entering differential diagnosis with CD or concomitant diseases. Thus, these data help further characterize and improve the use of siltuximab in real practice in terms of effectiveness and safety of long-term administration as well as consequences of treatment interruption.

The application of a multidisciplinary approach in the diagnosis of Castleman disease and Castleman-like lymphadenopathies: A 20-year retrospective analysis of clinical and pathological features.

BACKGROUND: Castleman disease (CD) comprises a group of rare and heterogeneous haematological disorders, including unicentric (UCD) and multicentric (MCD) forms, the latter further subdivided into HHV8-MCD, POEMS-MCD and idiopathic-MCD (iMCD). However, according to the Castleman Disease Collaborative Network guidelines, the diagnosis of CD can only be achieved through collaboration between clinicians and pathologists. METHODS: We applied these clinical and pathological criteria and implement with clonality testing to a retrospective cohort of 48 adult and paediatric Italian patients diagnosed with reactive lymphadenitis with CD-like histological features. RESULTS: We confirmed the diagnosis of CD in 60% (29/48) of the cases, including 12 (41%) UCD and 17 (59%; five HHV8-MCD, three POEMS-MCD and nine iMCD) MCD. Of the remaining 19 cases (40%) with multiple lymphadenopathy, 5 (26%) were classified as autoimmune diseases, 1 (5%) as autoimmune lymphoproliferative disorder, 1 (5%) as IgG4-related disease, 11 (83%) as reactive lymphadenitis and 1 (5%) as nodal marginal zone lymphoma. CONCLUSIONS: Our study emphasizes the importance of the multidisciplinary approach to reactive lymphadenitis with CD-like features in order to achieve a definitive diagnosis and choose the appropriate treatment.

Proliferation and apoptosis after whole-body irradiation: longitudinal PET study in a mouse model.

PURPOSE: A reliable method for regional in vivo imaging of radiation-induced cellular damage would be of great importance for the detection of therapy-induced injury to healthy tissue and the choice of adequate treatment of radiation emergency patients in both civilian and military events. This study aimed to investigate in a mouse model if positron emission tomography (PET) imaging with proliferation and apoptosis markers is potentially suitable for this purpose. METHODS: Four groups, including twenty mice (wild-type C57BL/6) each, were whole-body irradiated with 0 Gy, 0.5 Gy, 1 Gy, and 3 Gy and examined by PET over a six-month period at defined time points. 3'-[18F]fluoro-3'-deoxythymidine ([18F]FLT) and 2-(5-[18F]fluoropentyl)-2-methyl malonic acid ([18F]ML-10) were used to visualise proliferation and apoptosis. Regional standard uptake values were compared with respect to irradiation dose over time. Histologic data and peripheral blood cell values were correlated with the PET results. RESULTS: The hematopoietic bone marrow showed a significantly increased [18F]FLT signal at early time points after radiation exposure (day 3 and day 7). This correlated with blood parameters, especially leukocytes, and histological data. A significantly increased [18F]FLT signal also occurred in the gastrointestinal tract and thymus at early time points. An increased [18F]ML-10 signal related to irradiation doses was observed in the bone marrow on day 8, but there was a high variability of standard uptake values and no correlation with histological data. CONCLUSION: [18F]FLT showed potential to visualise the extent, regional distribution and recovery from radiation-induced cellular damage in the bone marrow, gastrointestinal tract and thymus. The potential of [18F]FLT imaging to assess the extent of bone marrow affected by irradiation might be especially useful to predict the subsequent severity of hematopoietic impairment and to adapt the therapy of the bone marrow reserve. [18F]ML-10 PET proved to be not sensitive enough for the reliable detection of radiation induced apoptosis.

Longitudinal Studies on Alzheimer Disease Mouse Models with Multiple Tracer PET/CT: Application of Reduction and Refinement Principles in Daily Practice to Safeguard Animal Welfare during Progressive Aging.

Longitudinal studies on mouse models related to Alzheimer disease (AD) pathology play an important role in the investigation of therapeutic targets to help pharmaceutical research in the development of new drugs and in the attempt of an early diagnosis that can contribute to improving people's quality of life. There are several advantages to enriching longitudinal studies in AD models with Positron Emission Tomography (PET); among these advantages, the possibility of following the principle of the 3Rs of animal welfare is fundamental. In this manuscript, good daily experimental practice focusing on animal welfare is described and commented upon, based on the experience attained from studies conducted in our Nuclear Medicine department.

The Spectrum of Neurological and Sensory Abnormalities in Gaucher Disease Patients: A Multidisciplinary Study (SENOPRO).

Gaucher disease (GD) has been increasingly recognized as a continuum of phenotypes with variable neurological and sensory involvement. No study has yet specifically explored the spectrum of neuropsychiatric and sensory abnormalities in GD patients through a multidisciplinary approach. Abnormalities involving the nervous system, including sensory abnormalities, cognitive disturbances, and psychiatric comorbidities, have been identified in GD1 and GD3 patients. In this prospective study, named SENOPRO, we performed neurological, neuroradiological, neuropsychological, ophthalmological, and hearing assessments in 22 GD patients: 19 GD1 and 3 GD3. First, we highlighted a high rate of parkinsonian motor and non-motor symptoms (including high rates of excessive daytime sleepiness), especially in GD1 patients harboring severe glucocerebrosidase variants. Secondly, neuropsychological evaluations revealed a high prevalence of cognitive impairment and psychiatric disturbances, both in patients initially classified as GD1 and GD3. Thirdly, hippocampal brain volume reduction was associated with impaired short- and long-term performance in an episodic memory test. Fourthly, audiometric assessment showed an impaired speech perception in noise in the majority of patients, indicative of an impaired central processing of hearing, associated with high rates of slight hearing loss both in GD1 and GD3 patients. Finally, relevant structural and functional abnormalities along the visual system were found both in GD1 and GD3 patients by means of visual evoked potentials and optical coherence tomography. Overall, our findings support the concept of GD as a spectrum of disease subtypes, and support the importance of in-depth periodic monitoring of cognitive and motor performances, mood, sleep patterns, and sensory abnormalities in all patients with GD, independently from the patient's initial classification.

Ropeginterferon alfa-2b treatment in a young patient with multi-refractory polycythemia vera and double JAK2 gene mutation: a case report.

This case report presents a 3-year-old female patient initially diagnosed with polycythemia vera (PV) in 2001. The patient exhibited elevated red blood cell (RBC) counts, high hemoglobin (Hb) levels, hyperleukocytosis, and moderate thrombocytosis, with sporadic abdominal pain and significant splenomegaly. Despite various treatments, including phlebotomies, hydroxyurea, and alpha-interferon, the patient struggled to maintain optimal hematocrit levels and experienced persistent symptoms. Subsequent genomic analysis revealed a rare JAK2 G301R mutation alongside the canonical JAK2 V617F mutation, potentially contributing to disease severity. In 2023, the patient started Ropeginterferon alfa-2b, leading to improved hematological parameters and symptom relief. The case underscores the challenges in managing PV, particularly in young patients, and highlights the potential clinical significance of additional JAK2 mutations/variants and the potential benefits of Ropeginterferon alfa-2b in achieving better disease control.

Longitudinal [18]UCB-H/[18F]FDG imaging depicts complex patterns of structural and functional neuroplasticity following bilateral vestibular loss in the rat.

Neuronal lesions trigger mechanisms of structural and functional neuroplasticity, which can support recovery. However, the temporal and spatial appearance of structure-function changes and their interrelation remain unclear. The current study aimed to directly compare serial whole-brain in vivo measurements of functional plasticity (by [18F]FDG-PET) and structural synaptic plasticity (by [18F]UCB-H-PET) before and after bilateral labyrinthectomy in rats and investigate the effect of locomotor training. Complex structure-function changes were found after bilateral labyrinthectomy: in brainstem-cerebellar circuits, regional cerebral glucose metabolism (rCGM) decreased early, followed by reduced synaptic density. In the thalamus, increased [18F]UCB-H binding preceded a higher rCGM uptake. In frontal-basal ganglia loops, an increase in synaptic density was paralleled by a decrease in rCGM. In the group with locomotor training, thalamic rCGM and [18F]UCB-H binding increased following bilateral labyrinthectomy compared to the no training group. Rats with training had considerably fewer body rotations. In conclusion, combined [18F]FDG/[18F]UCB-H dual tracer imaging reveals that adaptive neuroplasticity after bilateral vestibular loss is not a uniform process but is composed of complex spatial and temporal patterns of structure-function coupling in networks for vestibular, multisensory, and motor control, which can be modulated by early physical training.

Prenatal prediction of very late onset small-for-gestational age newborns in low-risk pregnancies.

OBJECTIVE: To find a multivariate model for predicting small-for-gestational age newborns at 36 weeks' gestation by using clinical, biochemical and ultrasound measurements. MATERIALS AND METHODS: We evaluated 564 low-risk pregnant women and recorded maternal age, maternal body mass index, maternal mean blood pressure, soluble fms-like tyrosine kinase-1 (multiples of the median), placental growth factor (multiples of the median), soluble fms-like tyrosine kinase-1/placental growth factor ratio, estimated fetal weight centile and mean uterine artery pulsatility index at 36 weeks. Binary logistic regression was used. Statistical significance was set at 95% level (p < 0.05). RESULTS: We found three multivariate models showing relatively small differences in predictive capability. Model 1 only included estimated fetal weight centiles (area under the curve [AUC] 0.86; R2 = 0.42; p < 0.0001), Model 2 estimated fetal weight centiles and placental growth factor (multiples of the median) (AUC 0.87; R2 = 0.44; p < 0.0001) and Model 3 estimated fetal weight centiles, placental growth factor (multiples of the median) and mean uterine artery pulsatility index (AUC 0.88; R2 = 0.45; p < 0.0001). CONCLUSION: Small-for-gestational age at delivery may be predicted by using a multivariate formula. The inclusion of parameters other than estimated fetal weight centile at 36 weeks' gestation modestly improves the predictive capability of the model. Clinical decisions should consider whether or not these slight differences deserve a change in current strategies.

Third trimester ultrasound estimated fetal weight for increasing prenatal prediction of small-for-gestational age newborns in low-risk pregnant women.

AIM: The early detection of small-for-gestational age (SGA) fetuses and newborns is pivotal in the prevention of perinatal mortality. OBJECTIVES: To compare the predictive capability of performing ultrasound-based estimated fetal weight (EFW) at 32 versus 36 weeks' gestation on the detection rate of SGA fetuses and SGA newborns at delivery, and to find a better cutoff level to consider a fetus at risk of being born small. MATERIAL AND METHODS: Nine hundred fifteen low-risk pregnant women were assessed at both 32 and 36 weeks' gestation. EFW centile was calculated in both occasions. The rate of SGA fetuses was compared. SGA fetuses were considered when both abdominal circumference (AC) and EFW were below the 10th centile from a total of 488 delivered at our Hospital. Paired comparisons between ultrasound at 32 and 36 weeks' gestation were done to predict SGA at delivery. Percentages of SGA fetuses were compared by chi-squared test. ANOVA test was used for comparing centiles among groups. Receiver operating characteristic (ROC) curve was used to find the best cutoff ultrasound centile to predict SGA at delivery. Statistical significance was previously set at 95% level (p < .05). RESULTS: Ultrasound-based EFW at 32 weeks showed 23 cases of SGA (2.5%) while at 36 weeks this rate increased up to 4% (37/915) (p < .000001). When comparing both outcomes, 2.8% of those catalogued as adequate-for-gestational age (AGA) at 32 weeks were cases of SGA at 36 weeks. In addition, 47.8% of those diagnosed as SGA were not confirmed at 36 weeks. Only 12.3% of SGA neonates were identified at 32 weeks' gestation ultrasound, while using the 36 weeks' gestation approach this rate increased up to 30.9%. So, only a low proportion of SGA neonates were SGA fetuses at any of these two gestational ages. However, the area under the curve (AUC) at 36 weeks was as high as 0.86. Being a matter of cutoff rather than a matter of choosing the correct variable, ROC analysis showed that the best cutoff for prediction having the best sensitivity (0.80) with the best specificity (0.77) was 28th centile of EFW. This represents 24.9% of the studied women (228/915). CONCLUSIONS: In general, ultrasound at 36 weeks has better performance detecting SGA fetuses than ultrasound at 32 weeks and we suggest to definitively change from 32 to 36 weeks in order to increase the detection rate of SGA fetuses. Moreover, in order to detect those fetuses who will grow below the lower level of the normal range in the last month of pregnancy, we suggest that those with EFW below the 28th centile at 36 weeks should be rescanned later in pregnancy to identify prenatally as many cases as we can of SGA newborns.

Personal Protective Equipment during the COVID-19 pandemic and operative time in cesarean section: retrospective cohort study.

INTRODUCTION: The covid-19 pandemic has meant a change in working protocols, as well as in Personal Protective Equipment (PPE). Obstetricians have had to adapt quickly to these changes without knowing how they affected their clinical practice. The aim of the present study was to evaluate how COVID-19 pandemic and PPE can affect operative time, operating room time, transfer into the operating room to delivery time and skin incision to delivery time in cesarean section. METHODS: This is a single-center retrospective cohort study. Women with confirmed or suspected SARS-CoV-2 infection having a cesarean section after March 7th, 2020 during the COVID-19 pandemic were included in the study. For each woman with confirmed or suspected SARS-CoV-2 infection, a woman who had a cesarean section for the same indication during the COVID-19 pandemic and with similar clinical history but not affected by SARS-CoV-2 was included. RESULTS: 42 cesarean sections were studied. The operating room time was longer in the COVID-19 confirmed or suspected women: 90 (73.0 to 110.0) versus 61 (48.0 to 70.5) minutes; p < .001. The transfer into the operating room to delivery time was longer, but not statistically significant, in urgent cesarean sections in COVID-19 confirmed or suspected women: 25.5 (17.5 to 31.75) versus 18.0 (10.0 to 26.25) minutes; p = .113. CONCLUSIONS: There were no significant differences in the operative time, transfer into the operating room to delivery time and skin incision to delivery time when wearing PPE in cesarean section. The COVID-19 pandemic and the use of PPE resulted in a significant increase in operating room time.

Are heterobivalent GRPR- and VPAC1R-bispecific radiopeptides suitable for efficient in vivo tumor imaging of prostate carcinomas?

Receptor-specific peptides labeled with positron emitters play an important role in the clinical imaging of several malignancies by positron emission tomography (PET). Radiolabeled heterobivalent bispecific peptidic ligands (HBPLs) can target more than one receptor type and by this - besides exhibiting other advantages - increase tumor imaging sensitivity. In the present study, we show the initial in vivo evaluation of the most potent heterobivalent gastrin-releasing peptide receptor (GRPR)- and vasoactive intestinal peptide receptor subtype 1 (VPAC1R)-bispecific radiotracer and determined its tumor visualization potential via PET/CT imaging. For this purpose, the most potent described HBPL was synthesized together with its partly scrambled heterobivalent monospecific homologs and its monovalent counterparts. The agents were efficiently labeled with 68Ga3+ and evaluated in an initial PET/CT tumor imaging study in a human prostate carcinoma (PCa) xenograft rat tumor model established for this purpose. None of the three 68Ga-HBPLs enabled a clear tumor visualization and a considerably higher involvement in receptor-mediated uptake was found for the GRPR-binding part of the molecule than for the VPAC1R-binding one. Of the monovalent radiotracers, only [68Ga]Ga-NODA-GA-PESIN could efficiently delineate the tumor, confirming the results. Thus, this work sets the direction for future developments in the field of GRPR- and VPAC1R-bispecific radioligands, which should be based on other VPAC1R-specific peptides than PACAP-27.

Virtual Reality for Motor and Cognitive Rehabilitation From Clinic to Home: A Pilot Feasibility and Efficacy Study for Persons With Chronic Stroke.

Aims: Continuity of care is an important issue in healthcare for persons after stroke. The present multi-center pilot study investigates the feasibility and efficiency of an innovative approach, the Human Empowerment Aging and Disability (HEAD), for digital-health motor and cognitive rehabilitation. The approach is explored within an in-clinic context (ClinicHEAD) and in continuity of care (HomeHEAD) for persons after chronic stroke. Methods: Thirty-four outpatients with chronic stroke (mean age 55 years, SD 13.7) participated. The HEAD VR protocol was administered in two consecutive phases: Phase I in clinic (ClinicHEAD) consisting of 4 weeks of 12 supervised HEAD rehabilitation sessions (45-min), including motor, cognitive and dual task for all participants; Phase II at home (HomeHEAD) consisted of 60 sessions of the same VR activities, 5 times/week for 3 months. All participants in the ClinicHEAD were allocated (ratio 1:2) to continue with tele-monitored home rehabilitation (HH, N = 11) or to follow usual care (UC, N = 23). Blind evaluation was carried out at baseline, after ClinicHEAD, after 3 months of HomeHEAD and at 3 months Follow-up. Primary outcomes were functional mobility [2-min Walking Test (2MWT)] and cognition [Montreal Cognitive Assessment (MoCA)]. Feasibility and acceptance were assessed with adherence to treatment and the System Usability Satisfaction. Within group analyses were done with dependent samples t-tests, and between groups HomeHEAD comparisons were carried out on change scores with independent samples t-test (p = 0.05, two tailed). Results: The HEAD protocol was feasible with good adherence both in the ClinicHEAD phase (92%) and HomeHEAD (89%) phase, along with good perceived system satisfaction. ClinicHEAD resulted in a significant increase in functional mobility (2MWT, p = 0.02) and cognition (MoCA, p = 0.003) and most secondary outcome variables. At 3 months follow up of HomeHEAD the HH_group showed a further significantly greater maintenance of functional mobility with respect to UC_group (p = 0.04). Conclusion: The HEAD VR protocol was feasible in clinical and at home tele-rehabilitation for persons in the chronic phase after stroke. In clinic the approach was effective in augmenting motor and cognitive abilities and at home it was effective in longterm maintenance of functional mobility, indicating its usefulness in continuity of care. Clinical Trial Registration: ClinicalTrials.gov, NCT03025126.

Early Palliative Home Care versus Hospital Care for Patients with Hematologic Malignancies: A Cost-Effectiveness Study.

Background: There is paucity of data on the potential value of early palliative home care for patients with hematologic malignancies. Objective: To compare costs, use of resources, and clinical outcomes between an early palliative home care program and standard hospital care for active-advanced or terminal phase patients. Patients and Methods: In this real-life, nonrandomized comparative study, the allocation of advanced/terminal phase patients to either home or hospital was based on pragmatic considerations. Analysis focused on resources use, events requiring blood unit transfusions or parenteral therapy, patient-reported symptom burden, mean weekly cost of care (MWC), cost-minimization difference, and incremental cost-effectiveness ratio (ICER). Results: Of 119 patients, 59 patients cared at home were more debilitated and had a shorter survival than the 60 in hospital group (p = 0.001). Nevertheless, symptom burden was similar in both groups. At home the mean weekly number of transfusions (1.45) was lower than that at hospital (2.77). Higher rate of infections occurred at hospital (54%) versus home (21%; <0.001). MWC for hospitalization was significantly higher in a 3:1 ratio versus home care. Compared with hospital, domiciliary assistance produced a weekly saving of € 2314.9 for the health provider, with a charge of € 85.9 for the family, and was cost-effective by an ICER of € -7013.9 of prevented days of care for avoided infections. Conclusions: Current findings suggest that costs of early palliative home care for patients with hematologic malignancies are lower than standard hospital care costs. Domiciliary assistance may also be cost-effective by reducing the number of days to treat infections.

Effects of an Innovative Telerehabilitation Intervention for People With Parkinson's Disease on Quality of Life, Motor, and Non-motor Abilities.

Parkinson's disease (PD) often leads to multifactorial motor and non-motor disabilities with resultant social restrictions. Continuity of care in this pathology, including a tailored home rehabilitation, is crucial to improve or maintain the quality of life for patients. The aim of this multicenter study was to test in a pilot sample of PD patients the efficiency and efficacy of the Human Empowerment Aging and Disability (HEAD) program. The virtual reality HEAD program was administered in two consecutive phases: (1) in clinic (ClinicHEAD, 12 45-minutes sessions, 3 sessions/week); (2) at home (HomeHEAD, 60 45-minutes sessions, 5 sessions/week). Thirty-one PD outpatients were enrolled [mean age (SD) = 66.84 (9.13)]. All patients performed ClinicHEAD, and after allocation (ratio 1:2) were assigned to the HomeHEAD or the Usual Care (UC) group. Motor, cognitive and behavioral outcome measures were assessed at enrollment (T0), at hospital discharge (T1), at 4 (T2) and 7 (T3) months after baseline. After ClinicHEAD (T1 vs. T0 comparison) a significant (p < 0.05) improvement in functional mobility, balance, upper limb mobility, global cognitive function, memory, quality of life and psychological well-being was observed. After the HomeHEAD intervention there was an additional enhancement for upper limb mobility. At T3 follow-up, the UC group that did not continue the HEAD program at home showed a worsening with respect to the HomeHEAD group in balance and functional mobility. Furthermore, in the HomeHEAD group, a positive association was observed between adherence, mental and physical health (SF-12). A trend was also registered between adherence and positive affect. The digital health patient-tailored rehabilitation program resulted in improving motor and non-motor abilities and quality of life in clinical setting, enhancing the motor function in telerehabilitation at home, and maintaining the non-motor abilities and quality of life at follow-up. In the near future, people with PD can be supported also at home with individualized rehabilitation strategies for a better quality of life and wellbeing along with lower costs for society.