Language-related motor facilitation in Italian Sign Language signers.

Linguistic tasks facilitate corticospinal excitability as revealed by increased motor evoked potential (MEP) induced by transcranial magnetic stimulation (TMS) in the dominant hand. This modulation of the primary motor cortex (M1) excitability may reflect the relationship between speech and gestures. It is conceivable that in healthy individuals who use a sign language this cortical excitability modulation could be rearranged. The aim of this study was to evaluate the effect of spoken language tasks on M1 excitability in a group of hearing signers. Ten hearing Italian Sign Language (LIS) signers and 16 non-signer healthy controls participated. Single-pulse TMS was applied to either M1 hand area at the baseline and during different tasks: (i) reading aloud, (ii) silent reading, (iii) oral movements, (iv) syllabic phonation and (v) looking at meaningless non-letter strings. Overall, M1 excitability during the linguistic and non-linguistic tasks was higher in LIS group compared to the control group. In LIS group, MEPs were significantly larger during reading aloud, silent reading and non-verbal oral movements, regardless the hemisphere. These results suggest that in hearing signers there is a different modulation of the functional connectivity between the speech-related brain network and the motor system.

Italian translation and cross-cultural validation of an assessment tool for participation in stroke survivors: the Frenchay Activities Index.

PURPOSE: Participation needs to be assessed objectively, to state accurate rehabilitation objectives. The Frenchay Activities Index (FAI) is a widely used tool to measure participation in stroke patients. To date, no cross-culturally validated Italian version of FAI is available. This study provides a translation and cross-cultural adaptation of FAI into Italian, assessing its validity and reliability in sub-acute stroke patients. METHODS: According to international guidelines, a multistep translation and cultural adaptation protocol of forward and backward translations was conducted by qualified linguists and independent native English translators and revised by a healthcare committee. Patients admitted to intensive inpatient rehabilitation after stroke were recruited. Structural validity, reliability (internal consistency, inter- and intra-rater reliability and measurement error), and construct validity were studied. RESULTS: One hundred and seventy-three patients were included in this study. No significant observations in terms of comprehensibility and conceptual equivalence of the FAI Italian version emerged. The exploratory factorial analysis revealed the presence of two subscales (i.e., domestic chores and work/leisure). The internal consistency resulted good for the first and second subscale (α = 0.821 and 0.716, respectively). Intra- and inter-reliability showed an ICC > 0.90 for both subscales. SEM = 5.75% and 2.33% and MDC = 15.85% and 6.48% were found for the first and second subscale, respectively. Construct validity of first subscale was satisfactory, as 100.0% a priori hypotheses were met, while for the second subscale it was moderate, as 66.6% a priori hypotheses were respected. CONCLUSION: FAI-I provides a tool for professionals to measure participation in Italian stroke patients in health and social care settings.

Predictors of Function, Activity, and Participation of Stroke Patients Undergoing Intensive Rehabilitation: A Multicenter Prospective Observational Study Protocol.

Background: The complex nature of stroke sequelae, the heterogeneity in rehabilitation pathways, and the lack of validated prediction models of rehabilitation outcomes challenge stroke rehabilitation quality assessment and clinical research. An integrated care pathway (ICP), defining a reproducible rehabilitation assessment and process, may provide a structured frame within investigated outcomes and individual predictors of response to treatment, including neurophysiological and neurogenetic biomarkers. Predictors may differ for different interventions, suggesting clues to personalize and optimize rehabilitation. To date, a large representative Italian cohort study focusing on individual variability of response to an evidence-based ICP is lacking, and predictors of individual response to rehabilitation are largely unexplored. This paper describes a multicenter study protocol to prospectively investigate outcomes and predictors of response to an evidence-based ICP in a large Italian cohort of stroke survivors undergoing post-acute inpatient rehabilitation. Methods: All patients with diagnosis of ischemic or hemorrhagic stroke confirmed both by clinical and brain imaging evaluation, admitted to four intensive rehabilitation units (adopting the same stroke rehabilitation ICP) within 30 days from the acute event, aged 18+, and providing informed consent will be enrolled (expected sample: 270 patients). Measures will be taken at admission (T0), at discharge (T1), and at follow-up 6 months after a stroke (T2), including clinical data, nutritional, functional, neurological, and neuropsychological measures, electroencephalography and motor evoked potentials, and analysis of neurogenetic biomarkers. Statistics: In addition to classical multivariate logistic regression analysis, advanced machine learning algorithms will be cross-validated to achieve data-driven prognosis prediction models. Discussion: By identifying data-driven prognosis prediction models in stroke rehabilitation, this study might contribute to the development of patient-oriented therapy and to optimize rehabilitation outcomes. Clinical Trial Registration: ClinicalTrials.gov, NCT03968627. https://www.clinicaltrials.gov/ct2/show/NCT03968627?term=Cecchi&cond=Stroke&draw=2&rank=2.

Behavioural disorders in Alzheimer's disease: the descriptive and predictive role of brain 18 F-fluorodesoxyglucose-positron emission tomography.

BACKGROUND: Alzheimer's disease (AD) has a high incidence in the elderly. Besides cognitive disorders, patients may also develop behavioural and psychological symptoms of dementia (BPSD), which can be particularly disabling for patients and families. BPSD encompass a wide range of symptoms, among which psychotic symptoms and disruptive behaviours often prompt the first related hospitalization and request for family support. The aetiological mechanism of BPSD has not yet been clarified, and no predictive or risk factors have been identified. The main objectives of our study are to describe the frequency of aggression/agitation and psychotic symptoms, defined 'positive BPSD', in a cohort of 60 AD patients, identify areas of the brain involved in behavioural symptomatology through brain 18 F-fluorodesoxyglucose-positron emission tomography (FDG-PET), and investigate a potential predictive role of brain FDG-PET in BPSD development. METHODS: A cohort of 60 AD patients was retrospectively enrolled and regularly followed for at least 3 years. Each subject underwent brain FDG-PET at the time of diagnosis. Patients were divided into three groups based on the presence of behavioural disturbances: present, absent, and developed later. RESULTS: Of the 60 AD patients in the cohort, 52% had positive BPSD: 17 at baseline and 14 during the 3-year follow-up. FDG-PET identified an association between hypometabolism in the bilateral temporal lobes and the presence of BPSD, and showed initial hypometabolism in the postero-temporal lobes 3 years before symptom onset. CONCLUSIONS: Positive BPSD are frequently manifested in AD. Our study identified the temporal lobes as the neurobiological substrate of positive BPSD and FDG-PET as a potential instument to predict their developement. Temporal lobes are involved in processing facial expression and recognizing emotions; an impairment of these functions could cause delusions and agitated/aggressive behaviour. To confirm the potential predictive role of FDG-PET in the onset of BPSD in AD, further studies are needed.

Analysis of Feasibility, Adherence, and Appreciation of a Newly Developed Tele-Rehabilitation Program for People With MCI and VCI.

Background: Patients with Mild Cognitive Impairment (MCI) and Vascular Cognitive Impairment (VCI) are at a high risk of progressing to dementia. Recent guidelines indicate the importance of promoting multidimensional and multi-domain interventions to prevent further decline. Due to its growing effectiveness, comparable to conventional face-to-face interventions, the use of technology is gaining relevance. Tele-rehabilitation systems have the potential to engage patients in multi-dimensional activity programs and to guarantee a low-cost continuum of care through remote control. A possible limitation of such programs is represented by the lack of familiarization with technology and computers in elderly people. The purpose of this study is to describe the feasibility, adherence, and appreciation of the GOAL Tele-R system, administered by a web-application through remote control in patients with MCI/VCI. Methods: Feasibility of the Tele-R system was evaluated by means of distribution of patients' attrition along the study phases, controlling for potential systematic bias in drop-out rates due to the technological device. Adherence was evaluated analyzing drop-out rates and indexes of carried out activities. Patients' appreciation was analyzed through ad hoc satisfaction questionnaire items. Results: Out of 86 approached patients, 25 (29%) were not enrolled, 30 (35%) dropped-out after randomization, and 31 (36%) completed the study (standard care group n = 12, the tele-R group n = 19). Compared to the tele-R group, rates of drop-outs resulted significantly higher for the standard care group (34 vs. 62%, respectively, p = 0.029). Taking into account baseline characteristics, females resulted in a statistically significant higher rate of drop-outs compared to males (66 vs. 27%, respectively, p = 0.003). Overall adherence to the proposed activities was 84% (85% for cognitive module and 83% for physical activity module). Concerning satisfaction, participants provided a good mean level of appreciation (3.7 ± 0.8, range 1-5), a positive feedback for usability, and a subjective perception of cognitive, emotional, and physical benefits due to the training. Conclusion: The GOAL Tele-R system seems a feasible technological rehabilitation program, reaching an acceptable level of adherence and appreciation in patients with an MCI/VCI condition. Clinical Trial Registration: www.ClinicalTrials.gov, ID: NCT03383549 (registration date: 26/dec/2017).

Low-cost single-point optoacoustic sensor for spectroscopic measurement of local vascular oxygenation.

Optical sensors developed for the assessment of oxygen in tissue microvasculature, such as those based on near-infrared spectroscopy, are limited in application by light scattering. Optoacoustic methods are insensitive to light scattering, and therefore, they can provide higher specificity and accuracy when quantifying local vascular oxygenation. However, currently, to the best of our knowledge, there is no low-cost, single point, optoacoustic sensor for the dedicated measurement of oxygen saturation in tissue microvasculature. This work introduces a spectroscopic optoacoustic sensor (SPOAS) for the non-invasive measurement of local vascular oxygenation in real time. SPOAS employs continuous wave laser diodes and measures at a single point, which makes it low-cost and portable. The SPOAS performance was benchmarked using blood phantoms, and it showed excellent linear correlation (R2=0.98) with a blood gas analyzer. Subsequent measurements of local vascular oxygenation in living mice during an oxygen stress test correlated well with simultaneous readings from a reference instrument.

Challenges in Alzheimer's Disease Diagnostic Work-Up: Amyloid Biomarker Incongruences.

BACKGROUND: Discordance among amyloid biomarkers is a challenge to overcome in order to increase diagnostic accuracy in dementia. OBJECTIVES: 1) To verify that cerebrospinal fluid (CSF) Aß42/Aß40 ratio (AßR) better agrees with Amyloid PET (Amy-PET) results compared to CSF Aß42; 2) to detect differences among concordant positive, concordant negative, and discordant cases, basing the concordance definition on the agreement between CSF AßR and Amy-PET results; 3) to define the suspected underlying pathology of discordant cases using in vivo biomarkers. METHOD: We retrospectively enrolled 39 cognitively impaired participants in which neuropsychological tests, apolipoprotein E genotype determination, TC/MRI, FDG-PET, Amy-PET, and CSF analysis had been performed. In all cases, CSF analysis was repeated using the automated Lumipulse method. In discordant cases, FDG-PET scans were evaluated visually and using automated classifiers. RESULTS: CSF AßR better agreed with Amy-PET compared to CSF Aß42 (Cohen's K 0.431 versus 0.05). Comparisons among groups did not show any difference in clinical characteristics except for age at symptoms onset that was higher in the 6 discordant cases with abnormal CSF AßR values and negative Amy-PET (CSF AßR+/AmyPET-). FDG-PET and all CSF markers (Aß42, AßR, p-Tau, t-Tau) were suggestive of Alzheimer's disease (AD) in 5 of these 6 cases. CONCLUSION: 1) CSF AßR is the CSF amyloid marker that shows the better level of agreement with Amy-PET results; 2) The use of FDG-PET and CSF-Tau markers in CSFAßR+/Amy-PET-discordant cases can support AD diagnosis; 3) Disagreement between positive CSF AßR and negative Amy-PET in symptomatic aged AD patients could be due to the variability in plaques conformation and a negative Amy-PET scan cannot be always sufficient to rule out AD.

Development and implementation of a stroke rehabilitation integrated care pathway in an Italian no profit institution: an observational study.

BACKGROUND: To standardize assessment and coordinate processes in stroke rehabilitation, an integrated care pathway (ICP) was developed in an Italian Rehabilitation and Research Institution by a knowledge-translation interdisciplinary process, from evidence-based guidelines to rehabilitation practice. The ICP was implemented in two pilot Tuscan rehabilitation Centers. AIM: The purpose of this study was to describe ICP development and assess the ICP effects on postacute stroke inpatient rehabilitation outcomes. DESIGN: Prospective observational study, before and after comparison. SETTING: Two Tuscan inpatient rehabilitation centers. POPULATION: Patients accessing either centers for intensive rehabilitation after acute stroke. METHODS: Two cohorts were prospectively recruited before (2015-2017) and after (2018) implementation of the pathway. The primary outcome was change in activities of daily living disability, assessed by the modified Barthel Index (mBI) from admission to discharge. Secondary outcomes included length of stay (LOS), adverse outcomes, and changes in communication ability, trunk control, pain, ambulation, bladder catheter (Y/N), bedsores (Y/N). RESULTS: In 2015-2017, 443 postacute stroke patients (mean age 77±11 years, 47% women), while in 2018, 84 patients (mean age 76±13 years, 61% women) were admitted to the two facilities. Comparing the 2018 vs. the 2015-17 cohort, the mean mBI increase was not substantially different (26 vs. 24 points), nor were LOS (37±18 vs. 36±16 days), adverse outcomes, discharge destination, and improvement of ambulation, pain, and communication (P>0.05). Instead, a significantly higher improvement of trunk control (trunk control test: 69.6±33.2 vs. 79.0±31.3, P=0.019), and a higher percentage of bedsore resolution (13% vs. 5%, P=0.033), and bladder catheter removal (37% vs. 17% P<0.001) were observed in 2018 vs. 2015-2017. CONCLUSIONS: Compared to prior practice, ICP was associated to improvement of trunk control recovery, bladder catheter removal, and bedsores resolution. Further ICP implementation on a larger scale is needed to verify improvements of stroke inpatient rehabilitation outcomes. CLINICAL REHABILITATION IMPACT: An evidence-based stroke rehabilitation ICP was interdisciplinary developed and implemented in two rehabilitation centers of a multicenter Italian health group. ICP implementation as to inpatient intensive postacute stroke rehabilitation was associated to improved trunk control recovery, bladder catheter removal, and bedsore resolution. Further ICP implementation will allow multicenter studies and quality benchmarking.

High Frequency of Crossed Aphasia in Dextral in an Italian Cohort of Patients with Logopenic Primary Progressive Aphasia.

BACKGROUND: Primary progressive aphasia (PPA) has been described as a neurodegenerative language disorder mainly affecting the left hemisphere. Few cases of right hemisphere damage in right-handed PPA subjects have been reported. This condition, named crossed aphasia in dextral (CAD), is relatively rare and probably related to an alteration during neurodevelopment of language networks. OBJECTIVE: To explore the prevalence of CAD in an Italian cohort of 68 PPA patients, in order to evaluate whether right hemisphere language lateralization could be a risk factor for PPA. METHODS: Clinical-demographic and cerebral [18F]-fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) scan were analyzed, resulting in 23 logopenic variant (lvPPA) patients, 26 non-fluent variant (nfvPPA) patients, and 19 semantic variant (svPPA) patients. SPM single subject routine was performed for diagnostic purposes in order to identify the hypometabolic pattern of each patient. Based on brain metabolic profile, PPA patients were divided in right and left lvPPA, nfvPPA, and svPPA. [18F]FDG-PET group analyses were performed with SPM two-sample t-test routine. RESULTS: 26% of lvPPA cases were identified as CAD based on right hypometabolic pattern. CAD patients did not differ from left lvPPA regarding demographic features and general cognitive performance; however, they performed better in specific working memory tasks and showed brain hypometabolism limited to the superior, middle, and supramarginal temporal gyri. CONCLUSION: Atypical lateralization of language function could determine a vulnerability of the phonological language loop and in that way could be a risk factor for lvPPA.

Primary Progressive Aphasia: Natural History in an Italian Cohort.

BACKGROUND/AIMS: Few longitudinal studies have explored the progression of cognitive and functional impairment of patients with primary progressive aphasia (PPA). The aims of the study were to describe the clinical, neuroimaging, and genetic features of a cohort of 68 PPA patients, and to outline the natural history of the disease. MATERIALS AND METHODS: A sample of 23 patients with the logopenic variant, 26 with the nonfluent/agrammatic variant, and 19 with the semantic variant was retrospectively collected and followed-up for a maximum of 6 years. Clinical-neuropsychological assessment, fluorodeoxyglucose positron emission tomographic imaging, and genetic analyses were acquired at baseline. Disease progression was evaluated in terms of language impairment, global cognitive decline, and functional dependency. RESULTS: During follow-up, one third of subjects presented total language loss, and 20% severe functional dependency. Global cognitive decline after the first year (hazard ratio, 5.93; confidence interval, 1.63-21.56) and high schooling (hazard ratio, 0.07; confidence interval, 0.008-0.74) represented risk factors for functional impairment. The apolipoprotein E status was associated with the progression of cognitive decline. Positive family history for dementia was frequent and 3 genetic autosomal dominant mutations were identified. CONCLUSIONS: There were no differences in the progression of PPA subtypes. Genetics plays an important role in disease onset and progression.

Biomarkers study in atypical dementia: proof of a diagnostic work-up.

BACKGROUND: An early differentiation between Alzheimer's Disease (AD) and other dementias is crucial for an adequate patients' management, albeit it may result difficult for the occurrence of "atypical presentations." Current diagnostic criteria recognize the importance of biomarkers for AD diagnosis, but still an optimal diagnostic work-up isn't available. OBJECTIVE: Evaluate the utility and reproducibility of biomarkers and propose an "optimal" diagnostic work-up in atypical dementia. METHODS: (1) a retrospective selection of "atypical dementia cases"; (2) a repetition of diagnostic assessment by two neurologists following two different diagnostic work-ups, each consisting of multiple steps; (3) a comparison between diagnostic accuracy and confidence reached at each step by both neurologists and evaluation of the inter-rater agreement. RESULTS: In AD, regardless of the undertaken diagnostic work-up, a significant gain in accuracy was reached by both neurologists after the second step, whereas in frontotemporal dementia (FTD), adding subsequent steps was not always sufficient to increase significantly the baseline accuracy. A relevant increment in diagnostic confidence was detectable after studying pathophysiological markers in AD, and after assessing brain metabolism in FTD. The inter-rater agreement was higher at the second step for the AD group when the pathophysiological markers were available and for the FTD group when the results of FDG-PET were accessible. CONCLUSIONS: In atypical cases of dementia, biomarkers significantly raise diagnostic accuracy, confidence, and agreement. This study introduces a proof of diagnostic work-up that combines imaging and CSF biomarkers and suggests distinct ways to proceed on the basis of a greater diagnostic likelihood.

Alzheimer's Disease Progression: Factors Influencing Cognitive Decline.

BACKGROUND: Alzheimer's disease (AD) patients present high variability in the rate of cognitive decline. Despite the wide knowledge on factors influencing dementia risk, little is known on what accounts for AD progression. Previous studies on this topic have mainly analyzed each factor separately without taking into account the interaction between genetic and non-genetic factors. OBJECTIVE: The aim of the present study is to evaluate the role of demographic, clinical, therapeutic, and genetic factors and their interaction on cognitive decline among newly diagnosed AD patients. METHODS: We retrospectively selected 160 AD patients diagnosed at the Neurology Unit of Careggi University Hospital of Florence. We evaluated the occurrence of rapid cognitive changes defined as the worsening of more than four points at the Mini-Mental State Examination after 2-year follow up period. RESULTS: Among the 160 AD patients, 50% presented rapid disease progression. Extrapyramidal signs at disease onset were predictors of worse outcome (OR 2.2), especially among Apolipoprotein E (APOE) ɛ4 allele carriers, while the presence of family history for dementia decreased the risk of rapid progression by about 50%. Higher educated ɛ4-carriers showed a slower AD progression. We identified the chronic use of aspirin as potential secondary preventative strategy for the non ɛ4-carriers. CONCLUSION: At dementia onset, some clinical and demographic data can be predictors of future progression. The outcomes of the present study support the already hypothesized interaction between genetic and non-genetic factors during disease course and suggest genetic-based approaches.

The Games for Older Adults Active Life (GOAL) Project for People With Mild Cognitive Impairment and Vascular Cognitive Impairment: A Study Protocol for a Randomized Controlled Trial.

Background: People living with Mild Cognitive Impairment (MCI) and Vascular Cognitive Impairment (VCI) are persons who do not fulfill a diagnosis of dementia, but who have a high risk of progressing to a dementia disorder. The most recent guidelines to counteract cognitive decline in MCI/VCI subjects suggest a multidimensional and multi-domain interventions combining cognitive, physical, and social activities. The purpose of this study is to test an innovative service that provides a multi-dimensional tele-rehabilitation program through a user-friendly web application. The latter has been developed through a participatory design involving MCI specialists, patients, and their caregivers. Particularly, the proposed tele-rehabilitation program includes cognitive, physical, and caregiver-supported social activities. The goal is to promote and preserve an active life style and counteract cognitive decline in people living with MCI/VCI. Methods:The study is a randomized controlled trial. Sixty subjects will be randomly assigned to the experimental group, who will receive the tele-rehabilitation program, or the control group, who will not receive any treatment. The trial protocol comprises three steps of assessment for the experimental group: at the baseline (T_0), after tele-rehabilitation program (T_1) and at follow-up after 12-months (T_2). Differently, the control group will be assessed twice: at the baseline and at 12-months follow-up. Both the experimental and the control group will be assessed with a multidimensional evaluation battery, including cognitive functioning, behavioral, functional, and quality of life measures. The tele-rehabilitation program lasts 8 weeks and includes cognitive exercises 3 days a week, physical activities 2 days a week, and social activities once a week. In addition, group will be given an actigraph (GENEActiv, Activisinghts Ltd., Cambridgshire, UK) to track physical and sleep activity. Discussion:Results of this study will inform on the efficacy of the proposed tele-rehabilitation to prevent or delay further cognitive decline in MCI/VCI subjects. The expected outcome is to counteract cognitive decline and improve both physical functioning and quality of life. Ethics and Dissemination:The study is approved by the Local Ethics Committee and registered in https://clinicaltrials.gov (NCT03383549). Dissemination will include submission to a peer-reviewed journal, patients, and healthcare magazines and congress presentations. Trial Registration: ClinicalTrials.gov ID: NCT03383549 (registration date: 26/dec/2017) Trial Funding: Bando FAS Salute 2014 Regione Toscana Version Identifier: ver 5-16/11/2018.

Low Florbetapir PET Uptake and Normal Aß1-42 Cerebrospinal Fluid in an APP Ala713Thr Mutation Carrier.

According to the literature, the APP Ala713Thr mutation is associated with Alzheimer's disease and cerebral amyloid angiopathy. We describe a case of dementia clinically compatible with frontotemporal dementia in an APP Ala713Thr mutation carrier in which both [18F]Florbetapir PET uptake and Aß1-42 cerebrospinal fluid levels were normal. Further evidences are required to establish if this association is only incidental.