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

Considering REM Sleep Behavior Disorder in the Management of Parkinson's Disease

Rapid eye movement (REM) sleep behavior disorder (RBD) is the result of the loss of physiological inhibition of muscle tone during REM sleep, characterized by dream-enacting behavior and widely recognized as a prodromal manifestation of alpha-synucleinopathies. Indeed, patients with isolated RBD (iRBD) have an extremely high estimated risk to develop a neurodegenerative disease after a long follow up. Nevertheless, in comparison with PD patients without RBD (PDnoRBD), the occurrence of RBD in the context of PD (PDRBD) seems to identify a unique, more malignant phenotype, characterized by a more severe burden of disease in terms of both motor and non-motor symptoms and increased risk for cognitive decline. However, while some medications (eg, melatonin, clonazepam, etc.) and non-pharmacological options have been found to have some therapeutic benefits on RBD there is no available treatment able to modify the disease course or, at least, slow down the neurodegenerative process underlying phenoconversion. In this scenario, the long prodromal phase may allow an early therapeutic window and, therefore, the identification of multimodal biomarkers of disease onset and progression is becoming increasingly crucial. To date, several clinical (motor, cognitive, olfactory, visual, and autonomic features) neurophysiological, neuroimaging, biological (biofluids or tissue biopsy), and genetic biomarkers have been identified and proposed, also in combination, as possible diagnostic or prognostic markers, along with a potential role for some of them as outcome measures and index of treatment response. In this review, we provide an insight into the present knowledge on both existing and future biomarkers of iRBD and highlight the difference with PDRBD and PDnoRBD, including currently available treatment options

Oligomeric Alpha-Synuclein and STX-1A from Neural-Derived Extracellular Vesicles (NDEVs) as Possible Biomarkers of REM Sleep Behavior Disorder in Parkinson's Disease: A Preliminary Cohort Study

REM sleep behavior disorder (RBD) has a tighter link with synucleinopathies than other neurodegenerative disorders. Parkinson's Disease (PD) patients with RBD have a more severe motor and cognitive impairment; biomarkers for RBD are currently unavailable. Synaptic accumulation of α-Syn oligomers and their interaction with SNARE proteins is responsible for synaptic dysfunction in PD. We verified whether oligomeric α-Syn and SNARE components in neural-derived extracellular vesicles (NDEVs) in serum could be biomarkers for RBD. Forty-seven PD patients were enrolled, and the RBD Screening Questionnaire (RBDSQ) was compiled. A cut-off score > 6 to define probable RBD (p-RBD) and probable non-RBD (p non-RBD) was used. NDEVs were isolated from serum by immunocapture, and oligomeric α-Syn and SNARE complex components VAMP-2 and STX-1 were measured by ELISA. NDEVs' STX-1A resulted in being decreased in p-RBD compared to p non-RBD PD patients. A positive correlation between NDEVs' oligomeric α-Syn and RBDSQ total score was found (p = 0.032). Regression analysis confirmed a significant association between NDEVs' oligomeric α-Syn concentration and RBD symptoms (p = 0.033) independent from age, disease duration, and motor impairment severity. Our findings suggest that synuclein-mediated neurodegeneration in PD-RBD is more diffuse. NDEVs' oligomeric α-Syn and SNARE complex components' serum concentrations could be regarded as reliable biomarkers for the RBD-specific PD endophenotype

Does the Community-based Combined Meeting Center Support Programme (MCSP) Make the Pathway to Day-care Activities Easier for People Living with Dementia? A Comparison Before and After Implementation of MCSP in Three European Countries

The "pathway to care" concept offers a helpful framework for preparing national dementia plans and strategies and provides a structure to explore the availability and accessibility of timely and effective care for people with dementia and support for their informal carers. Within the framework of the JPND-MEETINGDEM implementation project the pathways to regular day-care activities and the Meeting Centers Support Programme (MCSP), an innovative combined support form for people with dementia and carers, was explored. An exploratory, descriptive, qualitative, cross-country design was applied to investigate the pathways to day care in several regions in four European countries (Italy, Poland, United Kingdom, and the Netherlands). Before implementation of MCSP, of the four countries the United Kingdom had the most structured pathway to post-diagnostic support for people with dementia. MCSP introduction had a positive impact on the pathways to day-care activities in all countries. MCSP filled an important gap in post-diagnostic care, increasing the accessibility to support for both people with dementia and carers. Key elements such as program of activities, target group, and collaboration between healthcare and social services were recognized as success factors. This study shows that MCSP fills (part of) the gap between diagnosis and residential care and can therefore be seen as a pillar of post-diagnostic care and support. Further dissemination of Meeting Centers in Europe may have a multiple impact on the structure of dementia services in European countries and the pathways to day care for people with dementia and their carer(s)

A telerehabilitation platform for cognitive, physical and behavioural rehabilitation in elderly patients affected by dementia

Dementia is one of the main causes of disability in elderly people and its treatment becomes, year after year, an increasingly compelling priority for the public health system. In the last years, home assistance and telemedicine have paved the way to decrease the treatments’ costs and to improve the patients and caregivers quality of life quality. In this framework, the aim of ABILITY project is to design, develop and validate an integrated platform of services aimed at supporting and enhancing the rehabilitation process for patients with dementia at their homes. ABILITY platform allows the clinician to assign rehabilitation plans with a strong compliance monitoring, enabled by the technological solutions integrated, and the holistic approach to rehabilitation, as the plan includes physical, cognitive and behavioral therapies/exercises. The ABILITY platform will be assessed through a set of validation activities, involving a small group of pilot patients, and a Randomized Control Trial. In conclusion, the ABILITY project generates a series of assistive services inside a modular and flexible platform, adaptable to the single patient and his/her needs, increasing the treatment efficiency and efficacy with respect to the state of the art

Translation, Adaptation and Validation of the Five-Word Test (Test Delle 5 Parole, T5P) in an Italian Sample: A Rapid Screening for the Assessment of Memory Impairment

Discriminating between Alzheimer’s disease (AD), mild cognitive impairment (MCI) and functional memory disorders (FMD) can sometimes be difficult because amnesic syndrome can be confused with memory dysfunction due to aging and/or depression. This work aims to translate, adapt and validate the five-word test (FWT) in an Italian sample (Test delle 5 Parole, T5P). FWT is a screening memory task specifically built to discriminate the hippocampal memory deficit—typical of AD and amnesic MCI—from those related to functional disorders. We involved a large number of subjects (n = 264): 60 with AD, 80 with MCI, 46 with FMD, and 78 healthy controls (CTRL). Two traditional screening tests and the T5P were administered to all participants. Results showed an excellent convergent validity of the T5P (p < 0.05). Moreover, the T5P appeared as an effective test able to discriminate between the four conditions, except for FMD and CTRL. In particular, a total score of ≤9 allowed for accurately discriminating subjects with AD + MCI compared to participants with FMD + CTRL with high sensitivity (83.87%) and specificity (76.43%). Overall, the T5P is a simple, rapid and sensible test of the hippocampal memory that is recommended in clinical practice to screen persons with subjective/probable amnesic difficulties and to discriminate between patients with AD or MCI and CTRL

Translation, Adaptation and Validation of the Five-Word Test (Test Delle 5 Parole, T5P) in an Italian Sample: A Rapid Screening for the Assessment of Memory Impairment

Discriminating between Alzheimer’s disease (AD), mild cognitive impairment (MCI) and functional memory disorders (FMD) can sometimes be difficult because amnesic syndrome can be confused with memory dysfunction due to aging and/or depression. This work aims to translate, adapt and validate the five-word test (FWT) in an Italian sample (Test delle 5 Parole, T5P). FWT is a screening memory task specifically built to discriminate the hippocampal memory deficit—typical of AD and amnesic MCI—from those related to functional disorders. We involved a large number of subjects (n = 264): 60 with AD, 80 with MCI, 46 with FMD, and 78 healthy controls (CTRL). Two traditional screening tests and the T5P were administered to all participants. Results showed an excellent convergent validity of the T5P (p < 0.05). Moreover, the T5P appeared as an effective test able to discriminate between the four conditions, except for FMD and CTRL. In particular, a total score of ≤9 allowed for accurately discriminating subjects with AD + MCI compared to participants with FMD + CTRL with high sensitivity (83.87%) and specificity (76.43%). Overall, the T5P is a simple, rapid and sensible test of the hippocampal memory that is recommended in clinical practice to screen persons with subjective/probable amnesic difficulties and to discriminate between patients with AD or MCI and CTRL

Theory of Mind in Unsuccessful Neurocognitive Aging: Preliminary Evidence from an aMCI-Converter to AD and From an aMCI Reverter to Near-Normal Cognition

Background: Two case reports of patients with Mild Cognitive Impairment (MCI) are presented with the aim to study Theory of Mind (ToM) in the evolution from successful to unsuccessful neurocognitive aging. Methods: A 75-year-old man, six years of education, who converted to Alzheimer's Disease (AD) (Case 1), and a 60- year-old woman, five years of education, who reverted to near-normal aging (Case 2), are studied at Time 1 and at Time 2 after five years under the ToM profile and the neuropsychological profile (MMSE, Corsi-Span, Digit span forward/backward, delayed recall of Rey\u2019s complex figure task, test of Prose Memory, Naming Task, Token Task, Phonemic and Semantic Fluencies, Coloured Progressive Matrices, Attentive Matrices). Their results are compared with demographically matched healthy controls, and with AD patients for the former case and with MCI patients for the latter case. Findings: Case 1 showed the typical pattern of conversion from the MCI condition to the AD condition, with a decline in general cognitive functioning, in long-term memory, in language understanding and in frontal functions. Regarding ToM, a decline in the most complex levels of ToM competence (Strange Stories) was observed. Case 2 showed a pattern of reversion from the MCI condition to a near-normal aging condition, both under the NPS and the ToM functioning. Conclusion: Results are discussed in light of the possible protective factors (including ToM) operating against the switching to unsuccessful neurocognitive aging

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