Publications by authors named "Sara Bernini"

28 Publications

  • Page 1 of 1

Evaluation of the efficacy of physical therapy on cognitive decline at 6-month follow-up in Parkinson disease patients with mild cognitive impairment: a randomized controlled trial.

Aging Clin Exp Res 2021 May 12. Epub 2021 May 12.

IRCCS Mondino Foundation, Via Mondino 2, 20100, Pavia, Italy.

Background: In Parkinson's disease (PD), physical activity may represent a possible non-pharmacological intervention not only for improving motor symptoms but also for modulating cognitive impairment.

Aims: To evaluate the efficacy of an intensive physical program on cognitive functions in mid-stage PD patients with mild cognitive impairment (PD-MCI) over a 6-month follow-up.

Methods: This is a 6-month randomized controlled follow-up study. 40 PD-MCI patients were randomized to receive physical therapy (PT) or no specific intervention beside drug treatment (CT). Cognitive and motor assessments were performed at baseline (T0), 4 weeks after baseline (T1) and 6 months after T0. In a previous study, we reported a significant improvement in global cognitive functioning and attention/working-memory at T1. Here, we evaluated the residual effect of the training intervention at 6 months on both cognitive and motor performances.

Results: Intra-group analysis showed that at T2 most of cognitive and motor performances remained stable in the PT when compared to T0, while a significant worsening was observed in the CT. Between-group comparison at T2 showed significantly better results in PT than CT as regards MoCA and motor scales. The percentage change of cognitive and motor performances between T1 and T2 confirmed the benefit of physical therapy on global cognitive functioning scores (MMSE and MoCA).

Conclusions: In this follow-up extension of a longitudinal randomized controlled study, we demonstrated that physical therapy has a positive effect on cognitive functions, which extends beyond the duration of the treatment itself to, at least temporarily, reducing cognitive decline.

Trial Registration: Trial registration number (ClinicalTrials.gov): NCT04012086 (9th July 2019).
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http://dx.doi.org/10.1007/s40520-021-01865-4DOI Listing
May 2021

The Smart Aging Platform for Assessing Early Phases of Cognitive Impairment in Patients With Neurodegenerative Diseases.

Front Psychol 2021 15;12:635410. Epub 2021 Mar 15.

National Neurological Institute C. Mondino Foundation, Pavia, Italy.

Smart Aging is a serious game (SG) platform that generates a 3D virtual reality environment in which users perform a set of screening tasks designed to allow evaluation of global cognition. Each task replicates activities of daily living performed in a familiar environment. The main goal of the present study was to ascertain whether Smart Aging could differentiate between different types and levels of cognitive impairment in patients with neurodegenerative disease. Ninety-one subjects (mean age = 70.29 ± 7.70 years)-healthy older adults (HCs, = 23), patients with single-domain amnesic mild cognitive impairment (aMCI, = 23), patients with single-domain executive Parkinson's disease MCI (PD-MCI, = 20), and patients with mild Alzheimer's disease (mild AD, = 25)-were enrolled in the study. All participants underwent cognitive evaluations performed using both traditional neuropsychological assessment tools, including the Mini-Mental State Examination (MMSE), Montreal Overall Cognitive Assessment (MoCA), and the Smart Aging platform. We analyzed global scores on Smart Aging indices (i.e., accuracy, time, distance) as well as the Smart Aging total score, looking for differences between the four groups. The findings revealed significant between-group differences in all the Smart Aging indices: accuracy ( < 0.001), time ( < 0.001), distance ( < 0.001), and total Smart Aging score ( < 0.001). The HCs outperformed the mild AD, aMCI, and PD-MCI patients in terms of accuracy, time, distance, and Smart Aging total score. In addition, the mild AD group was outperformed both by the HCs and by the aMCI and PD-MCI patients on accuracy and distance. No significant differences were found between aMCI and PD-MCI patients. Finally, the Smart Aging scores significantly correlated with the results of the neuropsychological assessments used. These findings, although preliminary due to the small sample size, suggest the validity of Smart Aging as a screening tool for the detection of cognitive impairment in patients with neurodegenerative diseases.
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http://dx.doi.org/10.3389/fpsyg.2021.635410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005545PMC
March 2021

Virtual Reality as a Technological-Aided Solution to Support Communication in Persons With Neurodegenerative Diseases and Acquired Brain Injury During COVID-19 Pandemic.

Front Public Health 2020 16;8:635426. Epub 2021 Feb 16.

"Giustino Fortunato" University of Benevento, Benevento, Italy.

The COVID-19 poses an ongoing threat to lives around the world and challenges the existing public health and medical service delivery. The lockdown or quarantine measures adopted to prevent the spread of COVID-19 has caused the interruption in ongoing care and access to medical care including to patients with existing neurological conditions. Besides the passivity, isolation, and withdrawal, patients with neurodegenerative diseases experience difficulties in communication due to a limited access to leisure opportunities and interaction with friends and relatives. The communication difficulties may exacerbate the burden on the caregivers. Therefore, assistive-technologies may be a useful strategy in mitigating challenges associated with remote communication. The current paper presents an overview of the use of assistive technologies using virtual reality and virtual body ownership in providing communication opportunities to isolated patients, during COVID-19, with neurological diseases and moderate-to-severe communication difficulties. We postulate that the assistive technologies-based intervention may improve social interactions in patients with neurodegenerative diseases and acquired brain injury-thereby reducing isolation and improving their quality of life and mental well-being.
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http://dx.doi.org/10.3389/fpubh.2020.635426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921156PMC
March 2021

Cognitive Telerehabilitation for Older Adults With Neurodegenerative Diseases in the COVID-19 Era: A Perspective Study.

Front Neurol 2020 14;11:623933. Epub 2021 Jan 14.

Scientific Institute for Research, Hospitalization and Healthcare (IRCCS) Mondino Foundation, Pavia, Italy.

The COVID-19 pandemic is a global health problem that is radically transforming public and private healthcare organizations around the world, negatively affecting the rehabilitative treatments of non-COVID pathologies as well. In this situation, it becomes crucial to be able to guarantee the continuity of care also to all those patients with neurodegenerative diseases unable to reach healthcare services. Remote communication technologies are gaining momentum as potentially effective options to support health care interventions-including cognitive rehabilitation-while patients can stay safely at home. In this context, we are implementing HomeCoRe (i.e., Home Cognitive Rehabilitation software) in order to offer an innovative approach and a valid support for home-based cognitive rehabilitation in neurodegenerative diseases, such as mild cognitive impairment and early dementia. HomeCoRe has been developed within a research project between engineers and clinicians in order to obtain a usable and safe cognitive rehabilitation tool. This software has multiple advantages for patients and therapists over traditional approaches, as shown in its use in hospital settings. HomeCoRe could then represent an opportunity for accessing cognitive rehabilitation in all those situations where patients and therapists are not in the same location due to particular restrictions, such as COVID-19 pandemic.
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http://dx.doi.org/10.3389/fneur.2020.623933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840692PMC
January 2021

Frontal and Cerebellar Atrophy Supports FTSD-ALS Clinical Continuum.

Front Aging Neurosci 2020 26;12:593526. Epub 2020 Nov 26.

Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.

Background: Frontotemporal Spectrum Disorder (FTSD) and Amyotrophic Lateral Sclerosis (ALS) are neurodegenerative diseases often considered as a continuum from clinical, epidemiologic, and genetic perspectives. We used localized brain volume alterations to evaluate common and specific features of FTSD, FTSD-ALS, and ALS patients to further understand this clinical continuum.

Methods: We used voxel-based morphometry on structural magnetic resonance images to localize volume alterations in group comparisons: patients (20 FTSD, seven FTSD-ALS, and 18 ALS) versus healthy controls (39 CTR), and patient groups between themselves. We used mean whole-brain cortical thickness ( ) to assess whether its correlations with local brain volume could propose mechanistic explanations of the heterogeneous clinical presentations. We also assessed whether volume reduction can explain cognitive impairment, measured with frontal assessment battery, verbal fluency, and semantic fluency.

Results: Common (mainly frontal) and specific areas with reduced volume were detected between FTSD, FTSD-ALS, and ALS patients, confirming suggestions of a clinical continuum, while at the same time defining morphological specificities for each clinical group (e.g., a difference of cerebral and cerebellar involvement between FTSD and ALS). values suggested extensive network disruption in the pathological process, with indications of a correlation between cerebral and cerebellar volumes and in ALS. The analysis of the neuropsychological scores indeed pointed toward an important role for the cerebellum, along with fronto-temporal areas, in explaining impairment of executive, and linguistic functions.

Conclusion: We identified common elements that explain the FTSD-ALS clinical continuum, while also identifying specificities of each group, partially explained by different cerebral and cerebellar involvement.
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http://dx.doi.org/10.3389/fnagi.2020.593526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726473PMC
November 2020

A double-blind randomized controlled trial of the efficacy of cognitive training delivered using two different methods in mild cognitive impairment in Parkinson's disease: preliminary report of benefits associated with the use of a computerized tool.

Aging Clin Exp Res 2021 Jun 8;33(6):1567-1575. Epub 2020 Sep 8.

IRCCS Mondino Foundation, Pavia, Italy.

Background: The effectiveness of computer-based cognitive training (CCT) remains controversial, especially in older adults with neurodegenerative diseases.

Aims: To evaluate the efficacy of CCT in patients with Parkinson's disease and mild cognitive impairment (PD-MCI).

Methods: In this randomized controlled trial, 53 patients were randomized to receive CCT delivered by means of CoRe software, traditional paper-and-pencil cognitive training (PCT), or an unstructured activity intervention (CG). In each group, the intervention lasted 3 consecutive weeks (4 individual face-to-face sessions/week). Neuropsychological assessment was administered at baseline (T0) and post-intervention (T1). Outcome measures at T0 and T1 were compared within and between groups. The Montreal Overall Cognitive Assessment (MoCA) was taken as the primary outcome measure.

Results: Unlike the PCT group and the CG, the patients receiving CCT showed significant medium/large effect size improvements in MoCA performance, global cognition, executive functions, and attention/processing speed. No baseline individual/demographic variables were associated with greater gains from the intervention, although a negative correlation with baseline MoCA performance was found.

Conclusion: CCT proved effective in PD-MCI patients when compared with traditional PCT. Further follow-up assessments are being conducted to verify the retention of the gains and the potential ability of the tool to delay conversion to PD-dementia. Trial registration number (ClinicalTrials.gov): NCT04111640 (30th September 2019).
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http://dx.doi.org/10.1007/s40520-020-01665-2DOI Listing
June 2021

Exploring the relationship between Nutrition, gUT microbiota, and BRain AgINg in community-dwelling seniors: the Italian NutBrain population-based cohort study protocol.

BMC Geriatr 2020 07 23;20(1):253. Epub 2020 Jul 23.

IRCCS Mondino Foundation, Neuropsychology/Alzheimer's Disease Assessment Unit, Via Mondino 2, 27100, Pavia, Italy.

Background: Epidemiological evidence suggests that healthy diet is associated with a slowdown of cognitive decline leading to dementia, but the underlying mechanisms are still partially unexplored. Diet is the main determinant of gut microbiota composition, which in turn impacts on brain structures and functions, however to date no studies on this topic are available. The goal of the present paper is to describe the design and methodology of the NutBrain Study aimed at investigating the association of dietary habits with cognitive function and their role in modulating the gut microbiota composition, and brain measures as well.

Methods/design: This is a population-based cohort study of community-dwelling adults aged 65 years or more living in Northern Milan, Italy. At the point of presentation people are screened for cognitive functions. Socio-demographic characteristics along with lifestyles and dietary habits, medical history, drugs, functional status, and anthropometric measurements are also recorded. Individuals suspected to have cognitive impairment at the screening phase undergo a clinical evaluation including a neurological examination and a Magnetic Resonance Imaging (MRI) scanning (both structural and functional). Stool and blood samples for the gut microbiota analysis and for the evaluation of putative biological markers are also collected. For each subject with a confirmed diagnosis of Mild Cognitive Impairment (MCI), two cognitively intact controls of the same sex and age are visited. We intend to enrol at least 683 individuals for the screening phase and 240 persons for the clinical assessment.

Discussion: The NutBrain is an innovative study that incorporates modern and advanced technologies (i.e. microbiome and neuroimaging) into traditional epidemiologic design. The study represents a unique opportunity to address key questions about the role of modifiable risk factors on cognitive impairment, with a particular focus on dietary habits and their association with gut microbiota and markers of the brain-aging process. These findings will help to encourage and plan lifestyle interventions, for both prevention and treatment, aiming at promoting healthy cognitive ageing.

Trial Registration: Trial registration number NCT04461951 , date of registration July 7, 2020 (retrospectively registered, ClinicalTrials.gov ).
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http://dx.doi.org/10.1186/s12877-020-01652-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376643PMC
July 2020

A Machine Learning Approach for the Differential Diagnosis of Alzheimer and Vascular Dementia Fed by MRI Selected Features.

Front Neuroinform 2020 11;14:25. Epub 2020 Jun 11.

NMR Research Unit, Department of Neuroinflammation, Faculty of Brain Sciences, Queen Square MS Centre, UCL Queen Square Institute of Neurology, London, United Kingdom.

Among dementia-like diseases, Alzheimer disease (AD) and vascular dementia (VD) are two of the most frequent. AD and VD may share multiple neurological symptoms that may lead to controversial diagnoses when using conventional clinical and MRI criteria. Therefore, other approaches are needed to overcome this issue. Machine learning (ML) combined with magnetic resonance imaging (MRI) has been shown to improve the diagnostic accuracy of several neurodegenerative diseases, including dementia. To this end, in this study, we investigated, first, whether different kinds of ML algorithms, combined with advanced MRI features, could be supportive in classifying VD from AD and, second, whether the developed approach might help in predicting the prevalent disease in subjects with an unclear profile of AD or VD. Three ML categories of algorithms were tested: artificial neural network (ANN), support vector machine (SVM), and adaptive neuro-fuzzy inference system (ANFIS). Multiple regional metrics from resting-state fMRI (rs-fMRI) and diffusion tensor imaging (DTI) of 60 subjects (33 AD, 27 VD) were used as input features to train the algorithms and find the best feature pattern to classify VD from AD. We then used the identified VD-AD discriminant feature pattern as input for the most performant ML algorithm to predict the disease prevalence in 15 dementia patients with a "mixed VD-AD dementia" (MXD) clinical profile using their baseline MRI data. ML predictions were compared with the diagnosis evidence from a 3-year clinical follow-up. ANFIS emerged as the most efficient algorithm in discriminating AD from VD, reaching a classification accuracy greater than 84% using a small feature pattern. Moreover, ANFIS showed improved classification accuracy when trained with a multimodal input feature data set (e.g., DTI + rs-fMRI metrics) rather than a unimodal feature data set. When applying the best discriminant pattern to the MXD group, ANFIS achieved a correct prediction rate of 77.33%. Overall, results showed that our approach has a high discriminant power to classify AD and VD profiles. Moreover, the same approach also showed potential in predicting earlier the prevalent underlying disease in dementia patients whose clinical profile is uncertain between AD and VD, therefore suggesting its usefulness in supporting physicians' diagnostic evaluations.
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http://dx.doi.org/10.3389/fninf.2020.00025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300291PMC
June 2020

Unsuspected Involvement of Spinal Cord in Alzheimer Disease.

Front Cell Neurosci 2020 30;14. Epub 2020 Jan 30.

Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.

: Brain atrophy is an established biomarker for dementia, yet spinal cord involvement has not been investigated to date. As the spinal cord is relaying sensorimotor control signals from the cortex to the peripheral nervous system and vice-versa, it is indeed a very interesting question to assess whether it is affected by atrophy due to a disease that is known for its involvement of cognitive domains first and foremost, with motor symptoms being clinically assessed too. We, therefore, hypothesize that in Alzheimer's disease (AD), severe atrophy can affect the spinal cord too and that spinal cord atrophy is indeed an important imaging biomarker contributing to understanding neurodegeneration associated with dementia. : 3DT1 images of 31 AD and 35 healthy control (HC) subjects were processed to calculate volume of brain structures and cross-sectional area (CSA) and volume (CSV) of the cervical cord [per vertebra as well as the C2-C3 pair (CSA23 and CSV23)]. Correlated features ( > 0.7) were removed, and the best subset identified for patients' classification with the Random Forest algorithm. General linear model regression was used to find significant differences between groups ( ≤ 0.05). Linear regression was implemented to assess the explained variance of the Mini-Mental State Examination (MMSE) score as a dependent variable with the best features as predictors. : Spinal cord features were significantly reduced in AD, independently of brain volumes. Patients classification reached 76% accuracy when including CSA23 together with volumes of hippocampi, left amygdala, white and gray matter, with 74% sensitivity and 78% specificity. CSA23 alone explained 13% of MMSE variance. : Our findings reveal that C2-C3 spinal cord atrophy contributes to discriminate AD from HC, together with more established features. The results show that CSA23, calculated from the same 3DT1 scan as all other brain volumes (including right and left hippocampi), has a considerable weight in classification tasks warranting further investigations. Together with recent studies revealing that AD atrophy is spread beyond the temporal lobes, our result adds the spinal cord to a number of unsuspected regions involved in the disease. Interestingly, spinal cord atrophy explains also cognitive scores, which could significantly impact how we model sensorimotor control in degenerative diseases with a primary cognitive domain involvement. Prospective studies should be purposely designed to understand the mechanisms of atrophy and the role of the spinal cord in AD.
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http://dx.doi.org/10.3389/fncel.2020.00006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7002560PMC
January 2020

Early phases of cognitive disorders in the elderly patients: report of an Italian center for dementia.

Aging Clin Exp Res 2020 05 13;32(5):967-968. Epub 2019 Nov 13.

Neuropsychology/Alzheimer's Disease Assessment Unit, IRCCS C. Mondino Foundation, Via Mondino 2, 27100, Pavia, Italy.

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http://dx.doi.org/10.1007/s40520-019-01408-yDOI Listing
May 2020

HomeCoRe: Bringing Cognitive Rehabilitation at Home.

Stud Health Technol Inform 2019 Aug;264:1755-1756

IRCCS C. Mondino, Pavia, Italy.

CoRe is a system for cognitive rehabilitation that has been successfully used for several years in hospital settings. Leveraging on the positive survey results from the potential final users (patients and their home caregivers), we developed HomeCoRe. This new version of the system will allow discharged patients to continue the rehabilitation treatment at home.
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http://dx.doi.org/10.3233/SHTI190632DOI Listing
August 2019

A computer-based cognitive training in Mild Cognitive Impairment in Parkinson's Disease.

NeuroRehabilitation 2019 ;44(4):555-567

Neuropsychology/Alzheimer's Disease Assessment Unit, IRCCS Mondino Foundation, Pavia, Italy.

Background: There is no successful pharmacological treatment for cognitive impairment in Parkinson's Disease, therefore treatments capable of slowing down the progression of cognitive dysfunction are needed.

Objective: To evaluate the effectiveness of a cognitive training, supported by the CoRe computerized tool, in patients with Parkinson's Disease Mild Cognitive Impairment.

Methods: This is a prospective, open-unblinded, randomized, controlled study. After baseline cognitive assessment (T0), enrolled patients were randomized to receive motor rehabilitation plus cognitive intervention (G1) or motor rehabilitation only (G2). Follow-up assessments were scheduled 4 weeks (T1) and 6 months after (T2). Global cognitive functioning scores (MOCA and MMSE) were considered as primary outcome. Outcome measures at T0, T1 and T2 were compared within- and between-groups. A percentage change score between T0 and next assessments was calculated to identify patients who improved, remain stable or worsened.

Results: Differently from G2, G1 showed a medium/large effect size improvement in primary (MoCA) and secondary outcome, both between T0 and T1 and T0 and T2. Moreover, within G1, most patients improved their cognitive state compared to the baseline.

Conclusions: Patients trained with CoRe showed a better evolution of cognitive decline, while untreated patients tended to get worse over time.
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http://dx.doi.org/10.3233/NRE-192714DOI Listing
October 2019

Cognitive impairment in depression: recent advances and novel treatments.

Neuropsychiatr Dis Treat 2019 10;15:1249-1258. Epub 2019 May 10.

Center of Cognitive and Behavioral Disorders, IRCCS Fondazione Mondino, National Institute of Neurology, Pavia, Italy.

In the past, little or no attention was paid to cognitive disorders associated with depression (a condition sometimes termed pseudodementia). However, recent years have seen a growing interest in these changes, not only because of their high frequency in acute-stage depression, but also because they have been found to persist, as residual symptoms (in addition to affective and psychomotor ones), in many patients who respond well to antidepressant treatment. These cognitive symptoms seem to impact significantly not only on patients' functioning and quality of life, but also on the risk of recurrence of depression. Therefore, over the past decade, pharmacological research in this field has focused on the development of new agents able to counteract not only depressive symptoms, but also cognitive and functional ones. In this context, novel antidepressants with multimodal activity have emerged. This review considers the different issues, in terms of disease evolution, raised by the presence of cognitive disorders associated with depression and considers, particularly from the neurologist's perspective, the ways in which the clinical approach to cognitive symptoms, and their interpretation to diagnostic and therapeutic ends, have changed in recent years. Finally, after outlining the pharmacodynamics and pharmacokinetics of the first multimodal antidepressant, vortioxetine, it reports the main results obtained with the drug in depressed patients, also in consideration of the ever-increasing evidence on its different mechanisms of action in animal models.
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http://dx.doi.org/10.2147/NDT.S199746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520478PMC
May 2019

The Multidisciplinary Approach to Alzheimer's Disease and Dementia. A Narrative Review of Non-Pharmacological Treatment.

Front Neurol 2018 13;9:1058. Epub 2018 Dec 13.

Neurorehabilitation Unit, Department of Rehabilitation, HABILITA, Bergamo, Italy.

Alzheimer's disease (AD) and dementia are chronic diseases with progressive deterioration of cognition, function, and behavior leading to severe disability and death. The prevalence of AD and dementia is constantly increasing because of the progressive aging of the population. These conditions represent a considerable challenge to patients, their family and caregivers, and the health system, because of the considerable need for resources allocation. There is no disease modifying intervention for AD and dementia, and the symptomatic pharmacological treatments has limited efficacy and considerable side effects. Non-pharmacological treatment (NPT), which includes a wide range of approaches and techniques, may play a role in the treatment of AD and dementia. To review, with a narrative approach, current evidence on main NPTs for AD and dementia. PubMed and the Cochrane database of systematic reviews were searched for studies written in English and published from 2000 to 2018. The bibliography of the main articles was checked to detect other relevant papers. The role of NPT has been largely explored in AD and dementia. The main NPT types, which were reviewed here, include exercise and motor rehabilitation, cognitive rehabilitation, NPT for behavioral and psychological symptoms of dementia, occupational therapy, psychological therapy, complementary and alternative medicine, and new technologies, including information and communication technologies, assistive technology and domotics, virtual reality, gaming, and telemedicine. We also summarized the role of NPT to address caregivers' burden. Although NPT is often applied in the multidisciplinary approach to AD and dementia, supporting evidence for their use is still preliminary. Some studies showed statistically significant effect of NPT on some outcomes, but their clinical significance is uncertain. Well-designed randomized controlled trials with innovative designs are needed to explore the efficacy of NPT in AD and dementia. Further studies are required to offer robust neurobiological grounds for the effect of NPT, and to examine its cost-efficacy profile in patients with dementia.
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http://dx.doi.org/10.3389/fneur.2018.01058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6300511PMC
December 2018

Disease progression in relation to age at onset in a population with Alzheimer's Dementia.

Aging Clin Exp Res 2019 May 28;31(5):723-725. Epub 2018 Aug 28.

Neuropsychology/Alzheimer's Disease Assessment Unit, IRCCS C. Mondino Foundation, Via Mondino 2, 27100, Pavia, Italy.

One thousand and 679 Alzheimer's Disease patients (early onset EO: 152 and late onset LO: 1527) were evaluated after 12, 36 and 60 months. At baseline EO patients have higher Mini Mental State examination (MMSE) and fewer comorbidities in respect to LO group. The MMSE score did not significantly differ after 12, 36 and 60 months; a more marked worsening in instrumental daily activities was observed after 36 months in the EO compared with the LO group. These data allow to conclude that EO patients may have a slight faster progression in the disease within the first 3 years after the diagnosis, but in a longer follow-up no differences exist in respect to LO group. The literature failed to identify specific factors capable to influence the disease progression in AD. Our data are in substantial agreement with the literature and seem to confirm the great heterogeneity of AD patients.
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http://dx.doi.org/10.1007/s40520-018-1027-5DOI Listing
May 2019

Specific Patterns of White Matter Alterations Help Distinguishing Alzheimer's and Vascular Dementia.

Front Neurosci 2018 25;12:274. Epub 2018 Apr 25.

Department of Emergency Neurology, IRCCS Mondino Foundation, Pavia, Italy.

Alzheimer disease (AD) and vascular dementia (VaD) together represent the majority of dementia cases. Since their neuropsychological profiles often overlap and white matter lesions are observed in elderly subjects including AD, differentiating between VaD and AD can be difficult. Characterization of these different forms of dementia would benefit by identification of quantitative imaging biomarkers specifically sensitive to AD or VaD. Parameters of microstructural abnormalities derived from diffusion tensor imaging (DTI) have been reported to be helpful in differentiating between dementias, but only few studies have used them to compare AD and VaD with a voxelwise approach. Therefore, in this study a whole brain statistical analysis was performed on DTI data of 93 subjects (31 AD, 27 VaD, and 35 healthy controls-HC) to identify specific white matter patterns of alteration in patients affected by VaD and AD with respect to HC. Parahippocampal tracts were found to be mainly affected in AD, while VaD showed more spread white matter damages associated with thalamic radiations involvement. The genu of the corpus callosum was predominantly affected in VaD, while the splenium was predominantly affected in AD revealing the existence of specific patterns of alteration useful in distinguishing between VaD and AD. Therefore, DTI parameters of these regions could be informative to understand the pathogenesis and support the etiological diagnosis of dementia. Further studies on larger cohorts of subjects, characterized for brain amyloidosis, will allow to confirm and to integrate the present findings and, furthermore, to elucidate the mechanisms of mixed dementia. These steps will be essential to translate these advances to clinical practice.
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http://dx.doi.org/10.3389/fnins.2018.00274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5996902PMC
April 2018

Evaluation of an ontology-based system for computerized cognitive rehabilitation.

Int J Med Inform 2018 07 21;115:64-72. Epub 2018 Apr 21.

IRCCS Neurological National Institute C. Mondino Foundation, Pavia, Italy.

Objectives: This paper describes the results of a randomized clinical trial about the effectiveness of a computerized rehabilitation treatment on a sample of 31 patients affected by Parkinson disease.

Methods: Computerized exercises were administered by the therapists to the intervention group (n = 17) through the CoRe tool, which automatically generates a big variety of exercises leveraging on a stimuli set (words, sounds and images) organized into a dedicated ontology. A battery of standard neuropsychological tests was performed for patients' assessment at baseline, after the treatment (that lasted 1 month), and after 6 months from the treatment stop. The control group underwent a sham intervention.

Results: Results show a statistically significant clinical benefit from computerized rehabilitation with respect to sham treatment. For the intervention group, response time and response accuracy were integrated into a weighted score that accounts also for the specific cognitive burden of each exercise. Differently from the control group, the majority of patients in the intervention group showed an improvement in that score, more marked in the first week of treatment, and which lasts for the entire treatment period, which could account both for a quick learning effect and for an improvement of cognitive conditions. Good usability of CoRe, already observed in previous studies, was confirmed by the present trial, where the percentage of protocol completion in the intervention group is very high (all but one patient are above 90%).

Conclusions: The CoRe system showed to be effective to improve some cognitive abilities in patients with Parkinson disease. However, after the end of the training, the benefit is hardly maintained over time. These findings support the implementation of CoRe in the clinical routine and the continuation of the treatment after discharge through the use of a homecare version of the system.
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http://dx.doi.org/10.1016/j.ijmedinf.2018.04.005DOI Listing
July 2018

Smart Aging Platform for Evaluating Cognitive Functions in Aging: A Comparison with the MoCA in a Normal Population.

Front Aging Neurosci 2017 21;9:379. Epub 2017 Nov 21.

Headache Science Centre, C. Mondino National Neurological Institute, Pavia, Italy.

Smart Aging is a Serious games (SGs) platform in a 3D virtual environment in which users perform a set of screening tests that address various cognitive skills. The tests are structured as 5 tasks of activities of daily life in a familiar environment. The main goal of the present study is to compare a cognitive evaluation made with Smart Aging with those of a classic standardized screening test, the Montreal Cognitive Assessment (MoCA). One thousand one-hundred thirty-one healthy adults aged between 50 and 80 ( = 64.3 ± 8.3) were enrolled in the study. They received a cognitive evaluation with the MoCA and the Smart Aging platform. Participants were grouped according to their MoCA global and specific cognitive domain (i.e., memory, executive functions, working memory, visual spatial elaboration, language, and orientation) scores and we explored differences among these groups in the Smart Aging indices. One thousand eighty-six older adults ( = 64.0 ± 8.0) successfully completed the study and were stratified according to their MoCA score: Group 1 with MoCA < 27 ( = 360); Group 2 with 27 ≥ MoCA < 29 ( = 453); and Group 3 with MoCA ≥ 29 ( = 273). MoCA groups significantly differed in most of the Smart Aging indices considered, in particular as concerns accuracy (s < 0.001) and time (s < 0.001) for completing most of the platform tasks. Group 1 was outperformed by the other two Groups and was slower than them in these tasks, which were those supposed to assess memory and executive functions. In addition, significant differences across groups also emerged when considering the single cognitive domains of the MoCA and the corresponding performances in each Smart Aging task. In particular, this platform seems to be a good proxy for assessing memory, executive functions, working memory, and visual spatial processes. These findings demonstrate the validity of Smart Aging for assessing cognitive functions in normal aging. Future studies will validate this platform also in the clinical aging populations.
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http://dx.doi.org/10.3389/fnagi.2017.00379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5702318PMC
November 2017

Correlations among age, cognitive impairment, and comorbidities in Alzheimer's disease: report from a center for cognitive disorders.

Aging Clin Exp Res 2017 Dec 21;29(6):1299-1300. Epub 2017 Aug 21.

Neuropsychology/Alzheimer's Disease Assessment Unit, C. Mondino National Neurological Institute, IRCCS C. Mondino, Via Mondino 2, 27100, Pavia, Italy.

We report an update of our previous observations in Alzheimer's disease (AD) patients in the routine clinical practice considering in particular the interactions between age, concomitant pathologies, and treatment adherence. 2379 AD patients (M/F: 1058/1321, mean age: 74.1 ± 8.8) referred for a first visit to our center from September 2000 to April 2017. An increase of percentage of patients aged over 80 years along the years was confirmed (27% between September 2000 and December 2010, and 39% between January 2011 to April 2017). The patients over 80 years presented a Cumulative Illness Rating Scale (CIRS) significantly higher than patients under 80 years (p < 0.00001). Higher CIRS scores were associated with a lower treatment adherence (p < 0.0002) and greater cognitive impairment (p < 0.01). As people in advanced age with cognitive disorders will increase, our approach to dementing conditions has to change and fit to social and epidemiological modifications.
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http://dx.doi.org/10.1007/s40520-017-0807-7DOI Listing
December 2017

Modeling Alzheimer Disease Through Functional Independence and Participation.

Alzheimer Dis Assoc Disord 2017 Jul-Sep;31(3):218-224

*Neuro-Oncology Unit, IRCCS Regina Elena Cancer Institute, Rome †Department of Rehabilitation, Neurorehabilitation Unit, HABILITA Care & Research Rehabilitation Hospitals, Zingonia di Ciserano, Bergamo ‡Alzheimer Assessment Unit/Laboratory of Neuropsychology, IRCCS Neurological National Institute C. Mondino Foundation, Pavia, Italy.

Introduction: The relationship between cognitive and functional impairment in Alzheimer Disease (AD) at the earliest stages of the disease is not well characterized. This study aimed at investigating such relationships along AD evolution by means of the Disability Assessment for Dementia (DAD).

Methods: Consecutive pairs of AD outpatients and their primary informal caregivers were enrolled. Patients were evaluated by means of the Mini Mental State Examination and neuropsychological tests. A clinician completed the Clinical Dementia Rating Scale to stage dementia severity and interviewed the caregivers to complete the Neuropsychiatric Inventory to assess behavioral disturbances and the DAD to evaluate patients' functional competence.

Results: A total of 158 dyads were enrolled; the Mini Mental State Examination score was used to stratify patients into 4 groups (>24; 20 to 23.9; 10 to 19.9; <10) that were compared. The statistical analysis revealed that all the cognitive domains were positively related to functional independence, but only logical and executive functions seemed to predict autonomy. An intergroup comparison did not show significant differences in the DAD subscales measuring initiation, planning and organization, and performance. The role of education emerged, confirming the relevance of cognitive reserve.

Discussion: As the field moves toward earlier intervention in preclinical AD, the detection of early functional changes may drive the definition of trials on prevention or intervention for dementia.
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http://dx.doi.org/10.1097/WAD.0000000000000167DOI Listing
May 2018

Communication and pragmatic breakdowns in amyotrophic lateral sclerosis patients.

Brain Lang 2016 Feb 19;153-154:1-12. Epub 2016 Jan 19.

Division of General Neurology, National Neurological Institute "C. Mondino", Pavia, Italy; Department of Brain and Behavioral Sciences, University of Pavia, Italy.

While there is increasing attention toward cognitive changes in amyotrophic lateral sclerosis (ALS), the domain of pragmatics, defined as the ability to integrate language and context to engage in successful communication, remains unexplored. Here we tested pragmatic abilities in 33 non-demented ALS patients and 33 healthy controls matched for age and education through 6 different tasks, ranging from discourse organization to the comprehension of figurative language, further grouped in three composite measures for pragmatic production, pragmatic comprehension and global pragmatic abilities. For a subgroup of patients, assessment included executive functions and social cognition skills. ALS patients were impaired on all pragmatic tasks relative to controls, with 45% of the patients performing below cut-off in at least one pragmatic task, and 36% impaired on the global pragmatic score. Pragmatic breakdowns were more common than executive deficit as defined by the consensus criteria, and approximately as prevalent as deficits in social cognition. Multiple regression analyses support the idea of an interplay of executive and social cognition abilities in determining the pragmatic performance, although all these domains show some degree of independence. These findings shed light on pragmatic impairment as a relevant dimension of ALS, which deserves further consideration in defining the cognitive profile of the disease, given its vital role for communication and social interaction in daily life.
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http://dx.doi.org/10.1016/j.bandl.2015.12.002DOI Listing
February 2016

A review of cognitive impairment and differential diagnosis in idiopathic normal pressure hydrocephalus.

Funct Neurol 2015 Oct-Dec;30(4):217-28

Idiopathic normal pressure hydrocephalus (iNPH) is a complex and still underestimated pathology. In the early stages, the cognitive profile is characterized mainly by impairments of attention, psychomotor speed and memory, suggesting frontal involvement; patients with more advanced iNPH show overall cognitive deterioration. The memory impairment, however, seems to be milder than that seen in Alzheimer's disease (AD). Clinical and neuroimaging data are crucial for the diagnosis of iNPH, but the presence of different variables, such as comorbidities, and the possible overlapping with other neurodegenerative diseases, AD in particular, make the differential diagnosis difficult. To date studies seeking to identify possible biological markers have provided inconclusive results; moreover reliable indices predictive of a good response to surgery are still lacking. There is a need for further studies with longer follow-ups and for closer interaction among the different professionals involved.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4758774PMC
http://dx.doi.org/10.11138/fneur/2015.30.4.217DOI Listing
September 2016

Computer-based cognitive rehabilitation: the CoRe system.

Disabil Rehabil 2017 02 27;39(4):407-417. Epub 2015 Oct 27.

c IRCCS S. Maugeri Foundation , Pavia , Italy , and.

Purpose: This work aims at providing a tool for supporting cognitive rehabilitation. This is a wide field, that includes a variety of diseases and related clinical pictures; for this reason the need arises to have a tool available that overcomes the difficulties entailed by what currently is the most common approach, that is, the so-called pen and paper rehabilitation.

Methods: We first organized a big number of stimuli in an ontology that represents concepts, attributes and a set of relationships among concepts. Stimuli may be words, sounds, 2D and 3D images. Then, we developed an engine that automatically generates exercises by exploiting that ontology. The design of exercises has been carried on in synergy with neuropsychologists and speech therapists. Solutions have been devised aimed at personalizing the exercises according to both patients' preferences and performance.

Results: Exercises addressed to rehabilitation of executive functions and aphasia-related diseases have been implemented. The system has been tested on both healthy volunteers (n = 38) and patients (n = 9), obtaining a favourable rating and suggestions for improvements.

Conclusions: We created a tool able to automate the execution of cognitive rehabilitation tasks. We hope the variety and personalization of exercises will allow to increase compliance, particularly from elderly people, usually neither familiar with technology nor particularly willing to rely on it. The next step involves the creation of a telerehabilitation tool, to allow therapy sessions to be undergone from home, thus guaranteeing continuity of care and advantages in terms of time and costs for the patients and the National Healthcare System (NHS). Implications for rehabilitation Cognitive impairments can greatly impact an individual's existence, appreciably reducing his abilities and autonomy, as well as sensibly lowering his quality of life. Cognitive rehabilitation can be used to restore lost brain function or slow down degenerative diseases. Computerization of rehabilitation entails many advantages, but patients - especially elderly people - might be less prone to the use of technology and consequently reluctant towards this innovative therapeutic approach. Our software system, CoRe, supports a therapist during the administration of rehabilitation sessions: exercises can be generated dynamically, thus reducing repetitivity, and patients' performance trends automatically analysed to facilitate the assessment of their progress. Tests performed on both healthy subjects and patients provided useful information that allowed us to define an implementation strategy able to reduce patients' resistance to computerized rehabilitation as much as possible.
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http://dx.doi.org/10.3109/09638288.2015.1096969DOI Listing
February 2017

Clinical characteristics of population referred to an Italian center for dementia: an update.

Aging Clin Exp Res 2015 Oct 28;27(5):755-6. Epub 2015 Jul 28.

Alzheimer's Disease Assessment Unit, Laboratory of Neuropsychology, IRCCS C. Mondino National Neurological Institute, Via Mondino 2, 27100, Pavia, Italy.

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http://dx.doi.org/10.1007/s40520-015-0429-xDOI Listing
October 2015

Serious games for screening pre-dementia conditions: from virtuality to reality? A pilot project.

Funct Neurol 2014 Jul-Sep;29(3):153-8

Conventional cognitive assessment is based on a pencil-and-paper neuropsychological evaluation, which is time consuming, expensive and requires the involvement of several professionals. Information and communication technology could be exploited to allow the development of tools that are easy to use, reduce the amount of data processing, and provide controllable test conditions. Serious games (SGs) have the potential to be new and effective tools in the management and treatment of cognitive impairments Serious games for screening pre-dementia conditions: from virtuality to reality? A pilot project in the elderly. Moreover, by adopting SGs in 3D virtual reality settings, cognitive functions might be evaluated using tasks that simulate daily activities, increasing the "ecological validity" of the assessment. In this commentary we report our experience in the creation of the Smart Aging platform, a 3D SGand virtual environment-based platform for the early identification and characterization of mild cognitive impairment.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4264781PMC
July 2015

Treatment adherence in patients with Alzheimer's disease referred to an Italian center for dementia.

Aging Clin Exp Res 2015 Jun 5;27(3):395-6. Epub 2014 Nov 5.

Alzheimer's Disease Assessment Unit, Laboratory of Neuropsychology, C. Mondino National Neurological Institute, Via Mondino 2, 27100, Pavia, Italy,

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http://dx.doi.org/10.1007/s40520-014-0279-yDOI Listing
June 2015

Quality of life in Alzheimer disease: a comparison of patients' and caregivers' points of view.

Alzheimer Dis Assoc Disord 2015 Jan-Mar;29(1):50-4

*Laboratory of Neuropsychology/Alzheimer Assessment Unit, IRCCS Neurological National Institute C. Mondino Foundation †Department of Public Health, Neuroscience, Experimental and Forensic Medicine, University of Pavia, Pavia ‡Neurorehabilitation Unit, IRCCS NEUROMED, Pozzilli (Isernia), Italy.

Unlike in other chronic diseases, the Quality of Life (QoL) of patients affected by Alzheimer Disease (AD) has not been well established, primarily because of the difficulties stemming from the study of patients with cognitive disorders. Because no cure is currently available for AD, the optimization of QoL represents the best possible outcome attainable in all stages of disease, making QoL assessment mandatory. This study identified variables related to patients' QoL and examined the agreement between patients' and caregivers' QoL ratings. A total of 135 dyads (patient and principal caregiver) were enrolled in the study. Patients' QoL evaluations showed a negative relationship with depressive mood and a positive relationship with Activities of Daily Living (ADL), whereas caregivers' QoL ratings showed a negative relationship with patients' depressive mood and behavioral disturbances. Caregivers tended to underestimate patients' QoL compared with the patients' own self-evaluations, with patients' dependency in performing ADL and behavioral disorders as well as caregivers' burdens and depression being the main factors associated with the discrepancy in these evaluations. These findings suggest that the use of proxies as a substitute for the self-report of QoL data should be treated with caution, always accounting for the presence of potential bias.
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http://dx.doi.org/10.1097/WAD.0000000000000050DOI Listing
November 2015

[Neuropsychological evaluation and psychological intervention on patients with Parkinson's disease in physical rehabilitation].

G Ital Med Lav Ergon 2013 Jul-Sep;35(3):183-91

Objective: Parkinson's Disease (PD) is characterized by a wide range of motor and non-motor symptoms. In the last years the evaluation of cognitive functioning, emotional aspects and health status of PD patients has became ever-growing important.

Methods: In this article a neuropsychological and psychological assessment model, by means of tests and interviews, and a clinical approach to the narrative themes are described. Areas of clinical investigation: cognitive processing, emotional acceptance and behavioural adaptation to the disease, motivation to rehabilitation treatment, expectations regarding functional recovery, adherence, social and family perceived support, mood, awareness of possible cognitive deficits. Tests assessment (based on specific cognitive deficits related to PD): MMSE, FAB, TMTA-B, Phonological verbal fluency test, Stroop test, Geriatric Depression Scale (GDS) or Beck Depression Inventory- BDI-II and Parkinson's Disease Questionnaire-8 (PDQ-8). The psychological approach, which is part of an interdisciplinary rehabilitative intervention, is based on Cognitive Behavioural Therapy and it is focused on disease management even in the absence, sometimes, of a significant general emotional status modification and it is aimed at improving patient's adaptability, self-management and empowerment. In order to describe the model, the clinical and test data of two PD patients are illustrated.

Conclusions: The added value of this psychological approach lies in the clinical data integration of the test evaluation, the narrative aspects and the information mediated by the inter-professional team. This model allows a deeper and more personalized identification of the patient's subjective adjustment process according to his/her personal needs and resources.
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July 2014