Elisabetta Farina

Evaluating two group programmes of cognitive training in mild-to-moderate AD: Is there any difference between a ‘global’ stimulation and a ‘cognitive-specific’ one?

This study evaluated the efficacy of two different group procedures of non-pharmacological treatment in mild-to-moderate Alzheimers disease (AD). Thirty-two patients entered the study and were divided in groups of four subjects. We compared recreational activities (‘global’ stimulation) with a combination of procedural memory training on activities of daily living and neuropsychological rehabilitation of ‘residual’ functions (‘cognitive-specific’). All patients and caregivers were ensured psychological support. Both group treatments were delivered for six weeks. Multidimensional efficacy assessment of functional, behavioural and neuropsychological aspects was performed. Patients receiving ‘global’ stimulation showed a substantial reduction in behavioural disturbances (Neuropsychiatric Inventory [NPI]: frequency p = 0.034; severity p = 0.012); Revised Memory Behaviour Problems Checklist (frequency p = 0.008; reaction p = 0.027), and better performance in the Functional Living Skills Assessment (FLSA), a standardized direct measure of performance in everyday life (p = 0.021) and Verbal Fluency for Letters (p = 0.000). Patients receiving ‘cognitive-specific’ treatment improved only on the scale evaluating functional competence in daily living (Nurses’ Observation Scale for Geriatric Patients [NOSGER] p = 0.018). At follow-up (six months later), compared with baseline, patients following the ‘global’ stimulation treatment showed an improvement at caregiver distress on NPI (p = 0.04). No other significant difference was detected. Our results support the contention that a ‘global’ treatment can lead to a significant improvement in AD patients, both for behavioural and functional aspects. The ‘cognitive-specific’ treatment we used in this research did not show better efficacy.

Functional brain changes in early Parkinson's disease during motor response and motor inhibition

Motor impairment represents the main clinical feature of Parkinsons disease (PD). Cognitive deficits are also frequently observed in patients with PD, with a prominent involvement of executive functions and visuo-spatial abilities. We used event-related functional MRI (fMRI) and a paradigm based on visual attention and motor inhibition (Go/NoGO-task) to investigate brain activations in 13 patients with early PD in comparison with 11 healthy controls. The two groups did not report behavioural differences in task performance. During motor inhibition (NoGO-effect), PD patients compared to controls showed an increased activation in the prefrontal cortex and in the basal ganglia. They also showed a reduced and less coherent hemodynamic response in the occipital cortex. These results indicate that specific cortico-subcortical functional changes, involving not only the fronto-striatal network but also the temporal-occipital cortex, are already present in patients with early PD and no clinical evidence of cognitive impairment. We discuss our findings in terms of compensatory mechanisms (fronto-striatal changes) and preclinical signs of visuo-perceptual deficits and visual hallucinations.

Efficacy of recreational and occupational activities associated to psychologic support in mild to moderate Alzheimer disease : A multicenter controlled study

We evaluated the efficacy of a stimulation program mainly based on recreational and occupational activities, associated with a brief cycle of support psychotherapy for patients and caregivers, in mild to moderate Alzheimer Disease (AD) associated or not with cerebrovascular lesions. Sixty-seven patients and 31 controls from 2 Italian towns entered the study. The control group was comprised of AD subjects who voluntarily declined to participate in the program for practical reasons. Patients were divided in groups of 4 subjects: treatment was delivered for 6 weeks. Multidimensional efficacy assessment of functional, behavioral, and neuropsychologic aspects was performed. When comparing baseline with posttraining condition, patients displayed a substantial reduction in disruptive behavior, and a tendency to a general reduction of behavioral symptoms compared with controls (Revised Memory and Behavior Problems Checklist—RMBPC—symptoms frequency-total P=0.07; frequency of disruptive behavior P=0.008). This reduction was mirrored by a significant reduction of caregiver reaction to behavioral disturbances (RMBPC caregiver reaction-total P=0.035; reaction to disruptive behavior, P=0.011). At 3 months follow-up, the reduction of caregiver reaction to behavioral symptoms results was confirmed (RMBPC caregiver reaction-total P=0.014, caregiver reaction to disruptive behavior P=0.028). No other significant difference was detected. These results partially confirm findings of previous studies, showing that AD patients treated with similar techniques demonstrated an improvement in behavioral disturbances.

Spatio-Temporal Features of Visual Exploration in Unilaterally Brain-Damaged Subjects with or without Neglect: Results from a Touchscreen Test

Cognitive assessment in a clinical setting is generally made by pencil-and-paper tests, while computer-based tests enable the measurement and the extraction of additional performance indexes. Previous studies have demonstrated that in a research context exploration deficits occur also in patients without evidence of unilateral neglect at pencil-and-paper tests. The objective of this study is to apply a touchscreen-based cancellation test, feasible also in a clinical context, to large groups of control subjects and unilaterally brain-damaged patients, with and without unilateral spatial neglect (USN), in order to assess disturbances of the exploratory skills. A computerized cancellation test on a touchscreen interface was used for assessing the performance of 119 neurologically unimpaired control subjects and 193 patients with unilateral right or left hemispheric brain damage, either with or without USN. A set of performance indexes were defined including Latency, Proximity, Crossings and their spatial lateral gradients, and Preferred Search Direction. Classic outcome scores were computed as well. Results show statistically significant differences among groups (assumed p<0.05). Right-brain-damaged patients with USN were significantly slower (median latency per detected item was 1.18 s) and less efficient (about 13 search-path crossings) in the search than controls (median latency 0.64 s; about 3 crossings). Their preferred search direction (53.6% downward, 36.7% leftward) was different from the one in control patients (88.2% downward, 2.1% leftward). Right-brain-damaged patients without USN showed a significantly abnormal behavior (median latency 0.84 s, about 5 crossings, 83.3% downward and 9.1% leftward direction) situated half way between controls and right-brain-damaged patients with USN. Left-brain-damaged patients without USN were significantly slower and less efficient than controls (latency 1.19 s, about 7 crossings), preserving a normal preferred search direction (93.7% downward). Therefore, the proposed touchscreen-based assessment had evidenced disorders in spatial exploration also in patients without clinically diagnosed USN.

EEG Evidence of Posterior Cortical Disconnection in PD and Related Dementias

ABSTRACT Electroencephalogram (EEG) reactivity to eyes opening and 12-Hz photic stimulation was investigated in 14 healthy elderly subjects, 21 parkinsonian patients (PD), 7 demented parkinsonian patients (PDD), and 10 patients with Lewy body dementia (LBD) using global field synchronization (GFS). During eyes closed Theta GFS was increased in Parkinsons disease and patients and alpha1 GFS was decreased in LBD subjects. During 12-Hz intermittent photic stimulation (IPS), reactivity of posterior electrodes was decreased in PD and LBD patients. No reactivity was observed in PDD. Results are consistent with a graded posterior cortical disconnection in parkinsonian syndromes and with a model of dopamine-modulated thalamocortical interplay in visual processing.

A potential role for the PD1/PD-L1 pathway in the neuroinflammation of Alzheimer's disease

The interaction between PD1 on T lymphocytes and PD-L1 on antigen presenting cells (APC) modulates the balance between inflammation and tolerance by inducing IL-10 production and apoptosis of antigen-specific cells. We analyzed the PD1/PD-L1 pathway, annexin V (AV)-expression, and proliferation in amyloid-beta (Aβ)-stimulated PBMC of patients with Alzheimers disease (AD) (N = 35) or mild cognitive impairment (MCI) (N = 30) and of age-matched healthy controls (HC; N = 30). Results showed that PD1-expressing CD4(+) T cells, density of PD-L1 on CD14(+) APC, IL-10 production, and PD-L1-expressing/IL-10-producing CD14(+) APC were significantly reduced in AD and MCI patients compared to HC. Aβ-stimulated PD1/AV-expressing (apoptotic) CD4(+) T cells were also diminished, whereas proliferation was augmented in AD and MCI patients compared to controls. Finally, incubation of cells with PD-L1-neutralizing antibodies significantly decreased apoptosis of Aβ-specific CD4(+) T lymphocytes. An impairment of the PD-L1/PD1 pathway is present in AD and MCI. Such alteration results in reduced IL-10 production and diminished apoptosis of Aβ-specific CD4(+) T lymphocytes; these phenomena could play a role in the neuroinflammation accompanying AD.

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.

Direction and position factors in performance of line extension task by unilateral neglect subjects

In this study was investigated the influence of direction and position in the performance of a line extension task by patients with unilateral neglect, with the aim of exploring the role of perceptual and premotor factors in this task. Twenty-three right brain damaged patients (14 patients with left unilateral neglect) were asked to extend horizontal lines both leftward and rightward; lines were presented in three different positions (left, right and central). Patients with neglect significantly overextended the lines in all conditions, but particularly toward the sagittal mid plane of the body and leftward when the line was presented on the right. The global overextension seem to be related to concomitant hemianopsia. A crucial finding in neglect group was that left extensions reduced progressively on passing from right through central to left presentation, particularly in patients with lesions involving frontal regions or the basal ganglia. The last finding supports the hypothesis that left overextension does not exclude the coexistence of both perceptual and premotor factors (causing directional hypometria) in left unilateral neglect.

Not re-inventing the wheel: the adaptive implementation of the meeting centres support programme in four European countries.

ABSTRACT Objectives: The implementation of new health services is a complex process. This study investigated the first phase of the adaptive implementation of the Dutch Meeting Centres Support Programme (MCSP) for people with dementia and their carers in three European countries (Italy, Poland, the UK) within the JPND-MEETINGDEM project. Anticipated and experienced factors influencing the implementation, and the efficacy of the implementation process, were investigated. Findings were compared with previous research in the Netherlands. Method: A qualitative multiple case study design was applied. Checklist on anticipated facilitators and barriers to the implementation and semi-structured interview were completed by stakeholders, respectively at the end and at the beginning of the preparation phase. Results: Overall, few differences between countries were founded. Facilitators for all countries were: added value of MCSP matching needs of the target group, evidence of effectiveness of MCSP, enthusiasm of stakeholders. General barriers were: competition with existing care and welfare organizations and scarce funding. Some countries experienced improved collaborations, others had difficulties finding a socially integrated location for MCSP. The step-by-step implementation method proved efficacious. Conclusion: These insights into factors influencing the implementation of MCSP in three European countries and the efficacy of the step-by-step preparation may aid further implementation of MCSP in Europe.

ApoE and SNAP-25 Polymorphisms Predict the Outcome of Multidimensional Stimulation Therapy Rehabilitation in Alzheimer's Disease

Background. Alzheimer’s disease (AD) is a highly prevalent neurodegenerative disorder. Rate of decline and functional restoration in AD greatly depend on the capacity for neural plasticity within residual neural tissues; this is at least partially influenced by polymorphisms in genes that determine neural plasticity, including Apolipoprotein E4 (ApoE4) and synaptosomal-associated protein of 25 kDa (SNAP-25). Objective. We investigated whether correlations could be detected between polymorphisms of ApoE4 and SNAP-25 and the outcome of a multidimensional rehabilitative approach, based on cognitive stimulation, behavioral, and functional therapy (multidimensional stimulation therapy [MST]). Methods. Fifty-eight individuals with mild-to-moderate AD underwent MST for 10 weeks. Neuro-psychological functional and behavioral evaluations were performed blindly by a neuropsychologist at baseline and after 10 weeks of therapy using Mini-Mental State Examination (MMSE), Functional Living Skill Assessment (FLSA), and Neuropsychiatric Inventory (NPI) scales. Molecular genotyping of ApoE4 and SNAP-25 rs363050, rs363039, rs363043 was performed. Results were correlated with ΔMMSE, ΔNPI and ΔFLSA scores by multinomial logistic regression analysis. Results. Polymorphisms in both genes correlated with the outcome of MST for MMSE and NPI scores. Thus, higher overall MMSE scores after rehabilitation were detected in ApoE4 negative compared to ApoE4 positive patients, whereas the SNAP-25 rs363050(G) and rs363039(A) alleles correlated with significant improvements in behavioural parameters. Conclusions. Polymorphisms in genes known to modulate neural plasticity might predict the outcome of a multistructured rehabilitation protocol in patients with AD. These data, although needing confirmation on larger case studies, could help optimizing the clinical management of individuals with AD, for example defining a more intensive treatment in those subjects with a lower likelihood of success.