Enhancing cognitive training effects in Alzheimer's disease: rTMS as an add-on treatment.

The treatment of Alzheimer's disease (AD) in the field of non-pharmacological interventions is a challenging issue, given the limited benefits of the available drugs. Cognitive training (CT) represents a commonly recommended strategy in AD. Recently, repetitive transcranial magnetic stimulation (rTMS) has gained increasing attention as a promising therapeutic tool for the treatment of AD, given its ability of enhancing neuroplasticity. In the present randomized, double-blind, sham-controlled study, we aimed at investigating the add-on effect of a high frequency rTMS protocol applied over the left dorsolateral prefrontal cortex (DLPFC) combined with a face-name associative memory CT in the continuum of AD pathology. Fifty patients from a very early to a moderate phase of dementia were randomly assigned to one of two groups: CT plus real rTMS or CT plus placebo rTMS. The results showed that the improvement in the trained associative memory induced with rTMS was superior to that obtained with CT alone. Interestingly, the extent of the additional improvement was affected by disease severity and levels of education, with less impaired and more educated patients showing a greater benefit. When testing for generalization to non-trained cognitive functions, results indicated that patients in CT-real group showed also a greater improvement in visuospatial reasoning than those in the CT-sham group. Interestingly, this improvement persisted over 12 weeks after treatment beginning. The present study provides important hints on the promising therapeutic use of rTMS in AD

Evaluating Voting Competence in Persons with Alzheimer Disease

Voting by persons with dementia raises questions about their decision-making capacity. Methods specifically addressing voting capacity of demented people have been proposed in the US, but never tested elsewhere. We translated and adapted the US Competence Assessment Tool for Voting (CAT-V) to the Italian context, using it before 2006 elections for Prime Minister. Consisting of a brief questionnaire, this tool evaluates the following decision-making abilities: understanding nature and effect of voting, expressing a choice, and reasoning about voting choices. Subjects' performance was examined in relation to dementia severity. Of 38 subjects with Alzheimer's disease (AD) enrolled in the study, only three scored the maximum on all CAT-V items. MMSE and CAT-V scores correlated only moderately (r = 0.59; P < 0.0001) with one another, reflecting the variability of subjects' performance at any disease stage. Most participants (90%), although performing poorly on understanding and reasoning items, scored the maximum on the choice measure. Our results imply that voting capacity in AD is only roughly predicted by MMSE scores and may more accurately be measured by a structured questionnaire, such as the CAT-V. Among the decision-making abilities evaluated by the CAT-V, expressing a choice was by far the least affected by the dementing process

Psychoeducation on Stress and Anxiety Using Virtual Reality: A Mixed-Methods Study

Virtual reality can help individuals to manage stress and anxiety. In addition to its efficacy in reducing stress and anxiety through relaxation, virtual reality can be helpful for psychoeducation. However, to date, few studies have explored this topic. Therefore, this mixed-methods sequential explanatory study, aimed to investigate the usability, sense of presence, emotional response, and effect on learning of MIND-VR, a psychoeducational virtual experience created to offer information on stress and anxiety. Twenty healthcare workers (60% female; mean age 43 ± 10) tried MIND-VR. Psychometric outcomes served as quantitative variables, while participant interviews provided qualitative data. Results showed that the virtual reality psychoeducational experience: (a) was highly usable and satisfying; (b) increased positive emotions (i.e., happiness and surprise) and decreased negative emotions (i.e., fear, sadness) and state anxiety; (c) elicited a strong sense of presence, especially spatial presence; and (d) was practical, simple, motivating, and engaging for learning information about stress and anxiety. These findings offer promising insights into that virtual reality may be an effective tool to provide psychoeducation

Next Generation Sequencing Analysis in Early Onset Dementia Patients.

BackgroundEarly onset dementias (EOD) are rare neurodegenerative dementias that present before 65 years. Genetic factors have a substantially higher pathogenetic contribution in EOD patients than in late onset dementia.ObjectiveTo identify known and/or novel rare variants in major candidate genes associated to EOD by high-throughput sequencing. Common-risk variants of apolipoprotein E (APOE) and prion protein (PRNP) genes were also assessed.MethodsWe studied 22 EOD patients recruited in Memory Clinics, in the context of studies investigating genetic forms of dementia. Two methodological approaches were applied for the target-Next Generation Sequencing (NGS) analysis of these patients. In addition, we performed progranulin plasma dosage, C9Orf72 hexanucleotide repeat expansion analysis, and APOE genotyping.ResultsWe detected three rare known pathogenic mutations in the GRN and PSEN2 genes and eleven unknown-impact mutations in the GRN, VCP, MAPT, FUS, TREM2, and NOTCH3 genes. Six patients were carriers of only common risk variants (APOE and PRNP), and one did not show any risk mutation/variant. Overall, 69% (n = 9) of our early onset Alzheimer's disease (EAOD) patients, compared with 34% (n = 13) of sporadic late onset Alzheimer's disease (LOAD) patients and 27% (n = 73) of non-affected controls (ADNI, whole genome data), were carriers of at least two rare/common risk variants in the analyzed candidate genes panel, excluding the full penetrant mutations.ConclusionThis study suggests that EOD patients without full penetrant mutations are characterized by higher probability to carry polygenic risk alleles that patients with LOAD forms. This finding is in line with recently reported evidence, thus suggesting that the genetic risk factors identified in LOAD might modulate the risk also in EOAD

Predictors of Nursing Home Placement in a Cohort of European People with Alzheimer's Disease and Other Dementia Cases Enrolled in SCU-B or Non SCU-B Centers : The RECage Study

Background: Nursing home placement (NHP) can be the final step of patients with Alzheimer's disease. Objective: We aimed to identify NHP predictors among 508 people with dementia with a 3-year follow-up. Methods: We analyzed data from the international observational RECage study, involving 508 people with especially Alzheimer's disease and comparing a cohort enrolled by five centers with a Special Care Unit for BPSD (behavioral and psychological symptoms of dementia) and another one enrolled by six centers lacking this facility. The tertiary objective of the study was to assess the possible role of the SCU-B in delaying NHP. We assessed the relationship of the baseline characteristics with NHP by means of univariate analysis followed by Cox's multivariate model. Results: Patients' mean age was 78.1 years, 54.9% were women. Diagnosis mean age was 75.4 (±8.32) years; the main diagnosis was Alzheimer's disease (296; 58.4%). During follow-up, 96 (18.9%) patients died and 153 (30.1%) were institutionalized without a statistically significant difference between the two cohorts (p = 0.9626). The mean NHP time was 902 (95% CI: 870-934). The multivariable analysis without death as a competing risk retained four independent predictors of NHP: age increase (hazard ratio (HR) = 1.023, 95% CI: 1.000-1.046), patient education level increase (HR = 1.062, 95% CI: 1.024-1.101), Neuropsychiatric Inventory total increase (HR = 1.018; 95% CI: 1.011-1.026), and total Mini-Mental State Examination as a favorable factor (HR = 0.948, 95% CI: 0.925-0.971). Gender (females versus males: HR = 1.265, 95% CI: 0.899-1.781) was included in the final Cox's model for adjusting the estimates for. Conclusions: Our data partially agree with the predictors of NHP in literature including the effect of high education level. No caregivers' factors were statistically significant. Clinical trial registration: NCT03507504.</p