The pathway leading from amyloid-β deposition to cognitive impairment is believed to be a cornerstone of the pathogenesis of Alzheimer's disease (AD). However, what drives amyloid buildup in sporadic nongenetic cases of AD is still unknown. AD brains feature an inflammatory reaction around amyloid plaques, and a specific subset of the gut microbiota (GMB) may promote brain inflammation. We investigated the possible role of the GMB in AD pathogenesis by studying the association of brain amyloidosis with (1) GMB taxa with pro- and anti-inflammatory activity; and (2) peripheral inflammation in cognitively impaired patients. We measured the stool abundance of selected bacterial GMB taxa (Escherichia/Shigella, Pseudomonas aeruginosa, Eubacterium rectale, Eubacterium hallii, Faecalibacterium prausnitzii, and Bacteroides fragilis) and the blood expression levels of cytokines (pro-inflammatory cytokines: CXCL2, CXCL10, interleukin [IL]-1β, IL-6, IL-18, IL-8, inflammasome complex (NLRP3), tumor necrosis factor-alpha [TNF-α]; anti-inflammatory cytokines: IL-4, IL-10, IL-13) in cognitively impaired patients with (n = 40, Amy+) and with no brain amyloidosis (n = 33, Amy-) and also in a group of controls (n = 10, no brain amyloidosis and no cognitive impairment). Amy+ patients showed higher levels of pro-inflammatory cytokines (IL-6, CXCL2, NLRP3, and IL-1β) compared with both controls and with Amy- patients. A reduction of the anti-inflammatory cytokine IL-10 was observed in Amy+ versus Amy-. Amy+ showed lower abundance of E. rectale and higher abundance of Escherichia/Shigella compared with both healthy controls (fold change, FC = -9.6, p < 0.001 and FC = +12.8, p < 0.001, respectively) and to Amy- (FC = -7.7, p < 0.001 and FC = +7.4, p = 0.003). A positive correlation was observed between pro-inflammatory cytokines IL-1β, NLRP3, and CXCL2 with abundance of the inflammatory bacteria taxon Escherichia/Shigella (rho = 0.60, p < 0.001; rho = 0.57, p < 0.001; and rho = 0.30, p = 0.007, respectively) and a negative correlation with the anti-inflammatory E. rectale (rho = -0.48, p < 0.001; rho = -0.25, p = 0.024; rho = -0.49, p < 0.001). Our data indicate that an increase in the abundance of a pro-inflammatory GMB taxon, Escherichia/Shigella, and a reduction in the abundance of an anti-inflammatory taxon, E. rectale, are possibly associated with a peripheral inflammatory state in patients with cognitive impairment and brain amyloidosis. A possible causal relation between GMB-related inflammation and amyloidosis deserves further investigation.

The study shows that MT is effective to reduce BPSD in patients with moderate-severe dementia.

Some indicators imply a less than optimal quality of care (restraints, pressure sores, psychoactive drugs, and the lack of documentation of shared decision-making) and suggest that far advanced demented patients are not fully perceived as "terminal."

We undertook a randomised controlled trial to assess whether a music therapy (MT) scheme of administration, including three working cycles of one month spaced out by one month of no treatment, is effective to reduce behavioural disturbances in severely demented patients. Sixty persons with severe dementia (30 in the experimental and 30 in the control group) were enrolled. Baseline multidimensional assessment included demographics, Mini Mental State Examination (MMSE), Barthel Index and Neuropsychiatry Inventory (NPI) for all patients. All the patients of the experimental and control groups received standard care (educational and entertainment activities). In addition, the experimental group received three cycles of 12 active MT sessions each, three times a week. Each 30-min session included a group of three patients. Every cycle of treatment was followed by one month of wash-out. At the end of this study, MT treatment resulted to be more effective than standard care to reduce behavioural disorders. We observed a significant reduction over time in the NPI global scores in both groups (F(7,357) = 9.06, p < 0.001) and a significant difference between groups (F(1,51) = 4.84, p < 0.05) due to a higher reduction of behavioural disturbances in the experimental group at the end of the treatment (Cohen's d = 0.63). The analysis of single NPI items shows that delusions, agitation and apathy significantly improved in the experimental, but not in the control group. This study suggests the effectiveness of MT approach with working cycles in reducing behavioural disorders of severely demented patients.

Cognitive reserve (CR) is a potential mechanism to cope with brain damage. The aim of this study was to evaluate the effect of CR on a cognitive training (CT) in a group of patients with dementia. Eighty six participants with mild to moderate dementia were identified by their level of CR quantified by the CR Index questionnaire (CRIq) and underwent a cycle of CT. A global measure of cognition mini mental state examination (MMSE) was obtained before (T0) and after (T1) the training. Multiple linear regression analyses highlighted CR as a significant factor able to predict changes in cognitive performance after the CT. In particular, patients with lower CR benefited from a CT program more than those with high CR. These data show that CR can modulate the outcome of a CT program and that it should be considered as a predictive factor of neuropsychological rehabilitation training efficacy in people with dementia.