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.
Objective: to evaluate the performance of the 4 ‘A’s Test (4AT) in screening for delirium in older patients. The 4AT is a new test for rapid screening of delirium in routine clinical practice.Design: prospective study of consecutively admitted elderly patients with independent 4AT and reference standard assessments.Setting: an acute geriatrics ward and a department of rehabilitation.Participants: two hundred and thirty-six patients (aged ≥70 years) consecutively admitted over a period of 4 months.Measurements: in each centre, the 4AT was administered by a geriatrician to eligible patients within 24 h of admission. Reference standard delirium diagnosis (DSM-IV-TR criteria) was obtained within 30 min by a different geriatrician who was blind to the 4AT score. The presence of dementia was assessed using the Alzheimer's Questionnaire and the informant section of the Clinical Dementia Rating scale. The main outcome measure was the accuracy of the 4AT in diagnosing delirium.Results: patients were 83.9 ± 6.1 years old, and the majority were women (64%). Delirium was detected in 12.3% (n = 29), dementia in 31.2% (n = 74) and a combination of both in 7.2% (n = 17). The 4AT had a sensitivity of 89.7% and specificity 84.1% for delirium. The areas under the receiver operating characteristic curves for delirium diagnosis were 0.93 in the whole population, 0.92 in patients without dementia and 0.89 in patients with dementia.Conclusions: the 4AT is a sensitive and specific method of screening for delirium in hospitalised older people. Its brevity and simplicity support its use in routine clinical practice.
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.
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."
ObjectiveDelirium superimposed on dementia (DSD) is common in many settings. Nonetheless, little is known about the association between DSD and clinical outcomes. The study aim was to evaluate the association between DSD and related adverse outcomes at discharge from rehabilitation and at 1-year follow-up in older inpatients undergoing rehabilitation.DesignProspective cohort study.SettingHospital rehabilitation unit.ParticipantsA total of 2642 patients aged 65 years or older admitted between January 2002 and December 2006.MeasurementsDementia predating rehabilitation admission was detected by DSM-III-R criteria. Delirium was diagnosed with the DSM-IV-TR. The primary outcome was that of walking dependence (Barthel Index mobility subitem score of <15) captured as a trajectory from discharge to 1-year follow-up. A mixed-effects multivariate logistic regression model was used to analyze the association between DSD and outcome, after adjusting for relevant covariates. Secondary outcomes were institutionalization and mortality at 1-year follow-up, and logistic regression models were used to analyze these associations.ResultsThe median age was 77 years (interquartile range: 71–83). The prevalence of DSD was 8%, and the prevalence of delirium and dementia alone were 4% and 22%, respectively. DSD at admission was found to be significantly associated with almost a 15-fold increase in the odds of walking dependence (odds ratio [OR] 15.5; 95% Confidence Interval [CI] 5.6–42.7; P < .01). DSD was also significantly associated with a fivefold increase in the risk of institutionalization (OR 5.0; 95% CI 2.8–8.9; P < .01) and an almost twofold increase in the risk of mortality (OR 1.8; 95% CI 1.1–2.8; P = .01).ConclusionsDSD is a strong predictor of functional dependence, institutionalization, and mortality in older patients admitted to a rehabilitation setting, suggesting that strategies to detect DSD routinely in practice should be developed and DSD should be included in prognostic models of health care.
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