Etanercept in Alzheimer disease: A randomized, placebo-controlled, double-blind, phase 2 trial.

OBJECTIVES: To determine whether the tumor necrosis factor α inhibitor etanercept is well tolerated and obtain preliminary data on its safety in Alzheimer disease dementia. METHODS: In a double-blind study, patients with mild to moderate Alzheimer disease dementia were randomized (1:1) to subcutaneous etanercept (50 mg) once weekly or identical placebo over a 24-week period. Tolerability and safety of this medication was recorded including secondary outcomes of cognition, global function, behavior, and systemic cytokine levels at baseline, 12 weeks, 24 weeks, and following a 4-week washout period. This trial is registered with EudraCT (2009-013400-31) and ClinicalTrials.gov (NCT01068353). RESULTS: Forty-one participants (mean age 72.4 years; 61% men) were randomized to etanercept (n = 20) or placebo (n = 21). Etanercept was well tolerated; 90% of participants (18/20) completed the study compared with 71% (15/21) in the placebo group. Although infections were more common in the etanercept group, there were no serious adverse events or new safety concerns. While there were some interesting trends that favored etanercept, there were no statistically significant changes in cognition, behavior, or global function. CONCLUSIONS: This study showed that subcutaneous etanercept (50 mg/wk) was well tolerated in this small group of patients with Alzheimer disease dementia, but a larger more heterogeneous group needs to be tested before recommending its use for broader groups of patients. CLASSIFICATION OF EVIDENCE: This study shows Class I evidence that weekly subcutaneous etanercept is well tolerated in Alzheimer disease dementia.

Long-term effects of Abeta42 immunisation in Alzheimer's disease: follow-up of a randomised, placebo-controlled phase I trial.

BACKGROUND: Immunisation of patients with Alzheimer's disease with full-length amyloid-beta peptide (Abeta(42)) can clear amyloid plaques from the brain. Our aim was to assess the relation between Abeta(42) immune response, degree of plaque removal, and long-term clinical outcomes. METHODS: In June, 2003, consent for long-term clinical follow-up, post-mortem neuropathological examination, or both, was sought from 80 patients (or their carers) who had entered a phase I randomised, placebo-controlled trial of immunisation with Abeta(42) (AN1792, Elan Pharmaceuticals) in September, 2000. The follow-up study was completed in September, 2006. Plaques were assessed in terms of the percentage area of the cortex with Abeta immunostaining (Abeta load) and in terms of characteristic histological features reflecting plaque removal. Survival of all 80 individuals until severe dementia or death was assessed with a Cox proportional hazard model. FINDINGS: 20 participants--15 in the AN1792 group, five in the placebo group--died before follow-up started. A further 22 patients--19 in the AN1792 group, three in the placebo group--died during follow-up. Nine of the deceased patients, all in the AN1792 group, had given consent for post-mortem analysis; one of these who did not die with Alzheimer's disease was excluded. In the remaining eight participants who received immunisation and who were examined neuropathologically, mean Abeta load was lower than in an unimmunised control group that was matched for age at death (2.1% [SE 0.7] in treated participants vs 5.1% [0.9] in controls; mean difference 3.0%, 95% CI 0.6-5.4; p=0.02). Although there was considerable variation in Abeta load and degree of plaque removal among immunised participants, the degree of plaque removal varied significantly with mean antibody response attained during the treatment study period (Kruskal-Wallis p=0.02). Seven of the eight immunised patients who underwent post-mortem assessment, including those with virtually complete plaque removal, had severe end stage dementia before death. In the whole cohort, there was no evidence of improved survival (hazard ratio 0.93, 95% CI 0.43-3.11; p=0.86) or of an improvement in the time to severe dementia (1.18, 0.45-3.11; p=0.73) in the AN1792 group versus the placebo group. INTERPRETATION: Although immunisation with Abeta(42) resulted in clearance of amyloid plaques in patients with Alzheimer's disease, this clearance did not prevent progressive neurodegeneration.

The effect of link nurses on hospital readmission rates.

This study investigates whether visits to a patient early post-discharge by a member of the ward team (locality link nurse) reduces psychiatric hospital readmission rates for older people and improves the physical and psychological state of the patient. This is a summary of the paper the full version can be accessed at nursingtimes.net.

Keep music live: music and the alleviation of apathy in dementia subjects.

BACKGROUND: A recent Cochrane report concluded that more and better quality research is required to investigate the effectiveness of music therapy in reducing problems in behavioral, social, emotional and cognitive domains in patients with dementia. This randomized placebo-controlled trial with blinded observer rater aimed to explore whether music, live or pre-recorded, is effective in the treatment of apathy in subjects with moderate to severe dementia. METHODS: Thirty-two subjects meeting ICD-10 diagnostic criteria for moderate to severe dementia and fulfilling diagnostic criteria for apathy were exposed to live interactive music, passive pre-recorded music or silence for 30 minutes. Each subject was randomized to 30-minute music or silent periods and was video recorded and the muted recording analyzed every 3 minutes using dementia care mapping to assess the quality of engagement to the blinded music intervention. RESULTS: Compared to low baseline levels of positive engagement (12.5%) in the silent placebo period, the majority of subjects (69%), regardless of dementia severity, showed a significant and positive engagement to live music. Engagement to pre-recorded music was non-significant, with just 25% of all subjects showing positive engagement. No subjects showed any evidence of experiencing a state of ill-being during either the live or pre-recorded music sessions. CONCLUSIONS: During the intervention, live interactive music has immediate and positive engagement effects in dementia subjects with apathy, regardless of the severity of their dementia. Pre-recorded music is non-harmful but less clearly beneficial.

Lavender oil as a treatment for agitated behaviour in severe dementia: a placebo controlled study.

OBJECTIVE: To determine whether aromatherapy with lavender oil is effective in the treatment of agitated behaviour in patients with severe dementia. DESIGN: A placebo controlled trial with blinded observer rater. SETTING: A long-stay psychogeriatric ward. PATIENTS: Fifteen patients meeting ICD-10 diagnostic criteria for severe dementia and suffering from agitated behaviour defined as a minimum score of three points on the Pittsburgh Agitation Scale (PAS). INTERVENTION: A 2% lavender oil aromatherapy stream was administered on the ward for a two hour period alternated with placebo (water) every other day for a total of ten treatment sessions. ASSESSMENTS: For each subject 10 total PAS scores were obtained. Five during treatment and five during placebo periods. RESULTS: Nine patients (60%) showed an improvement, five (33%) showed no change and one patient (7%) showed a worsening of agitated behaviour during aromatherapy compared with placebo. A comparison of the group median PAS scores during aromatherapy showed a significant improvement in agitated behaviour during aromatherapy compared with placebo (median PAS scores 3 c.f. 4; Wilcoxon Signed-Ranks test p = 0.016 (one-tailed)). CONCLUSIONS: Lavender oil administered in an aroma stream shows modest efficacy in the treatment of agitated behaviour in patients with severe dementia.