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P22. Treatment of dementia

Detailed programme and abstracts

P22. Treatment of dementia (Wednesday 2 Nov., 10.30 - 12.00)

P22.1. A clinical trial investigating the effects of Fortasyn Connect (in a medical food) in prodromal Alzheimer’s disease: results of the LipiDiDiet study

SOININEN Hilkka, VISSER Pieter-Jelle, KIVIPELTO Miia, HARTMANN Tobias

The specific nutrient combination Fortasyn Connect is present in a Food for Special Medical Purposes (FSMP) for the dietary management of early Alzheimer’s disease (AD). Extensive preclinical investigation, much of which took place in the LipiDiDiet programme1 indicated that this nutrient combination has effects on multiple biological pathways that contribute to an overall neuroprotective effect.  Earlier randomised controlled trials (RCTs) with this intervention have shown an improved memory performance in drug-naïve mild AD patients, and an excellent safety profile. Together these data suggest that this nutritional approach is a suitable candidate for early intervention, providing the rationale for the LipiDiDiet study1, which was designed to investigate the effects in a previously unstudied population, prodromal AD.

The LipiDiDiet study (NTR1705) was a 24-month, double-blind, parallel-group, multi-centre, multi-country RCT in subjects with prodromal AD (criteria Dubois et al., 2007), receiving the nutrition combination or an iso-caloric control product once daily. Main study visits took place at baseline, 6, 12 and 24 months. Primary outcome was a cognitive function composite score (z-score) based on five items from a modified neuropsychological test battery (mNTB). Secondary- and exploratory outcomes included the memory domain from the mNTB, MRI brain atrophy rates, CDR-SOB, other cognitive and laboratory parameters, tolerance and safety.

After completion of the 24-month RCT subjects were offered optional successive 12-month double blind extension studies. The 24-month RCT was completed in 2015, and the majority of the eligible study completers opted to continue for each extension year. First results indicated the intervention had favourable effects on several of the main outcome measures of the 24-month RCT. The main study results will be presented at the conference.

1Funded by the EU FP7, project LipiDiDiet, Grant Agreement N°211696

P22.2. Treatment with antipsychotic medication in relation to national directives in people with dementia in a Swedish context

KARLSSON Staffan, HALLBERG R Ingalill, MIDLÖV  Patrik, FAGERSTRÖM Cecilia

Background: The aim of this study was to explore trends in treatment with antipsychotic medication in Swedish dementia care in the most recent empirical studies on the treatment with antipsychotic treatment and relate it to directives and recommendations from national authorities.

Methods: The study included; two scoping review studies and two empirical studies. The scoping studies were review of published data in electronic databases as well as Swedish recommendations and directives in the area.

Results: The last decade, recommendations were developed regarding antipsychotic medication in Sweden, in the beginning overviewing to be more and more specific and restrictive. The scoping review showed that the treatment with antipsychotic drugs varied between 6%-38%, and was higher in younger older persons and those with moderate cognitive impairment and living in nursing homes for people with dementia. A trend of a decreased treatment with antipsychotics was seen over the last 15 years. The empirical studies showed that the medication with antipsychotics decreased from 23.5 % in 2001 to 12 % in 2007, for older people in general as well as for older people with dementia. In older people with dementia only, 10% were utilizing antipsychotic medication, with no difference between those in ordinary homes compared to those in nursing homes.

Conclusions: Directives from Swedish national authorities seems to have had an impact on antipsychotic medication in people with dementia. The treatment with antipsychotic medication decreased, while other psychotropic medication increased. National directives complemented with systematic follow-ups may possibly be even more effective.

Conclusion: Treatment with orexin suppressed phagocytosis and degradation of Aβ. Further investigation suggested that the effects of orexin may be mainly on, or mediated through actin. Further investigations concerning the effects of orexin antagonists may be able to offer new methods to arrest the progress of, or possibly treat, AD.

P22.3. Psychotropic polypharmacy in patients with dementia

NØRGAARD Ane, JENSEN-DAHM Christina, GASSE Christiane, ZAKARIAS Johanne Købstrup, WALDEMAR Gunhild

Background: Antipsychotics and other psychotropic drugs are frequently used to treat neuropsychiatric symptoms in patients with dementia, even though the evidence for effect is limited. Concerns have been raised about the safety of antipsychotics, but combined use of antipsychotics and other psychotropics (psychotropic polypharmacy) may also pose a risk for the patients. We aimed to investigate the prevalence and predictors of concomitant use of psychotropic drugs in patients with dementia in Denmark.

Methods: Based on data from nationwide registers we included all patients with dementia on January 1, 2012. We obtained information about redeemed prescriptions, demographics and somatic and psychiatric comorbidity. Prescriptions with overlapping treatment periods were used to identify concomitant use. We conducted a multivariate logistic regression to evaluate factors independently associated with prescription of other psychotropic drugs in addition to antipsychotic treatment.

Results: We identified 34,553 patients with dementia (3.5%) among 974,431 Danish residents aged≥65. Psychotropic polypharmacy with at least two different psychotropic drug classes occurred in 25.3% (8,728). Among patients treated with antipsychotics 75.8% (5,403) used other psychotropic drug during the antipsychotic treatment period. Younger age, female sex, nursing home residency, number of other drugs used in 2011, and prior psychiatric diagnosis were associated with psychotropic polypharmacy among antipsychotic drug users.

Conclusion: Use of other psychotropic drugs in combination with antipsychotics was frequent in dementia patients. Patients with dementia living in nursing homes already characterized by frailty had a higher risk of receiving combinations of psychotropic drugs. The potential consequences for patients safety calls for further investigations.

P22.4. Aducanumab (BIIB037) phase 3 clinical trials: assessing efficacy and safety in people with early Alzheimer’s disease

VIGLIETTA Vissia, O’GORMAN John, WILLIAMS Leslie, TIAN Ying, DOODY Rachelle, SALLOWAY Stephen, BARKHOF Frederik, VELLAS Bruno, SANO Mary, AISEN Paul, SANDROCK Alfred

The presence of amyloid-beta (Aβ)-containing plaques in the brain is a hallmark of Alzheimer’s disease (AD), which precedes the development of dementia by up to 20 years (Villemagne et al, 2013). It is thought that early intervention with therapies that target Aβ, before substantial brain damage occurs, will be more likely to benefit patients than treatment later in the disease course. Aducanumab (BIIB037), a human monoclonal antibody that selectively targets aggregated Aβ, is being investigated as a disease-modifying treatment for AD. Results from an ongoing Phase 1 trial designed to evaluate the safety of aducanumab showed reduced amyloid plaques and slowing of clinical decline. The main safety findings were amyloid-related imaging abnormalities (ARIA) resulting from fluid shifts from vessels within the brain and observed with magnetic resonance imaging (MRI).

We describe the design of two large ongoing Phase 3 trials (ENGAGE and EMERGE) initiated to test the efficacy and safety of aducanumab in people with early AD. These trials, identical in design, are currently recruiting ~1350 participants per trial, 50-85 years of age, who have early AD (including mild cognitive impairment due to AD and mild AD) and evidence of brain amyloid plaques (detected by positron emission tomography [PET] scan). For the initial 18-month period, participants will be randomly assigned (1:1:1) to monthly intravenous low- or high-dose aducanumab or placebo. Participants may then enter a 24-month extension in which all participants will receive active drug. Those who previously received placebo will be randomly assigned (1:1) to either low- or high-dose aducanumab. The main outcome measures of the Phase 3 aducanumab trial will be changes in cognitive impairment and ability to perform activities of daily living. Other outcome measures will include safety, and other patient- and informant/care-partner-reported assessments of behavior, health status, and caregiver burden.

P22.5. Have opioids replaced antipsychotics in the treatment of behavioral symptoms in dementia?

JENSEN-DAHM Christina, NØRGAARD Ane, GASSE Christiane, WALDEMAR Gunhild

Background: Antipsychotics are often prescribed to treat neuropsychiatric symptoms (NPS) in dementia, but have been associated with serious adverse events and increased mortality, which has led to safety regulations worldwide. Recently it has been suggested that opioids may be used to treat NPS. The aim of this study was to investigate time trends of antipsychotic and opioid drug use in patients with dementia in Denmark from 2000-2013.

Methods: Population-based observational study with time series of cross-sectional studies and conducted by use of Danish nationwide registers including the entire elderly population (age≥65) of Denmark.  The registers were used to identify patients with dementia and identify users of opioids and antipsychotics from 2000 to 2013.

Results: From 2000 to 2013 prevalence of antipsychotic drug use among patients with dementia decreased by 35.8% (from 31.3% to 20.1%), but during the same period opioids increased by 37.9% (from 24.2% to 33.8%). Among elderly without dementia antipsychotic drug use decreased by 37.8% (from 4.5% to 2.8%) and opioid use increased by 15.4% (from 14.9% to 17.2%).

Conclusion: From 2000 to 2013 the use of antipsychotics among patients with dementia decreased, but during the same period use of opioids increased. The marked increase could be explained by a higher awareness among physicians of the importance of sufficient pain treatment. However, the high use of opioids is concerning and the association with a decrease in antipsychotics suggest that opioids may be used for managing NPS and to some extent have replaced antipsychotics.

P22.6. The relevance of functional and global clinical trials scales in clinical trials

BULLOCK Roger, FARLOW Martin, OLIN Jason

Since the development of the first treatments for persons with Alzheimer disease, regulatory authorities have required demonstration of treatment benefits to be shown on a test of cognitive function, as well as shown on either a functional assessment or a clinician’s global rating scale. The reason for requiring two outcomes reflected the thinking of the times.  This led to uncertainty regarding how to interpret change on a sensitive test of cognitive function.

As a result, regulatory authorities asked for a functional outcome to be included, usually a carer assessments of activities of daily living (ADL). Alternatively, a global rating by the clinician was allowed. These scales are not useful to clinical practice. They require rater training, are time-consuming, and can be demanding for carers and patients alike. These additional outcomes helped provide assurance to regulatory reviewers that change seen on a sensitive cognitive test is also mirrored on a measure that is more closely related to the overall function of the person with Alzheimer disease.

More recent treatments are being developed that could be used in the earliest forms of Alzheimer disease or that could change the course of the disease. Some of these researchers have argued that functional and global ratings are now no longer relevant. We review Alzheimer disease trials included for regulatory registration, finding that overall, ADL and global outcomes detect treatment effects across the stages of the disease. We conclude that measures of ADLs and global function remain important indicators of treatment benefit and are relevant sources of clinical information to both regulatory authorities and practicing clinicians.  

 

 
 

Last Updated: Tuesday 10 January 2017

 

 
  • Acknowledgements

    The 26th AE Conference in Copenhagen received funding under an operating grant from the European Union’s Health Programme (2014-2020). Alzheimer Europe and Alzheimerforeningen gratefully acknowledge the support of all conference sponsors.
  • European Union
  • Roche
 
 

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