New research, presented at the Alzheimer’s Association International Conference (21–26 July, IL, USA), focuses on the treatment of non-cognitive symptoms of individuals with Alzheimer’s disease (AD). Behavioral and psychological symptoms of dementia include: agitation, anxiety, apathy, depression, wandering, hallucinations, insomnia, incontinence and disinhibition, and these often cause the greatest challenges to caregivers and reduction in quality of life.
There are currently no US FDA-approved drug treatments for these symptoms associated with AD, and any treatments currently utilized to control the non-cognitive symptoms are approved for other indications and prescribed ‘off-label’.
“These under-recognized and undertreated symptoms in people with Alzheimer’s and other dementias are often very difficult to live with and challenging to treat,” commented Maria Carrillo, Alzheimer’s Association Chief Science Officer. “One of the ‘untold stories’ of Alzheimer’s is the regular occurrence and overwhelming impact of these symptoms on the lives of people with Alzheimer’s, their family members and caregivers.”
“It is very important that as we continue to make advances in treating and preventing the memory and thinking symptoms of Alzheimer’s and other dementias, we also focus on therapeutic strategies for the behavioral and other non-cognitive symptoms,” Carrillo added.
The Alzheimer’s Association currently recommends psychosocial interventions as first-line therapies for the treatment of dementia-related behaviors, including validation therapy, reminiscence and other personalized treatments.
In the case that the AD-related behavior does not respond to non-pharmacologic approaches, psychotropic medications, such as antipsychotics, antidepressants and anticonvulsants, may be considered. These are utilized with extreme caution and regular evaluation, as the FDA has previously found that the use of antipsychotics to treat AD-related behaviors was associated with increased mortality.
A synthetic cannabinoid treatment, nabilone, may be effective in treating agitation in people with AD, according to the results of a recent randomized, double-blind clinical trial. During the 14-week trial, 39 participants, who were 77% male and had an average age of 87, were given nabilone in capsule form for 6 weeks, followed by 6 weeks of treatment with a placebo.
The results suggested that agitation, as well as other behavioral symptoms, were improved significantly in those taking nabilone compared to placebo.
“Currently prescribed treatments for agitation in Alzheimer’s do not work in everybody, and when they do work the effect is small and they increase [the] risk of harmful side effects, including increased risk of death. As a result, there is an urgent need for safer medication options,” remarked Krista Lanctôt, Senior Scientist at Sunnybrook Health Sciences Centre (ON, Canada).
“These findings suggest that nabilone may be an effective treatment for agitation; however, the risk of sedation must be carefully monitored. A larger clinical trial would allow us to confirm our findings regarding how effective and safe nabilone is in the treatment of agitation for Alzheimer’s.”
It has also been noted that many people living with AD experience changes in their sleep pattern, insomnia and daytime sleepiness. Researchers at the Lighting Research Center at Rensselaer Polytechnic Institute (NY, USA) have evaluated whether a tailored lighting system could help improve sleep, mood and behavior in AD patients, particularly those in nursing homes.
“Given that light/dark patterns are a person’s primary cues to the current time, the constant dim light typically experienced by people living in residential care facilities may be an underlying cause of the sleep pattern disturbances so commonly found in this population,” said Mariana Figueiro, Director of the Lighting Research Center.
Positive effects were observed in the short-term study, and these continued to improve as the study was carried out long-term.
Furthermore, researchers from Norwich Medical School University of East Anglia (Norwich, UK) have analyzed the existing data from the UK Clinical Practice Research Datalink and three clinical trials involving individuals with AD to evaluate the benefits and potential risks of prescribing ‘Z-drugs’ to treat insomnia in these patients.
So-called ‘Z-drugs’, including zolpidem, zopiclone and zaleplon, are non-benzodiazepine hypnotic drugs prescribed for the treatment of insomnia, but are thought to cause falls, fractures and confusion. Individuals with dementia are particularly vulnerable to these effects.
The use of Z-drugs in these patients was found to be associated with a 40% increased risk of fractures, but the study did not identify a higher risk of falls, infections or stroke.
“Fractures in people with dementia can have a devastating impact, including loss of mobility, increased dependency and worsening dementia,” remarked Chris Fox, Professor of Psychiatry.
Fox concluded that: “We desperately need better alternatives to the drugs currently being prescribed for sleep problems and other non-cognitive symptoms of dementia. Wherever possible, suitable non-pharmacological alternatives should be considered, and where Z-drugs are prescribed, patients should receive care that reduces or prevents the occurrence of falls.”
Sources: Krista Lanctôt et al. Nabilone improves agitation in patients with moderate-to-severe Alzheimer’s disease: preliminary results of a placebo-controlled, double-blind, cross-over trial. Presented at: Alzheimer’s Association International Conference, Chicago, IL, USA, 22–26 July 2018; Mariana Figueiro et al. Tailored lighting intervention to improve sleep, mood and behavior in Alzheimer’s disease patients. Presented at: Alzheimer’s Association International Conference, Chicago, IL, USA, 22–26 July 2018; Chris Fox et al. Beyond anti-psychotics: exploring efficacy and harms of Z-drugs for sleep disturbance on the progression of key dementia outcomes. Presented at: Alzheimer’s Association International Conference, Chicago, IL, USA, 22–26 July 2018.
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