New leads on treating dementia and Alzheimer’s

A new research study provides an explanation for why clinical trials of drugs reducing proteins in the brain that were thought to cause dementia and Alzheimer’s have failed. The study has opened the way for potential new treatments with existing drugs | Human Molecular Genetics | via ScienceDaily

In an article in the journal, Human Molecular Genetics,  researchers assembled evidence from a wide range of human studies and animal models of dementia-related diseases to show that inflammation is a major cause, not just a consequence. The new work turns previous thinking around. The genetic linkages imply that the inflammation comes first — and the tissue damage second.

Project leader Professor Robert Richards explains that by reducing some elements of inflammation, it may be possible to reduce dementia symptoms:

“With this new understanding of the disease, we now need to test existing anti-inflammatory drugs for their effectiveness in treating dementia,” he says.

Full story at ScienceDaily

Journal reference: Robert I Richards, Sarah A Robertson, Daniel L Kastner |  Neurodegenerative diseases have genetic hallmarks of autoinflammatory disease | Human Molecular Genetics |  April 2018

 

Costs of potentially inappropriate medication use in residential aged care facilities

This review found that the use of potentially inappropriate medications (PIMs) for older adults in residential care facilities is high and that these medications represent a substantial cost which has the potential to be lowered. Further research should investigate whether medication reviews in this population could lead to potential cost savings and improvement in clinical outcomes.

Harrison, S. L. et al | Costs of potentially inappropriate medication use in residential aged care facilities | BMC Geriatrics; 2018; vol. 18 (no. 9)

15 years of dementia treatment in 15 papers

Age and Ageing journal has published a free online collection of 15 papers to provide an update on the advances of pharmacological and non-pharmacological interventions in dementia over the last 15 years.

Image source: academic.oup.com

The published studies reflect the efficacy of the current anti-dementia treatments, preventive treatments of cardio and cerebrovascular incidents known to be risk factors for dementia, alongside the use of antidepressant medication and non-pharmacological interventions for treatment of behavioural and psychopathological symptoms of dementia. We also address the future preventative steps and therapeutic strategies currently in development to combat the devastating consequences of dementia.

 

These papers are all free to read, download and share from the Age and Ageing journal website. The full collection can be viewed here, or individual papers accessed below.

Currently available anti-dementia treatments

• The effect of treatment with selective serotonin reuptake inhibitors in comparison to placebo in the progression of dementia: a systematic review and meta-analysis. Jones HE, Joshi A, Shenkin S, Mead GE. Age Ageing 2016;45(4):448-456
• Long-term cognitive and functional decline in late onset Alzheimer’s disease: therapeutic implications. Holmes C, Lovestone Age Ageing 2003;32(2):200-4.
• Evolution of the evidence on the effectiveness and cost-effectiveness of acetylcholinesterase inhibitors and memantine for Alzheimer’s disease: systematic review and economic model. Hyde C, Peters J, Bond M, et al. Age Ageing 2013;42(1):14-20.
• Associations of acetylcholinesterase inhibitor treatment with reduced mortality in Alzheimer’s disease: a retrospective survival analysis. Mueller C, Perera G, Hayes RD, Shetty H, Stewart R. Age Ageing. 2017:1-7.
• Comparative analysis of mortality in patients with Alzheimer’s disease treated with donepezil or galantamine. López-Pousa S, Olmo JG, Franch JV, et al. Age Ageing 2006;35(4):365-71.
• Acetylcholinesterase inhibitors for Alzheimer’s disease: anti-inflammatories in acetylcholine clothing! Tabet N. Age Ageing 2006;35(4):336-8.
• Observational cohort study: deprivation and access to anti-dementia drugs in the UK. Cooper C, Lodwick R, Walters K, et al. Age Ageing 2016;45(1):148-54.
• Efficacy and safety of a novel acetylcholinesterase inhibitor octohydroaminoacridine in mild-to-moderate Alzheimer’s disease: a Phase II multicenter randomised controlled trial. Xiao S, Wang T, Ma X, et al. Age Ageing 2017;46(5):767-773.

Non-pharmacological interventions

• Sauna bathing is inversely associated with dementia and Alzheimer’s disease in middle-aged Finnish men. Laukkanen T, Kunutsor S, Kauhanen J, Laukkanen JA. Age Ageing 2017;46(2):245-249.
• Lower risk of incident dementia among Chinese older adults having three servings of vegetables and two servings of fruits a day. Lee ATC, Richards M, Chan WC, Chiu HFK, Lee RSY, Lam LCW Age Ageing 2017;46(5):773-779.
• The use of non-pharmacological interventions for dementia behaviours in care homes: findings from four in-depth, ethnographic case studies. Backhouse T, Killett A, Penhale B, Gray R. Age Ageing 2016;45(6):856-863.

Management of vascular risk factors for dementia

• New horizons: the management of hypertension in people with dementia. Harrison JK, Van Der Wardt V, Conroy SP, et al. Age Ageing 2016;45(6):740-746.
• Thromboprophylaxis in atrial fibrillation and association with cognitive decline: systematic review. Moffitt P, Lane DA, Park H, O’Connell J, Quinn TJ. Age Ageing 2016;45(6):767-775.

Drug use in people with dementia

• The burden of psychotropic drug prescribing in people with dementia: a population database study. Guthrie B, Clark SA, McCowan C. Age Ageing 2010;39(5):637-42.
• Drug use in persons with and without Alzheimer’s disease aged 90 years or more.Taipale H, Koponen M, Tanskanen A, Tolppanen AM, Tiihonen J, Hartikainen S. Age Ageing 2016;45(6):900-904.

Two older drugs could be ‘repurposed’ to fight dementia

“Depression and cancer drugs offer hope for dementia sufferers,” Sky News reports. The headline is prompted by a study looking at the effect of two drugs – one used to treat depression and another being trialed for cancer treatment – on neurodegenerative diseases | NHS Choices

This early stage experimental research has demonstrated a beneficial neurological effect of trazodone and dibenzoylmethane on mice with diseases mimicking neurodegenerative diseases.

It is important to acknowledge that this is animal research and therefore the drugs might not have the same effect when they are trialled on humans.

That being said, trazodone is already an approved drug for depression and sleep problems and has therefore already passed safety tests. If the mechanisms of neurodegeneration in humans and mice are similar, it is possible trazodone could be used in the future in treating Alzheimer’s and other neurodegenerative diseases.

These early tests are promising. However, these drugs need to be proven effective and safe in people with neurodegenerative diseases before becoming available.

Even if these are proven safe and effective, it is often a lengthy process from the start of human clinical trials to drugs being marketed and available to healthcare providers. This is especially true for long-term conditions where progression may be slow. Therefore, it could well be several years before these drugs are available for the treatment of neurodegenerative diseases.

Read the full analysis here

The original research abstract is available here

NICE takes key role in new European project for faster access to Alzheimer’s disease drugs

Patients’ priorities will be brought to the fore in new Alzheimer’s project | NICE

NICE is taking part in a European project to speed up the development of new drugs to treat Alzheimer’s disease.

The ROADMAP initiative aims to establish a sustainable platform for real world evidence generation on Alzheimer’s disease.

The new project provides a unique and game-changing opportunity to gather evidence from other sources, such as electronic health records, and discover what outcomes are important to patients and carers.

Alzheimer’s disease, and the different ways it presents and progresses in different people, poses a difficulty for traditional clinical trials which do not always provide answers decision makers such as NICE would be looking for when assessing new drugs to treat the disease.

Read the full news story here

Inequalities in receipt of mental and physical healthcare in people with dementia

Cooper, C. et al. Age Ageing. Published online: December 4 2016

Background: UK Dementia Strategies prioritise fair access to mental and physical healthcare. We investigated whether there are inequalities by deprivation or gender in healthcare received by people with dementia, and compared healthcare received by people with and without dementia.

Conclusions: people with dementia, in particular women, appear to receive less primary healthcare, but take more psychotropic medication that may negatively impact their physical health. Reducing these inequalities and improving access of people with dementia to preventative healthcare could improve the health of people with dementia.

Read the full article here

New Drugs for Dementia

Image source: Public Health England

This briefing outlines the challenges in developing new drugs to treat dementia, and provides an overview of UK and international research activities to accelerate progress in this field.

The key points in this POSTnote are:

• Current drug treatments marginally alleviate symptoms. Psychosocial interventions provide valuable support but access to them is patchy.
• The development of drugs that address the underlying diseases is challenging due to their complexity.
• Investing in research and development on dementia drugs is financially risky for the pharmaceutical industry. Drug development is an expensive and slow process and there has been a high failure rate in developing drugs. as they fail to yield positive results during clinical trials.
• Understanding dementia requires analysis of large amounts of data and therefore a collaborative approach. A robust regulatory and legal framework is needed for privacy, data access and data standardisation so that study outputs can be shared.
• There are new UK and international initiatives working to accelerate research and support collaboration. There are over ten potential disease-modifying drugs in development that may be available in the next five years. Stakeholders call for continued funding to ensure that the value of current investment is realised.
• The first disease-modifying drug will be expensive and will not treat all types of dementia. There is growing consensus that treatment needs to start as early as possible, potentially even before symptoms emerge. Clinical implementation will be practically and ethically complex.
• A healthy and active lifestyle may reduce an individual risk of developing dementia. While further research is needed, improving public health could reduce the number of new cases in the long term.

Full report via Parliamentary Office of Science and Technology