Tag Archives: Dementia

Accumulation of amyloid beta in the brain impairs memory and cognitive ability in people with Alzheimer’s. New findings published in Nature Communications show that the cause of amyloid beta pathology might be more versatile than previously known. Researchers believe that these new findings may be of significance to the development of new medications.

The accumulation of the protein amyloid beta in the brain is a sign of Alzheimer’s disease. Sufficiently large quantities cause plaque, which blocks the function of the nerve cells and thereby impair the patient’s memory and cognitive ability.

A small proportion of Alzheimer’s patients have a hereditary risk gene, which causes overproduction of amyloid beta in the brain. In all other cases, the cause of the disease has so far been explained by the body’s lack of ability to break down and remove amyloid beta. However, these new findings provide a more nuanced picture:

“In our study, we show that accumulation of amyloid in the brain is associated with high levels of specific amyloid peptides in the cerebrospinal fluid. This means that overproduction of amyloid beta may contribute to development of Alzheimer’s disease in some people, even if they do not carry the hereditary risk gene for Alzheimer’s. The fact that the disease in these individuals can be attributed to both the overproduction of and problems in breaking down amyloid beta may be of significance to the future development of drugs and treatments”, explained Niklas Mattsson, a researcher at Lund University and specialist physician at Skåne University Hospital.

The study noted increased levels of amyloid beta in a large group of patients with no hereditary risk gene. More than 330 people from Sweden participated in the study, some of whom suffered from mild cognitive disorders (which may be an early sign of Alzheimer’s), while others were part of a control group of healthy individuals.

Source: Lund University

A new study in the journal Nature Communications shows that cells normally associated with protecting the brain from infection and injury also play an important role in rewiring the connections between nerve cells. While this discovery sheds new light on the mechanics of neuroplasticity, it could also help explain diseases like autism spectrum disorders, schizophrenia, and dementia, which may arise when this process breaks down and connections between brain cells are not formed or removed correctly.

While the constant reorganization of neural networks – called neuroplasticity – has been well understood for some time, the basic mechanisms by which connections between brain cells are made and broken have eluded scientists.

Performing experiments in mice, the researchers employed a well-established model of measuring neuroplasticity by observing how cells reorganize their connections when visual information received by the brain is reduced from two eyes to one.

The researchers found that in the mice’s brains microglia responded rapidly to changes in neuronal activity as the brain adapted to processing information from only one eye. They observed that the microglia targeted the synaptic cleft – the business end of the connection that transmits signals between neurons. The microglia “pulled up” the appropriate connections, physically disconnecting one neuron from another, while leaving other important connections intact.

The researchers also pinpointed one of the key molecular mechanisms in this process and observed that when a single receptor – called P2Y12 – was turned off the microglia ceased removing the connections between neurons.

These findings may provide new insight into disorders that are the characterized by sensory or cognitive dysfunction, such as autism spectrum disorders, schizophrenia, and dementia. It is possible that when the microglia’s synapse pruning function is interrupted or when the cells mistakenly remove the wrong connections – perhaps due to genetic factors or because the cells are too occupied elsewhere fighting an infection or injury – the result is impaired signaling between brain cells.

Source: University of Rochester Medical Center (URMC)

The Active and Assisted Living Programme (AAL), which aims to improve the conditions of life for older adults through the use information and communication technology (ICT), has opened its 2016 call, Living well with dementia.

The objective of the call is to advance the contribution of ICT to integrated solutions that enable the well being of people living with dementia and their communities, including their family, caregivers, neighbourhood, service providers and care system. The call aims to support innovative, transnational and multi-disciplinary collaborative projects with a clear route to market and added value for the different types of end users. A key priority underlying this challenge will be to bring together technologies and services to create ICT-based solutions addressing the specific aspirations and challenges of people living with dementia and their communities.

The submission deadline is 26 May 2016, 5PM CET. To learn more about the call or to register to watch the live webcast on 8 March, please visit the AAL website.

Alzheimer Europe and Alzheimerforeningen are now accepting abstracts for the 26th Alzheimer Europe Conference, which will take place from October 31 – November 2, 2016, in Copenhagen, Denmark.

Abstracts for oral and poster presentations can be submitted in the following categories:

Dementia-friendly society – Involving people with dementia, Perceptions and image of dementia, Art and dementia, Dementia-friendly communities
Policies and Strategies – Dementia strategies, Legal issues, Care financing, Minority groups
Innovative care – Hospital care, Post-Diagnostic support, Residential care, End-of-life care
Medical aspects – Timely diagnosis, Risk factors and prevention of dementia, Behavioural and psychological aspects of dementia, Treatment of dementia

The call for abstracts will close on April 30, 2016. More information is available on their website.

The European Medicines Agency (EMA) has released draft revised guidelines on medicines for the treatment of Alzheimer’s disease and other types of dementias for a six-month public consultation.

EMA follows a multi-stakeholder approach to facilitate research and development of more effective medicines. The revised guidelines take into account comments received at EMA’s workshop on the clinical investigation of medicines for the treatment of Alzheimer’s disease in November 2014. This workshop brought together a wide range of stakeholders, including patient representatives, regulators, pharmaceutical industry and independent experts. The aim of the workshop was to ensure that during the revision of its guidelines, EMA would be able to consider the most up-to-date scientific developments in understanding and treating Alzheimer’s disease and views from experts in the field. The revised guidelines also build on EMA scientific advice provided for a number of specific development plans for Alzheimer’s disease in recent years, as well as the qualification of several biomarkers for the selection of patients in clinical trials.

The revised guideline specifically addresses the:

impact of new diagnostic criteria for Alzheimer’s disease, including early and even asymptomatic disease stages, on clinical trial design
choice of parameters to measure trial outcomes and the need for distinct assessment tools for the different disease stagesin Alzheimer’s (different signs and symptoms, differences in changes over time, severity)
potential use of biomarkers and their temporal relationship with the different phases of Alzheimer’s disease at different stages of medicine development (mechanism of action, use as diagnostic test, enrichment of study populations, stratification of subgroups, safety and efficacy markers etc.)
design of long-term efficacy and safety studies

Comments received during the consultation will be taken into account in the finalisation of the guideline.

Stakeholders are invited to send their comments by 31 July 2016. To learn more, visit the EMA website.

Source: EMA

A study conducted on mice offers a new type of immunotherapy approach for treating Alzheimer’s disease. This involves amplifying a specific population of T lymphocytes that regulate immune and neuroinflammatory mechanisms that develop during the disease.

These results are published in the journal Brain.

In recent years, a body of substantive work has enabled the start of gaining further insight into complex immune and neuroinflammatory mechanisms associated with Alzheimer’s disease. The researchers offer further proof of concept on the efficacy of innovative immunotherapy strategy in mice that is based on an immunomodulation approach.

Researchers have shown, in earlier work with mice, that a specific population of T lymphocytes, known as T regulators (or Treg), modulated specific Ab peptide T lymphocytes that accumulate in the brains of sick people. Researchers chose to evaluate the effect of Treg cells on disease progression using a mouse model.

To do this, they either depleted or amplified Treg cells at the early stage of the disease. They found that a Treg deficiency accelerated the onset of cognitive disorders and was associated with a decrease in the presence of microglial cells in deposits of Ab peptide.

By contrast, prolonged Treg amplification using low doses of interleukin-2 injected intraperitoneally increases the microglial cell response and delays the onset of memory impairment.

This immunomodulation approach involving the injection of low doses of interleukin-2, already tested in some bone marrow transplant clinical protocols and for type 1 diabetes, now seems to be a new therapeutic strategy for Alzheimer’s disease. Researchers are already planning a pilot clinical trial in humans and are also considering the possibility of modulating some specific sub-populations of T lymphocytes to refine the response.

Source: Inserm

Scientists have revealed that protein clumps associated with Alzheimer’s disease are also found in the brains of people who have had a head injury.

Although previous research has shown that these clumps, called amyloid plaques, are present shortly after a brain injury – this study shows the plaques are still present over a decade after the injury.

The findings may help explain why people who have suffered a serious brain injury appear to be at increased risk of dementia. Although extensive research now suggests major head injury increases dementia risk in later life, scientists do not know the biological changes that cause this effect.

In the research, published in the journal Neurology, the team studied nine patients with moderate to severe traumatic brain injuries. Many had sustained these in road traffic accidents, such as being hit by a car, between 11 months to 17 years prior to the study. The patient underwent a brain scan that used a technique that allows scientists to view amyloid plaques. These proteins are thought to be a hallmark of Alzheimer’s disease, and their formation may trigger other changes that lead to the death of brain cells.

The team also scanned the brains of healthy volunteers, and people with Alzheimer’s disease. The patients with head injury were found to have more amyloid plaques than the healthy volunteers, but fewer than those with Alzheimer’s disease.

In the head injury patients, the amyloid plaques were found to be centred mainly in two brain areas: the posterior cingulate cortex – a highly active area in the centre of the brain involved in controlling attention and memory, and the cerebellum – a region at the base of the brain involved in motor control and coordination.

In a second part of the study, the team assessed damage to so-called white matter. This is the ‘wiring’ of the brain, and enables brain cells to communicate with each other. The results showed that amyloid plaque levels in the posterior cingulate cortex were related to the amount of white matter damage, suggesting that injury to the brain’s wiring may be linked to the formation of amyloid plaques.

Source: Imperial College London

A study has found that blocking a receptor in the brain responsible for regulating immune cells could protect against the memory and behaviour changes seen in the progression of Alzheimer’s disease.

It was originally thought that Alzheimer’s disease disturbs the brain’s immune response, but this latest study, published in the journal Brain, adds to evidence that inflammation in the brain can in fact drive the development of the disease. The findings suggest that by reducing this inflammation, progression of the disease could be halted.

The team hopes the discovery will lead to an effective new treatment for the disease, for which there is currently no cure.

The researchers used tissue samples from healthy brains and those with Alzheimer’s, both of the same age. The researchers counted the numbers of a particular type of immune cell, known as microglia, in the samples and found that these were more numerous in the brains with Alzheimer’s disease. In addition, the activity of the molecules regulating the numbers of microglia correlated with the severity of the disease.

The researchers then studied these same immune cells in mice which had been bred to develop features of Alzheimer’s. They wanted to find out whether blocking the receptor responsible for regulating microglia, known as CSF1R, could improve cognitive skills. They gave the mice oral doses of an inhibitor that blocks CSF1R and found that it could prevent the rise in microglia numbers seen in untreated mice as the disease progressed. In addition, the inhibitor prevented the loss of communication points between the nerve cells in the brain associated with Alzheimer’s, and the treated mice demonstrated fewer memory and behavioural problems compared with the untreated mice.

Importantly, the team found the healthy number of microglia needed to maintain normal immune function in the brain was maintained, suggesting the blocking of CSF1R only reduces excess microglia.

Source: University of Southampton

Men taking androgen deprivation therapy (ADT) for prostate cancer were almost twice as likely to be diagnosed with Alzheimer’s disease in the years that followed than those who didn’t undergo the therapy, an analysis of medical records from two large hospital systems has shown. Men with the longest durations of ADT were even more likely to be diagnosed with Alzheimer’s disease.

The findings, published in the Journal of Clinical Oncology, do not prove that ADT increases the risk of Alzheimer’s disease. But the authors say they clearly point to that possibility, and are consistent with other evidence that low levels of testosterone may weaken the aging brain’s resistance to Alzheimer’s.

For the study, researchers evaluated two large sets of medical records, one from the Stanford health system and the other from Mt. Sinai Hospital in New York City. The researchers scanned the records of 1.8 million patients from Stanford Health Care, and, through a prior institutional research agreement, 3.7 million patients from Mount Sinai Hospital.

Among this cohort, they identified about 9,000 prostate cancer patients at each institution, 16,888 of whom had non-metastatic prostate cancer. A total of 2,397 had been treated with androgen deprivation therapy. The researchers compared these ADT patients with a control group of non-ADT prostate cancer patients, matched according to age and other factors.

Using two different methods of statistical analysis, the team showed that the ADT group, compared to the control group, had significantly more Alzheimer’s diagnoses in the years following the initiation of androgen-lowering therapy. By the most sophisticated measure, members of the ADT group were about 88 percent more likely to get Alzheimer’s.

Source: Penn Medicine

The EU Joint Programme – Neurodegenerative Disease Research (JPND) has announced a rapid-action call inviting leading scientists in the field to bring forward novel approaches that will enhance the use of brain imaging for neurodegenerative disease research.

Imaging techniques such as MR, PET and EEG mapping have brought about a dramatic improvement in the understanding of neurodegenerative diseases such as Alzheimer’s disease. In recent years, access to cutting-edge imaging technologies and platforms has expanded, and advances have been made in the harmonisation of acquisition procedures across scanners and vendors. However, fully capitalising on the use of brain imaging technologies for neurodegeneration research will require the development of new methodologies and the ability to achieve image acquisition and analysis at scale and at the global level.

The aim of the call is to establish a limited number of transnational working groups to address the key challenges facing the use of new and innovative brain imaging techniques in neurodegenerative disease research. The working groups will be community-led and will establish ‘best practice’ guidelines and/or methodological frameworks to overcome these barriers. Each working group can bid up to €50,000 for the support of its activities, which are expected to run for a maximum of 9 months.

According to Professor Philippe Amouyel, Chair of the JPND Management Board:

“JPND recognises that state-of-the-art brain imaging techniques are a vital resource for neurodegenerative disease research. However, achieving scalability for these technologies poses new challenges. For this reason, we’ve launched a rapid-action call inviting international research teams to address the most urgent issues in harmonisation and alignment in neuroimaging. The establishment of effective new guidelines and methodological frameworks will represent a critical step toward the full exploitation of brain imaging in neurodegenerative disease research.”

The following neurodegenerative diseases are included in the call:

Alzheimer’s disease and other dementias
Parkinson’s disease and PD‐related disorders
Prion diseases
Motor neuron diseases
Huntington’s disease
Spinocerebellar ataxia (SCA)
Spinal muscular atrophy (SMA)

Proposals must be submitted by 23:59H C.E.T. on March 10, 2016.

For more information about the call, please click here.