Tag Archives: prevention

A new study has found that a healthy diet, regular physical activity and a normal body mass index can reduce the incidence of protein build-ups that are associated with the onset of Alzheimer’s disease.

In the study, 44 adults ranging in age from 40 to 85 (mean age: 62.6) with mild memory changes but no dementia underwent an experimental type of PET scan to measure the level of plaque and tangles in the brain. Researchers also collected information on participants’ body mass index, levels of physical activity, diet and other lifestyle factors. Plaque, deposits of a toxic protein called beta-amyloid in the spaces between nerve cells in the brain; and tangles, knotted threads of the tau protein found within brain cells, are considered the key indicators of Alzheimer’s.

The study, published in the American Journal of Geriatric Psychiatry, found that each one of several lifestyle factors — a healthy body mass index, physical activity and a Mediterranean diet — were linked to lower levels of plaques and tangles on the brain scans. (The Mediterranean diet is rich in fruits, vegetables, legumes, cereals and fish and low in meat and dairy, and characterized by a high ratio of monounsaturated to saturated fats, and mild to moderate alcohol consumption.)

Earlier studies have linked a healthy lifestyle to delays in the onset of Alzheimer’s. However, the new study is the first to demonstrate how lifestyle factors directly influence abnormal proteins in people with subtle memory loss who have not yet been diagnosed with dementia. Healthy lifestyle factors also have been shown to be related to reduced shrinking of the brain and lower rates of atrophy in people with Alzheimer’s.

The next step in the research will be to combine imaging with intervention studies of diet, exercise and other modifiable lifestyle factors, such as stress and cognitive health.

Reprinted from materials provided by UCLA.

A gene associated with Alzheimer’s disease and recovery after brain injury may show its effects on the brain and thinking skills as early as childhood, according to a study published in Neurology.

Prior studies showed that people with the epsilon(ε)4 variant of the apolipoprotein-E gene are more likely to develop Alzheimer’s disease than people with the other two variants of the gene, ε2 and ε3.

For the study, 1,187 children ages three to 20 years had genetic tests and brain scans and took tests of thinking and memory skills. The children had no brain disorders or other problems that would affect their brain development, such as prenatal drug exposure.

Each person receives one copy of the gene (ε2, ε3 or ε4) from each parent, so there are six possible gene variants: ε2ε2, ε3ε3, ε4ε4, ε2ε3, ε2ε4 and ε3ε4.

The study found that children with any form of the ε4 gene had differences in their brain development compared to children with ε2 and ε3 forms of the gene. The differences were seen in areas of the brain that are often affected by Alzheimer’s disease. In children with the ε2ε4 genotype, the size of the hippocampus, a brain region that plays a role in memory, was approximately 5 percent smaller than the hippocampi in the children with the most common genotype (ε3ε3). Children younger than 8 and with the ε4ε4 genotype typically had lower measures on a brain scan that shows the structural integrity of the hippocampus.

“These findings mirror the smaller volumes and steeper decline of the hippocampus volume in the elderly who have the ε4 gene,” said study author Linda Chang, MD, of the University of Hawaii in Honolulu.

In addition, some of the children with ε4ε4 or ε4ε2 genotype also had lower scores on some of the tests of memory and thinking skills. Specifically, the youngest ε4ε4 children had up to 50 percent lower scores on tests of executive function and working memory, while some of the youngest ε2ε4 children had up to 50 percent lower scores on tests of attention. However, children older than 8 with these two genotypes had similar and normal test scores compared to the other children.

Limitations of the study include that it was cross-sectional, meaning that the information is from one point in time for each child, and that some of the rarer gene variants, such as ε4ε4 and ε2ε4, and age groups did not include many children.

Criteria for folding in structure-based models of proteins” has been published in The Journal of Chemical Physics. This research was supported in part by JPND through the MisingLink project, selected in the 2013 cross-disease analysis call.

Researchers have shown how brain connections, or synapses, are lost early in Alzheimer’s disease and demonstrated that the process starts — and could potentially be halted — before telltale plaques accumulate in the brain. Their work, published online by Science, suggests new therapeutic targets to preserve cognitive function early in Alzheimer’s disease.

The researchers show in multiple Alzheimer’s mouse models that mechanisms similar to those used to “prune” excess synapses in the healthy developing brain are wrongly activated later in life. By blocking these mechanisms, they were able to reduce synapse loss in the mice.

Currently, there are five FDA-approved drugs for Alzheimer’s, but these only boost cognition temporarily and do not address the root causes of cognitive impairment in Alzheimer’s. Many newer drugs in the pipeline seek to eliminate amyloid plaque deposits or reduce inflammation in the brain, but the new research from Boston Children’s suggests that Alzheimer’s could be targeted much earlier, before these pathologic changes occur.

“Synapse loss is a strong correlate of cognitive decline,” says Beth Stevens, assistant professor in the Department of Neurology at Boston Children’s, senior investigator on the study and a recent recipient of the MacArthur “genius” grant. “We’re trying to go back to the very beginning and see how synapse loss starts.”

The researchers looked at Alzheimer’s — a disease of aging — through an unusual lens: normal brain development in infancy and childhood. Through years of research, the Stevens lab has shown that normal developing brains have a process to “prune” synapses that aren’t needed as they build their circuitry.

“Understanding a normal developmental process deeply has provided us with novel insight into how to protect synapses in Alzheimer’s and potentially a host of other diseases,” says Stevens, noting that synapse loss also occurs in frontotemporal dementia, Huntington’s disease, schizophrenia, glaucoma and other conditions.

In the Alzheimer’s mouse models, the team showed that synapse loss requires the activation of a protein called C1q, which “tags” synapses for elimination. Immune cells in the brain called microglia then “eat” the synapses — similar to what occurs during normal brain development. In the mice, C1q became more abundant around vulnerable synapses before amyloid plaque deposits could be observed.

When Stevens and colleagues blocked C1q, a downstream protein called C3, or the C3 receptor on microglia, synapse loss did not occur.

“Microglia and complement are already known to be involved in Alzheimer’s disease, but they have been largely regarded as a secondary event related to plaque-related neuroinflammation, a prominent feature in progressed stages of Alzheimer’s,” notes Soyon Hong, the Science paper’s first author. “Our study challenges this view and provides evidence that complement and microglia are involved much earlier in the disease process, when synapses are already vulnerable, and could potentially be targeted to preserve synaptic health.”

A human form of the antibody Stevens and Hong used to block C1q, known as ANX-005, is in early therapeutic development with Annexon Biosciences (San Francisco) and is being advanced into the clinic. The researchers believe it has potential to be used someday to protect against synapse loss in a variety of neurodegenerative diseases.

“One of the things this study highlights is the need to look for biomarkers for synapse loss and dysfunction,” says Hong. “As in cancer, if you treat people at a later stage of Alzheimer’s, it may already be too late.”

The researchers also found that the beta-amyloid protein, C1q and microglia work together to cause synapse loss in the early stages of Alzheimer’s. The oligomeric form of beta-amyloid (multiple units of beta-amyloid strung together) is already known to be toxic to synapses even before it forms plaque deposits, but the study showed that C1q is necessary for this effect. The converse was also true: microglia engulfed synapses only when oligomeric beta-amyloid was present.

Source: Reprinted from materials provided by Boston Children’s Hospital
Paper: “Complement and microglia mediate early synapse loss in Alzheimer mouse models”

The National Institutes of Health, USA has released recommendations that provide a framework for a bold and transformative Alzheimer’s disease research agenda.

Developed at the February 2015 Alzheimer’s Disease Research Summit 2015: Path to Treatment and Prevention, the highly anticipated recommendations provide the wider Alzheimer’s research community with a strategy for speeding the development of effective interventions for Alzheimer’s and related dementias.

These recommendations call for a change in how the academic, biopharmaceutical and government sectors participating in Alzheimer’s research and therapy generate, share and use knowledge to propel the development of critically needed therapies.

Researchers have the first conclusive proof that changes to lifestyle among the over-60s can slow mental decline – raising the prospects of dementia prevention programmes that cut your risk of the disease.

Findings from a two-year study of more than 1,200 60 to 77-year-olds in Finland, published in The Lancet medical journal, reveal that a group who received thorough advice about diet, regular exercise sessions, brain training and health check-ups performed better in cognitive tests than a group who received only the standard medical advice.

The results are significant, as it is believed to be the first randomised and controlled trial to conclusively demonstrate that keeping the body healthy in later life also benefits the brain. The participants will now be followed up over seven years to see if those who received the intensive healthcare intervention are less likely to develop dementia.

Overall scores in mental tests after two years were 25 per cent better in the group who received the intensive health programme. In particular areas they were even more striking. Scores for executive functioning – the brain’s ability to organise thought processes – were 83 per cent higher in the intervention group, while mental processing speeds were 150 per cent higher. All participants in the trial were judged to have a high risk of dementia at the start.

The study’s lead investigator is Miia Kivipelto of the Karolinska Instituet, Sweden, who is also the coordinator of the JPND-supported MIND-AD project which is developing multinational strategies for multi-modal preventive trials for Alzheimer’s Disease.

Source:  The Independent

Experts in innovation in care and risk reduction recently met at the third Global Dementia Legacy event in Japan to explore how new technology can improve the lives of those with dementia, as well as looking at whether lifestyle choices can reduce the risk of developing dementia.

JPND chair, Philippe Amouyel presented JPND approaches in this area on day two of the conference. His slides can be viewed at the link below.

The fourth, and final legacy event will take place in Washington, DC, USA in February 2015.

A total of fifteen international consortia have been proposed for funding under two JPND Transnational calls between a total of 18 countries.

These new projects are aiming to analyse neurodegenerative diseases across traditional clinical boundaries, and also to begin “pilot” studies for the design of preventive strategies.

The projects are supported under two JPND transnational calls for proposals entitled:

The calls were launched in December 2013 with a pre-proposal deadline of March 2014. Sixteen countries participated in each call.

The project proposals have been proposed for funding by the respective Peer Review Panels based on scientific evaluation and by the respective Call Steering Committees based on budget availability.

For further information on the projects proposed for funding, click on the links below.