Category Archives: Research News (General)

Enhanced lifestyle counselling prevents cognitive decline even in people who are carriers of the APOE4 gene, a common risk factor of Alzheimer’s disease, according to a new study published in JAMA Neurology.

The two-year FINGER trial involved 60–77 year-old people living in Finland with risk factors for memory disorders. The study participants were divided into two groups: one of the groups was given regular lifestyle counselling and the other enhanced lifestyle counselling. Enhanced counselling involved nutrition counselling, physical and cognitive exercises and support in managing the risk of cardiovascular diseases.

Earlier findings from the FINGER trial have shown that the regular lifestyle counselling group had a significantly increased risk of cognitive and functional impairment compared to the intervention group, i.e. the group receiving enhanced counselling.

Now the researchers analysed whether the presence of the APOE4 gene affected the intervention results. The analysis included 1,109 persons of whom 362 were carriers of the APOE4 gene.

The findings show that enhanced lifestyle counselling prevented cognitive decline despite the presence of the risk gene. Analyses carried out within the groups also indicate that the intervention results might even be better in carriers of the APOE4 gene.

Paper: “Effect of the Apolipoprotein E Genotype on Cognitive Change During a Multidomain Lifestyle Intervention

Reprinted from materials provided by the University of Eastern Finland

New research sheds light on how a breakdown in the brain’s vascular system predates the accumulation of toxic plaques and tangles in the brain that bring about Alzheimer’s disease.

Nearly 50 percent of all dementias, including Alzheimer’s, begins with the breakdown of the smallest blood vessels in the brain and their protective “gatekeeper cells,” according to the study, published in Nature Medicine.

That catastrophe causes a communications failure called small vessel disease. Many people with that disease also have white matter disease, the wearing away of fatty myelin that allows neurons to transfer messages within the brain network. In an animal model, researchers found that brain deterioration associated with dementia may start as early 40 in humans.

For more than 25 years, scientists have known that white matter disease impedes a person’s ability to learn or remember new things, slows thinking and causes people to fall more often due to balance issues. They identified a link between crippled small blood vessels in the brain and white matter disease but didn’t know what started that process until now.

The study explains that pericytes, gatekeeper cells that surround the brain’s smallest blood vessels, play a critical role in white matter health and disease via fibrinogen, a protein that circulates in blood. Fibrinogen develops blood clots so wounds can heal. When gatekeeper cells are compromised, an unhealthy amount of fibrinogen slinks into the brain and causes white matter and brain structures, including axons (nerve fibers) and oligodendrocytes (cells that produces myelin), to die.

In a mouse model, the researchers used an enzyme known to reduce fibrinogen in blood and the brain. White matter volume in the mice returned to 90 percent of their normal state, and white matter connections were back to 80 percent productivity, the study found.

Paper: “Pericyte degeneration causes white matter dysfunction in the mouse central nervous system”

Reprinted from materials provided by USC.

ALS and frontotemporal dementia (FTD) are two neurodegenerative diseases with a toxic relationship, according to a new paper published in Nature Medicine. The study describes how a mutation in a gene, called C9ORF72, leads to toxicity in nerve cells—causing 10 percent of all cases of ALS, and an additional 10 percent of FTD.

To understand how this happens, the researchers extracted blood from ALS patients carrying the C9ORF72 mutation, and reprogrammed these blood cells into the motor nerve cells that degenerate and die in the disease. They also extracted blood from healthy patients, reprogrammed these blood cells into motor nerve cells, and used gene editing to delete the C9ORF72 gene.

Whether patient-derived or gene-edited, all motor nerve cells with the mutation had reduced amounts of the protein normally made by the C9ORF72 gene. Furthermore, by adding supplemental C9ORF72 protein, the researchers could stop the motor nerve cells from degenerating.

Through a series of experiments, the researchers revealed that the motor nerve cells use C9ORF72 protein to build lysosomes—which are cellular compartments used to engulf and break down toxic proteins and other garbage.

Without enough lysosomes, the cells accumulate two key types of garbage. The first type is a large, toxic protein produced by the mutated C9ORF72 gene itself. The second type is an excessive number of receptors, or molecules that receive signals from a neurotransmitter known as glutamate. These receptors respond to glutamate by causing the motor nerve cell to activate. Too much activation can kill a motor nerve cell.

The researchers are now using patient-derived motor nerve cells to test potential drugs—with a focus on those that affect lysosomes.

Paper: “Haploinsufficiency leads to neurodegeneration in C9ORF72 ALS/FTD human induced motor neurons”

Reprinted from materials provided by the Keck School of Medicine at USC.

A team has developed a system to model Huntington’s in human embryonic stem cells for the first time. In a report published in Development, they describe early abnormalities in the way Huntington’s neurons look, and how these cells form larger structures that had not previously been associated with the disease.

Huntington’s is one of the few diseases with a straightforward genetic culprit: One hundred percent of people with a mutated form of the Huntingtin (HTT) gene develop the disease. The mutation takes the form of extra DNA, and causes the gene to produce a longer-than-normal protein.

Research on Huntington’s has thus far relied heavily on animal models of the disease. Suspecting that the disease works differently in humans, the researchers developed a cell-based human system for their research. They used the gene editing technology CRISPR to engineer a series of human embryonic stem cell lines, which were identical apart from the number of DNA repeats that occurred at the ends of their HTT genes.

When cells divide, they typically each retain one nuclei. However, some of these mutated cells flaunted up to 12 nuclei—suggesting that neurogenesis, or the generation of new neurons, was affected.

Treatments for Huntington’s have typically focused on blocking the activity of the mutant HTT protein. However, this research shows that the brain disruption may actually be due to a lack of HTT protein activity. The researchers created cell lines that completely lacked the HTT protein. These cells turned out to be very similar to those with Huntington’s pathology, corroborating the idea that a lack of the protein—not an excess of it—is driving the disease.

Article:  “Chromosomal instability during neurogenesis in Huntington’s disease.”
Reprinted from materials provided by Rockefeller University.

People with Alzheimer’s disease are known to have disturbances in their internal body clocks that affect sleep/wake cycle and may increase their risk of developing the disorder. Now, new research published in JAMA Neurology indicates that such circadian rhythm disruptions also occur much earlier in people whose memories are intact but whose brain scans show early, preclinical evidence of Alzheimer’s disease.

Previous studies conducted in people and in animals have found that levels of amyloid fluctuate in predictable ways during the day and night. Amyloid levels decrease during sleep, and several studies have shown that levels increase when sleep is disrupted or when people don’t get enough deep sleep.

The researchers tracked circadian rhythms in 189 cognitively normal, older adults with an average age of 66. Of the participants, 139 had no evidence of the amyloid protein that signifies preclinical Alzheimer’s. Most had normal sleep/wake cycles, although several had circadian disruptions that were linked to advanced age, sleep apnea or other causes.

But among the other 50 subjects — who either had abnormal brain scans or abnormal cerebrospinal fluid — all experienced significant disruptions in their internal body clocks, determined by how much rest they got at night and how active they were during the day. Disruptions in the sleep/wake cycle remained even after the researchers statistically controlled for sleep apnea, age and other factors.

By tracking activity during the day and night, the researchers could tell how scattered rest and activity were throughout 24-hour periods. Subjects who experienced short spurts of activity and rest during the day and night were more likely to have evidence of amyloid buildup in their brains, the researchers said.

Paper: “Circadian Rest-Activity Pattern Changes in Aging and Preclinical  Alzheimer Disease”
Reprinted from materials provided by Washington University School of Medicine.

A new study published in Scientific Reports shows that low levels of alcohol consumption may tamp down inflammation and help the brain clear away toxins, including those associated with Alzheimer’s disease.

The research focused on the glymphatic system, the brain’s unique cleaning process that was first described by the same researchers in 2012. They showed how cerebral spinal fluid (CSF) is pumped into brain tissue and flushes away waste, including the proteins beta amyloid and tau that are associated with Alzheimer’s disease and other forms of dementia. Subsequent research has shown that the glymphatic system is more active while we sleep, can be damaged by stroke and trauma, and improves with exercise.

The new study, which was conducted in mice, looked at the impact of both acute and chronic alcohol exposure.  When they studied the brains of animals exposed to high levels of alcohol over a long period of time, the researchers observed high levels of a molecular marker for inflammation, particularly in cells called astrocytes which are key regulators of the glymphatic system.  They also noted impairment of the animal’s cognitive abilities and motor skills.

Animals that were exposed to low levels of alcohol consumption, analogous to approximately 2 ½ drinks per day, actually showed less inflammation in the brain and their glymphatic system was more efficient in moving CSF through the brain and removing waste, compared to control mice who were not exposed to alcohol.  The low dose animals’ performance in the cognitive and motor tests was identical to the controls.

Paper: “Beneficial effects of low alcohol exposure, but adverse effects of high alcohol intake on glymphatic function.”

Reprinted from materials provided by the University of Rochester Medical Center

Directly involving the thousands of family members and friends who serve as ‘informal carers’ for people with dementia in the evaluation of patients’ symptoms and behaviour could offer improved insights for healthcare professionals and help alleviate feelings of stress, guilt and isolation felt by many who fulfil these duties, a new study published in Dementia has found.

The findings highlight a need for more structured educational programmes covering broader knowledge around the disease for informal carers, who often have no formal training or support networks to depend on. Information on disease progression, guidelines on dealing with challenging behaviours and financial and legal advice could better prepare carers about what to expect.

The research, conducted by an inter-disciplinary team of experts, collated insights from carers and health care professionals and identified key themes which capture the main challenges faced by carers, as well as the type of support they want from health care services.

Previous research found that informal caregivers of people with dementia often display increased levels of depression and stress as well as poor self-rated health.

The new findings show that existing health and social care services are often fragmented which can make communication between healthcare professionals and care providers difficult. Healthcare professionals also stated that while they have a theoretical knowledge of the disease, they felt they often lack knowledge of how it is to live with dementia which can make it difficult to know how best to support caregivers.

The researchers say they hope that the findings will lead to improvements in dementia care with a goal of creating a better educational package for carers.

Paper: “Caregivers’ interactions with health care services – Mediator of stress or added strain? Experiences and perceptions of informal caregivers of people with dementia – A qualitative study”
Reprinted from materials provided by the University of Lincoln.

Increasing the amount of social interaction for people with dementia living in care homes to just one hour a week improves quality of life when combined with personalised care, according to a new study.

A large-scale trial  found that the approach also saves money.

Previous research has found that in many care homes, residents have as little as two minutes of social interaction per day.

The new research, published in PLOS Medicine, upskilled key care home staff to deliver person-centred care. That involves simple measures such as talking to residents about their interests and involving them in decisions around their own care.

When combined with just one hour a week of social interaction, the programme improved quality of life and reduced agitation and aggression in people with dementia.

The trial involved more than 800 people with dementia across 69 care. Two ‘care staff champions’ at each home were trained over four day-long sessions to take simple measures that such as involve talking to residents about their interests and decisions around their own care. Importantly, the approach also saved money compared to standard care.  Researchers say the next key challenge is to roll the programme out across care homes to benefit the lives of people with dementia living in these facilities.

Paper: “Impact of person-centred care training and person-centred activities on quality of life, agitation, and antipsychotic use in people with dementia living in nursing homes: A cluster-randomised controlled trial”
Reprinted from materials provided by University of Exeter.

After more than a decade of research, this much we know: it’s good for your brain to know another language.

A new study, published in Neuropsychologia,  goes further, however, focusing specifically on the effects of knowing a second language for patients with Alzheimer’s disease (AD) and mild cognitive impairment (MCI).

Unlike previous studies using CT scans, the researchers  used high-resolution, whole-brain MRI data and sophisticated analysis techniques to investigate language and cognition control areas in the frontal regions of the brain, and medial temporal lobe structures that are important for memory and are brain areas known to atrophy in MCI and AD patients.

Their sample included 34 monolingual MCI patients, 34 multilingual MCI patients, 13 monolingual AD patients and 13 multilingual AD patients.

The researchers say that their findings suggest that multilingualism is associated with increased brain plasticity and cognitive reserve. Moreover, their study indicates, they say, that people who speak more than one language may in some circumstances compensate for AD-related tissue loss by accessing alternative networks or other brain regions for memory processing, a hypothesis they hope to test in future studies.

Paper: “Structural brain differences between monolingual and multilingual patients with mild cognitive impairment and Alzheimer disease: Evidence for cognitive reserve”
Reprinted from materials provided by Concordia University.

Scientists developing a rapid, practical test for the early diagnosis of prion diseases have modified the assay to offer the possibility of improving early diagnosis of Parkinson’s disease and dementia with Lewy bodies.

The findings were published in Acta Neuropathologica Communications.

The group tested 60 cerebral spinal fluid samples, including 12 from people with Parkinson’s disease, 17 from people with dementia with Lewy bodies, and 31 controls, including 16 of whom had Alzheimer’s disease. The test correctly excluded all the 31 controls and diagnosed both Parkinson’s disease and dementia with Lewy bodies with 93 percent accuracy.

Importantly, test results were available within two days, compared to related assays that require up to 13 days. The group conducted the tests using Real-Time Quaking-Induced Conversion (RT-QuIC), an assay developed and refined over the past decade.

Multiple neurological disorders, including Parkinson’s disease and dementia with Lewy bodies, involve the abnormal clumping of a protein called alpha-synuclein into brain deposits called Lewy bodies. The pathological processes in these diseases resemble prion diseases in mammal brains. Like prion diseases, Parkinson’s disease and dementia with Lewy bodies result in progressive deterioration of brain functions.

The researchers continue to adapt the RT-QuIC assay to detect additional types of neurological diseases with greater accuracy using the least invasive patient sample possible—whether that is blood, skin, nasal brushings, or other samples. The group also has trained many international colleagues to use and advance the test.

Article: “Rapid and ultra-sensitive quantitation of disease-associated α-synuclein seeds in brain and cerebrospinal fluid by αSyn RT-QuIC” 
Reprinted from materials provided by NIH/National Institute of Allergy and Infectious Diseases.