Cognitive Impairment in Mice With Dementia Reversed

It’s a significant development for treating that disease and those similar to it.

Reversing memory deficits and impairments in spatial learning is a major goal in the field of dementia research. A lack of knowledge about cellular pathways critical to the development of dementia, however, has stood in the way of significant clinical advance. But now, researchers at the Lewis Katz School of Medicine at Temple University (LKSOM) are breaking through that barrier. They show, for the first time in an animal model, that tau pathology — the second-most important lesion in the brain in patients with Alzheimer’s disease — can be reversed by a drug.

“We show that we can intervene after disease is established and pharmacologically rescue mice that have tau-induced memory deficits,” explained senior investigator Domenico Praticò, MD, Scott Richards North Star Foundation Chair for Alzheimer’s Research, Professor in the Departments of Pharmacology and Microbiology, and Director of the Alzheimer’s Center at Temple at LKSOM. The study, published online in the journal Molecular Neurobiology, raises new hope for human patients affected by dementia.

The researchers landed on their breakthrough after discovering that inflammatory molecules known as leukotrienes are deregulated in Alzheimer’s disease and related dementias. In experiments in animals, they found that the leukotriene pathway plays an especially important role in the later stages of disease.

“At the onset of dementia, leukotrienes attempt to protect nerve cells, but over the long term, they cause damage,” Dr. Praticò said. “Having discovered this, we wanted to know whether blocking leukotrienes could reverse the damage, whether we could do something to fix memory and learning impairments in mice having already abundant tau pathology.”

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After 16 weeks of treatment, animals were administered maze tests to assess their working memory and their spatial learning memory. Compared with untreated animals, tau mice that had received zileuton performed significantly better on the tests. Their superior performance suggested a successful reversal of memory deficiency.

To determine why this happened, the researchers first analyzed leukotriene levels. They found that treated tau mice experienced a 90-percent reduction in leukotrienes compared with untreated mice. In addition, levels of phosphorylated and insoluble tau, the form of the protein that is known to directly damage synapses, were 50 percent lower in treated animals. Microscopic examination revealed vast differences in synaptic integrity between the groups of mice. Whereas untreated animals had severe synaptic deterioration, the synapses of treated tau animals were indistinguishable from those of ordinary mice without the disease.

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The study is especially exciting because zileuton is already approved by the Food and Drug Administration for the treatment of asthma. “Leukotrienes are in the lungs and the brain, but we now know that in addition to their functional role in asthma, they also have a functional role in dementia,” Dr. Praticò explained.

“This is an old drug for a new disease,” he added. “The research could soon be translated to the clinic, to human patients with Alzheimer’s disease.”

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Study: Alcohol Use Disorders are the Biggest Risk Factor for Dementia

Alcohol use disorders — defined by the authors as disorders involving hospitalization — must have a neurodegenerative effect at causing dementia.

Alcohol use disorders are the most important preventable risk factors for the onset of all types of dementia, especially early-onset dementia. This according to a nationwide observational study, published in The Lancet Public Health journal, of over one million adults diagnosed with dementia in France.

This study looked specifically at the effect of alcohol use disorders, and included people who had been diagnosed with mental and behavioural disorders or chronic diseases that were attributable to chronic harmful use of alcohol.

Of the 57,000 cases of early-onset dementia (before the age of 65), the majority (57%) were related to chronic heavy drinking.

The World Health Organization (WHO) defines chronic heavy drinking as consuming more than 60 grams pure alcohol on average per day for men (4-5 Canadian standard drinks) and 40 grams (about 3 standard drinks) per day for women.

As a result of the strong association found in this study, the authors suggest that screening, brief interventions for heavy drinking, and treatment for alcohol use disorders should be implemented to reduce the alcohol-attributable burden of dementia.

“The findings indicate that heavy drinking and alcohol use disorders are the most important risk factors for dementia, and especially important for those types of dementia which start before age 65, and which lead to premature deaths,” says study co-author and Director of the CAMH Institute for Mental Health Policy Research Dr. Jürgen Rehm. “Alcohol-induced brain damage and dementia are preventable, and known-effective preventive and policy measures can make a dent into premature dementia deaths.”

Dr. Rehm points out that on average, alcohol use disorders shorten life expectancy by more than 20 years, and dementia is one of the leading causes of death for these people.

For early-onset dementia, there was a significant gender split. While the overall majority of dementia patients were women, almost two-thirds of all early-onset dementia patients (64.9%) were men.

Alcohol use disorders were also associated with all other independent risk factors for dementia onset, such as tobacco smoking, high blood pressure, diabetes, lower education, depression, and hearing loss, among modifiable risk factors. It suggests that alcohol use disorders may contribute in many ways to the risk of dementia.

“As a geriatric psychiatrist, I frequently see the effects of alcohol use disorder on dementia, when unfortunately alcohol treatment interventions may be too late to improve cognition,” says CAMH Vice-President of Research Dr. Bruce Pollock. “Screening for and reduction of problem drinking, and treatment for alcohol use disorders need to start much earlier in primary care.” The authors also noted that only the most severe cases of alcohol use disorder — ones involving hospitalization — were included in the study. This could mean that, because of ongoing stigma regarding the reporting of alcohol-use disorders, the association between chronic heavy drinking and dementia may be even stronger.

Curcumin Found to Improve Memory in Study of Those With Mild Memory Loss

Good research on countering age-related cognitive problems with a simple remedy of curcumin. This is especially important when pharmaceutical corporations such as Pfizer are doing less research on Alzheimer’s and dementia.

The sample size of this study may also be relatively small, but its methodology looks rigorous enough, and turmeric has already been found to have considerable health benefits.

Daily consumption of a certain form of curcumin — the substance that gives Indian curry its bright color — improved memory and mood in people with mild, age-related memory loss, according to the results of a study conducted by UCLA researchers.

The research, published online Jan. 19 in the American Journal of Geriatric Psychiatry, examined the effects of an easily absorbed curcumin supplement on memory performance in people without dementia, as well as curcumin’s potential impact on the microscopic plaques and tangles in the brains of people with Alzheimer’s disease.

Found in turmeric, curcumin has previously been shown to have anti-inflammatory and antioxidant properties in lab studies. It also has been suggested as a possible reason that senior citizens in India, where curcumin is a dietary staple, have a lower prevalence of Alzheimer’s disease and better cognitive performance.

“Exactly how curcumin exerts its effects is not certain, but it may be due to its ability to reduce brain inflammation, which has been linked to both Alzheimer’s disease and major depression,” said Dr. Gary Small, director of geriatric psychiatry at UCLA’s Longevity Center and of the geriatric psychiatry division at the Semel Institute for Neuroscience and Human Behavior at UCLA, and the study’s first author.

The double-blind, placebo-controlled study involved 40 adults between the ages of 50 and 90 years who had mild memory complaints. Participants were randomly assigned to receive either a placebo or 90 milligrams of curcumin twice daily for 18 months.

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The people who took curcumin experienced significant improvements in their memory and attention abilities, while the subjects who received placebo did not, Small said. In memory tests, the people taking curcumin improved by 28 percent over the 18 months. Those taking curcumin also had mild improvements in mood, and their brain PET scans showed significantly less amyloid and tau signals in the amygdala and hypothalamus than those who took placebos.

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The researchers plan to conduct a follow-up study with a larger number of people. That study will include some people with mild depression so the scientists can explore whether curcumin also has antidepressant effects. The larger sample also would allow them to analyze whether curcumin’s memory-enhancing effects vary according to people’s genetic risk for Alzheimer’s, their age or the extent of their cognitive problems.

“These results suggest that taking this relatively safe form of curcumin could provide meaningful cognitive benefits over the years,” said Small, UCLA’s Parlow-Solomon Professor on Aging.

Study: First Brain Training Exercise Linked to Dementia Prevention Found

A related and thought provoking quote: “Our mind is all we’ve got. Not that it won’t lead us astray sometimes, but we still have to analyze things out within ourselves.” — Bobby Fischer

Aging research specialists have identified, for the first time, a form of mental exercise that can reduce the risk of dementia.

The cognitive training, called speed of processing, showed benefits up to 10 years after study participants underwent the mental exercise program, said Frederick W. Unverzagt, PhD, professor of psychiatry at Indiana University School of Medicine.

The proportion of participants who underwent the training and later developed dementia was significantly smaller than among those who received no cognitive training, the researchers said.

There were measurable benefits even though the amount of training was small and spread out over time: 10 one-hour sessions over six weeks initially and up to eight booster sessions after that.

Research Finds Where the Earliest Signs of Alzheimer’s Occur in the Brain

This discovery has considerable potential for stopping the devastation Alzheimer’s often induces in those who develop the disease.

Researchers at Lund University in Sweden have for the first time convincingly shown where in the brain the earliest signs of Alzheimer’s occur. The discovery could potentially become significant to future Alzheimer’s research while contributing to improved diagnostics.

In Alzheimer’s, the initial changes in the brain occur through retention of the protein, ?-amyloid (beta-amyloid). The process begins 10-20 years before the first symptoms become noticeable in the patient.

In Nature Communications, a research team headed by Professor Oskar Hansson at Lund University has now presented results showing where in the brain the initial accumulation of ?-amyloid occurs. It is in the inner parts of the brain, within one of the brain’s most important functional networks — known as the default mode network.

“A big piece of the puzzle in Alzheimer’s research is now falling into place. We previously did not know where in the brain the earliest stages of the disease could be detected. We now know which parts of the brain are to be studied to eventually explain why the disease occurs,” says Sebastian Palmqvist, associate professor at Lund University and physician at Skåne University Hospital.

The default mode network is one of several networks, each of which has a different function in the brain. It is most active when we are in an awake quiescent state without interacting with the outside world, for example, when daydreaming. The network belongs to the more advanced part of the brain. Among other things, it processes and links information from lower systems.

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The difficulty of determining which individuals are at risk of developing dementia later in life, in order to subsequently monitor them in research studies, has been an obstacle in the research world. The research team at Lund University has therefore developed a unique method to identify, at an early stage, which individuals begin to accumulate ?-amyloid and are at risk.

The method combines cerebrospinal fluid test results with PET scan brain imaging. This provides valuable information about the brain’s tendency to accumulate ?-amyloid.

In addition to serving as a roadmap for future research studies of Alzheimer’s disease, the new results also have a clinical benefit:

“Now that we know where Alzheimer’s disease begins, we can improve the diagnostics by focusing more clearly on these parts of the brain, for example in medical imaging examinations with a PET camera,” says Oskar Hansson, professor at Lund University, and medical consultant at Skåne University Hospital.

Although the first symptoms of Alzheimer’s become noticeable to others much later, the current study shows that the brain’s communication activity changes in connection with the early retention of ?-amyloid. How, and with what consequences, will be examined by the research team in further studies.