Alzheimer’s Patients Test Deep Brain Stimulation to Boost Memory

(CBSnews) Norma-Jean McLaren has been living with two electrodes implanted into her brain for almost a year.

“You can feel them, they’re like bumps,” said McLaren on a recent fall morning as she touched the top of her skull.

She traced her hand down her neck, where there is a wire connecting the electrodes to a battery-powered neurostimulator in her chest. This device provides a steady stream of electrical impulses to a part of her brain that regulates memory.

McLaren’s husband of 35 years, Nathan Edelson, described the device as a “brain pacemaker.”

“The most important thing is the voltage, they check it every three months, and do objective memory testing,” Edelson explained, referring to a specialized medical team at Toronto Western Hospital and Johns Hopkins University, in Baltimore, that has been conducting a clinical trial across Canada and the U.S.

Their main focus is the effect of deep brain stimulation on the progression of memory loss in Alzheimer’s disease.

Early research published in 2010 indicated that deep brain stimulation, which is routinely used to treat the symptoms of Parkinson’s disease, could slow down or even halt cognitive decline in Alzheimer’s patients.

Following the recent publication of a new round of results in the trial, the team at Toronto Western is hopeful the technique could help people like McLaren retain, or perhaps even regain, their faculties of memory.

McLaren, 69, was diagnosed with Alzheimer’s two years ago. She had been seeing a neurologist for five years prior to that, since the disease runs in her family.

“I saw it coming,” said McLaren. “I think my grandfather had Alzheimer’s. My father definitely had it, and my sister has it now.”

When Edelson heard about the trial at Toronto Western in early 2015, he said McLaren immediately wanted to sign up, despite the requirement of undergoing brain surgery to implant the electrodes into her brain. Patients remain awake through the procedure so they can communicate with the surgeons. The doctors ask memory questions while they operate to make sure they’re targeting the right area.

It may seem like an extreme step, but McLaren didn’t hesitate.

“She didn’t need to be hearing lots of evidence of risks, she just knew the risk of not doing it was further decline,” said Edelson.

“She wanted to do whatever was available to slow it down – for the kids too.”

The couple’s children, who are 49 and 38 years old, have not shown any signs of the disease so far.

More than 5.4 million Americans live with Alzheimer’s, a disease that involves an abnormal build-up of proteins in the brain’s memory circuits. One in three seniors will die with Alzheimer’s or another dementia. Once diagnosed, most people live another six to nine years, during which time the disease causes the function of their brain circuits to deteriorate irreversibly.

“Imagine taking a picture of the U.S. at night, and the lights are on in certain areas, but New York State is completely blacked out,” said Dr. Andres Lozano, the head of neurosurgery at Toronto Western Hospital, who is leading the clinical trial that McLaren is part of.

“Alzheimer’s is like that. Lights are out in certain areas of the brain, and what we set out to do five, six years ago, is figure out whether these lights would stay out forever, or whether we can use deep brain stimulation to turn them back on.”

Edelson believes the trial has helped improve his wife’s quality life.

“A year ago, before the operation, if we had people over for dinner, Norma-Jean would sit quietly and sometimes with anxiety.

And now if we have people over she’ll participate actively in the conversation,” said Edelson, adding that McLaren also keeps her body and mind active by going for daily walks with friends and former students.

The couple both taught at the University of British Columbia, in Vancouver, for over two decades, before McLaren gave up her position at the School of Community and Regional Planning.

“She’s capable of doing more than she thinks she is. Like, I make dinner but she usually makes her own breakfast and lunch,” he said.

“And I clean the house!” McLaren interjected playfully.

But the disease has taken a toll.

“I think I have to rely on him more,” said McLaren, turning to face her husband.

“I think we were always close. But I have to rely on you more.”

“In some ways it’s just a different kind of relationship,” said Edelson. “

We don’t have much of the same conversations we used to, but we have other conversations, and we’re both hopeful that this can be reversed.”

The clinical trial is now transitioning into its third and final phase, which will take an additional three to five years to complete, according to Lozano. Phase III will involve about 100 patients.

The results from Phase II, involving 42 patients with mild Alzheimer’s disease, were published in September 2016 in the Journal of Alzheimer’s Disease. Half of the 42 patients who underwent the surgery were administered electrical currents through the electrodes, while the other half acted as a control group and did not receive electrical currents.

Over a 12-month period, those age 65 and over who received the deep brain stimulation saw

“a trend toward … benefit on clinical outcomes,” the study said, concluding that “there may be slowing of cognitive decline.”

(Younger patients did not benefit from the treatment and may have actually worsened; the researchers aren’t sure why.)

“We discovered that, yes we can – in a specific group of patients in particular – we can turn those lights back on,” said Lozano.

“We think we’re making great progress. It’s totally different and novel to other, drug approaches, and some people in the Alzheimer’s community may think it’s wacky – but we need to be bold with a disease like Alzheimer’s.”

Alzheimer’s is currently the sixth-leading cause of death in the U.S., and the numbers are growing as the population ages. According to the Alzheimer’s Association, Alzheimer’s and other dementia will cost the nation about $236 billion this year alone.

“We have to admire the courage of patients in this trial,” said Lozano. “They aren’t willing to accept this [deterioration], but they allow us to go directly into the brain and stimulate the circuits that decline as Alzheimer’s progresses.”

Memory Testing

On a recent sunny morning, McLaren and Edelson entered the same, modest doctor’s office at Toronto Western Hospital for the fourth time in nine months. McLaren squeezed her husband’s hand as she sat down and confessed to the neuropsychologist sitting opposite her that she felt “anxious.”

“Well, hopefully we won’t do anything too stressful for you today,” Dr. Mary Pat McAndrews, one of the researchers overseeing the trial alongside Lozano, responded with a smile.

“We just want to do a little bit of work looking at things like memory, OK?” She laughed lightly as McLaren grimaced, and commenced a routine memory test, which involved showing a series of objects to McLaren – a wristwatch, a stethoscope, a pair of scissors – and asking her to name them.

“She does well with tests like the objects. But some tests, like when we ask her to read a series of words and then immediately after recall them, she has difficulty,” sad McAndrews.

“I know both Nathan and Norma-Jean feel there is an improvement, that she is more present in conversation – but in terms of cognitive outcome, throughout the trial her condition has remained stable.”

Asked whether this trial could help discover a cure for Alzheimer’s, McAndrews warned that the disease was too complicated to think in terms of a single “cure.”

“Alzheimer’s isn’t just one thing, isn’t caused by one thing, and probably isn’t going to be cured by any one strategy,” said McAndrews.

She said it’s crucial for researchers to utilize big data and collaborate across different research and medical centers,

“so that once there is a cure that can actually stop Alzheimer’s in its tracks, we can rescue or revive memory abilities.”

“What we believe that this stimulation is going to be able to do – what we’ve seen so far its able to do – is to actually influence, impact or up-regulate those memory circuits,” she said.

While both Lozano and McAndrews appeared optimistic about the potential of deep brain stimulation for reducing memory loss in Alzheimer’s patients, proving whether it works will not be easy. The next phase of the clinical trial will require 100 participants, and so far they only have three.

“The challenge that this clinical trial is having is that people don’t know they have it [Alzheimer’s] or they’re in denial,” said Edelson.

“It’s in the early stages right now that there’s the best chance for recovery.”

For their family, the need for medical progress is urgent and personal.

“[It] isn’t whether there will be a cure in our lifetime, but whether there will be one over the next couple of years while Norma-Jean can still benefit from it. As long as she can keep healthy and active, something will come along.”

McLaren finds that having the electrodes and the prospect of being included in the next phase of the trial help quell her fears of future deterioration.

“I think I don’t wake up every day criticizing myself, or going into the loss,” said McLaren. “I think I’m better than I was, and the trial here has given me hope for sure.

“I don’t want my kids to go through what I’m going through. I’m hoping they never have to.”



© 2016 CBS Interactive Inc. All Rights Reserved.



Ability to Recognize and Recall Odors May Identify Risk for Alzheimer’s Disease

(Massachusetts General Hospital) A non-invasive protocol testing the ability to recognize, remember and distinguish between odors was able to identify older individuals who — according to genetic, imaging and more detailed memory tests — were at increased risk of Alzheimer’s disease. The report of a study by a team of Massachusetts General Hospital (MGH) investigators has been published online in Annals of Neurology.

“There is increasing evidence that the neurodegeneration behind Alzheimer’s disease starts at least 10 years before the onset of memory symptoms,” says Mark Albers, MD, PhD, of the MGH Department of Neurology, the principal investigator and corresponding author of the report.

“The development of a digitally-enabled, affordable, accessible and non-invasive means to identify healthy individuals who are at risk is a critical step to developing therapies that slow down or halt Alzheimer’s disease progression.”

It is well known that brain circuits that process olfactory information can be affected by Alzheimer’s disease, and several studies have documented a diminished ability to identify odors in affected individuals.

Other studies have associated deficits in odor identification with established Alzheimer’s disease biomarkers and with greater rates of cognitive decline, but the most commonly used test of olfactory ability — the University of Pennsylvania Smell Identification Test — has a number of limitations and does not take into account the great variation in olfactory ability among healthy individuals.

The battery of four tests developed by the MGH team addresses both olfactory and cognitive functions:

  • In the OPID (Odor Percept IDentification)-10 test, participants are presented with a battery of 10 odors — menthol, clove, leather, strawberry, lilac, pineapple, smoke, soap, grape or lemon. After experiencing each odor for two seconds, they are asked whether the scent is familiar and then asked to choose among four words — from the names listed above — for the one that best describes the odor.
  • Participants then complete the Odor Awareness Scale (OAS), a previously validated questionnaire that assesses their overall attention to environmental odors and how they are affected emotionally and behaviorally by scents.
  • The OPID-20 test includes the 10 odors previously presented and an additional 10 — banana, garlic, cherry, baby powder, grass, fruit punch, peach, chocolate, dirt and orange. Participants are first asked whether a presented odor was included in the OPID-10 test and then asked which word best describes the odor. Their ability to remember odors from the first test determines their POEM (Percepts of Odor Episodic Memory) score.
  • In the Odor Discrimination (OD) test, participants are presented with two consecutive odors and asked whether they were different or the same, a process that is repeated 12 times with different paired scents.

The study recruited 183 participants, most of whom were enrolled in ongoing studies at the MGH-based Massachusetts Alzheimer’s Disease Research Center. At the time of the olfactory testing, 70 were cognitively normal, 74 tested normal on cognitive tests but were personally concerned about their cognitive abilities, 29 had mild cognitive impairment and 10 had been diagnosed with possible or probable Alzheimer’s disease. As part of the studies they were enrolled in, all of them had comprehensive medical and neurological examinations — including annual tests of their memory and cognitive abilities — and several had brain imaging studies of Alzheimer’s-associated factors.

Results of the OPID-20 test significantly differentiated among the four groups of participants, and those results correlated with the thinning of two brain regions — the hippocampus and the entorhinal cortex — previously associated with Alzheimer’s risk. Participants’ ability to remember a previously presented aroma, as reflected in the POEM score, also showed significant differences between the two cognitively normal groups and participants with Alzheimer’s disease, whose results were no better than chance.

Because the ability of normal individuals to recognize and discriminate between odors can vary by as much as 40 times, the POEM scores of the two cognitively normal groups were compared with what would have been predicted based on their ability to identify and differentiate between odors, as reflected in the OAS and OD tests. That comparison determined whether each individual was a good or poor POEM performer, and poor POEM performers were more likely to have the variant of the APOE gene associated with increased Alzheimer’s risk. While results of an annual test of short-term memory improved year-to-year for the good POEM performers, no such improvement was seen among the poor performers, who also showed thinning of the entorhinal cortex.

Albers and his colleagues are currently recruiting participants for a larger-scale study to validate these results.

“It is well recognized that early diagnosis and intervention are likely to produce the most effective therapeutic strategy for Alzheimer’s disease — preventing the onset or the progression of symptoms,” he says.

“If these results hold up, this sort of inexpensive, noninvasive screening could help us identify the best candidates for novel therapies to prevent the development of symptoms of this tragic disease.”


Journal Reference:

Alefiya Dhilla Albers, Josephine Asafu-Adjei, Mary K. Delaney, Kathleen E. Kelly, Teresa Gomez-Isla, Deborah Blacker, Keith A. Johnson, Reisa A. Sperling, Bradley T. Hyman, Rebecca A. Betensky, Lloyd Hastings, Mark W. Albers. Episodic Memory of Odors Stratifies Alzheimer Biomarkers in Normal Elderly. Annals of Neurology, 2016; DOI: 10.1002/ana.24792

Copyright © 2007-2016. The General Hospital Corporation. All Rights Reserved.


Study Offers New Insight into How Alzheimer’s Begins

(University of Texas Medical Branch at Galveston) A new study from The University of Texas Medical Branch at Galveston offers important insight into how Alzheimer’s disease begins within the brain. The researchers found a relationship between inflammation, a toxic protein and the onset of the disease. The study also identified a way that doctors can detect early signs of Alzheimer’s by looking at the back of patients’ eyes.

“Early detection of Alzheimer’s warning signs would allow for early intervention and prevention of neurodegeneration before major brain cell loss and cognitive decline occurs,” said lead author Ashley Nilson, a neuroscience graduate student.

“Using the retina for detecting AD and other neurodegenerative diseases would be non-invasive, inexpensive and could become a part of a normal screening done at patient checkups.”

UTMB researchers have previously found evidence that a toxic form of tau protein may underlie the early stages of Alzheimer’s. Brain cells depend on tau protein to form highways for the cell to receive nutrients and get rid of waste.

In some neurodegenerative diseases like Alzheimer’s, the tau protein changes into a toxic form called tau oligomers and begins clumping into neurofibrillary tangles. When this happens, molecular nutrients can no longer move to where they are needed and the oligomers produce toxic effects leading to the eventual death of the brain cells.

It’s becoming increasingly clear that inflammation within the brain plays an important role in Alzheimer’s development and progression. Inflammation and loss of connections between nerves within the brain happen before the formation of the tangles that are characteristic of this disease. It’s possible that the tau oligomers may be responsible for this inflammation.

In a recent paper in the Journal of Alzheimer’s Disease, UTMB’s research team detailed their investigation on the relationship between inflammation, toxic tau and Alzheimer’s onset by performing systematic analyses of brain and retina samples from people with Alzheimer’s and a mouse model of Alzheimer’s.

The results demonstrated that the toxic tau may induce inflammation in Alzheimer’s. The toxic tau spreads between connected brain regions, which may initiate inflammation in these new regions. This situation can create a cycle of toxic tau, inflammation and cell death throughout the brain over time.

Beyond determining eye health and corrective lens prescriptions, having an eye exam can alert health care professionals of several different health conditions including diabetic complications, high cholesterol and high blood pressure. Now, UTMB researchers found that retina tissue that they studied can show evidence of toxic tau and inflammation.

“Our findings suggest that the degeneration of nerve cells due to chronic inflammation induced by the tau oligomers may be combated through the combination of anti-tau oligomer and anti-inflammatory therapeutics for the treatment of Alzheimer’s and related diseases,” said senior author Rakez Kayed, associate professor in the UTMB Department of Neurology.

“Our is continuing to expand our understanding of neurodegenerative diseases.”


Journal Reference:

Ashley N. Nilson, Kelsey C. English, Julia E. Gerson, T. Barton Whittle, C. Nicolas Crain, Judy Xue, Urmi Sengupta, Diana L. Castillo-Carranza, Wenbo Zhang, Praveena Gupta, Rakez Kayed. Tau Oligomers Associate with Inflammation in the Brain and Retina of Tauopathy Mice and in Neurodegenerative Diseases. Journal of Alzheimer’s Disease, 2016; 1 DOI: 10.3233/JAD-160912

©Copyright 2016 The University of Texas Medical Branch at Galveston.

Too Much Fatty Food Could Set Children Up for Mental Problems

(Springer) Chances are that children who eat excessive amounts of fatty foods will not only become obese, but will develop cognitive and psychiatric problems when they are older. This is because, according to a recent study, diets rich in fat deplete the levels of a key protein known to help synapses in the brain to work properly. In turn, this leads to a dip in several forms of cognitive functions, such as behavioral flexibility and memory.

“These changes from a young age onwards are more the result of the fatty foods themselves, and the impact they have on young brains, rather than arising from the mere fact of being obese,” notes Urs Meyer from ETH Zurich in Switzerland in Springer Nature’s journal Molecular Psychiatry.

Together with Pascale Chavis from the INMED Institute in Marseille in France, they co-directed the first study providing molecular mechanisms for how high-fat diets during adolescence negatively affect normal brain functioning and cognition.

The researchers conducted a study in mice, and observed cognitive defects as early as four weeks after the mice were fed high-fat foods. These were evident even before the animals started gaining weight and appeared specifically in mice fed high-fat foods during adolescence, and not in mice fed the same diets during adulthood.

In order to get at the mechanisms underlying such observations, the authors focused on a frontal region in the brain known as the prefrontal cortex. In humans, the prefontal cortex is associated with the planning of complex actions and decision making, expressing one’s personality and controlling one’s social behavior.

Several human studies had shown how fat-rich diets can reduce performance on executive tasks such as problem solving and working memory, in particular in adolescents. This seems worrying in light of a marked drop in the quality of diets over the past few decades and the poor understanding of the impact these diets have on our neurons.

These effects might be particularly relevant for adolescents, according to the study authors, as adolescence is a key period of increased caloric needs and heightened appetite for young people. It is the time when they start making more choices themselves about what to eat.

Adolescents eating high-fat diets may also be prone to cognitive deficits due to the immature character of the prefrontal cortex during this time frame.

“This brain region is very interesting,” notes French INSERM investigator Chavis, “because, unlike the rest of the brain, it is not fully developed until early adulthood.”

Researchers believe this relative immaturity makes the prefrontal cortex very sensitive to suboptimal experiences occurring during adolescence such as trauma, excessive stress or drug abuse.

“Our study highlights that the quality of the food eaten by teenagers may also be particularly important for an optimal maturation of the prefrontal cortex,” says Marie Labouesse, lead author of the study.

“We think this adolescent vulnerability to high-fat foods might be due to the hypersensitivity of a protein known as reelin,” notes Labouesse.

The researchers saw that the prefrontal cortex of mice fed high-fat foods had fewer neurons expressing reelin and this only happened when the diets were fed during the adolescent period. The authors then zoomed in, looking at synapses, those small microscopic structures that allow neurons to communicate between each other. The reelin protein is known to regulate synaptic function, and in particular synaptic plasticity, i.e. the ability of synapses to become stronger or weaker in response to a change in brain activity.

“We saw that plasticity in the prefrontal cortex was impaired in animals fed high-fat foods during adolescence; and quite remarkably we then observed that when restoring reelin levels, both synaptic plasticity and cognitive functions went back to normal,” notes Chavis.

“Our findings that high-fat diets during adolescence disrupt functioning of the adult prefrontal cortex suggest that a careful nutritional balance during this sensitive period is pivotal for reaching the full capacity of adult prefrontal functions,” says Labouesse.”Although we still need to find out the exact mechanisms by which reelin neurons get depleted during adolescence, it looks like high-fat foods could kick-start changes in how the prefrontal cortex of younger people develops.”

These findings may help explain how unhealthy foods and obesity are increasingly linked to the development of neuropsychiatric and neurological conditions.

Reelin deficiency is also a feature repeatedly documented in brain disorders such as schizophrenia or Alzheimer’s disease.

“Although more studies on this topic are definitely needed,” warns Meyer, “high-fat diets could potentially exacerbate the reelin and synaptic deficits in patients with mental illnesses such as schizophrenia or Alzheimer’s disease or even aggravate cognitive anomalies.”

“Reelin is now established as being a key player in the regulation of normal brain functions. The fact that the reelin protein displays vulnerability towards the negative effects of unhealthy foods is fascinating from the scientific perspective, but also very worrying when we think of the potential impact this might have for human health,” concludes Chavis.


Journal Reference:

M A Labouesse, O Lassalle, J Richetto, J Iafrati, U Weber-Stadlbauer, T Notter, T Gschwind, L Pujadas, E Soriano, A C Reichelt, C Labouesse, W Langhans, P Chavis, U Meyer. Hypervulnerability of the adolescent prefrontal cortex to nutritional stress via reelin deficiency. Molecular Psychiatry, 2016; DOI: 10.1038/mp.2016.193

© Springer, Part of Springer Science+Business Media


Dementia Game ‘Shows Lifelong Navigational Decline’

(BBC News) The findings, presented at the Neuroscience 2016 conference, harnessed data from 2.4 million people who downloaded the game.

Getting lost is one of the first symptoms of Alzheimer’s disease.

And the researchers at University College London believe the results could help make a dementia test.

Sea Hero Quest is a nautical adventure to save an old sailor’s lost memories.

The world’s largest dementia research experiment, which takes the form of a video game, has indicated the ability to navigate declines throughout life.

With the touch of a smartphone screen, players sail a boat round desert islands and icy oceans.

The game anonymously records the player’s sense of direction and navigational ability as they work their way through the levels.

Some require them to weave through waterways and fire a flare back home, while others challenge them to memorise a sequence of buoys and then sail round them.

Data harnessed from the flare levels is the first to have been analysed, by scientists at University College London.

And it suggests the sense of direction declines consistently after the teenage years.

Players aged 19 were 74% accurate at firing the flare back home, but accuracy fell year by year until it reached 46% at age 75.

Dr Hugo Spiers told the BBC: “What we’re able to announce to the world is it does decline across the lifespan, the ability to shoot the flare back to the target – that sense of direction.”

The data also suggests men have a slight better sense of direction than women and that the Nordic nations outperform the rest in the world, although it is not yet clear why.

Ideas include:

  • people in better health, common in Nordic countries, retain their navigational abilities longer
  • coastal nations create better navigators
  • a genetic “Viking blood” boost to navigational skills

The point of the research is to develop a way of diagnosing dementia in its earliest stages – something not yet possible.

Becoming completely disorientated is normally rare, but is more common in people with Alzheimer’s disease.

Having a record of the normal decline in the internal compass could help doctors spot patients developing Alzheimer’s.

Dr Spiers added: “The value of a future test built from Sea Hero Quest is that we will be able to provide a diagnostic for Alzheimer’s dementia and a tool that allows us to monitor performance in drug trials.”

Hilary Evans, the chief executive of Alzheimer’s Research UK, said: “Sadly, we hear all too frequently of people getting lost and being found miles away from home.

“Researchers believe that these problems with spatial navigation could form the basis of a diagnostic test for the early stages of diseases like Alzheimer’s, which could add a valuable tool to a clinician’s diagnostic armoury.

“For any new diagnostic tool to be effective, it must take into account natural variation in a particular skill or ability across the population.”

The data collection from 2.4 million people passing some time in the evening or on the way to work would have taken 9,400 years in the lab.

This project was funded by Deutsche Telekom and the game was designed by Glitchers.

Michael Hornberger, a professor of applied dementia research at the University of East Anglia, said:

“The amount of data that has already been generated by people playing Sea Hero Quest all around the world is phenomenal and is enabling us to reveal a vital global benchmark of how people, of all ages and from all over the use spatial navigation.”


By James Gallagher Health and science reporter, BBC News website

Copyright © 2016 BBC.



Probiotics Improve Cognition in Alzheimer’s Patients

(Frontiers) For the first time, scientists have shown that probiotics — beneficial live bacteria and yeasts taken as dietary supplements — can improve cognitive function in humans. In a new clinical trial, scientists show that a daily dose of probiotic Lactobacillus and Bifidobacterium bacteria taken over a period of just 12 weeks is enough to yield a moderate but significant improvement in the score of elderly Alzheimer’s patients on the Mini-Mental State Examination (MMSE) scale, a standard measure of cognitive impairment.

Probiotics are known to give partial protection against certain infectious diarrheas, irritable bowel syndrome, inflammatory bowel disease, eczema, allergies, colds, tooth decay, and periodontal disease. But scientists have long hypothesized that probiotics might also boost cognition, as there is continuous two-way communication between the intestinal microflora, the gastrointestinal tract, and the brain through the nervous system, the immune system, and hormones (along the so-called “microbiota-gut-brain axis”). In mice, probiotics have indeed been shown to improve learning and memory, and reduce anxiety and depression- and OCD-like symptoms. But prior to the present study there was very limited evidence of any cognitive benefits in humans.

Here, the researchers, from Kashan University of Medical Sciences, Kashan, and Islamic Azad University, Tehran, Iran, present results from a randomized, double-blind, controlled clinical trial on a total of 52 women and men with Alzheimer’s between 60 and 95 years of age. Half of the patients daily received 200 ml milk enriched with four probiotic bacteria Lactobacillus acidophilus, L. casei, L. fermentum, and Bifidobacterium bifidum (approximately 400 billion bacteria per species), while the other half received untreated milk.

At the beginning and the end of the 12-week experimental period, the scientists took blood samples for biochemical analyses and tested the cognitive function of the subjects with the MMSE questionnaire, which includes tasks like giving the current date, counting backwards from 100 by sevens, naming objects, repeating a phrase, and copying a picture.

Over the course of the study, the average score on the MMSE questionnaire significantly increased (from 8.7 to 10.6, out of a maximum of 30) in the group receiving probiotics, but not in the control group (from 8.5 to 8.0). Even though this increase is moderate, and all patients remained severely cognitively impaired, these results are important because they are the first to show that probiotics can improve human cognition. Future research, on more patients and over longer time-scales, is necessary to test if the beneficial effects of probiotics become stronger after longer treatment.

“In a previous study, we showed that probiotic treatment improves the impaired spatial learning and memory in diabetic rats, but this is the first time that probiotic supplementation has been shown to benefit cognition in cognitively impaired humans,” says Professor Mahmoud Salami from Kashan University, the senior author of the study.

Treatment with probiotics also resulted in lower levels of triglycerides, Very Low Density Lipoprotein (VLDL), high-sensitivity C-Reactive Protein (hs-CRP) in the blood of the Alzheimer patients, and likewise a reduction in two common measures (called “Homeostatic Model Assessment,” HOMA-IR and HOMA-B) of insulin resistance and the activity of the insulin-producing cells in the pancreas.

“These findings indicate that change in the metabolic adjustments might be a mechanism by which probiotics affect Alzheimer’s and possibly other neurological disorders,” says Salami. “We plan to look at these mechanisms in greater detail in our next study.”

Walter Lukiw, Professor of Neurology, Neuroscience and Ophthalmology and Bollinger Professor of Alzheimer’s disease at Louisiana State University, who reviewed the study but was not involved in the research, said:

“This early study is interesting and important because it provides evidence for gastrointestinal (GI) tract microbiome components playing a role in neurological function, and indicates that probiotics can in principle improve human cognition.

This is in line with some of our recent studies which indicate that the GI tract microbiome in Alzheimer’s is significantly altered in composition when compared to age-matched controls, and that both the GI tract and blood-brain barriersbecome significantly more leaky with aging, thus allowing GI tract microbial exudates (e.g. amyloids, lipopolysaccharides, endotoxins and small non-coding RNAs) to access Central Nervous System compartments.”

The study is published in the open-access journal Frontiers in Aging Neuroscience.

Citation probiotics-improve-cognition-in-alzheimers-patients/

by michielbdijkstra

Journal Reference:

Elmira Akbari, Zatollah Asemi, Reza Daneshvar Kakhaki, Fereshteh Bahmani, Ebrahim Kouchaki, Omid Reza Tamtaji, Gholam Ali Hamidi, Mahmoud Salami. Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer’s Disease: A Randomized, Double-Blind and Controlled Trial. Frontiers in Aging Neuroscience, 2016; 8 DOI: 10.3389/fnagi.2016.00256


Brain Training May Help Fight Dementia

(University of Sydney) Researchers at the University of Sydney have found that engaging in computer-based brain training can improve memory and mood in older adults with mild cognitive impairment — but training is no longer effective once a dementia diagnosis has been made.

The team, comprising researchers from the Brain and Mind Centre, reviewed more than 20 years of research and showed that brain training could lead to improvements in global cognition, memory, learning and attention, as well as psychosocial functioning (mood and self-perceived quality of life) in people with mild cognitive impairment. Conversely, when data from 12 studies of brain training in people with dementia was combined, results were not positive.

The results are published today in the American Journal of Psychiatry.

Mild cognitive impairment involves a decline in memory and other thinking skills despite generally intact daily living skills, and is one of strongest risk factors for dementia. People with mild cognitive impairment are at one-in-10 risk of developing dementia within a year — and the risk is markedly higher among those with depression.

Brain training is a treatment for enhancing memory and thinking skills by practising mentally challenging computer-based exercises — which are designed to look and feel like video games.

Dr Amit Lampit from the School of Psychology, who led the study said the results showed brain training could play an important role in helping to prevent dementia.

“Our research shows that brain training can maintain or even improve cognitive skills among older people at very high risk of cognitive decline — and it’s an inexpensive and safe treatment,” Dr Lampit said.

To arrive at their conclusions, the team combined outcomes from 17 randomised clinical trials including nearly 700 participants, using a mathematical approach called meta-analysis, widely recognised as the highest level of medical evidence.

The team has used meta-analysis before to show that brain training is useful in other populations, such as healthy older adults and those with Parkinson’s disease.

“Taken together, these wide-ranging analyses have provided the necessary evidence to pursue clinical implementation of brain training in the aged-care sector — while continuing research aimed at improving training effectiveness,” Dr Lampit said.

Associate Professor Michael Valenzuela, leader of the Regenerative Neuroscience Group at the Brain and Mind Centre, believes new technology is the key to moving the field forward.

“The great challenges in this area are maintaining training gains over the long term and moving this treatment out of the clinic and into people’s homes. ” Associate Professor Valenzuela said.

“This is exactly what we are working on right now.”

Associate Professor Valenzuela is one of the leaders of the multi-million-dollar Australian Maintain your Brain trial that will test if a tailored program of lifestyle modification, including weekly brain training over four years, can prevent dementia in a group of 18,000 older adults.

What is a Meta-analysis?

A meta-analysis is a statistical technique that begins by searching for all possible studies on a precise question, assessing their quality, and then mathematically combining these to produce an overall numerical result. Meta-analysis can allows researchers to identify fundamental characteristics of the studies that are contributing to the overall pattern of results.

What is Brain Training?

Brain training is a treatment for enhancing memory and thinking skills by practising mentally challenging exercises on computer. Exercises are designed to look and feel like video games and are based on neuropsychological principles to target specific cognitive domains.

For a Diagnosis of Dementia, These Conditions Need to be Satisfied:

  1. impairment on multiple cognitive domains
  2. a definite decline in cognitive function
  3. exclusion of any possible medical causes for this decline, and
  4. the person is no longer able to carry out day-to-day tasks.

The last criterion – being able to do one’s daily activities independently – is pivotal to distinguishing between cognitive impairment and dementia.





Long-Term Use of Opioid Patches Common with Alzheimer’s Disease

(University of Eastern Finland) Approximately seven percent of persons with Alzheimer’s disease use strong pain medicines, opioids, for non-cancer pain for a period longer than six months, according to a recent study conducted at the University of Eastern Finland. One third of people initiating opioid use became long-term users, and long-term use was heavily associated with transdermal opioid patches. The results were published in PAIN.

The researchers found that long-term use of opioids was approximately as common among persons with Alzheimer’s disease as it was among those without it. However, long-term use of transdermal patches was twice as common among persons with Alzheimer’s disease, while tablet form opioids were more common among those without Alzheimer’s disease.

In addition, long-term opioid use together with benzodiazepines was common, which is worrying as both medicines cause drowsiness. The use of opioids was studied from the date of Alzheimer’s disease diagnosis until death or admission into a long-term care facility. Those with active cancer treatment were excluded from the analysis.

Long-term opioid use is a problematic practice for non-cancer pain. Evidence of its benefits is limited, and the risk of adverse effects is increased compared to short-term treatment. Further, research on the benefits and adverse effects of long-term opioid use is very scarce among older adults and especially those with dementia.

Changing doses and stopping medication when using patch-form opioids requires more time and thus, entails more careful monitoring. Pain, the need for analgesics, and possible adverse effects related to analgesics should be assessed regularly among persons with dementia.

The study is part of the MEDALZ cohort, which included 67,215 persons with Alzheimer’s disease diagnosed during 2005-2011, of whom 13,111 initiated opioid use. Each person with the disease was matched with a comparison person without Alzheimer’s disease of the same age, gender and region of residence. Data for the study were derived from Finnish nationwide registers.


Research article:

Long-term use of opioids for non-malignant pain among community-dwelling persons with and without Alzheimer’s disease in Finland: a nationwide register-based study. Aleksi Hamina, Heidi Taipale, Antti Tanskanen, Anna-Maija Tolppanen, Niina Karttunen, Liisa Pylkkänen, Jari Tiihonen, Sirpa Hartikainen. PAIN, published online 14.11.2016. doi: 10.1097/j.pain.0000000000000752

© University of Eastern Finland