Category Archives: Alzheimers/Dementia

New Biological Definition Of Alzheimer’s Advances

Posted on by

Historically, Alzheimer’s Dementia (AD) has been defined by visible symptoms, simply because that was all that was available. Around the mid 1990’s, various researchers began pushing for the development of a biologically-based specification of the disease, separate from the manifested symptoms. Among other things, this allows reasoning about the onset of AD before manifestation of symptoms, much like cancer or heart disease. It is believed that the AD process may begin decades before any outward sign of memory loss or other decline.

In 2007, leading AD clinicians formed an international working group (IWG) and proposed using amyloid PET scans, MRI, CSF (cerebrospinal fluid) levels of Aβ and tau, genetic testing, brain structural changes, and subtle cognitive changes to diagnose AD at an earlier stage than before. The NIA/AA (National Institute of Aging, and the Alzheimer’s Association) set up a separate leadership group, and in 2011 it proposed a related set of diagnostic guidelines for AD research that utilized separate criteria for three stages of disease: preclinical AD, mild cognitive impairment, and dementia. The current NIA/AA research framework draws on these two efforts and their personnel.

The workers stress, both in the framework publication and in an associated editorial, that this work is directed at research, and will only slowly begin appearing in the clinical context. But it is expected that the new framework will markedly improve research communication and advances.

Links to media articles on the new framework:
New biological research framework for Alzheimer’s seeks to spur discovery
Alzheimer’s disease redefined: New research framework defines Alzheimer’s by brain changes, not symptoms
New Definition of Alzheimer’s Hinges on Biology, Not Symptoms

Links to two different publications of the framework:
NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease
NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease

All the links have been added to Neuro-Psych and to Alzheimers > Neurology & Neuroplasticity

Maybe Flashing Lights For Alzheimer’s Therapy?

Posted on by

Mice again, but not drugs. Instead, it’s the promising use of strobe-type flashing lights to modify brain waves (neuromodulation) to induce changes beneficial to Alzheimer’s sufferers.

It has been previously noted that both human Alzheimer’s sufferers and the mice models of Alzheimer’s exhibit disrupted gamma waves, which are the highest frequency waves and are associated with higher cognitive events. The study placed mice, genetically engineered to mimic Alzheimer’s symptoms, in a box with strobe lights flashing at 40 cycles per second for an hour a day. This stimulated the visual cortex of the mice to generate more gamma waves, which set in motion an apparent sequence of biological events: A change in gene expression causes microglia (immune cells in the brain) to change shape, going into scavenger mode, where they better perform their usual housekeeping role, clearing away cellular debris, including amyloid-β.

Note how complex the brain and how difficult the science: In Brain Inflammation & Alzheimer’s, we discussed work showing that Alzheimer’s-type inflammatory response on the part of microglia can lead to increase in the deposit of amyloid-β, whereas the present work shows the microglia being stimulated to improve the removal of amyloid-β.

Here is a link to a recent Nature magazine news feature article on the MIT work and related work on the role of brain waves. The article is an excellent explication of the work and how it affects how the brain works:
How flashing lights and pink noise might banish Alzheimer’s, improve memory and more

Below are links to a number of media articles on the work. The first group deals with the MIT group’s earlier report from 2016:
Flashing light therapy’ for Alzheimer’s
Beating Alzheimer’s With Brain Waves
Unique visual stimulation may be new treatment for Alzheimer’s
LED Lights May Be a Promising New Alzheimer’s Treatment, MIT Study Says
Toward Treating Alzheimer’s Disease with Brain Waves
Here is the earlier research article:
Gamma frequency entrainment attenuates amyloid load and modifies microglia

Here are links to media articles on the more recent research:
Alzheimer’s Memory Loss May Be Reversible, MIT Study Says
How does the Sp3-HDAC2 Complex Reduce Synaptic Function in Alzheimer’s?

And here is the more recent research report:
The Transcription Factor Sp3 Cooperates with HDAC2 to Regulate Synaptic Function and Plasticity in Neurons

Light therapy (sitting bathed in light every morning) has been successfully used for treating the form of depression known as Seasonal Affective Disorder (SAD) (see e.g., Take Light, Not Drugs). If this strobe-approach to Alzheimer’s is successful with humans, Alzheimer’s treatment could utilize a similar therapeutic approach, or even possibly the two therapies could be combined when appropriate.

All of the links have been added to Alzheimer’s > Treatment

Diagnosing Dementia & MCI Using Computers

Posted on by

The first two bodies of work below use computer-based games to research the decline of 3D navigational skills (one of the first symptoms exhibited by the onset of dementia of all kinds), and the diagnosis of mild cognitive impairment (MCI), respectively. The third study reports on the correlation that “Less Daily Computer Use is Related to Smaller Hippocampal Volumes in Cognitively Intact Elderly”.

Sea Hero Quest

Sea Hero Quest is a collaboration between Alzheimer’s Research UK, Deutsche Telekom, the game designers Glitchers and scientists at 7 British universities. Recognizing that one of the first symptoms of dementia is loss of navigational skills, Sea Hero Quest mobile was designed to help researchers to understand the mental processes involved in 3D navigation, while at the same time providing a sea journey quest taken by a son attempting to recover the memories his father has lost to dementia. There are three sections to the game: navigation, shooting flares to test orientation, and chasing creatures. Each section is scientifically valid as well as fun and exciting. The game was launched in 2016 and, according to its website (below), nearly 3 million people have played the game up to now,. This amount of play has generated effectively 80 years worth of data, in turn equivalent to about 12,000 years of typical lab-based dementia research.

Here are three links to media articles about the game:
Sea Hero Quest: the mobile phone game helping fight dementia
Game shows that ability to navigate declines at young age
https://blog.strong-brain.com/wp-admin/post.php?post=2135&action=edit
Here is the Wikipedia entry for the game:
Sea Hero Quest [Wikipedia]
And here is the actual game site on the web, where you can download the Mobile and/or VR versions of the game:
Sea Hero Quest [Site]

Virtual Super Market (VSM)

The study reported here uses as “Virtual Super Market” Virtual Reality (VR) brain-training-style program to assess mild cognitive impairment on the part of the player. It is of definite interest since the testing game and assessment can be carried out without an administrator. Here is a link to a media article about the work:
Mild cognitive impairment (MCI) detected with brain training game

Here are a link to the original study together with an earlier prototype work:
A Preliminary Study on the Feasibility of Using a Virtual Reality Cognitive Training Application for Remote Detection of Mild Cognitive Impairment
Can a Virtual Reality Cognitive Training Application Fulfill a Dual Role? Using the Virtual Supermarket Cognitive Training Application as a Screening Tool for Mild Cognitive Impairment

Computer Use Time Can Correlate With Cognitive Decline

The study followed 27 ‘cognitively-healthy’, dementia-free adults aged 65 or older over 9 years in Portland. On the one hand, the study used MRI scans to measure the volume of the volunteers’ hippocampus, and on the other hand, data on computer use among participants was collected via mouse movement detection software. Embedded sensor technology monitored their mobility, sleep, socialisation, digital activities and medication intake. The research results showed that an additional hour of computer use each day was linked to a 0.025% larger hippocampal volume, leading to the conclusion that lower computer usage could be used to predict cognitive decline.

Here is a link to a media article about the study:
Computer use could help predict early-stage Alzheimer’s

Here is the original research study:
Less Daily Computer Use is Related to Smaller Hippocampal Volumes in Cognitively Intact Elderly

Here is the Wikipedia entry for Hippocampus:
Hippocampus [Wikipedia]

All the links have been added to Diagnosis & Tests.

Diabetes Drug Reverses Alzheimers — In Mice

Posted on by

It is fairly well established that diabetes and high blood sugar are serious risk factors for Alzheimers (see Alzheimer’s Linked To Sugar & Diabetes and also: Diabetes and Alzheimer’s linked, Alzheimer’s disease
and diabetes
, and research review: Type 2 Diabetes as a Risk Factor for Alzheimer’s Disease: The Confounders, Interactions, and Neuropathology Associated With This Relationship)

So it would seem to be great news that the use of an established drug for treating human diabetes might also directly treat Alzheimer’s or at least the symptoms thereof in mice models. However this snarky, but all-too-true, comment from Hacker News summarizes the situation:

This would be great news if we [had] not cured mice many times before of Alzheimer’s. Unfortunatly all the drugs that have worked in mice failed when tested in humans.

Of course, this might be the magic time. Since the drug is already approved for human use, we’ll find out much sooner whether it works for Alzheimer’s. Here are four media articles about the work (all with similar titles):

A Diabetes Drug Has ‘Significantly Reversed Memory Loss’ in Mice With Alzheimer’s
Diabetes drug ‘significantly reverses memory loss’ in mice with Alzheimer’s
Diabetes drug ‘significantly reverses memory loss’ in mice with Alzheimer’s
Diabetes drug “significantly reverses memory loss” in mice with Alzheimer’s
And here is the original research article:
Neuroprotective effects of a triple GLP-1/GIP/glucagon receptor agonist in the APP/PS1 transgenic mouse model of Alzheimer’s disease

The three links in the first paragraph have been added to Risk Factors. The links regarding the diabetes drug have been added to Treatment > Drugs.

Serious Exercise May Seriously Defer Aging

Posted on by

We’ve previously posted a number of links in Health > Physical Exercise about the value of physical exercise, and more information about that value just keeps rolling in. And it’s not just physical benefits provided by exercise —- the second part of this post describes cognitive benefits from exercise. So choose some form of fairly intense exercise, and get with it!

Exercise In Old Age: Preserve The Immune System & Muscle Mass

Two recently reported studies show that serious exercise into the 80’s can maintain an immune system similar to a 20-year old’s, and can also significantly reduce loss of muscle mass. Here are two media articles about the studies:
How exercise in old age prevents the immune system from declining
A lifetime of regular exercise slows down aging, study finds

And here are the two original studies:
Major features of immunesenescence, including reduced thymic output, are ameliorated by high levels of physical activity in adulthood
Properties of the vastus lateralis muscle in relation to age and physiological function in master cyclists aged 55–79 years

Exercise To Delay Cognitive Decline

In the last several years, a number of studies have shown that typical cognitive decline due to aging can be delayed by exercise. Here are a links to a number of media articles dealing with groups of the research studies:
Intensive Exercise May Delay Cognitive Decline by 10 Years
xercise May Slow Down Brain Aging By 10 Years: Study
Taking The Stairs Can Slow Down Brain Aging: Study
Exercise May Slow Brain Aging by 10 Years for Older People
Exercise might slow rate of mental decline by 10 years for older people
Study: Exercise may slow mental decline by 10 years
Intensive Exercise May Delay Cognitive Decline by 10 Years

Here are links to the research articles:
Leisure-time physical activity associates with cognitive decline. The Northern Manhattan Study (Abstract)
Ideal Cardiovascular Health and Cognitive Aging in the Northern Manhattan Study
Differences between chronological and brain age are related to education and self-reported physical activity
Effect of Physical Exercise on Cognitive Performance in Older Adults with Mild Cognitive Impairment or Dementia: A Systematic Review

All the links mentioned in this post have been added to both
Health > Physical Exercise and Aging.

Brain Inflammation & Alzheimer’s

Posted on by

A current article, published on this year’s solstice (21 Dec), has excited Alzheimer’s researchers about the possibility of a refinement of the line of attack on the disease. The deposit of amyloid plaques is widely regarded as the core cause of the death of masses of brain neurons, the direct cause of Alzheimer’s symptoms. Most drug development efforts have targeted removal of the plaques, and almost all have failed (see The hard truth about Alzheimer’s drugs, link filed in Treatment > Drugs). The only one with any promise is Aducanumab, which only seems to have value if taken in very early stages of Alzheimer’s, and will be hugely expensive (see the article at end).

Besides the development of amyloid plaques, tangles of tau proteins inside the neurons, together with signs of activated/irritated immune cells called microglia are also found extensively in the brains of Alzheimer’s patients. The activated/irritated microglia can be caused by such things as a mild injury or a virus, and are also provoked by the deposit of amyloid. The newly published paper suggests that there may be an interaction or even feedback loop between deposit of amyloid and the irritated microglia. A key part of the process is the formation inside the microglia of a protein complex called an inflammasome. This complex both signals to other microglia to provoke further inflammation, but also releases specks of a protein called ASC. These specks appear to act as seeds for further deposit of amyloid, and the resulting amyloid plaques have ASC specks at their core. The first media article below compares this to the “grit inside a pearl”.

The research was mostly carried out on mice, though examining the brains of deceased Alzheimer’s patients showed substantial amounts of amyloid plaque containing ASC specs at core. In parts of the mice experiments, it was shown that presence or absence of ASC affected the generation of amyloid, and in other parts of the experiments, it was shown that when antibodies to ASC were injected, it interfered with the seeding effect for amyloid by ASC.

Thus, attacking inflammation and the action of ASC now seems like a promising way forward.

Here are two media articles about the study:

Brain inflammation sows the seeds of Alzheimer’s
Do Microglia Spread Aβ Plaques?

Here is the original study article:
Microglia-derived ASC specks cross-seed amyloid-β in Alzheimer’s disease

All three of these links have been added to Alzheimers > Neurology & Neuroplasticity

And here is an article about the drug Aducanumab (link added to Treatment > Drugs):
Robert Chen, MD-PhD candidate in Alzheimer’s research: What were the key findings from the Aducanumab phase 1 clinical trials? [Reprinted as: Aducanumab Is Showing Promise As An Alzheimer’s Treatment, But It’s Still Early]

Mediterranean/MIND Diet Seriously Fights Alzheimer’s/Dementia

Posted on by

Striking findings from two large-scale studies and two smaller studies show that following the Mediterranean diet or the related MIND diet can reduce the risk of dementia by one-third! The studies were reported at the recent 2017 Alzheimer’s Association International Conference in London.

The first study (Neuroprotective Diets …. abstract, full text) looked at the eating habits of almost 6,000 older adults (average age of 68) enrolled in the Health and Retirement Study, sponsored by the U.S. National Institute on Aging. The study is representative of the total US population, and as such, the results are widely applicable to the general public. Specifically, following the Mediterranean or MIND diet in general leads to 30%–35% lower risk of cognitive impairment during aging. Especially notable is the fact that the benefits appear to be a ‘sliding scale:’ “The more people stayed on those diets, the better they functioned cognitively,” said lead researcher Claire McEvoy.

The second study (The Mind Diet and Incident Dementia, Findings from the Women’s Health Initiative Memory Study; sponsored by National Institutes on Aging) examined the MIND diet’s effectiveness for more than 7,000 women. Similar to the first study, women closely following the MIND guidelines were 34% less likely to develop Alzheimer’s disease, while those moderately following the guidelines were 21%–24% less likely to develop Alzheimer’s.

An important observation is that these diets were originally developed to help improve cardiovascular health. Thus, following these diets will provide potential protection for both brain and heart health.

The third study (from Sweden: Which Dietary Index May Predict Preserved Cognitive Function in Nordic Older Adults?) enrolled more than 2,000 people and found that those eating a healthy diet called the Nordic Prudent Dietary Pattern (a diet related to the Mediterranean and MIND diets) for more than six years experienced better brain health.

The fourth study looked at the problem in the opposite direction. It looked at 330 people (average age 80) who followed a dietary pattern encouraging inflammation (so a diet “opposite” to the Mediterranean/MIND diets). These people performed poorly on brain games, and MRI scans showed that they also had a smaller total volume of brain gray matter. So this study negatively corroborates the outcomes of the first 3 studies.

Here is the Alzheimer’s Association Press Release about the four studies:
Healthy Eating Habits May Preserve Cognitive Function And Reduce The Risk Of Dementia

And here are several media stories about the presentations:
Mediterranean style diet may prevent dementia
Mediterranean-style diet linked to lower risk of dementia
Fight Dementia With Food: Following A Mediterranean Diet May Improve Brain Health, Studies Suggest
A Healthy Diet May Help Ward Off Dementia
Could the Mediterranean Diet Help Fight Dementia? Here’s What We Know

All the links have been added to Health > Diet

Evolution, Genetics, and Alzheimer’s

Posted on by

Numerous trials have been run hoping to develop and validate drugs which would either slow, stop, or reverse the development of Alzheimer’s in humans. Yet over several decades none have succeeded. Almost all of these attempts have been based on the “amyloid hypothesis”, and consequently, some researchers have started looking in new directions.

One exciting such new direction involves mitochondrial DNA, which we inherit from our mothers, but not our fathers. This difference might account for the fact that people whose family history showed Alzheimer’s on their mother’s side were more likely to get Alzheimer’s than people whose family history only showed Alzheimer’s on the father’s side. So various mitochondrial diseases and failures could be genetically responsible for the development of Alzheimer’s in the brain.

It is widely regarded that most non-human primates do not exhibit Alzheimer’s, although they exhibit related symptoms and brain changes. The new study focused on the idea that thus, Alzheimer’s ought to have come about in human beings due to some evolutionarily recent change in our brains setting us apart from existing primate species. The study focused on one such change, the development of “retrotransposons”, or so-called “jumping genes”.

An excellent extended exposition of this work is available at
When copy-paste attacks: A possible answer to the mystery of Alzheimer’s disease

Another article about the work is
‘Jumping genes’ may set the stage for brain cell death in Alzheimer’s, other diseases

The research publication itself is at
The Alu neurodegeneration hypothesis: A primate-specific mechanism for neuronal transcription noise, mitochondrial dysfunction, and manifestation of neurodegenerative disease

Links to the articles and the research publication have been posted in Alzheimers > Risk Factors > Genetics.

Dementia: Hope & Despair for Patient & Caregiver

Posted on by

Dasha Kiper has written a remarkable long piece about her year plus caring for a dementia patient. A shorter form was published as The deviousness of dementia while the longer version appeared as

Hope Is the Enemy: Caring for a patient suffering from dementia means coming to terms with the frustrating paradoxes of memory and language.

 
Links to both versions have been posted on Strong Brain in both
Alzheimers > Caregivers and Alzheimers > Coping Stories

Five New Links on Risk Factors for Alzheimer’s

Posted on by

Five links were added in:

Alzheimers > Risk Factors

Here are the new links:
Type 2 diabetes linked with reduced cognitive function     …shown that people with diabetes have abnormal blood flow regulation in the brain, namely impaired ability to increase blood flow and deliver sugar and oxygen to the brain during episodes of increased mental activity

High Blood Sugar May Boost Alzheimer’s Risk     Insulin resistance can inhibit signaling between brain cells and affect memory…

Too much TV could raise the risk of Alzheimer’s, study suggests     It turns out that too much TV might damage your brain and also raise the risk of developing Alzheimer’s disease…

Survey: Risk Factors     The most important risk factors—age, family history and heredity—can’t be changed, but emerging evidence suggests there may be other factors we can influence.

Infection Inflicts A Persistent Decrease In IQ: A Danish Study With 180,000 Participants     A recent danish study … showed that infections can impair cognitive ability