Alzheimer’s memory loss may be reversed by blocking a key enzyme

Targeting an enzyme that interferes with memory-forming processes in Alzheimer’s patients can be an effective treatment for memory loss, according to a new study. A team of scientists from the Massachusetts Institute of Technology (MIT) in the U.S. found that it may be possible to reverse Alzheimer’s related memory loss with drugs that selectively impede the ability of the Histone deacetylase-2 (HDAC2) enzyme to interfere with the communication between brain cells.

Previously, scientists failed to target HDAC2because the drugs that were used also impeded other roles of the enzyme, causing toxic side effects.

The new research has shown that blocking a molecule called sp3 that binds to HDAC2 might effectively stop them both from disrupting the communication between brain cells that is crucial for memory.

"If we can remove the blockade by inhibiting HDAC2 activity or reducing HDAC2 levels," explains Seniorauthor Prof. Li-Huei Tsai, director of the Picower Institute for Learning and Memory at MIT, "then we can remove the blockade and restore expression of all these genes necessary for learning and memory."

For over a decade, Prof. Tsai has been researching the role that enzymes called HDACs play in memory loss. In2007, she discovered that blocking HDAC activity in mice could reverse memory loss. There are around a dozen types of HDAC in humans.

Alzheimer's disease is the most common form of dementia, affecting around 850,000 people in the UK. This neurodegenerative disease gradually diminishes a person’s ability to remember, think, reason, and make decisions.

There is no cure for thedisease and scientists do not know the causes of the disease. It is more common among people over 60 years, but it can affect younger people as well.

The new study focuses on the disruption of a process called synaptic plasticity, which is thought to be crucial for memory and learning.

Research has revealed that synapses – the connections between brain cells – are "plastic" and are not fixed as the soldered joints in electronic circuits.

Scientists define synaptic plasticity as a biological process whereby synapses change over time, depending on specific patterns of activity.

Read more Exercise may protect against cognitive decline

Scientists previously tested compounds that inhibit HDAC2, but most these produced side effects, such as interfering with HDAC1. HDAC1 is crucial for cell proliferation, especially in red and white blood cells.

Therefore, in this new study, Prof. Tsai and his team sought to find a way to target only the HDAC2 activity that impedes memory. The team searched for proteins that help the enzyme to bind to the relevant genes.

To find the diabolical pairing, the researchers examined the expression of genes in postmortem brain samples taken from people who didn’t have Alzheimer’s.

Of these samples some brains had high and some had low levels of HDAC2, which helped the researchers to identify more than 2,000 genes that might be involved with HDAC2 activity.

Next, a technique called gene knockdown was used to prevent the expression of HDAC2 and other genes in mice. This narrowed down the search to a gene that made the protein Sp3.

Fragments of HDAC2 were used to connect with Sp3 in the mice. This effectively mopped up the proteins and prevented them from forming a complex with complete HDAC2 enzymes.

This clean-up was useful and it helped restore mice’s nerve functions, providing evidence that the enzyme and its helper were both required to latch onto the histones and DNA and prevent them from working.

The study was published in the journal Cell Reports.

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Does Memory Loss Always Mean Dementia?

Dementia or senility isn’t a specific disease. Instead, it is a broad category of symptoms that affect the brain and causes memory loss. The loss of memory affects social abilities and cognitive skills that are severe enough to interfere with daily life.

The most common form of dementia is Alzheimer’s disease, which accounts for 60%-80% of all dementia cases. Other common types of dementia include vascular dementia – accounting for 25%, Lewy body dementia – accounting for 15% and frontotemporal dementia. A person can be affected by more than one type of dementia.

Every 3 seconds, someone in the world develops dementia. There were an estimated 46.8 million people worldwide living with dementia in 2015 and this number is believed to be close to 50 million people in 2017. 5.2% of people over the age of 60 are living with dementia globally. The number of people with dementia will almost double every 20 years, reaching 75 million in 2030 and 131.5 million in 2050. Developing countries will see much of theincrease. Currently, around 58% of people with dementia live in low- and middle-income countries, but this will rise to 68% by 2050. The fastest growth in the elderly population is taking place in China, India, and their south Asian and western Pacific neighbors.

There are about 5.7 million people of all ages are affected with Alzheimer’s disease in the USA. Almost two thirds of Americans with Alzheimer’s are women.

According to Alzheimer’s Society, UK, an estimated 850,000 people are affected by dementia in the UK, with the number expected to rise to over 1 million by 2025. It is expected that 225,000 people will develop dementia this year that is 1 person every 3 minutes.

Does Memory Loss Mean A Person Has Dementia?

Although loss of memory usually occurs in dementia, loss of memory alone does not mean a person has dementia. People lose some degree of memory as they get older. Naturally occurring memory loss isn’t considered dementia. At least 2 of thefollowing cognitive functions must be significantly damaged to be considered dementia:

1. Loss of memory
2. Problem communicating or understanding language
3. Inability to focus
4. Inability to make decisions or judgments
5. Lack of visual perception

What are the Types of Dementia?

The different types of dementia include:

• Alzheimer’s disease. It is the most common for of dementia, accounting for 60 to 80 percent of all dementia cases. Alzheimer’s causes problems with memory, thinking and behavior.
• Vascular dementia. It is the second most common type of dementia, which occurs after a stroke.
• Dementia with Lewy Bodies (DLB). It is a form of progressive dementia that leads to a decline in thinking, reasoning and independent function due to abnormal microscopic deposits that damage brain cells over time.
• Parkinson’s disease dementia. It is a cognitive impairment that ultimately affects many people with Parkinson's disease.
• Mixed dementia. In this type of dementia, abnormal characteristics of more than one type of dementia occur simultaneously.
• Frontotemporal dementia (FTD). It is a group of disorders caused by progressive nerve cell loss in the brain's frontal lobes (the areas behind the forehead) or its temporal lobes (the regions behind the ears).
• Huntington’s disease. It is a progressive brain disorder caused by a defective gene. This disease causes changes in the central area of the brain, which affect movement, mood and thinking skills.
• Creutzfeldt-Jakob disease (CJD). It is the most common human form of a group of rare, fatal brain disorders known as prion diseases.
• Normal pressure hydrocephalus (NPH). It is a brain disorder in which excess cerebrospinal fluid accumulates in the brain's ventricle, causing thinking and reasoning problems, difficulty walking, and loss of bladder control.
• Wernicke-Korsakoff Syndrome. It is a chronic memory disorder caused by severe deficiency of thiamine (vitamin B-1). Korsakoff syndrome is most commonly caused by alcohol misuse, but certain other conditions also can cause the syndrome.
• Posterior cortical atrophy (PCA). It is the gradual and progressive degeneration of the outer layer of the brain (the cortex) in the part of the brain located in the back of the head (posterior).

Are there Warning Signs One Should Watch Out For?

What Are the Stages of Dementia?

Dementia may have several stages such as, mild, moderate or severe. A dementia patient may fall into 2 different stages at once. Progression of a patient’s condition cannot be determined by the stages of dementia. A patient may remain in a particular stage for a few months or a several years. Progression of the disease varies in patient to patient.

What Are the Causes of Dementia?

Death of the nerve cells in the brain causes dementia. Dementia may be caused by head injury, stroke or a brain tumor. Since, death of brain cells may occur in different parts of the brain, dementia’s affect on people may vary from person to person.

What Are the Signs and symptoms of Dementia?

Dementia, in its early stage may have signs like forgetting things, difficulty performing tasks that were previously done without effort, losing common items such as keys, glasses etc. Difficulty learning new things is a very common early sign of dementia. Many Alzheimer’s patients or patients with other forms of dementia are unaware about their problems. The behavioral changes become evident with the progression of the disease. Patients fail to perform simple tasks, such as putting on clothes or going to the bathroom. Some patients may forget their phone numbers, addresses or their date of birth. They may be unaware about their surrounding environment. Some patients may forget to take their food, which may lead to marked weight loss. At the late stages of dementia, patients often cannot recognize their friends or family members. They lose their ability to communicate effectively. They become unable to care for themselves and need help of others to perform daily activities. As the disease progresses, patients start to forget how to walk or how to get up from a chair.

Can Dementia Be Reversed?

Doctors may identify the causes of certain dementia, therefore conditions can be reversed with proper treatment.

• When dementia-like conditions occur from fever or other infections such as meningitis, encephalitis, syphilis, Lyme disease. Dementia from immune disorders such as leukemia and multiple sclerosis can also be reversed.
• Dementia from metabolic problems and abnormalities of endocrine.
• When nutritional deficiencies cause dementia.
• When dementia is caused by poisoning.
• Subdural hematomas
• Rarely, brain tumors can cause dementia
• Reactions to medication

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Oral health may be linked to cognitive decline

According to new research published in the Journal of the American Geriatrics Society, there may be a link between oral health and the progression of cognitive decline.

"Clinical evidence suggests that the frequency of oral health problems increases significantly in cognitively impaired older people, particularly those with dementia,” said lead researcher Bei Wu, PhD, of Duke University's School of Nursing in Durham, North Carolina in the US.

"In addition, many of the factors associated with poor oral health — such as poor nutrition and systemic diseases like diabetes and cardiovascular disease — are also associated with poor cognitive function,” he added.

The researchers caution, however, that more studies are needed.

Findings came from the first systematic review of studies focused on oral health and cognition. These two important areas of research are important because in a growing older adult population, some 36% of people over age 70 are already living with some degree of cognitive decline. Researchers believe that a common inflammatory pathway may hold the key to a link between oral hygiene and cognitive impairment, if such a link exists.

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Poor oral health has been blamed for heart disease, due to the spread of bacteria and oral health problems may be aggravated by diabetes and HIV/AIDS due to reduction of body’s resistance to infection.

Alzheimer's Association estimates around 5.4 million people in the US have Alzheimer's disease - the most common form of dementia.

To look for a link between oral health and cognitive status, Dr. Wu and her colleagues combed through 56 studies published between January1993 and March 2013 that examined the relationship between oral health and change in cognitive health or dementia incidence. They analyzed relevant cross-sectional (data collected at one specific point in time) and longitudinal (data collected over an extended period of time).

Some of the studies analyzed found that dental health measures, such as the number of teeth, the number of cavities, and the presence of gum disease, were linked to an increased risk of cognitive decline or dementia. Which is interesting considering a 2013 study found gum disease bacteria in the brains of Alzheimer’s disease patients — but this study in no way proved that gum disease causes Alzheimer’s disease. It just acknowledged an association.

However, researchers involved with the current review also noted that the findings based on the number of teeth or cavities are conflicting, and limited studies suggested that the dental conditions such as gingivitis are associated with cognitive decline. Similarly, the team didn’t regularly find that cognitive decline was associated with greater loss of teeth or number of decayed teeth. However, it is likely that "methodological limitations play a major role in explaining the inconsistent findings," they wrote.

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"There is not enough evidence to date to conclude that a causal association exists between cognitive function and oral health. For future research, we recommend that investigators gather data from larger and more population representative samples, use standard cognitive assessments and oral health measures, and use more sophisticated data analyses," Dr. Wu said.

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People with rosacea are at higher risk of Alzheimer’s

According to a new study people with rosacea – the facial redness affecting millions of people – are at an increased risk of developing dementia, particularly Alzheimer's disease, compared with people without the condition. The study also found that older patients and patients who were diagnosed by a hospital dermatologist were at the highest risk of developing Alzheimer’s.

However, the researchers were quick to point out that people with rosacea should not be overly concerned about the finding.

“It is important for patients to remember that having rosacea does not guarantee that they will develop Alzheimer’s disease,” said lead author Dr. Alexander Egeberg of the department of dermato-allergology at Herlev and Gentofte Hospital, in Copenhagen, Denmark.

Read more BellyFat May Cause Cognitive Impairment

“In fact, while the risk in rosacea patients may be slightly increased compared with the general population, the absolute risk [to any one patient] is still quite low,” he said.

Rosacea is very common, where some estimates suggest up to 1 in 10 people may have it. According to the National Rosacea Society, approximately 16 million Americans suffer from it. Around 1 in every 600 people in the UK are diagnosed with the condition each year. It most commonly affects people with fair skin, but can also occur in people of Asian and African origin. The condition is often mistaken for eczema, acne, or some other skin condition. Rosacea occurs in both men and women, but tends to be more common in women. Most cases are first diagnosed in people aged 30 to 50. There are no cures for the condition, but some medicines can alleviate symptoms.

The study was conducted by the team because there is evidence rosacea is linked with higher levels of certain proteins that have also been implicated in various neurological disorders, such as Alzheimer's disease and other forms of dementia. The proteins in question here are matrix metalloproteinases and antimicrobial peptides.

For the new study, Dr. Egeberg’s team analyzed data from the Danish nationalhealth registry system covering the period 1997-2012. The nation’s entire population – nearly 6 million men and women – were included, out of whom 83,500 had rosacea.

Individuals were followed until December 31, 2012, migration, a diagnosis of dementia, or death from any cause, whichever came first. Altogether, just over 99,000 developed dementia, including around 29,000 who were diagnosed with Alzheimer's disease.

After analysis, researchers found that people with rosacea had a 7% increased risk of dementia and a 25% increased risk of Alzheimer’s, compared with patients who did not have the skin condition. Older people were at higher risk.

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The results also varied between men and women, where women with rosacea were at 28% increased risk of Alzheimer’s and men were at 16% increased risk.

For women, the raised risk of Alzheimer's linked to rosacea was 28 percent, whereas for men with the skin disorder it was 16 percent.

When the analysis was limited to cases of rosacea that had been diagnosed by a hospital dermatologist, the researchers found the increased risk of dementia was 42%, while the risk was 92% for Alzheimer’s disease.

Dr. Egeberg says:

"A subtype of patients have prominent neurological symptoms such as burning and stinging pain in the skin, migraines, and neuropsychiatric symptoms, suggesting a link between rosacea and neurological diseases."

"Indeed," he continues, "emerging evidence suggests that rosacea may be linked with neurological disorders including Parkinson's disease and now also Alzheimer's disease."

He says that the risk may be explained by certain underlying mechanisms shared by rosacea and Alzheimer's disease, but it is no known whether one causes the other.

The team suggests doctors should look out for symptoms of cognitive impairment in older patients with rosacea, and that only further studies can affirm if treating rosacea may also improve patients' risk of developing dementia.

The findings are published in the Annals of Neurology, a journal of the American Neurological Association and Child Neurology Society.

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Belly Fat May Cause Cognitive Impairment

A team of scientists from 3 Irish universities – St. James's Hospital and Trinity College Dublin, both in Northern Ireland, and Nutrition Innovation Centre for Food and Health at Ulster University – found that having higher levels of belly fat in old age is associated with a decrease in cognitive function.

Prevalence of Alzheimer’s and other forms of dementia is growing with the rise in average age of population. Currently, an estimated 47 million people worldwide are affected by dementia. This number is expected to rise to 75 million by 2030.

Scientists are trying to understand the risk factors involved in dementia as it will help us with potential interventions to lower the risk of this condition developing as we age. One such risk factor is obesity.

Earlier studies have shown that overweight or obese adults do not perform as well on tests of memory and visuospatial ability compared to those who are a normal weight. However, researchers aren’t sure if this trend continues into older age.

While previous studieshave looked into this matter, the results produced were contradictory. Since each study involved different forms of cognitive test, it is difficult to conduct a meta-analysis with the pooled results.

For this new study, the researchers set out to answer this question more conclusively using a large-scale trial. [Read more High-fat diet damages brain, affecting learning and memory]

The scientists from the three universities used data from the Trinity Ulster Department of Agriculture aging cohort study, which is a cross-border collaborative research project gathering data from thousands of adults over the age of 60 in Northern Ireland and Ireland.

Each of the 5,186 participants was assessed using a number of cognitive tests.

The team found that a higher waist to hip ratio was linked with reduced cognitive function. This could be due to an increased secretion of inflammatory markers by belly fat, which in previous studies had been linked with a higher risk of cognitive impairment.

On the contrary, bodymass index (BMI) measurements did not show the same trend; in fact, higher BMI was found to protect cognitive function. Researchers believe this is because BMI is a crude measure of body fat and cannot differentiate between fat and fat-free mass (muscle); it only takes into account weight and height.  

How cognition is influenced by belly fat?

Researchers believe that belly fat's impact on cognition might be due to high secretion of inflammatory markers – particularly C-reactive protein. This chemical is produced when fat cells send out signals. Increased levels of this have previously been linked to cognitive decline.

It should also be noted that according to studies, levels of inflammatory markers in the blood increases in the lead-in to dementia, before symptoms appear. 

Hemoglobin A1C (HbA1C) is another molecule that seemed crucial. When during their analysis, the researchers controlled for levels of HbA1C, the significant effect of belly fat on cognition disappeared.

The prevalence of obesity and dementia are putting enormous burdens on the society. Studies like this are crucial because by reducing obesity we may be able to curtail the prevalence of dementia.

The findings are published in the British Journal of Nutrition.

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