Lead exposure linked to Alzheimer’s disease: ICMR study

Lead exposure can lead to Alzheimer’s - a progressive disease that destroys memory and other important mental function, scientists at the Indian Council of Medical Research-led National Institute of Nutrition (ICMR-NIN) have established through laboratory-based studies.

Lead is a common pollutant that can get into environment from a number of commonly used materials like paints, cosmetics, batteries, glass and low grade toys, and is known to affect the central nervous system after prolonged exposure.

Its role as a risk factor in development of neurodegenerative diseases is also established through various studies globally.

“Recent lab-based studies conducted at ICMR-NIN have now established the possible link between lead exposure and Alzheimer’s disease,” said ICMR in a statement.

A team led by ICMR- NIN’s senior scientist Dr Suresh Challa has shown the molecular mechanism involved in the development of lead induced Alzheimer’s disease through in vitro studies.

“In fact, Alzheimer’s Disease has a complex pathophysiology which involves initially formation of beta amyloid plaques and tangles in the brain. In addition, oxidative stress and inflammation are known to be involved in the progression of the disease, with loss of memory and neuronal cell death. In this scenario, our study investigated the basic molecular mechanism behind the involvement of lead in Alzheimer’s disease,” said Dr Challa

The scientists simulated brain cells in vitro with beta amyloid peptides like in Alzheimer’s disease and the effect of lead exposure was then studied. It showed increased cell death and increased levels of pro-apoptotic marker proteins.

Also, the proteins involved in neurodevelopment and regeneration have depleted. Such effects led to decreased expression levels of synaptophysin (membrane protein), finally leading to loss of memory as in Alzheimer’s disease.

“Maternal exposure to lead during pregnancy can cause developmental reprogramming which can lead to higher risk and early onset of Alzheimer’s disease in later life of the child. Since lead exposure is an important public health concern, the current findings could be another piece in solving the puzzle towards understanding the intracellular mechanism of Alzheimer’s disease. Such findings may as well help in developing preventive and management strategies for elderly,” said Dr R Hemalatha, director, ICMR-NIN.

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Alzheimer's: Head device reduces memory loss in 7 out of 8 people

An open-label clinical trial working with eight people with Alzheimer's disease concluded that a new wearable device that emits electromagnetic impulses was able to significantly improve memory loss in seven of these participants within 2 months. 

Alzheimer's disease affects millions of people in the United States and worldwide, but as yet there is no cure for this progressive neurodegenerative condition.

The condition's main physiological characteristic is the aggregation of beta-amyloid and tau protein in the brain, which disrupt normal communication pathways between brain cells.

Scientists have been aware of this aspect of Alzheimer's for years but have so far been unable to prevent the aggregates from forming, or to dissolve them once formed — not in humans, at least.

But now, researchers affiliated with NeuroEM Therapeutics — a medical device company based in Phoenix, AZ — have developed a wearable device that, according to their recent open-label clinical trial, can significantly reduce memory loss in Alzheimer's by disaggregating toxic protein formed in the brain.

The device has the shape of a cap, and it emits electromagnetic waves in a frequency that, as preclinical studies in mice have shown, can help reverse memory loss. The research team that conducted the clinical trial reports the groundbreaking results in a study paper .

"Despite significant efforts for nearly 20 years, stopping or reversing memory impairment in people with Alzheimer's disease has eluded researchers," notes one of the researchers, Dr. Amanda Smith, who is the director of clinical research at the University of South Florida Health's Byrd Alzheimer's Institute in Tampa.

    "These results provide preliminary evidence that [transcranial electromagnetic treatment] administration we assessed in this small [Alzheimer's disease] study may have the capacity to enhance cognitive performance in patients with mild to moderate disease."
    Dr. Amanda Smith

'Highly significant improvement' at 2 months

For the trial, the researchers worked with eight participants with mild to moderate Alzheimer's disease and their caretakers, who received instructions on how to use the therapeutic device at home. The participants received the treatment twice a day for 2 months, and each session lasted just 1 hour.

By the end of the 2 months, none of the participants had experienced any side effects. Brain scans conducted by the researchers at the end of the study showed that the eight individuals had not developed tumors or brain bleeding as a result of having used the device.

To assess whether the treatment had helped the participants, the investigators used The Alzheimer's Disease Assessment Scale-Cognitive Subscale test (ADAS-cog), the most widely recognized method of assessing cognitive function.

The team found that seven of the eight participants saw an increase of over 4 points in cognitive performance on the ADAS-cog scale after 2 months. This, the researchers explain, is as if the participants' cognitive function had "rejuvenated" by a year.

"We were particularly surprised that this highly significant improvement in the ADAS-cog was maintained even 2 weeks after treatment was completed," says Dr. Gary Arendash, CEO of NeuroEM Therapeutics. "The most likely explanation for continued benefit after cessation of treatment is that the Alzheimer's Disease process itself was being affected," he adds.

The researchers also collected blood and cerebrospinal fluid samples from the participants both at baseline and at the end of the clinical trial.

In analyzing them, they found that the intervention appeared to have led to the disaggregation of beta-amyloid plaques and tau tangles, which are associated with progressive cognitive function impairment in Alzheimer's.

Furthermore, MRI scans also suggested that after the 2-month treatment period, the participants had better communication between brain cells present in the cingulate cortex, which plays a key role in cognitive function — including decision making.

Further steps

The researchers behind the innovative device also note that they received the best feedback they could have received: all of the participants decided to hang onto the devices they got as part of the clinical trial.

"Perhaps the best indication that the 2 months of treatment was having a clinically important effect on the [Alzheimer's disease] patients in this study is that none of the patients wanted to return their head device to the University of South Florida/Byrd Alzheimer's Institute after the study was completed," says Dr. Arendash.

The team is particularly excited about the device's effect on toxic brain plaques. They say that drugs tested in clinical trials have, so far, been much less successful in disaggregating these disruptive buildups.

So, the investigators do not plan on stopping at this small clinical trial. Going forward, they have offered the current trial's participants' the opportunity to take part in a much larger clinical trial, which the research team is now organizing.

All the former participants have accepted this offer. The new trial is due to last around 17 months, on average, and will include about 150 participants with a diagnosis of mild to moderate Alzheimer's disease.

The medical device company hope that they will be able to gain Food and Drug Administration (FDA) approval for their technology over the next couple of years and make the device available to the public by 2021.

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Health Risks Associated With Daytime Naps

Who doesn’t love a good nap during the day? It feels like the perfect way to catch up on deficit sleep from the night, to recharge your batteries and refresh yourself. But while it may be tempting to take one for all the relaxation it offers, it could also indicate some major health disorder including Alzheimer's Disease, according to a latest research. The research found that Alzheimer’s first targets the brain cells that keep us awake during the day. This tends to make us sleepier during the day.  That means that if you are one of those who feel sleepy during the day you could be at risk of developing the neurological disease.

In September last year, another study,  said that those who feel sleepy during the day are nearly three times more likely to develop Alzheimer’s disease than those who have a good night’s sleep. Those who report being very sleepy during the day are more likely to have brain deposits of beta-amyloid — a protein that’s a hallmark for Alzheimer’s disease — years later. The finding, said that poor quality sleep could encourage this form of dementia to develop, suggesting that getting adequate night-time sleep could be a way to help prevent Alzheimer’s disease.

Heart disease: Another research associated daytime napping with the risk of developing cardiovascular disease (CVD) and death. The study found that people who slept for longer than the recommended duration of six to eight hours a day had an increased risk of dying or developing heart disease or stroke.

Insomnia: Daytime naps can disrupt your sleep at night causing sleeplessness. This is why those who experience sleep problems at night should make sure to get treatment for their problems instead of routinely trying to catch up on lost sleep during the day.

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The reason behind drastic memory loss in Alzheimer’s patients

An alteration in a gene may speed up the loss of memory and thinking skills in people who are already at the risk of Alzheimer's disease, according to a study. 

According to researchers, people with Alzheimer’s risk, who have the gene mutation called the BDNF Val66Met allele, or the Met allele may have a more rapid decline of memory and thinking skills. Further, people with the gene mutation, who also had more beta-amyloid — a sticky protein that can build up into plaques found in the brains of people with Alzheimer’s disease — had an even steeper rate of decline. “Because this gene can be detected before the symptoms of Alzheimer’s start, and because this presymptomatic phase is thought to be a critical period for treatments that could delay or prevent the disease, it could be a great target for early treatments,” said Ozioma Okonkwo, from the University of Wisconsin in Madison, US. 

For the study, published in the journal Neurology, the team followed 1,023 people with an average age of 55 for up to 13 years who were at risk of Alzheimer’s but were still healthy during the onset. On tests of verbal learning and memory, those with no gene mutation improved by 0.002 units per year, while the scores of people with the mutation declined by 0.021 units per year. This could be because, “when there is no mutation, it is possible the BDNF gene and the protein it produces are better able to be protective, thereby preserving memory and thinking skills”, Okonkwo said. 

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Ways of Preventing Alzheimer's

Alzheimer’s strikes fear in all of us. The thought of losing your mind as you grow older is terrifying and made worse by the fact that, before now, there appeared to be little we could do to slow down or avoid Alzheimer’s, which is the most common form of dementia.Today, research has found many factors that raise or diminish the risk of Alzheimer's disease. Following these tips, you could slash your chances of developing the disease:

 

1. Check out your ankle
Low blood flow in your foot is a clue to trouble in your brain and a simple test can reveal its cognitive state and your likelihood of stroke and dementia. The theory is that the health of your blood vessels is similar throughout the body. The degree of clogged arteries and blood flow in the feet can suggest atherosclerosis in cerebral blood vessels. Ask your doctor for an ankle-brachial index (ABI) test which involves an ultrasound device and a blood pressure cuff that compares blood pressure in your ankle to that in your arm. To remedy any impairment of blood flow your GP may advise stepped-up exercise or a change in diet/medication.

2. Antioxidant-rich foods
Certain foods infuse your brain with antioxidants that can slow memory decline and help prevent Alzheimer’s. All fruit and vegetables are good but at the top of the list are black raspberries, elderberries, raisins and blueberries.

3. Beware of bad fats
The type of fat you eat changes your brain’s functioning for better or worse. Stay away from saturated fats which strangle brain cells causing them to become inefficient. Buy low fat or fat-free dairy products including milk, cheese and ice cream. Cut down on deep-fried foods.

4. Chocolate Treat
Cocoa, the main ingredient in chocolate, has sky-high concentrations of antioxidants called flavanols, which possess strong heart and brain-protecting properties. Drinking cocoa increases blood flow to the brain. Cocoa powder has twice as many flavanols as dark chocolate, which has twice a many as milk chocolate. White chocolate has zero. 

5. Grow a bigger brain
Your brain starts to shrink when you reach 30 or 40 so it takes longer to learn. However scientists now believe you can increase the size of your brain through learning. Try studying, learning new things or broadening your circle of friends for stimulation.

6. The Estrogen Evidence
 68 per cent of Alzheimer’s patients are women, possibly because midway through life, they lose the protection that is provided by estrogen, which boosts memory. Unless your GP says otherwise, start taking estrogen immediately at the time of menopause – starting any later opens you up to the risk of dementia and stroke.

7. Raise good cholesterol
It’s well known that having a high level of good-type HDL blood cholesterol protects you from heart disease, but it can also save your brain. Researchers claim it blocks sticky stuff that destroys brain cells and acts as an anti-inflammatory to lessen brain damage. Ways to ramp up good cholesterol include exercise, drinking moderate amounts of alcohol and losing weight.

8. Google something
Doing an internet search can stimulate aging brains even more than reading a book. And MRI scans show that savvy surfers have twice as many sparks of brain activity as novices. Go online to search for information, things to buy, or games to play. Although it’s not known how much it will benefit your brain, it’s better than passive pursuits.

9. The ApoE4 gene
One in four of you reading this has a specific genetic time bomb that makes you three to ten times more susceptible to developing late-onset Alzheimer’s. The gene is called apolipoprotein E4. If you inherit a single variant of ApoE4 from one parent, your Alzheimer’s risk triples. If you inherit a double dose from both parents, your risk rises by 10 times. Ask your doctor about a DNA test to reveal your ApoE4 genotype.

10. Say yes to coffee
Coffee is emerging as a tonic for the aging brain. It is anti-inflammatory, helps block the ill effects of cholesterol in the brain and cuts the risks of stroke, depression and diabetes, all promoters of dementia. It is also high in antioxidants and caffeine which stop neuronal death and lessen diabetes, high blood pressure, and strokes that bring on dementia. For most people, a moderate daily intake of coffee, two to four cups, won’t hurt and may help.

11. Dangers of weight loss

 Unexplained weight loss after age 60 or so may be a sign of Alzheimer’s. A study showed that women with the disease started losing weight at least 10 years before dementia was diagnosed. Among women of equal weight, those who went on to develop dementia slowly became thinner over three decades and, when diagnosed, weighed an average 12lb less than women who were free of Alzheimer’s. Talk to your doctor about unexplained weight loss after 60.
12. Drink wine
A daily glass of wine may help delay dementia. Research says that alcohol is an anti-inflammatory and raises good cholesterol which helps ward off dementia. High antioxidants in red wine give it additional anti-dementia clout. Such antioxidants act as artery relaxants, dilating blood vessels and increasing blood flow which encourages cognitive functioning. 

13. Know the early signs
Memory problems are not the first clue. You may notice a decline in depth perception, for example you reach to pick up a glass of water and miss it. Or you misjudge the distance in walking across a street.

Doing a jigsaw puzzle or reading a map may also be confusing. Losing your sense of smell can also be an early clue, as well as asking the same question repeatedly or misplacing belongings in odd places (like putting keys in the fridge). Be aware of memory problems as the earlier the signs are spotted, the more successful lifestyle changes and medications are likely to be.

14. A Mediterranean diet
The Mediterranean diet, no matter where you live, can help save your brain from memory deterioration and dementia. Studies consistently find that what the Greeks and Italians eat is truly brain food. Following this diet – rich in green leafy vegetables, fish, fruits, nuts, legumes, olive oil and a little vino – can cut your chances of Alzheimer’s by nearly half. Rather than depending on just one food or a few nutrients, it is a rich menu of many complex brain benefactors, including an array of antioxidants, which shield brain cells from oxidative damage.

15. Middle Age Obesity
Your brain cares if you are fat. A study showed obese people had 8% less brain tissue and overweight people had 4% less brain tissue than people of average weight, which according to some scientists hugely increases the risk of Alzheimer’s. Moreover, brain shrinkage occurred in areas of the brain targeted by Alzheimer’s, which are critical for planning, long-term memory, attention and executive functions, and control of movement.

Tackle signs of rising weight early, when you are young or middle-aged. Oddly, being obese after the age of 70 does not raise the risk of Alzheimer’s but that doesn’t mean you should neglect exercise as it is the best way of stimulating cognitive functioning and may delay the onset of Alzheimer’s at any age.

 

16. Get a good night’s sleep

 A lack of sleep is toxic to brain cells. Sleep has surprising powers to protect your brain against memory loss and Alzheimer’s. It is a wonder drug that helps manipulate levels of the dreaded brain toxin peptide beta-amyloid, a prime instigator of Alzheimer’s, which according to one scientist puts you at accelerated risk. Research has also found that sleeping an average of five hours or less a night is linked to large increases in dangerous visceral abdominal fat, which can cause diabetes and obesity that can lead to Alzheimer’s. Take naps and seek treatment for sleep disorders.

17. Have an extended social circle
Studying the brain of a highly sociable 90-year-old woman who died from Alzheimer’s, researchers in Chicago found that having a large social network provided her with strong “cognitive reserve” that enabled her brain not to realize she had Alzheimer’s. Why this happens is a mystery, but interacting with friends and family seems to make the brain more efficient. It finds alternative routes of communication to bypass broken connections left by Alzheimer’s. So see friends and family often and expand your social network. The stronger the brain reserve you build through life, the more likely you are to stave off Alzheimer’s symptoms.

18. Deal with stress
When you are under stress, your body pours out hormones called corticosteroids, which can save you in a crisis. But persistent stress reactions triggered by everyday events like work frustration, traffic and financial worries can be dangerous. Over time, it can destroy brain cells and suppress the growth of new ones, actually shrinking your brain. Sudden traumatic events like the death of a loved one or a life-changing event like retirement can leave a hangover of severe psychological stress that precedes dementia. Be aware that chronic stress can increase older people’s vulnerability to memory decline and dementia. Seek professional advice. Antidepressants, counseling, relaxation techniques and other forms of therapy may head off stress-related memory loss if treated early. 

19. Take care of your teeth
Bad gums may poison your brain. People with tooth and gum disease tend to score lower in memory and cognition tests, according to US dental researchers who found that infection responsible for gum disease gives off inflammatory byproducts that travel to areas of the brain involved in memory loss.

Consequently, brushing, flossing and preventing gum disease may help keep your gums and teeth healthy but may also make your memory sharper. In another study, older people with the most severe gingivitis – inflamed gums – were two to three times more likely to show signs of impaired memory and cognition than those with the least.

20. Get enough Vitamin B12
As you age, blood levels of vitamin B12 go down and the chance of Alzheimer’s goes up. Your ability to absorb it from foods diminishes in middle age, setting the stage for brain degeneration years later. Researchers at Oxford University found that a brain running low on B12 actually shrinks and a shortage can lead to brain atrophy by ripping away myelin, a fatty protective sheath around neurons. It can also trigger inflammation, another destroyer of brain cells. Take 500 to 1000mcg of vitamin B12 daily after the age of 40. If you or an older family member has unexplained memory loss, fatigue or signs of dementia, be sure to get tested for vitamin B12 deficiency by your GP.

 

21. Vinegar in everything

 There is plenty of evidence that  vinegar decreases risk factors that may lead to memory decline, namely high blood sugar, insulin resistance, diabetes, pre-diabetes and weight gain. Researchers in Phoenix, Arizona, have noted in studies of humans and animals that the acidic stuff packs potent glucose-lowering effects. Studies have also found it can curb appetite and food intake, helping prevent weight gain and obesity, which are associated with diabetes, accelerated dementia and memory loss. Pour on the vinegar – add it to salad dressings, eat it by the spoonful, even mix it into a glass of drinking water. Any type of vinegar works.
22. Have your eyes checked
If you preserve good or excellent vision as you age, your chances of developing dementia drop by an astonishing 63%. And if it’s poor, just visiting an optician for an eye test and possible treatment at least once in later life cuts your dementia odds by about the same amount. Exactly how vision problems promote dementia is not clear but impaired vision makes it difficult to participate in mental and physical activities such as reading and exercising, as well as social activities, all believed to delay cognitive decline. Be aware that your eyes reflect and influence how your brain is functioning, especially as you age. Don’t tolerate poor vision, as often it can be corrected.

23. Eat curry or take curcumin pills
Curry powder contains the yellow-orange spice turmeric, packed with curcumin, a component reported to stall memory decline. One study showed elderly Indians who ate even modest amounts of curry did better in cognitive tests. Curcumin works by blocking the build-up of Alzheimer’s-inducing amyloid plaques (deposits found in the brains of sufferers) then nibbles away at existing plaque to slow cognitive decline.

It is recommended to eat two or three curries a week, and make it a yellow curry. Otherwise, sprinkle the spice on your food. Read more about the many benefits of Curcumin.

24. Diabetes control
Having type 2 diabetes makes you more vulnerable to Alzheimer’s. Studies show it may double or triple your risk and the earlier diabetes takes hold, the higher the odds of dementia. Some experts refer to Alzheimer’s as “diabetes of the brain”. The two disorders have similar causes – obesity, high blood pressure, high cholesterol, high fat and high sugar diets, low physical activity as well as high blood sugar. In short, diabetes can deliver a double whammy to the brain, destroying neurons and increasing inflammation. Do everything possible to keep blood sugar levels low and stick to a low-saturated-fat diet and regular exercise.

25. Drink more tea
Evidence suggests that tea stalls the cognitive loss that precedes Alzheimer’s and that the more tea you drink, the sharper your ageing memory is. Tea’s secret is no mystery. The leaves are packed with compounds able to penetrate the blood-brain barrier and block neuronal damage.

One particular green tea antioxidant can block the toxicity of beta-amyloid, which kills brain cells. Make a point of drinking black and green tea. Don’t add milk - it can reduce tea’s antioxidant activity by 25%.

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Mediterranean Diet, Exercise Can Cut Risk Of Alzheimer's

Mediterranean diet, regular physical activity and a normal body mass index can reduce the incidence of protein build-ups that are associated with the onset of Alzheimer's disease, says a study.

The findings showed that each one of several lifestyle factors - a healthy body mass index, physical activity and a Mediterranean diet - were linked to lower levels of plaques and tangles on the brain scans. Plaque, deposits of a toxic protein called beta-amyloid in the spaces between nerve cells in the brain; and tangles, knotted threads of the tau protein found within brain cells, are considered the key indicators of Alzheimer's.

The Mediterranean diet is rich in fruits, vegetables, legumes, cereals and fish and low in meat and dairy, and characterised by a high ratio of monounsaturated to saturated fats, and mild to moderate alcohol consumption.

Earlier studies have linked a healthy lifestyle to delays in the onset of Alzheimer's disease.

However, the new study is the first to demonstrate how lifestyle factors directly influence abnormal proteins in people with subtle memory loss who have not yet been diagnosed with dementia, the researchers said. "The study reinforces the importance of living a healthy life to prevent Alzheimer's, even before the development of clinically significant dementia," said lead author David Merrill, Psychiatrist at the University of California, Los Angeles.

Healthy lifestyle factors have also been shown to be related to reduced shrinking of the brain and lower rates of atrophy in people with Alzheimer's.

Older age is the leading non-modifiable risk factor for Alzheimer's disease.

"The fact that we could detect this influence of lifestyle at a molecular level before the beginning of serious memory problems surprised us," Merrill added.

In the study, 44 adults ranging in age from 40 to 85 with mild memory changes but no dementia underwent an experimental type of positron emission tomography (PET) scan to measure the level of plaque and tangles in the brain.

Researchers also collected information on participants' body mass index, levels of physical activity, diet and other lifestyle factors.
"The work lends key insight not only into the ability of patients to prevent Alzheimer's disease, but also physicians' ability to detect and image these changes," Merrill noted in the paper appearing in the American Journal of Geriatric Psychiatry.

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Smell, eye tests may detect Alzheimer's early

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While scientists are closer to developing a blood test to predict the onset of Alzheimer's disease, Indian-origin professor Davangere Devanand and other researchers have found our eyes and sense of smell could well hold the key to detecting the disorder early in a cheaper and easier way.

A decreased ability to identify odour might indicate the development of cognitive impairment and Alzheimer's disease, while examinations of the eye could indicate the build-up of beta-amyloid, a protein associated with Alzheimer's in the brain, the findings of four research trials showed.

"In the face of the growing worldwide Alzheimer's disease epidemic, there is a pressing need for simple, less invasive diagnostic tests that will identify the risk of Alzheimer's much earlier in the disease process," said Heather Snyder, director of medical and scientific operations, Alzheimer's Association.

Early detection is essential for early intervention and prevention, when new treatments become available, Snyder noted.

Clinically, at this time it is only possible to detect Alzheimer's late in its development, when significant brain damage has already occurred.

Beta-amyloid protein is the primary material found in the sticky brain "plaques" characteristic of Alzheimer's disease.

In a study led by Devanand, professor of psychiatry at Columbia University Medical Centre in the US, researchers investigated a multi-ethnic sample of 1,037 non-demented elderly people in New York City and found that in 757 subjects who were followed, lower odour identification scores on a smell identification test were significantly associated with the transition to dementia and Alzheimer's disease.

"Odour identification deficits were associated with the transition to dementia and Alzheimer's disease, and with cognitive decline in cognitively intact participants, in our community sample," Devanand noted.

In a separate study researchers found that amyloid levels detected in the retina were significantly correlated with brain amyloid levels as shown by PET (Positron emission tomography) imaging.

The results of the studies were reported Sunday at the Alzheimer's Association International Conference in Copenhagen, Denmark.