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What prevents Alzheimers?

HRT May Prevent Alzheimer’s in High-Risk Women

Hormone replacement therapy (HRT) introduced early during the menopausal transition may protect against Alzheimer’s dementia in women carrying the APOE4 gene, new research suggests. Results from a cohort study of almost 1200 women showed that use of HRT was associated with higher delayed memory scores and larger entorhinal and hippocampal brain volumes ― areas that are affected early by Alzheimer’s disease (AD) pathology.

HRT was also found to be most effective, as seen by larger hippocampal volume, when introduced during early perimenopause. «Clinicians are very much aware of the susceptibility of women to cognitive disturbances during menopause,» lead author Rasha Saleh, MD, senior research associate, Norwich Medical School, University of East Anglia, United Kingdom, told Medscape Medical News.

«Identifying the at-risk APOE4 women and early HRT introduction can be of benefit. Confirming our findings in a clinical trial would be the next step forward,» Saleh said.

The findings were published online January 9 in Alzheimer’s Research and Therapy.

Personalized Approaches

Saleh noted that estrogen receptors are localized in various areas of the brain, including cognition-related areas. Estrogen regulates such things as neuroinflammatory status, glucose utilization, and lipid metabolism.

«The decline of estrogen during menopause can lead to disturbance in these functions, which can accelerate AD-related pathology,» she said. HRT during the menopausal transition and afterward is «being considered as a strategy to mitigate cognitive decline,» the investigators write. Early observational studies have suggested that oral estrogen «may be protective against dementia,» but results of clinical trials have been inconsistent, and some have even shown «harmful effects,» they add. The current researchers were «interested in the personalized approaches in the prevention of AD,» Saleh said. Preclinical and pilot data from her group have shown that women with APOE4 have «better cognitive test scores with nutritional and hormonal interventions.» This led Saleh to hypothesize that HRT would be of more cognitive benefit for those with vs without APOE4, particularly when introduced early during the menopausal transition.

To investigate this hypothesis, the researchers analyzed baseline data from participants in the European Prevention of Alzheimer’s Dementia (EPAD) cohort. This project was initiated in 2015 with the aim of developing longitudinal models over the entire course of AD prior to dementia clinical diagnosis.

Participants were recruited from 10 European countries. All were required to be at least 50 years old, to have not been diagnosed with dementia at baseline, and to have no medical or psychiatric illness that could potentially exclude them from further research.

The current study included 1178 women (mean age, 65.1 years), who were divided by genotype into non-APOE4 and APOE4 groups. HRT treatment for current or previous users included estrogen alone or estrogen plus progestogens via oral or transdermal administration routes, and at different doses.

The four tests used to assess cognition were the Mini-Mental State Examination dot counting to evaluate verbal working memory, the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total score, the Four Mountain Test, and the supermarket trolley virtual reality test.

Brain MRI data were collected. The researchers focused on the medial temporal lobe as the «main brain region regulating cognition and memory processing.» This lobe includes the hippocampus, the parahippocampus, the entorhinal cortex, and the amygdala.

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«Critical Window»

The researchers found a «trend» toward an APOE-HRT interaction (P-interaction = .097) for the total RBANS score. In particular, it was significant for the RBANS delayed memory index, where scores were consistently higher for women with APOE4 who had received HRT compared with all other groups (P-interaction = .009).

Within-genotype group comparisons showed that HRT users had a higher RBANS total scale score and delayed memory index (P = .045 and P = .002, respectively), but only among APOE4 carriers. Effect size analyses showed a large effect of HRT use on the Four Mountain Test score and the supermarket trolley virtual reality test score (Cohen’s d =.988 and 1.2, respectively).

«This large effect was found only in APOE4 carriers,» the investigators note.

Similarly, a moderate to large effect of HRT on the left entorhinal volume was observed in APOE4 carriers (Cohen’s d = .63).

In members of the APOE4 group who received HRT, the left entorhinal and left and right amygdala volumes were larger compared with both no-APOE4 and non-HRT users (P-interaction = .002, .003, and .005, respectively). Similar trends were observed for the right entorhinal volume (P = .074).

In addition, among HRT users, the left entorhinal volume was larger (P = .03); the right and left anterior cingulate gyrus volumes were smaller (P = .003 and .062, respectively); and the left superior frontal gyrus volume was larger (P = .009) in comparison with women who did not receive HRT, independently of their APOE genotype.

Early use of HRT among APOE4 carriers was associated with larger right and left hippocampal volume (P = .035 and P = .028, respectively) ― an association not found in non-APOE4 carriers. The association was also not significant when participants were not stratified by APOE genotype.

«The key important point here is the timing, or the ‘critical window,’ when HRT can be of most benefit,» Saleh said. «This is most beneficial when introduced early, before the neuropathology becomes irreversible.»

Study limitations include its cross-sectional design, which precludes the establishment of a causal relationship, and the fact that information regarding the type and dose of estrogen was not available for all participants.

HRT is not without risk, Saleh noted. She recommended that clinicians «carry out various screening tests to make sure that a woman is eligible for HRT and not at risk of hypercoagulability, for instance.»

Risk-Benefit Ratio

Commenting for Medscape Medical News, Howard Fillit, MD, cofounder and chief science officer at the Alzheimer’s Drug Discovery Foundation, called the study «exactly the kind of work that needs to be done.»

Fillit, who was not involved with the current research, is a clinical professor of geriatric medicine, palliative care medicine, and neuroscience at Mount Sinai Hospital, New York City.

He compared the process to that of osteoporosis. «We know that if women are treated [with HRT] at the time of the menopause, you can prevent the rapid bone loss that occurs with rapid estrogen loss. But if you wait 5, 10 years out, once the bone loss has occurred, the HRT doesn’t really have any impact on osteoporosis risk because the horse is already out of the barn,» he said.

Although HRT carries risks, «they can clearly be managed; and if it’s proven that estrogen or hormone replacement around the time of the menopause can be protective [against AD], the risk-benefit ratio of HRT could be in favor of treatment,» Fillit added.

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The study was conducted as part of the Medical Research Council (MRC, UK) NuBrain Consortium. The investigators and Fillit have reported no relevant financial relationships.

Alzheimers Res Ther. Published online January 9, 2023. Full article

Batya Swift Yasgur MA, LSW is a freelance writer with a counseling practice in Teaneck, NJ. She is a regular contributor to numerous medical publications, including Medscape and WebMD, and is the author of several consumer-oriented health books as well as Behind the Burqa: Our Lives in Afghanistan and How We Escaped to Freedom (the memoir of two brave Afghan sisters who told her their story).

For more Medscape Neurology news, join us on Facebook and Twitter.

Credits: Lead image: Axel Kock/Dreamstime Medscape Medical News © 2023
Cite this: HRT May Prevent Alzheimer’s in High-Risk Women — Medscape — Jan 17, 2023.

Alzheimer’s Prevention Diet: What Foods Help Prevent Alzheimer’s

Alzheimer's Prevention Diet

Alzheimer’s is a terribly sad disease characterized by deterioration of memory, skills, and thinking ability. It is devastating for individuals and their families, and currently affects around 5.8 million Americans. This number is expected to nearly triple to 14 million by 2060.

Whilst there is no cure, research has shown that lifestyle factors can play a key role in protecting brain health and therefore in Alzheimer’s prevention. This means there is plenty we can do to prevent and slow the onset of cognitive decline through simple lifestyle changes such as diet improvements, exercise, social engagement, less stress, and better sleep.

What Is Alzheimer’s?

Alzheimer’s, a form of dementia, is a progressive brain disorder that slowly degenerates a person’s memory and thinking abilities. Eventually, the simplest tasks become impossible. The majority of people who experience this disease, have late onset Alzheimer’s, which begins to show symptoms at 60-70 years of age. More rarely, people between the ages of 30 and 60 can experience early-onset Alzheimer’s.

Brain Health

What Causes Alzheimer’s?

Physical damage to brain tissue is the main cause of Alzheimer’s. This is largely the loss of connection between neurons (nerve cells) in the brain due to a build-up of specific proteins. This leads to a loss of clear messaging between different parts of the brain and the rest of our body.

Scientists are still not clear on what causes this but it is likely to be a combination of genetic, environmental, and lifestyle factors. Now, we can control two of these for the most part, particularly lifestyle, so there is a lot we can do to reduce our risk of developing Alzheimer’s. Absolutely central are our dietary choices.

Difference Between Dementia And Alzheimer’s

Dementia itself is not a disease, but rather an umbrella term for the processes of losing the ability to think, remember, analyze, and make decisions. These processes are devastating for those affected and are categorically not a normal part of aging, as they are often mistaken to be.

Alzheimer’s is just one disease that fits within the dementia category, and it’s by far the most common, accounting for around 60-70 percent of cases.

Can Alzheimer’s Be Prevented?

Drs. Dean and Ayesha Sherzai are leading neurologists working to understand and prevent Alzheimer’s. Their wonderful book, The Alzheimer’s Solution, explains how the disease can be prevented in up to 90 percent of people, by implementing five lifestyle interventions: exercise regularly, improve sleep, challenge and engage the brain, reduce stress, and eat a plant-based diet.

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There Is A Connection Between The Digestive System And The Brain?

Although it is strange to think of our digestive system or gut having influence over our brain, there is a much stronger connection than most people realize. Also known as the ‘enteric nervous system,’ (ENS) our gut shares many neurotransmitters, with our central nervous system (CNS). This can lead to gut health impacting on diseases generally associated with the brain, such as Alzheimer’s.

BEST DIET FOR Alzheimer’s Prevention

So, diet is a key factor in reducing our risk of diseases like Alzheimer’s, but what foods should we be eating? According to the Sherzai’s plan, vegetables, fruits, pulses, grains, and healthy fats are what the brain needs to thrive and ward off neurological diseases. They recommend a fully plant-based diet.

The DASH Diet

Dietary Approaches to Stop Hypertension—the DASH diet—aims to reduce and maintain healthy blood pressure. It focuses on reducing sodium, increasing intake of vegetables, and allowing some consumption of whole grains, poultry, fish, and nuts.

Blood pressure may seem unrelated to cognitive function but the two are actually connected. Midlife high blood pressure has been connected to an increased risk of developing dementia symptoms later in life, although more research is needed to show whether lowering midlife blood pressure can actually lower the incidences of Alzheimer’s.

Mediterranean Diet

This approach is rich in fruits, nuts, vegetables, beans, legumes, grains, fish, and unsaturated fats. Intake of meat, dairy and sugar is very low, so this diet has been linked to good heart health and reduced risk of type 2 diabetes and stroke, as well as death from any cause.

Research has also shown there is a probable link between this diet and reduced cognitive problems.


The MIND diet incorporates features of both the DASH and Mediterranean diets. It has specific recommended foods: leafy green veg, most other vegetables, nuts, berries, legumes, whole grains, olive oil, “poultry”, seafood and even wine (in moderation).

It also has a “to avoid” list, which includes butter, cheese, red meat, fast foods, and pastries but does it work?

A study that used food questionnaires and brain function tests was able to show that, in participants over the age of 80, those sticking closely to the MIND diet had brains younger by eight years than their counterparts, who didn’t follow the diet.

So, removing the big dietary offenders—red meat, butter, cheese—seems to be key to brain health.

Alzheimer's Prevention Diet

What Foods Prevent Alzheimer’s?

There is no one food that we can point to and say “this prevents Alzheimer’s” but it’s when we combine a wide range of plant-based foods that we get the best outcome. On the Sherzai’s list of “brain-nourishing foods” are:

All kinds of beans – these have been shown to reduce stroke risk, lower cholesterol, and regulate blood glucose.

Berries – by far the most delicious way of keeping our brains safe, Harvard research shows they can lower the risk of cognitive decline.

Coffee – perhaps the best news to be found here, caffeine can help stimulate protective neurochemicals in the brain such as acetylcholine. As much as this may tempt us to hit the coffee machine all through the day, it is important to avoid caffeine in the afternoons, to ensure we get the all important restorative sleep we need to further stave off cognitive decline.

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Quinoa – this supergrain contains fibre, zinc, vitamin E, phosphorus, and selenium, whilst also being a great source of protein. These are all great for building brain cells!

Other foods we should include in our brain-healthy diets are:

  • Leafy green veg (kale, spinach, mustard greens, collards, and more)
  • Nuts
  • Olive oil
  • Seeds
  • Spices
  • Dark chocolate

For a more detailed lowdown on how each of these foods can contribute to Alzheimer’s prevention head here.

Foods to Avoid

With the good, there unfortunately has to be some bad, so which foods are more of a brain drain than brain gain?

Trans fats, saturated fats, salt and calorie-dense processed foods are the key enemies here.

Saturated Fats – almost all meat and dairy products, along with processed products like pastries, cookies, and cakes, contain high levels of saturated fat. A 2018 meta-analysis discovered that higher intake of dietary saturated fats led to a 39 percent increase in Alzheimer’s risk. So, a vegan diet that avoids all these products is the way to go.

Red and Processed Meats – if their contribution to causing cancer isn’t bad enough, meats like sausages, bacon, pepperoni, and chorizo contain preservatives, saturated fats, and high levels of salt. These cause inflammation and can damage blood vessels in our brains.

Fried or Fast Food – full of trans fats, these foods are to be avoided to reduce our Alzheimer’s risk. Research has found they can be incorporated into the brain cell membranes and alter our neurons’ ability to communicate. This has led to researchers discovering a link between trans fats and depression, as well as growing evidence for their role in Alzheimer’s.

Cheese – Drs. Sherzai identify cheese in their top 10 foods to avoid, as it is often high in both saturated fats and salt.

Salt – due to its well-established link to high blood pressure, salt has been identified as a key risk factor for Alzheimer’s. Newer studies have shown that salt could increase levels of tau protein in our brains and build-up of this protein is a key element of Alzheimer’s.

Other things off the table are:

  • Excess alcohol
  • Sweets and desserts
  • Most high-calorie foods (fast and processed food)

Alzheimer's Prevention Diet

What Else Can I Do To Prevent Alzheimer’s Disease?

Drs. Sherzai’s 5 strands of Alzheimer’s prevention give us an excellent starting point and identify lifestyle changes we can all make.

They even highlight that implementing just one of the following additions can reduce your Alzheimer’s risk, but when applied all together can reduce your risk by up to 90 percent!

Healthy Diet

As established above, a diet rich in fruits, vegetables, and grains, and low in saturated fats, trans fats, and salt is going to give us the best chance of preventing Alzheimer’s. The best way to achieve this is though a plant-based vegan diet that is rich in specific Alzheimer’s prevention foods, such as leafy greens, beans, berries, and nuts.

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Our brains need healthy fats and antioxidants to thrive, and a diet heavy on meat, dairy, and processed foods is never going to give us those.

Mental Stimulation

Use or lose it, the saying goes. And this is certainly true of our brains. We can stimulate our grey matter with games and puzzles, by enrolling in a new course, learning a new skill, or taking up a new hobby. But challenging the brain is key to keeping it healthy.

Quality Sleep

The importance of sleep cannot be understated when it comes to cognitive health. Sleep is our body regenerating and recharging, so it makes sense that without sufficient rest, our brains will suffer over time.

Avoiding alcohol is another key factor in achieving good quality sleep, and we would do well to avoid screens before bed. Meditation is also an excellent way of increasing the quality of your rest, particularly if practised before bedtime.


Regular Physical Exercise

Regular exercise is a pillar of a healthy lifestyle and is also central to healthy cognitive function. Research shows that exercise reduces oxidative stress and inflammation, thereby helping our brains stay healthy.

Social Engagement

There is a clear link between higher levels of social engagement, particularly in the older population and a reduced risk of dementia.

By spending quality time with family and friends, or even having a simple positive interaction with a stranger, we are protecting and promoting brain cell function, and helping to build important grey matter in the brain.

Stress Management

Stress equals inflammation for the human body, including the brain. Inflammation can cause structural damage and negatively impact our body’s ability to clear harmful toxins and waste products.

Practising meditation, mindful breathing, journaling, even a quick dance around the kitchen, alongside other natural stress remedies, can be very effective ways of reducing daily stress.

Vascular Health

Vascular health encompasses a variety of factors but most commonly, blood pressure. By maintaining a healthy blood pressure, we reduce our risk of cognitive injuries including dementia.

Lifestyle aspects, such as healthy diet and exercise, are direct factors in blood pressure control, so managing our salt intake and being cardiovascularly healthy are absolutely key.

What’s New In The Fight Against Alzheimer’s?

Research into new Alzheimer’s treatments has been slow in the last 15 years, although new treatments and innovations are appearing. Treatment, whilst absolutely key, is only half the battle. Dementia is not a normal part of aging, so future focus should surely be on prevention methods, rather than treatment, and positive lifestyle choices are still the most influential factor in Alzheimer’s prevention.


Alzheimer’s is a heartbreaking disease that is rarely part of the normal aging process, and whilst there is no cure, lifestyle choices are our best tool when it comes to prevention. By maximizing the positive benefits we can get from diet, exercise, sleep, social engagement, and stress management, we give our brains the best chance of fighting off cognitive decline.

Diet is absolutely central, and a plant-based vegan diet provides all the healthy fats and antioxidants a healthy brain needs. If you haven’t made the switch yet, it’s never too late and our 31 day vegan challenge is a great helping hand to guide you along the road to a healthier diet, and a healthier brain!

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