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Study Finds Multiple Rare, Damaging Genetic Variants That Increase Alzheimer’s Risk

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Scientists at the Vrije University (VU) of Amsterdam have identified rare damaging genetic variants that increase Alzheimer’s disease (AD) risk.

“Our results provide additional evidence for a major role for amyloid-β precursor protein processing, amyloid-β aggregation, lipid metabolism, and microglial function in AD,” the authors wrote in a paper published in the journal Nature Genetics on Monday.

Using gene-based burden analysis in place of the more common genome-wide association studies (GWAS), the researchers found a strong link between rare, damaging variants in ATP8B4 and ABCA1 with AD risk, and a signal in ADAM10, as well as rare-variant burden in the genes RIN3, CLU, ZCWPW1 and ACE, according to GenEngNews.

Damaging mutations in  ATP8B4 — an ATPase enzyme — occur in 3.6% of early-onset patients, 3.1% of late-onset patients, and 2.1% of individuals without dementia, the study found.

“We find that missense mutations [in  ATP8B4 ] associate with a higher increased risk (1.6-fold increased risk in early-onset AD cases compared to non-carriers) compared to truncating mutations (1.2-fold), which suggests that the deleterious effects may be due to gain-of-function missense mutations.” senior author, Henne Holstege, an assistant professor of clinical genetics at VU said, reported GenEngNews.

Coming to gene variation in ABCA1, the study found that mutations in the gene occur in 1.5% of early-onset patients, 1.1% of late-onset patients, and 0.52% of individuals without dementia.

“Here, truncating mutations associate with a higher risk of AD (4.7-fold increase) compared to missense mutations (2.7-fold), which suggests that damaging or losing protein function underlies the observed increased risk,” Holstege noted.

As for variants in ADAM10, the results showed that the mutations occur in only 0.23% of early-onset patients, 0.05% of late-onset patients, and 0.02% of individuals without dementia.

“Carrying a damaging variant is associated with a 9-fold increased risk of AD,” Holstege commented. “These variants include protein truncating and missense variants, suggesting that losing protein function or protein impairment underlies the increased risk.”

Numerous studies in favor notwithstanding, the β-amyloid theory of AD is hotly debated on account of the lack of effectiveness of AD drugs that target β-amyloid deposition or degradation.

However, the recent success of amyloid-clearing agents such as Aducanumab or Lecanemab might change the views.

“Early treatment with Aducanumab or Lecanemab may be very important for effectivity,” Holstege suggested. “Additionally, the field needs to focus on generating treatments that ‘correct’ or support the endogenous mechanisms involved in protein processing and clearance. When applied to at-risk individuals before the onset of disease such agents may prevent a load of amyloid or other aggregating proteins to accumulate to disease-associated levels.”

Holstege believes that larger studies with international collaborations will help uncover more genes associated with the high risk of AD.

Nevertheless, the findings of this study will help open up opportunities to better understand and treat AD in patients.





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Feeling Tired All The Time? Possible Causes And Solutions

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Long days of work, lack of sleep, and stress at the office can be the most common factors that make you feel tired. However, feeling “tired all the time” (TATT) without known reasons can be an indication of an underlying health issue that needs immediate attention.

Finding the exact cause of the lingering tiredness can be the first step toward solving the symptom.

Health conditions that cause fatigue:

1. Anemia – Anemia is one of the most common causes of fatigue. A person who has anemia does not have enough red blood cells in the body, causing symptoms such as tiredness, dizziness, feeling cold and crankiness.

Most often, anemia is caused by iron deficiency. Hence, the condition can be best resolved by including iron-rich foods in the diet and use of iron supplements.

2. Sleep Apnea – It causes the body to stop breathing momentarily during sleep. The condition can affect the quality of sleep and hence make you feel fatigued.

For milder cases of sleep apnea, lifestyle changes such as losing weight or quitting smoking can help solve the sleep disorder. In more severe cases where there is an obstruction in breathing, surgeries and therapies can help.

3. Diabetes – A person who has diabetes has changes in blood sugar level, which can cause fatigue. A patient who is already on diabetic medication can also experience tiredness as a side effect of the medication.

Early identification and taking the correct treatment is the key to managing diabetes. Losing extra weight and having a healthy diet also help in the treatment.

4. Thyroid – Thyroid diseases can be due to an overactive or an underactive thyroid gland. In people who have an underactive thyroid (hypothyroidism), the metabolism slows down leading to symptoms such as lethargy and fatigue. In people with an overactive thyroid (hyperthyroidism), the metabolism speeds up leading to fatigue and difficulty sleeping.

Right diet and lifestyle choices, along with medications, can help in thyroid management.

5. Infections – A person can show symptoms of fatigue when the body is fighting a viral or bacterial infection. Infections ranging from the flu to HIV can cause tiredness.

Along with fatigue, other symptoms such as fever, headache, body aches, shortness of breath and appetite loss can also accompany the infection. Treating the symptoms and taking adequate rest helps in faster recovery.

6. Food allergies – Fatigue may be an early warning sign of hidden food allergies and autoimmune disorders such as celiac disease. Identifying the allergen using a food allergy test or through an elimination diet can help in allergy treatment.

7. Heart disease – If you feel exhausted from an activity that used to be easy, then it is good to check your heart health, as fatigue can be an indication of underlying heart disease.

8. Depression/ anxiety – Fatigue can also be an indicator of a mental health disorder such as depression or anxiety. A combination of medication and psychotherapy can help relieve symptoms.

Lifestyle causes

Apart from serious health conditions, certain lifestyle habits such as dehydration, poor diet, stress and insufficient sleep can cause exhaustion. Having a well-balanced diet, regular exercise and routine sleep can help solve fatigue caused by lifestyle habits.

Published by Medicaldaily.com



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How To Overcome Your Sleep Debt And Reclaim Energy

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Picture this: you’re burning the midnight oil, studying or binge-watching your favorite shows, all at the expense of a good night’s sleep. Have you ever stopped to think about the toll it takes on your body and mind? The consequences can be more serious than you might realize.

Not getting enough sleep can translate into a multitude of issues, including weight gain, lack of focus, tiredness, a haze of confusion, and even depression. If you too are encountering similar issues lately then chances are you have a sleep debt.

Wondering what is sleep debt?

People from 13-18 years of age need 8 hours of sleep, whilst adults beyond that age will require at least 7 hours of snooze.

Sleep debt is a collection of the total hours you haven’t slept or traded your sleep for something else. Sleep debt keeps piling up as a person falls short of the total hours of sleep recommended for an adult, according to the Centers for Disease Control and Prevention.

And when you keep letting go of your sleep for other activities, the body adapts to the new normal and effects start to reflect on the energy levels, which deplete.

“However, like every other debt out there, this too has a repayment option,” Dr. Kunal Kumar, medical director of the Sleep Center at Einstein Medical Center in Philadelphia, told Livestrong.

Below are some expert-vetted ways you can pay back the sleep debt. (Courtesy: Livestrong and Sleepfoundation)

Just like financial debt, imagine sleep debt as a debt you owe to your body. It needs to be repaid. The good news is that catching up on sleep is indeed possible.

  • Maintain a set sleep schedule: Overhauling the sleep schedule is a pretty difficult task to achieve, and it’s best to do that gradually. Create a set sleep schedule by making some small changes to your routine. Instead of making abrupt shifts in your bedtime or wake-up time, adjust them gradually by 15 to 30-minute increments.
  • Minimize your gadget usage: Wind down activities and minimize electronic usage before bed to promote better sleep. Relax and prepare for quality sleep by dimming the lights and setting an alarm for 30 minutes to an hour before bed.
  • Reshuffle your sleeping arrangements: Are you finding it hard to get a good night’s sleep due to excessive sweating? Well, here’s a handy solution: consider upgrading to a cooling mattress or opting for cooling sheets. These innovative sleep essentials can help regulate your body temperature, and keep you comfortably cool throughout the night, ensuring a more blissful slumber. Memory foam pillows can work wonders in relieving neck and back discomfort in case you are struggling with backache.
  • Improve the bedroom environment: Create a sleep-friendly bedroom environment by adjusting the temperature for comfort, and blocking out disruptive lights, or noises that might disturb your restful slumber. And if your mattress, pillow, or sheets are worn out or no longer providing the support you need, consider treating yourself to new ones.

Published by Medicaldaily.com



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Omega-3 Fatty Acids Slow The Progression Of Amyotrophic Lateral Sclerosis: Study

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Omega-3 fatty acids are known for a range of health benefits, from promoting brain and heart health to reducing inflammation and protection against several chronic conditions.

In a new study, researchers found that omega-3 acids, especially the type found in foods like flaxseeds, walnuts, chia seeds, canola oil and soybean oil, can slow down the progression of amyotrophic lateral sclerosis (ALS).

It is a debilitating nervous system disease that gradually worsens over time and can be fatal. The condition results in a loss of muscle control and affects the nerve cells in the brain and spinal cord. It is also known as Lou Gehrig’s disease after the baseball player who was diagnosed with it.

The initial symptoms of the disease include muscle weakness, difficulty in walking and hand movements. The symptoms can slowly progress to difficulties with chewing, swallowing, speaking and breathing.

The exact cause of ALS is not known. However, around 10% of people get it from a risk gene passed down from a family member. It is estimated that more than 32,000 people in the U.S. live with the condition.

In the latest study, researchers from Harvard T.H. Chan School of Public Health in Massachusetts evaluated 449 people living with ALS in a clinical trial. The team assessed the severity of their symptoms, the progression of their disease, along with the levels of omega-3 fatty acids in their blood, for 18 months.

The study suggested that alpha-linolenic acid (ALA), a type of omega-3 found in plants, is particularly beneficial in slowing the progression of ALS. The participants with the highest levels of ALA had a 50% reduced risk of death during the study period compared to those with the lowest levels of ALA.

Researchers also found a reduction in death risk in participants who had eicosapentaenoic acid, the type of omega-3 fatty acid found in fatty fish and fish oil, and linoleic acid found in vegetable oils, nuts and seeds.

A previous study conducted by the same team suggested that a diet high in ALA and higher blood levels of the nutrient could reduce the risk of developing the condition.

“In this study, we found that among people living with ALS, higher blood levels of ALA were also associated with a slower disease progression and a lower risk of death within the study period. These findings, along with our previous research suggest that this fatty acid may have neuroprotective effects that could benefit people with ALS,” said Kjetil Bjornevik, the lead author of the study.

Published by Medicaldaily.com



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