Targets Of Alzheimer’s Disease Prevention Research
Researchers are exploring these and other interventions that may help prevent, delay, or slow Alzheimer’s dementia or age-related cognitive decline. Other research targets include:
- New drugs to delay onset or slow disease progression
- Diabetes treatment
- Blood pressure- and lipid-lowering treatments
- Sleep interventions
- Vitamins such as B12 plus folic acid supplements and D
- Combined physical and mental exercises
Determination Of Cell Viability
RBMVECs were cultured at a density of 1.7 à 104 cells per well. Cells were treated as described above for 48 hr. After 48 hr of incubation, the medium was carefully removed and cells were washed twice with phosphate buffered saline before the plates were fixed with 70% acetone. SRB assays were performed on the fixed plates. In brief, 100 μl of SRB reagent was added to the dried wells of a 96-well plate, then the plate was incubated at room temperature for 12 hr. After incubation, the SRB reagent was decanted and the plate was washed three times with 1% acetic acid. The plate was dried at 60°C, and then, cell morphology was observed under a reflected light microscope. Images were taken and cell viability was compared. The 96-well plates containing the cells were treated with 10 mM Tris base for 4 hr. Spectral data were collected under a 96-well plate reader at 510 nm to calculate the inhibition concentration .
B Mouse Models Of Alzheimer’s Disease And Exercise
van Praag and colleagues showed that voluntary exercise alone increased dentate gyrus neurogenesis. This is separate from environmental enrichment, which also increases neurogenesis.
Ambree and colleagues showed the interaction between an active lifestyle and AD pathology in female TgCRND8 mice carrying human APPswe+ind gene. These mice were housed in enriched housing in their cages. Four months in this environment resulted in a significant reduction of beta-amyloid plaques and amyloid angiopathy . Costa and colleagues , in a similar study, showed that the environmental enrichment in transgenic mice improved the cognitive functioning and decreased the brain A pathology. Adlard and colleagues used the TgCRND8 transgenic mouse model and showed that 5 months of voluntary exercise resulted in a decrease in extracellular A plaques in the frontal cortex , the cortex at the level of the hippocampus , and the hippocampus . Long-term exercise also enhanced the rate of learning of TgCRND8 animals in the Morris water maze, with significant reductions in escape latencies over the first 3 trial days.
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Which Medicines Are Used To Treat Alzheimers Disease
There is no cure for Alzheimers disease, but available medications temporarily slow the worsening of dementia symptoms and help with behavioral problems that may appear during the course of the disease.
Four medications representing two drug classes are currently approved by the Food and Drug Administration to treat the symptoms of Alzheimers disease. These drugs are the cholinesterase inhibitors and a NMDA antagonist.
Cholinesterase inhibitors. The cholinesterase inhibitors are all approved to treat the symptoms of mild to moderate Alzheimer’s disease . Cholinesterase inhibitors include:
- Donepezil
- Rivastigmine and Exelon patch
- Galantamine
These drugs work by blocking the action of acetylcholinesterase, the enzyme responsible for destroying acetylcholine. Acetylcholine is one of the chemicals that helps nerve cells communicate. Researchers believe that reduced levels of acetylcholine cause some of the symptoms of Alzheimer’s disease. By blocking the enzyme, these medications increase the concentration of acetylcholine in the brain. This increase is believed to help improve some memory problems and reduce some of the behavioral symptoms seen in patients with Alzheimers disease.
These medications do not cure Alzheimers disease or stop the progression of the disease. The most common side effects of these drugs are nausea, diarrhea, and vomiting. Some people may have loss of appetite, insomnia or bad dreams.
Pillar #: Healthy Diet
In Alzheimers disease, inflammation and insulin resistance injure neurons and inhibit communication between brain cells. Alzheimers is sometimes described as diabetes of the brain, and a growing body of research suggests a strong link between metabolic disorders and the signal processing systems. By adjusting your eating habits, however, you can help reduce inflammation and protect your brain.
Manage your weight. Extra pounds are a risk factor for Alzheimers disease and other types of dementia. A major study found that people who were overweight in midlife were twice as likely to develop Alzheimers down the line, and those who were obese had three times the risk. Losing weight can go a long way to protecting your brain.
Cut down on sugar.Sugary foods and refined carbs such as white flour, white rice, and pasta can lead to dramatic spikes in blood sugar which inflame your brain. Watch out for hidden sugar in all kinds of packaged foods from cereals and bread to pasta sauce and low or no-fat products.
Enjoy a Mediterranean diet. Several epidemiological studies show that eating a Mediterranean diet dramatically reduces the risk of decline from cognitive impairment and Alzheimers disease. That means plenty of vegetables, beans, whole grains, fish and olive oiland limited processed food.
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Determination Of Ros Levels
RBMVECs were cultured at a density of 1.7 Ã 104 cells per well. Cells were treated as described above for 48 hr. The medium was removed after incubation and cells were washed with PBS. The cells were incubated with DCFH-DA for 30 min, and ROS levels were measured under a fluorescence plate reader .
Benefits Of The Mediterranean Diet
The article also makes mention of the fact that Mediterranean diets are associated with a lower risk of Alzheimers and cognitive decline. Previous studies have shown that people in Mediterranean countries such as Italy and Greece have a longer life expectancy and lower instances of cardiovascular disease and dementia than populations where other diets are the norm. Mediterranean folks tend to eat large amounts of fresh fruit and vegetables, cereals, beans and legumes. Extra-virgin olive oil is a primary source of fat for people in that region.
The thinking is that extra-virgin olive oil is better than fruits and vegetables alone, said Dr. Pratico, and as a monounsaturated vegetable fat it is healthier than saturated animal fats.
It is clear that diet is extremely important to our overall well-being. Our diets not only supply us with the necessary energy required throughout the day, they also have long-term ramifications. Though this study by no means proposes that eating olive oil is a way to completely prevent dementia, its definitely food for thought. Maybe next time I need to buy cooking oil, Ill reach for the olive oil first.
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Strengths And Limitations Of The Study
The of the study high quality assessment of diet and cognition and availability of neuropathologic data, said Dr. Dhana.
Similarly, Dr. Nikolaos Scarmeas, an associate professor of clinical neurology at Columbia University in New York City, noted:
This is a quite important study because associations between nutrition and brain neuropathology have not been investigated. Very few, if any, studies have information on both ends: dietary habits and cognition during life and measures of brain changes from autopsy.
Dr. Scarmeas was not involved with the recent study.
The study authors also note that the investigation had a few limitations. For example, they acknowledge the possibility of the dietary information being inaccurate since it was based on self-reports. To address the potential inaccuracies in the dietary reports, the researchers averaged the MIND diet score obtained from assessments conducted over multiple years.
The limitation is the generalizability of the findings because that study was conducted among older white volunteers, added Dr. Dhana.
Speaking about future research directions, Dr. Dhana said, I think it is of great scientific interest to identify other modifiable lifestyle factors that have protective effects on cognitive functioning independent of pathology and other common brain pathologies.
Amyloid Hypothesis Versus Tau Hypothesis
A central but controversial issue in the pathogenesis of AD is the relationship between amyloid deposition and NFT formation. Evidence shows that abnormal amyloid metabolism plays a key pathogenic role. At high concentrations, the fibrillar form of Ab has been shown to be neurotoxic to cultured neurons.
Cultured cortical and hippocampal neurons treated with Ab protein exhibit changes characteristic of apoptosis , including nuclear chromatin condensation, plasma membrane blebbing, and internucleosomal DNA fragmentation. The fibrillar form of Ab has also been shown to alter the phosphorylation state of tau protein.
The identification of several point mutations within the APP gene in some patients with early-onset familial AD and the development of transgenic mice exhibiting cognitive changes and SPs also incriminate Ab in AD. The apolipoprotein E E4 allele, which has been linked with significantly increased risk for developing AD, may promote inability to suppress production of amyloid, increased production of amyloid, or impaired clearance of amyloid with collection outside of the neuron.
Autopsies have shown that patients with 1 or 2 copies of the APOE E4 allele tend to have more amyloid. Additional evidence comes from recent experimental data supporting the role of presenilins in Ab metabolism, as well as findings of abnormal production of Ab protein in presenilin-mutation familial Alzheimer disease.
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Genetic Variants Reduce Risk Of Alzheimers Disease
5 February 2020
A DNA study of over 10,000 people by UCL scientists has identified a class of gene variants that appear to protect against Alzheimers disease.
The findings, published in Annals of Human Genetics, suggest these naturally occurring gene variants reduce the functioning of proteins called tyrosine phosphatases, which are known to impair the activity of a cell signalling pathway known as PI3K/Akt/GSK-3. This pathway is important for cell survival.
The research builds on previous studies in mice and rats, which suggested inhibiting the function of these proteins might be protective against Alzheimer’s disease, but this is the first time such an effect has been demonstrated in people.
Researchers believe the PI3K/Akt/GSK-3 signalling pathway could be a key target for therapeutic drugs and the findings also strengthen evidence that other genes could be linked to either elevated or reduced risk of Alzheimers disease.
These results are quite encouraging. It looks as though when naturally-occurring genetic variants reduce the activity of tyrosine phosphatases then this makes Alzheimer’s disease less likely to develop, suggesting that drugs which have the same effect might also be protective, said the studys lead author, Professor David Curtis .
In this study, scientists analysed DNA from 10,000 people: half with Alzheimer’s disease and half without.
What Is Alzheimer’s Disease
Alzheimers disease is a brain disorder that cannot be stopped or reversed. The disease severely affects memory, thinking, learning and organizing skills and eventually affects a persons ability to carry out simple daily activities. Alzheimers disease is not a normal part of the aging process.
Alzheimers is a disease whose symptoms worsen over time. In fact, scientists believe the disease process may go on for 10 years or longer before the first symptoms of Alzheimers disease appear.
When memory problems do begin to be noticeable, they are often identified as mild cognitive impairment . At this stage, intellectual function is affected but the ability to function and live independently remain intact as the brain compensates for disease-related changes.
In some people, MCI can hold steady at this stage. However, people with MCI are at high risk for progressing to dementia. Alzheimers disease is the most common form of dementia. With dementia, in contrast to MCI, daily function is affected.
As dementia due to Alzheimers disease progresses to late stages, affected individuals cannot carry on a conversation, recognize family and friends, or care for themselves.
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Do Genes Cause Diseases
Genetic mutations can cause diseases. If a person inherits a genetic mutation that causes a certain disease, then he or she will usually get the disease. Sickle cell anemia, cystic fibrosis, and some cases of early-onset Alzheimer’s disease are examples of inherited genetic disorders.
Other changes or differences in genes, called genetic variants, may increase or decrease a person’s risk of developing a particular disease. When a genetic variant increases disease risk but does not directly cause a disease, it is called a genetic risk factor.
Identifying genetic variants may help researchers find the most effective ways to treat or prevent diseases such as Alzheimer’s in an individual. This approach, called precision medicine, takes into account individual variability in genes, environment, and lifestyle for each person.
The expression of geneswhen they are switched on or offcan be affected, positively and negatively, by environmental and lifestyle factors, such as exercise, diet, chemicals, or smoking. The field of epigenetics is studying how such factors can alter a cell’s DNA in ways that affect gene activity.
Can Controlling High Blood Pressure Prevent Alzheimer’s Disease
Controlling high blood pressure is known to reduce a person’s risk for heart disease and stroke. The NASEM committee of experts concluded that managing blood pressure when it’s high, particularly for middle-aged adults, also might help prevent or delay Alzheimer’s dementia.
Many types of studies show a connection between high blood pressure, cerebrovascular disease , and dementia. For example, it’s common for people with Alzheimer’s-related changes in the brain to also have signs of vascular damage in the brain, autopsy studies show. In addition, observational studies have found that high blood pressure in middle age, along with other cerebrovascular risk factors such as diabetes and smoking, increase the risk of developing dementia.
Clinical trialsthe gold standard of medical proofare underway to determine whether managing high blood pressure in individuals with hypertension can prevent Alzheimer’s dementia or cognitive decline.
One large clinical trialcalled SPRINT-MIND found that lowering systolic blood pressure to less than 120 mmHg, compared to a target of less than 140 mmHg, did not significantly reduce the risk of dementia. Participants were adults age 50 and older who were at high risk of cardiovascular disease but had no history of stroke or diabetes.
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Tips For Starting And Sticking With An Exercise Plan
If youve been inactive for a while, starting an exercise program can be intimidating. But remember: a little exercise is better than none. In fact, adding just modest amounts of physical activity to your weekly routine can have a profound effect on your health.
Choose activities you enjoy and start smalla 10-minute walk a few times a day, for exampleand allow yourself to gradually build up your momentum and self-confidence.
Cholinergic Neurotransmission And Alzheimer Disease
The cholinergic system is involved in memory function, and cholinergic deficiency has been implicated in the cognitive decline and behavioral changes of AD. Activity of the synthetic enzyme choline acetyltransferase and the catabolic enzyme acetylcholinesterase are significantly reduced in the cerebral cortex, hippocampus, and amygdala in patients with AD.
The nucleus basalis of Meynert and diagonal band of Broca provide the main cholinergic input to the hippocampus, amygdala, and neocortex, which are lost in patients with AD. Loss of cortical CAT and decline in acetylcholine synthesis in biopsy specimens have been found to correlate with cognitive impairment and reaction-time performance. Because cholinergic dysfunction may contribute to the symptoms of patients with AD, enhancing cholinergic neurotransmission constitutes a rational basis for symptomatic treatment.
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Age Distribution For Alzheimer Disease
The prevalence of AD increases with age. AD is most prevalent in individuals older than 60 years. Some forms of familial early-onset AD can appear as early as the third decade, but familial cases constitute less than 10% of AD overall.
More than 90% of cases of AD are sporadic and occur in individuals older than 60 years. Of interest, however, results of some studies of nonagenarians and centenarians suggest that the risk may decrease in individuals older than 90 years. If so, age is not an unqualified risk factor for the disease, but further study of this matter is needed.
Savva et al found that in the elderly population, the association between dementia and the pathological features of AD is stronger in persons 75 years of age than in persons 95 years of age. These results were achieved by assessing 456 brains donated to the population-based Medical Research Council Cognitive Function and Ageing Study from persons 69-103 years of age at death.
Studies have demonstrated that the relationship between cerebral atrophy and dementia persist into the oldest ages but that the strength of association between pathological features of AD and clinical dementia diminishes. It is important to take age into account when assessing the likely effect of interventions against dementia.
How Is Alzheimers Disease Diagnosed
These tests are used to diagnose Alzheimers disease or to rule out other medical conditions that cause symptoms similar to Alzheimers disease:
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Pillar #: Stress Management
Chronic or persistent stress can take a heavy toll on the brain, leading to shrinkage in a key memory area, hampering nerve cell growth, and increasing the risk of Alzheimers disease and dementia. Yet simple stress management tools can minimize its harmful effects and protect your brain.
Breathe! Quiet your stress response with deep, abdominal breathing. Restorative breathing is powerful, simple, and free!
Schedule daily relaxation activities. Keeping stress under control requires regular effort. Learning relaxation techniques such as meditation, progressive muscle relaxation, or yoga can help you unwind and reverse the damaging effects of stress.
Nourish inner peace. Regular meditation, prayer, reflection, and religious practice may immunize you against the damaging effects of stress.
Make fun a priority. All work and no play is not good for your stress levels or your brain. Make time for leisure activities that bring you joy, whether it be stargazing, playing the piano, or working on your bike.
Keep your sense of humor. This includes the ability to laugh at yourself. The act of laughing helps your body fight stress.