Biomarkers Of Amyloid Accumulation
The amyloid-related or molecular biomarkers of AD are CSF A142 and amyloid PET. Low A1-42 reflects brain amyloid deposition and shows very high concordance with amyloid PET. This pathological change is found in AD and prodromal AD with a sensitivity exceeding 90%.1818. Cummings J, Lee G, Ritter A, Sabbagh M, Zhong K. Alzheimer’s disease drug development pipeline: 2019. Alzheimers Dement . 2019;5:272-93. The most widely used amyloid imaging agent is -PiB. It binds to A aggregates with high affinity, and is capable of differentiating individuals with AD from those with normal cognition. Researchers found comparable sensitivity of CSF A1-42 levels and PiB PET for the detection of AD pathology.4343. Counts SE, Ikonomovic MD, Mercado N, Vega IE, Mufson EJ. Biomarkers for the early detection and progression of Alzheimer’s disease. Neurotherapeutics. 2017;14:35-53.
Lifetime Risk Of Alzheimer’s Dementia
Lifetime risk is the probability that someone of a given age who does not have a particular condition will develop the condition during his or her remaining life span. Data from the Framingham Heart Study were used to estimate lifetime risks of Alzheimer’s dementia by age and sex., As shown in Figure , the study found that the estimated lifetime risk for Alzheimer’s dementia at age 45 was approximately one in five for women and one in 10 for men. The risks for both sexes were slightly higher at age 65.
FIGURE 4
Tip : Take Steps To Slow The Advancement Of Symptoms
Even when youve been diagnosed with Alzheimers disease or dementia, there is still a great deal that you can do to slow its progress. The same healthy lifestyle changes and mental stimulation techniques that are used to prevent or delay the onset of dementia can also be effective in slowing the progression of the disease and maintaining your independence for longer.
1. Get moving. Regular exercise stimulates the brains ability to maintain old connections, make new ones, and slow deterioration of your cognitive abilities.
2. Reach out to others. The more you connect face-to-face with others, the more you engage socially, the better your cognitive function will be.
3. Eat well. Eating a brain-healthy diet, such as the Mediterranean diet, can help reduce inflammation, protect neurons, and promote better communication between brain cells.
4. Seek mental stimulation. By continuing to learn new things and challenge your brain, you can strengthen your cognitive skills and stay mentally active for longer.
5. Improve your sleep. Getting quality sleep can flush out brain toxins and avoid the build-up of damaging plaques.
6. Manage stress. Unchecked stress takes a heavy toll on the brain, shrinking a key memory area, hampering nerve cell growth, and worsening Alzheimers symptoms. Relaxation practices and other stress management techniques can help you ease the tension and regain control.
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Biomarkers Based In Brain Samples In Clinical Research
Lipids have key roles in maintaining normal physiological functions in the body, such as energy storage, signal transduction, maintenance of cell membrane structure, and cell transport . Disordered lipid metabolism is closely related to neurological diseases and affects cognitive function . Lipid metabolites and pathways strategy can be used to study the role of lipids. In this way, lipids can be classified into eight main categories: fatty acids, glycerolipids, glycerophospholipids, sphingolipids, saccharolipids, polyketides, prenol lipids, and sterols . Glycerophospholipids, sphingolipids, and cholesterol are localized mainly to neuronal membranes and myelin.
TABLE 2. Metabolic biomarker in blood for Alzheimers disease patients in clinical.
The biomarker studies described above suggest that AD research using brain tissue or CSF has made considerable progress. However, obtaining samples is invasive and carries risks for older patients. Even though such samples may offer direct information on brain status, such samples are unlikely to be used for the clinical diagnosis.
Alzheimer Auguste D And The Defining Of A Disease
. Reprinted from The Lancet, 349, Maurer et al., Auguste D and Alzheimer’s disease, 1546-9, 1997, with permission from Elsevier.
Alzheimer presented the clinical and pathological findings from Auguste D.s case at the meeting of Southwest German Psychiatrists held in Tübingen, in 1906 and his lecture was published under the title A Characteristic Disease of the Cerebral Cortex the following year. He described and beautifully recorded characteristic changes in the neurofibrils revealed by the Bielschowsky silver stain at autopsy. Thick fibrils accumulated in apparently normal-appearing cells until eventually, the nucleus and cytoplasm disappeared, and only a tangled bundle of fibrils indicated the site where once the neuron had been located. Severe neuronal loss was observed and over the entire cortex, and in large numbers especially in the upper layers, miliary foci could be found which represented the sites of deposition of a peculiar substance. Many years later, hyperphosphorylated tau was found to be the key component of the tangles and amyloid- the peculiar substance that formed the core of the plaques. Psychoanalytic studies presented at the meeting received more attention than Alzheimers paper and were the ones to get reported in the local press. However, in 1910 Kraepelin coined the term Alzheimers disease in the eighth edition of his Handbook of Psychiatry, declaring it to be a specific clinical-pathological disease entity.
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Highlights From The Canadian Chronic Disease Surveillance System
According to the World Health Organization, 47.5;million people live with dementia, including Alzheimer’s disease, worldwide.Footnote 1 As these conditions progress, they become highly debilitating for affected individuals and lead to major health impacts. With a growing and aging population, the number of Canadians living with dementiaFootnote i is expected to increase in future decades, with corresponding implications for health care needs and use. By 2031, it is projected that the total annual health care costs for Canadians with dementia will have doubled those from two decades earlier, from $8.3;billion to $16.6;billion.Footnote 2
Using data from the Canadian Chronic Disease Surveillance System , the Public Health Agency of Canada is able to conduct national surveillance for diagnosed dementia, including Alzheimer’s disease, to support the planning and evaluation of related policies, programs, and services. This fact sheet presents an overview of these new estimates on diagnosed dementia and highlights information on associated health impacts collected through the National Population Health Study of Neurological Conditions.Footnote 3
Coping With A Dementia Diagnosis Tip : Reach Out To Others
Receiving a dementia diagnosis can leave you feeling isolated and alone. You may feel cut off from friends and family who arent able to fully understand what youre going through. You may retreat into your shell for fear of being a burden to others. Or you may even worry about how your relationships could change once people learn you have dementia. While these worries are natural, theyre not a reason to isolate yourself. At this difficult time, the love and support of others can have a huge impact on your mood and outlook.
Living with Alzheimers or another dementia is not easy, but there is help for this journey. Dont wait for others to offer support; be proactive and reach out. The more support you have, the better youll be able to cope with symptoms and continue to enrich your life.
Stay connected with family and friends. Maintaining your closest relationships and continuing to enjoy social activities can make a world of difference to your health and attitude. As we age, retirement, relocation, and the loss of loved ones can often shrink our social networks, but its never too late to build new, meaningful friendships.
Seek spiritual counsel. Religious leaders can offer real comfort to believers, as well as ongoing social contact. Even people who do not regularly attend religious services may look towards religion following a diagnosis of dementia. If youre not religious, you may prefer to speak to a therapist or counselor.
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Diagnosing Alzheimers Can Be Difficult
It is tricky to diagnose Alzheimers disease because it shares symptoms with many other complications of aging, such as stroke, tumors, sleep disturbances, Parkinsons disease and other forms of dementia. Even side effects from certain medications can mimic the signs of the disease.
Until now, diagnosis was based on observation of the constellation of symptoms associated with the mind-robbing disorder, such as forgetfulness, fuzzy thinking, confusion, difficulty concentrating, or changes in behavior, personality, and the ability to function normally. In addition, extensive neuropsychological evaluations look at such factors as how quickly people can process information, solve problems or remember words. Other standard medical tests, such as blood and urine tests, can spot other potential causes of the problem. Thanks to advances in a type of brain imaging technique called a PET scan, scientists are able, in a research setting, to identify what researchers believe is one of Alzheimers biological markers: amyloid plaques. Another PET scan innovation, currently under development, may be able to detect the abnormal protein tau, thought to be another telltale sign of Alzheimers.
But even with better testing, a conclusive diagnosis can remain elusive. Researchers are finding that Alzheimers symptoms and the presence of amyloid and tau do not necessarily go hand in hand.
The First Use Of Alzheimers Disease
Alzheimer later published his descriptions of several similar patients in 1909 and Kraepelin included Ms. Deters case in the 1910 edition of his widely respected psychiatry textbook. It was Kraepelin who named this dementia after his junior colleague.Auguste Deter was not an elderly woman at the onset of her illness, and Alzheimers disease was therefore regarded as a presenile dementia to distinguish it from the familiar senile dementia thought to result from aging-related vascular disease. Further investigation, however, showed that plaques and tangles were present in the brains of the majority of older adults with symptoms of dementia.
In the late 1960s, the British psychiatrists Tomlinson and Roth described the importance of these plaques in older adults, and in 1970 Dr. Roth questioned the meaningfulness of the age criterion that distinguished AD from senile dementia of the Alzheimers type.
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Psychological And Psychosocial Therapies
Psychological therapies for dementia include some limited evidence for reminiscence therapy , some benefit for cognitive reframing for caretakers, unclear evidence for validation therapy and tentative evidence for mental exercises, such as cognitive stimulation programs for people with mild to moderate dementia. A 2020 Cochrane review found that offering personally tailored activities could help reduce challenging behavior and may improve quality of life. The reviewed studies were unable to draw any conclusions about impact on individual affect or on improvements for the quality of life for the caregiver.
Adult daycare centers as well as special care units in nursing homes often provide specialized care for dementia patients. Daycare centers offer supervision, recreation, meals, and limited health care to participants, as well as providing respite for caregivers. In addition, home care can provide one-to-one support and care in the home allowing for more individualized attention that is needed as the disorder progresses. Psychiatric nurses can make a distinctive contribution to people’s mental health.
Some London hospitals found that using color, designs, pictures and lights helped people with dementia adjust to being at the hospital. These adjustments to the layout of the dementia wings at these hospitals helped patients by preventing confusion.
Cognitive Training
Personally Tailored Activities
What Are The Symptoms Of Alzheimers Disease
Early on, Alzheimers disease may be hard to notice. The first signs are usually memory loss and difficulty finding the right words for everyday things. However, many people have trouble with memory but dont have Alzheimers so its important to visit a doctor to work out the exact cause of memory problems.
Other common symptoms of Alzheimers disease include:
- vagueness in daily conversation
Alzheimers disease is sometimes classified into 3 stages, based on the severity of symptoms:
Symptoms will progress differently between people, depending on what areas of the brain are affected. A persons symptoms may also change from day to day and can become worse with stress, illness or tiredness.
Watch the video below to learn more about the early signs of dementia.
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Diagnosis Of Dementia Due To Alzheimer’s Disease
- Obtaining a medical and family history from the individual, including psychiatric history and history of cognitive and behavioral changes.
- Asking a family member to provide input about changes in thinking skills and behavior.
- Conducting problem-solving, memory and other cognitive tests, as well as physical and neurologic examinations.
- Having the individual undergo blood tests and brain imaging to rule out other potential causes of dementia symptoms, such as a tumor or certain vitamin deficiencies.
- In some circumstances, using PET imaging of the brain to find out if the individual has high levels of beta-amyloid, a hallmark of Alzheimer’s; normal levels would suggest Alzheimer’s is not the cause of dementia.
- In some circumstances, using lumbar puncture to determine the levels of beta-amyloid and certain types of tau in CSF; normal levels would suggest Alzheimer’s is not the cause of dementia.
Plasma Biomarkers Of Ad
Other approaches using genomics, transcriptomics, metabolomics, lipidomics, and proteomics have been used to generate different AD biomarkers. One study showed that altered microRNAs resulting from the failure of synaptic function are potential plasma biomarkers of AD.5959. Siedlecki-Wullich D, Català-Solsona J, Fábregas C, Hernández I, Clarimon J, Lleó A, et al. Altered microRNAs related to synaptic function as potential plasma biomarkers for Alzheimer’s disease. Alzheimers Res Ther. 2019;11:46. Another study comparing AD patients with healthy controls showed decreased platelet levels of one member of the a disintegrin and metalloproteinase family: ADAM10, the primary -secretase of APP, which plays an important role in reducing generation of A peptide. The same study showed decreased presenilin levels in platelets and leukocytes. Presenilin is the catalytic site of -secretase, one enzyme in the reaction that generates A peptide. Levels of the -site APP-cleaving enzyme 1 , also known as -secretase, were also decreased in leukocytes and presented no differences in platelets.6060. Bram JM, Talib LL, Joaquim HP, Sarno TA, Gattaz WF, Forlenza OV. Protein levels of ADAM10, BACE1, and PSEN1 in platelets and leukocytes of Alzheimer’s disease patients. Eur Arch Psychiatry Clin Neurosci. 2019;269:963-72.
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How Does Alzheimer’s Disease Affect The Brain
Scientists continue to unravel the complex brain changes involved in Alzheimers disease. Changes in the brain may begin a decade or more before symptoms appear. During this very early stage of Alzheimers, toxic changes are taking place in the brain, including abnormal buildups of proteins that form amyloid plaques and tau tangles. Previously healthy neurons stop functioning, lose connections with other neurons, and die. Many other complex brain changes are thought to play a role in Alzheimers as well.
The damage initially appears to take place in the hippocampus and the entorhinal cortex, which are parts of the brain that are essential in forming memories. As more neurons die, additional parts of the brain are affected and begin to shrink. By the final stage of Alzheimers, damage is widespread and brain tissue has shrunk significantly.
Metabolomics Analysis And Alzheimers Disease
The US Food and Drug Administration defines a biological marker as an indicator of normal biologic or pathogenic processes or pharmacological responses to a therapeutic intervention. In general, biomarkers in the body are essential not only for the early diagnosis of a disease but also in the assessment of prognosis, classification of disease progression, and disease-modifying treatment . Several biochemical processes, such as the metabolism of amyloid precursor protein , phosphorylation of tau protein , oxidative stress, impaired energetics, mitochondrial dysfunction, inflammation, dysregulation of membrane lipids, and disruption of neurotransmitter pathways, are affected in AD . These changes can be reflected by biomarkers. Therefore, the metabolomics analysis provides a new method to reveal the nature of a multifactorial disease.
Several MA studies have reported that AD involves disordered metabolism of branched-chain amino acids , phosphatidylcholine , glycerophospholipids, and sphingolipids . MA is a new frontier in the diagnosis of multifactorial chronic disease because hundreds of metabolites can be detected rapidly and simultaneously .
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Health Environmental And Lifestyle Factors
Research suggests that a host of factors beyond genetics may play a role in the development and course of Alzheimers. There is a great deal of interest, for example, in the relationship between cognitive decline and vascular conditions such as heart disease, stroke, and high blood pressure, as well as conditions such as diabetes and obesity. Ongoing research will help us understand whether and how reducing risk factors for these conditions may also reduce the risk of Alzheimers.
A nutritious diet, physical activity, social engagement, and mentally stimulating pursuits have all been associated with helping people stay healthy as they age. These factors might also help reduce the risk of cognitive decline and Alzheimers. Researchers are testing some of these possibilities in clinical trials.
What Happens If A Doctor Thinks It’s Alzheimer’s Disease
If a primary care doctor suspects mild cognitive impairment or possible Alzheimers, he or she may refer the patient to a specialist who can provide a detailed diagnosis or further assessment. Specialists include:
- Geriatricians, who manage health care in older adults and know how the body changes as it ages and whether symptoms indicate a serious problem
- Geriatric psychiatrists, who specialize in the mental and emotional problems of older adults and can assess memory and thinking problems
- Neurologists, who specialize in abnormalities of the brain and central nervous system and can conduct and review brain scans
- Neuropsychologists, who can conduct tests of memory and thinking
Memory clinics and centers, including Alzheimers Disease Research Centers, offer teams of specialists who work together to diagnose the problem. Tests often are done at the clinic or center, which can speed up diagnosis.
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