Dementias Associated With Aging And Neurodegeneration
Various disorders and factors contribute to dementia, resulting in a progressive and irreversible loss of neurons and brain functions. Currently, there are no cures for these neurodegenerative disorders.
Some specific causes of dementia disorders are explained below.
Alzheimers disease is the most common cause of dementia in older adults. As many as 5 million Americans age 65 and older may have the disease. In most neurodegenerative diseases, certain proteins abnormally clump together and are thought to damage healthy neurons, causing them to stop functioning and die. In Alzheimers, fragments of a protein called amyloid form abnormal clusters called plaques between brain cells, and a protein called tau forms tangles inside nerve cells.
It seems likely that damage to the brain starts a decade or more before memory and other cognitive problems appear. The damage often initially appears in the hippocampus, the part of the brain essential in forming memories. Ultimately, the abnormal plaques and tangles spread throughout the brain, and brain tissue significantly shrinks.
As Alzheimers disease progresses, people experience greater memory loss and other cognitive difficulties. Problems can include wandering and getting lost, trouble handling money and paying bills, repeating questions, taking longer to complete normal daily tasks, and personality and behavior changes.
Clinically, FTD is classified into two main types of syndromes:
Forms of VCID include:
Advice For People Living With Lewy Body Dementia
Coping with a diagnosis of LBD and all that follows can be challenging. Getting support from family, friends, and professionals is critical to ensuring the best possible quality of life. Creating a safe environment and preparing for the future are important, too. Take time to focus on your strengths, enjoy each day, and make the most of your time with family and friends. Here are some ways to live with LBD day to day.
Your family and close friends are likely aware of changes in your thinking, movement, or behavior. You may want to tell others about your diagnosis so they can better understand the reason for these changes and learn more about LBD. For example, you could say that you have been diagnosed with a brain disorder called Lewy body dementia, which can affect thinking, movement, and behavior. You can say that you will need more help over time. By sharing your diagnosis with those closest to you, you can build a support team to help you manage LBD.
As LBD progresses, you will likely have more trouble managing everyday tasks such as taking medication, paying bills, and driving. You will gradually need more assistance from family members, friends, and perhaps professional caregivers. Although you may be reluctant to get help, try to let others partner with you so you can manage responsibilities together. Remember, LBD affects your loved ones, too. You can help reduce their stress when you accept their assistance.
Plan for Your Future
Ethical Issues Surrounding Normalization Of Dementia
Although beyond the scope of this commentary, we briefly note ethical questions that arise from the WHO public health framework recommendations. Most people agree that high-quality dementia care is a worthwhile goal. First, it is the beneficent thing to do. Second, dementia is a disease of the elderly, and most elderly people have spent a lifetime contributing to society. Accordingly, it seems just that they are cared for by society in their old age dependency.
Unfortunately, good dementia care as outlined in Stage VI is expensive. In reality, implementing a nationwide policy of comprehensive dementia care could potentially bankrupt the US health care system unless the funding for this care could be provided through savings in other areas . There is a very real trade-off between care for dementia patients and care for the rest of society. A utilitarian viewpoint might argue against comprehensive dementia care, because channeling resources to care for younger and more productive members of society might improve average or overall happiness or utility. Accordingly, the principles of justice and beneficence that support comprehensive dementia care might be at odds with a guiding utilitarian framework.
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New Developments In Dementia Research In 2019
Despite no new drugs for dementia in 15 years, we are seeing progress with different treatments and other breakthroughs. Here we celebrate just a few of this year’s highlights in dementia research.
Alzheimer’s Society researchers continue to make an impact on dementia research.
They are taking great strides towards new treatments, learning how best to prevent dementia, and understanding how we can support people with dementia and their families today.
Here we share 7 highlights from dementia research in 2019, and how research funded by Alzheimer’s Society has played a key role.
The Trajectory Of Decline
FTD is a progressive neurodegenerative condition patients worsen over time in the cognitive domains where they have difculty. But the trajectory of decline is not linear. During an initial mild stage, there can be a relatively prolonged period of subtle and insidious change that involves few fundamental problems. The changes that do emerge are typically restricted to the type of difculty that brought the patient to medical attention in the rst place. For example, people with semantic dementia may have a gradual decline in single word comprehension and vocabulary, and people with progressive nonuent aphasia can have increasing difculty with grammatical comprehension and expression. People who have a disorder of personality and social behavior can have gradually worsening behavior. Because FTD is progressive, however, observing no change at all over a prolonged period should raise questions about a diagnosis of FTD.
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Diagnosis Treatment And Research
The Lewy Body Dementia Association maintains a list of its scientific and medical advisors. Many of these physicians see patients at their clinics or may make referrals to other specialists in your area. See . For general tips on finding a doctor, visit .
The Alzheimers Disease Education and Referral Center maintains a list of research centers funded by the National Institute on Aging at NIH where you may find medical specialists in Lewy body dementia: www.nia.nih.gov/alzheimers/alzheimers-disease-research-centers.
The American Academy of Neurology has a find a neurologist page on its website: .
The American Association for Geriatric Psychiatry has a physician finder on its website: .
New Advances Provide Hope For Alzheimer’s Patients
Dr. Jeffrey Cummings examines drug pipeline for treatments, and finds reason for optimism.
Dr. Jeffrey Cummings
Newswise Dr. Jeffrey L. Cummings, UNLV research professor and a leading expert on Alzheimers disease clinical trials, led a five-year review of all Alzheimers drugs in the development pipeline. He says today there is more hope than ever that we’ll one day solve Alzheimers. The paper, Alzheimer’s disease drug development pipeline: 2020, was published this week in the journal Alzheimer’s & Dementia: Translational Research & Clinical Interventions. The first time his team published an analysis of experimental drugs in 2014, they quantified a 99 percent failure rate of all therapies in the pipeline. It was the first analysis of its kind and has proven enormously popular with roughly 67,000 downloads and 260 citations. Currently, there are 121 unique therapies in 136 clinical trials in the pipeline. We recently met with Cummings from the UNLV School of Integrated Health Sciences to understand what has changed in the world of Alzheimers drug development over the last five years.
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Caring For A Person With Lewy Body Dementia
As someone who is caring for a person with LBD, you will take on many different responsibilities over time. You do not have to face these responsibilities alone. Many sources of help are available, from adult day centers and respite care to online and in-person support groups.
Below are some important actions you can take to adjust to your new roles, be realistic about your situation, and care for yourself. See the Resources section for more information.
Educate Others About LBD
Most people, including many healthcare professionals, are not familiar with LBD. In particular, emergency room physicians and other hospital workers may not know that people with LBD are extremely sensitive to antipsychotic medications. Caregivers can educate healthcare professionals and others by:
- Informing hospital staff of the LBD diagnosis and medication sensitivities, and requesting that the persons neurologist be consultedbefore giving any drugs to control behavior problems.
- Sharing educational pamphlets and other materials with doctors, nurses, and other healthcare professionals who care for the person with LBD.
- Teaching family and friends about LBD so they can better understand your situation.
Care for Yourself
Address Family Concerns
Helping Children and Teens Cope with LBD
The organizations listed in the Resources section can help with information about caregiver services and support.
Therapeutic Targets For Disease Modification In Ad
The recognition of core and secondary pathophysiological mechanisms in AD has led to the identification of molecular targets for the development of specific drugs. In fact, more than 200 pharmaceutical compounds are currently undergoing phase 2 and 3 trials. These compounds can be grossly divided into anti-amyloid agents and drugs that target other pathological pathways. Anti-amyloid compounds can be subdivided into drugs designed to block or inhibit the overproduction or aggregation of A, or to favour its clearance from the brain , whereas the latter group can be subdivided according to predominant mechanism of action of the drug, i.e., neurotransmitter and cell-signalling agents, glial cell modulators, neuroprotective agents, and Tau-based therapies . Studies involving stem-cell and gene therapy are also under way, but at more incipient stages of experimental validation.
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Practical Tips On Medications To Manage Difficult Behaviors In Dementia
You may be now wondering just how doctors are supposed to manage medications for difficult dementia behaviors.
Here are the key points that I usually share with families:
- Before resorting to medication: its essential to try to identify what is triggering/worsening the behavior, and its important to try non-drug approaches, including exercise.
- Be sure to consider treating possible pain or constipation, as these are easily overlooked in people with dementia. Geriatricians often try scheduling acetaminophen 2-3 times daily, since people with dementia may not be able to articulate their pain. We also titrate laxatives to aim for a soft bowel movement every 1-2 days.
- No type of medication has been clinically shown to improve behavior for most people with dementia. If you try medication for this purpose, you should be prepared to do some trial-and-error, and its essential to carefully monitor how well the medication is working and what side-effects may be happening.
- Antipsychotics and benzodiazepines work fairly quickly, but most of the time they are working through sedation and chemical restraint. They tend to cloud thinking further. It is important to use the lowest possible dose of these medications.
- Antidepressants take a while to work, but are generally well-tolerated. Geriatricians often try escitalopram or citalopram in people with dementia.
Potential For An Alzheimers Treatment Appears To Be Closer Than Ever
There may be nothing quite as gut-wrenching as sitting at the bedside of a loved one, watching helplessly as their life comes to an end. Perhaps the only thing more painful is when that loved one no longer recognizes you, slipping away not knowing who it was holding their hand.
Alzheimers is the only disease among the top 10 causes of death in America that cannot be prevented, cured or even slowed. Over a decade and billions of dollars have been spent on research to find a cure for Alzheimers, yet none have thus far proved real clinical benefit. If the elusive cure for Alzheimers isnt found soon, scientists estimate that by 2050 someone in the United States will develop the disease every 33 seconds.
While these statistics paint a pretty bleak picture, Cynthia Lemere, Ph.D., Associate Professor of Neurology at Brigham and Womens Hospital and Harvard Medical School, assured BioSpace that hope is not lost. Despite the many failed drug trials, Lemere says the horizon is finally looking optimistic and expects to see multiple treatments approved within the next few years.
Any therapy developed at this point is going to be probably good for one subsection of that 5.8 million people with Alzheimers disease. And maybe not even that population, but maybe the population that doesnt yet have Alzheimers disease but has the changes going on in their brain of Alzheimers, so we know that theyre on the track, Lemere said.
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Normalization Of Dementia: Goals And Barriers
An estimated 8.8 percent of the United States population over age 64 has dementia . For society to provide beneficent care for this population, it is imperative to develop strategies to normalize the experience of dementia. The World Health Organization promotes a framework in which societies progress through six stages of dementia acceptance . Stage I is ignoring the problem. By Stage VI, dementia achieves normalization, in which the diagnosis is accepted as a disability and patients are included in society as much as possible. To achieve this stage, society must find a way to bestow meaning and value on the lives of people with dementia, despite their functional limitations, by creating dementia-friendly communities . If Drs. Woods and Daniels could direct Mr. Farnal to successful social programsand direct others like him who wish to remain employed to work participation programs that bestow at least some degree of autonomyMr. Farnal and other patients with dementia might be able to feel hope despite their future of inevitable functional decline.
Other Neurodegenerative Diseases And Conditions That Include Dementia Or Dementia
Doctors have identified many other conditions that can cause dementia or dementia-like symptoms. The diseases have different symptoms that involve body and brain functions, and affect mental health and cognition.
Argyrophilic grain disease is a common, late-onset degenerative disease that affects brain regions involved in memory and emotion. It causes cognitive decline and changes in memory and behavior, with difficulty finding words. The diseases signs and symptoms are indistinguishable from late-onset AD. Confirmation of the diagnosis can be made only at autopsy.
Creutzfeldt-Jakob disease is a rare brain disorder that is characterized by rapidly progressing dementia. Scientists found that infectious proteins called prions become misfolded and tend to clump together, causing the brain damage. Initial symptoms include impaired memory, judgment, and thinking, along with loss of muscle coordination and impaired vision. Some symptoms of CJD can be similar to symptoms of other progressive neurological disorders, such as Alzheimers disease.
Secondary dementias occur in people with disorders that damage brain tissue. Such disorders may include multiple sclerosis, meningitis, and encephalitis, as well as Wilsons disease . People with malignant brain tumors may develop dementia or dementia-like symptoms because of damage to their brain circuits or a buildup of pressure inside the skull.
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Pathological Mechanisms In Ad
Neurofibrillary tangles , another pathological hallmark of the disease, are largely constituted by intracellular aggregates of paired helical filaments , which arise from the collapse of the neuronal cytoskeleton. The structure and function of microtubules are impaired as a consequence of the abnormal hyperphosphorylation of Tau protein, which precludes its ability to stabilize the monomers of alpha- and beta-tubulin. Hyperphosphorylated Tau aggregates into oligomers to form PHFs to further originate NFTs. Several protein kinases are involved in this process, namely glycogen synthase kinase-3 beta , cyclin-dependent kinase-5 , and extracellular signal-related kinase-2 these enzymes may also be regarded as potential targets for disease-modification, upon their inhibition by specific drugs. GSK-3, the most important Tau kinase in neurons, is overactive in AD and its overexpression has been shown to hyperphosphorylate Tau in transgenic mouse models of AD,. The inhibition of GSK-3 not only precludes the hyperphosphorylation of Tau, but also yields the dephosphorylation of its abnormally hyperphosphorylated epitopes by the action of protein phosphatases. Therefore, the interruption and reversal of this process may restore microtubular structure and function. Moreover, GSK-3 inhibition downregulates the amyloidogenic cleavage of APP, which provides further evidence of the cross-talk between these two major pathological cascades in AD.
No Easy Solutions But Improvement Is Usually Possible
As many of you know, behavior problems are difficult in dementia in large part because there is usually no easy way to fix them.
Many probably too many older adults with Alzheimers and other dementias are being medicated for their behavior problems.
If your family is struggling with behavior problems, I know that reading this article will not quickly solve them.
But I hope this information will enable you to make more informed decisions. This way youll help ensure that any medications are used thoughtfully, in the lowest doses necessary, and in combination with non-drug dementia behavior management approaches.
To learn about non-drug management approaches, I recommend this article: 7 Steps to Managing Difficult Dementia Behaviors
And if you are looking for a memory care facility, try to find out how many of their residents are being medicated for behavior. For people with Alzheimers and other dementias, its best to be cared for by people who dont turn first to chemical restraints such as antipsychotics and benzodiazepines.
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The Protein Called Tau
What is damaging the frontal and temporal lobes of people with FTD, causing these devastating changes in language, behavior, or both? By carefully examining the brains of people who died of FTD, scientists discovered that, in all forms of FTD, the most prominent feature was an abnormal metabolism of the protein tau. The condition is termed tauopathy.
The tau protein is an essential building block of the cytoskeleton of brain cells, or neurons. The cytoskeleton maintains the unique shape of the neuron and its long axon projecting from the cell body to the synaptic space adjacent to another neuron. The axon allows communication from one neuron to the next, producing networks of neurons that sustain our cognitive and social functioning. The cytoskeleton is also crucial in delivering substances down the axon to where they are needed at its active distant terminus. In FTD, tau function can be interrupted in several ways. For example, there may be an imbalance of the various forms of tau that are normally found in the brain tau may become chemically altered at crucial points that impair its function or it may become profoundly depleted in the brain.