Dementia: Why we find it difficult to stay awake in the day and sleep at night?

Study Suggests Tau Tangles, Not Amyloid Plaques, Drive Daytime Napping That Precedes Dementia

Researchers and caregivers have noted that excessive daytime napping can develop long before the memory problems associated with Alzheimer’s disease begin to unfold. Prior studies have considered this excessive daytime napping to be compensation for poor nighttime sleep caused by Alzheimer’s-related disruptions in sleep-promoting brain regions, while others have argued that the sleep problems themselves contribute to the progression of the disease. But now UC San Francisco scientists have provided a striking new biological explanation for this phenomenon, showing instead that Alzheimer’s disease directly attacks brain regions responsible for wakefulness during the day.

two people talk in a lab
Lea Grinberg (right), MD, PhD, the senior study author

The new research demonstrates that these brain regions (including the part of the brain impacted by narcolepsy) are among the first casualties of neurodegeneration in Alzheimer’s disease, and therefore that excessive daytime napping – particularly when it occurs in the absence of significant nighttime sleep problems – could serve as an early warning sign of the disease. In addition, by associating this damage with a protein known as tau, the study adds to evidence that tau contributes more directly to the brain degeneration that drives Alzheimer’s symptoms than the more extensively studied amyloid protein.

“Our work shows definitive evidence that the brain areas promoting wakefulness degenerate due to accumulation of tau – not amyloid protein – from the very earliest stages of the disease,” said study senior author Lea T. Grinberg, MD, PhD, an associate professor of neurology and pathology at the UCSF Memory and Aging Center and a member of the Global Brain Health Institute and UCSF Weill Institute for Neurosciences.

Wakefulness Centers Degenerate in Alzheimer’s Brains

In the new study, published August 12, 2019, in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, lead author Jun Oh, a Grinberg lab research associate, and colleagues precisely measured Alzheimer’s pathology, tau protein levels and neuron numbers in three brain regions involved in promoting wakefuless from 13 deceased Alzheimer’s patients and seven healthy control subjects, which were obtained from the UCSF Neurodegenerative Disease Brain Bank.

Compared to healthy brains, Oh and colleagues found that the brains of Alzheimer’s patients had significant tau buildup in all three wakefulness-promoting brain centers they studied – the locus coeruleus (LC), lateral hypothalamic area (LHA), and tuberomammillary nucleus (TMN) – and that these regions had lost as many as 75 percent of their neurons.

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Jun Oh, lead author of the study. 

“It’s remarkable because it’s not just a single brain nucleus that’s degenerating, but the whole wakefulness-promoting network,” Oh said. “Crucially this means that the brain has no way to compensate because all of these functionally related cell types are being destroyed at the same time.”

Oh and colleagues also studied brain samples from seven patients with progressive supranuclear palsy (PSP) and corticobasal disease (CBD), two distinct forms of neurodegenerative dementia caused by tau accumulation. In contrast to the Alzheimer’s disease brains, wakefulness-promoting neurons appeared to be spared in the PSP and CBD brains, despite comparable levels of tau buildup in these tissue samples.

“It seems that the wakefulness-promoting network is particularly vulnerable in Alzheimer’s disease,” Oh said. “Understanding why this is the case is something we need to follow up in future research.”

Studies Point to Role of Tau Protein in Alzheimer’s Symptoms

The new results are in line with an earlier study by Grinberg’s group which showed that people who died with elevated levels of tau protein in their brainstem – corresponding to the earliest stages of Alzheimer’s disease – had already begun to experience changes in mood, such as anxiety and depression, as well as increased sleep disturbances.

“Our new evidence for tau-linked degeneration of the brain’s wakefulness centers provides a compelling neurobiological explanation for those findings,” Grinberg said. “It suggests we need to be much more focused on understanding the early stages of tau accumulation in these brain areas in our ongoing search for Alzheimer’s treatments.”

These studies add to a growing recognition among some researchers that tau buildup is more closely linked to the actual symptoms of Alzheimer’s than the more widely studied amyloid protein, which has so far failed to yield effective Alzheimer’s therapies.

For instance, another recent study by the Grinberg lab measured tau buildup in the brains of patients who died with different clinical manifestations of Alzheimer’s disease, including variants that involved language impairment or visual problems instead of more typical memory loss. They found that differences in local tau burden in these patients’ brains closely matched their symptoms: patients with language impairments had more tau accumulation in language related brain areas than in memory regions, while patients with visual problems had higher tau levels in visual brain areas.

“This research adds to a growing body of work showing that tau burden is likely a direct driver of cognitive decline,” Grinberg said.

Increased focus on the role of tau in Alzheimer’s suggests that treatments currently in development at UCSF’s Memory and Aging Center and elsewhere that directly tackle tau pathology have the potential to improve sleep and other early symptoms of Alzheimer’s disease, in addition to holding a key to slowing the progress of the disease overall, the authors say.

Authors: See study online for full list of authors.

Funding: This study was supported by The Rainwater Foundation and grants from the National Institutes of Health (R01AG064314, R01AG060477, P50AG023501, P01AG019724, K24AG053435), the Global Brain Health Institute, and the São Paulo Research Foundation (FAPESP).

Disclosures: The authors declare no conflicts of interest.

The University of California, San Francisco (UCSF) is exclusively focused on the health sciences and is dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. It includes UCSF Health, which comprises three top-ranked hospitals, as well as affiliations throughout the Bay Area.

Source
August 2019| The Regents of The University of California – Alzheimer’s Disease Destroys Neurons that Keep Us Awake By Nicholas Weiler

Apathy: The forgotten symptom of dementia

Press Release
July 2019| University of Exeter – Apathy: The forgotten symptom of dementia

Apathy is the most common neuropsychiatric symptom of dementia, with a bigger impact on function than memory loss – yet it is under-researched and often forgotten in care.

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Photo by weedlyr on Pexels.com

A new study has found that apathy is present nearly half of all people with dementia, with researchers finding it is often distinct from depression.

Although common, apathy is often ignored as it is less disruptive in settings such as care homes than symptoms like aggression. Defined by a loss of interest and emotions, it is extremely distressing for families and it is linked with more severe dementia and worse clinical symptoms.

Now, research led by the University of Exeter and presented at the Alzheimer’s Association International Conference in LA has analysed 4,320 people with Alzheimer’s disease from 20 cohort studies, to look at the prevalence of apathy over time.

At the start of the study, 45% presented with apathy, and 20% had persistent apathy over time. Researchers found that a proportion had apathy without depression, which suggests that the symptom might have its own unique clinical and biological profile when compared to apathy with depression and depression only.

Miguel de Silva Vasconcelos, PhD student at the University of Exeter and King’s College London, said : “Apathy is an under-researched and often ignored symptom of dementia. It can be overlooked because people with apathy seem less disruptive and less engaging, but it has a huge impact on the quality of life of people living with dementia, and their families. Where people withdraw from activities, it can accelerate cognitive decline and we know that there are higher mortality rates in people with apathy. It’s now time this symptom was recognised and prioritised in research and understanding.”

Professor Clive Ballard, of the University of Exeter Medical School, said: “Apathy is the forgotten symptom of dementia, yet it can have devastating consequences. Our research shows just how common apathy is in people with dementia, and we now need to understand it better so we can find effective new treatments. Our WHELD study to improve care home staff training through personalised care and social interaction included an exercise programme that improved apathy, so we know we can make a difference. This is a real opportunity for interventions that could significantly benefit thousands of people with dementia.”

The presentation was entitled ‘The Course of Apathy in People with Dementia’.

Alzheimer associations in Asia

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Many caregivers in Asia can agree, it’s super hard to find resources and in some countries, it’s hard even to know where to start. When we go online there are so many websites and resources, it’s hard to even know where to start. It’s hard especially when a lot of information tends to be advertisements for private organisations promoting their services. When this post from Monica Cations post popped up on twitter, it was like, wow, what a great idea!

Let’s have one for countries in Asia. The list is below is one for Asia, and if you wish to view the full list of organisations, you can visit https://www.alz.co.uk/associations

Bangladesh *                     www.alzheimerbd.com

Brunei **                            demensia.brunei@gmail.com

China                                     www.adc.org.cn

Hong Kong SAR                 www.hkada.org.hk

Indonesia                            www.alzi.or.id

Japan                                    www.alzheimer.or.jp

Macau SAR                         www.mada.org.mo

Malaysia                              www.adfm.org.my

Philippines                          www.alzphilippines.com

Republic of Korea             www.silverweb.or.kr

Singapore                            www.alz.org.sg

Sri Lanka                              www.alzlanka.org

TADA Chinese Taipei       www.tada2002.org.tw

Thailand                               www.azthai.org

Stressed and exhausted caregivers need better support

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Up to 80 per cent of community care for older adults is provided by unpaid informal caregivers. In the absence of government supports, many of them struggle with exhaustion, stress and depression.
(Shutterstock)

Jenny Ploeg, McMaster University and Maureen Markle-Reid, McMaster University

When Brenda retired from paid work, it was like a care-giving tsunami.

Her dad and stepmom moved in with her, her husband had a heart attack and she became a grandma — all within six months.

Brenda is one of 8.1 million Canadians who have taken on challenging unpaid roles — as informal caregivers for people living with physical or cognitive conditions or chronic life-limiting illnesses.

Her stress increased as her parents started to deteriorate physically and mentally. She tried to stay ahead of the ever-changing situation, but became exhausted after her dad started waking in the middle of the night and getting dressed to go out.

She looked on the internet for support in her care-giving role.

As co-scientific directors of the Aging, Community and Health Research Unit at McMaster University, we are working together with older adults with multiple conditions and caregivers like Brenda to promote optimal aging at home.

Our research shows that current health and social services do not address the complex needs of older adults or their family caregivers.

It also suggests that web-based interventions may help reduce depressive symptoms, anxiety and stress or distress for these caregivers.

Who cares for the caregivers?

Older adults with chronic conditions rely heavily on their family caregivers to coordinate their care, monitor medication and accompany them to appointments.

In fact, 70 to 80 per cent of community care for older adults is provided by informal caregivers as opposed to formal care providers.

Increasingly, these older adults have multiple chronic conditions (MCC), such as dementia and stroke, not just one. And as this prevalence of multiple conditions increases worldwide, it’s associated with poor health and higher health-care use and costs.

Women represent a slight majority of Canadian caregivers at 54 per cent and spend more time per week on caregiving than males.

Caregivers report that they do not receive adequate home care or respite services to support them in their roles. There are, for instance, long wait lists for long-term care beds.

Research shows that caregivers spent $12.6 million in one year on expenses related to their roles.
(Shutterstock)

While caregiving is rewarding, many informal caregivers experience stress and anxiety leading to their own poor mental and physical health.

Informal caregivers feel overwhelmed with multiple requests for their time and frustrated when they can’t plan too far in advance.

“I felt like I was spending a lot of time waiting. Waiting for people to get ready. Waiting for people to get back to me. Waiting at appointments,” said Brenda.

Some reach a crisis point and leave their loved ones in the hospital emergency room because they are unable to continue in their caregiving role. This contributes to an already overburdened acute-care system.

Web-based supports can help

We conducted a systematic review and meta-analysis that examined the impact of different types of internet-based interventions on caregiver mental health outcomes.

One example of such a web-based support is My Tools 4 Care, developed by our colleague Dr. Wendy Duggleby at the University of Alberta and her team.

We found evidence that internet-based interventions had a positive effect on reducing depressive symptoms, stress, distress and anxiety in caregivers of adults with a chronic condition.

Internet-based interventions reduce caregiver depression and anxiety.
(Shutterstock)

The most effective category of online support was information and/or education with or without professional psychological support. Information provided together with combined peer and professional psychological support was also effective, to a lesser extent.

However, although many websites for caregivers provide valuable information, we found that they need to be easier to navigate and use.

Caregivers in our study made recommendations to improve the content and format of online resources. Suggestions included: Providing personalized information about local resources; sharing practical caregiving tips and strategies; creating opportunities to connect online with other caregivers; and having user-friendly features that are easy to navigate.

Nova Scotia leads the way

Caregiving comes with costs to the caregivers — to their health and to their finances.

Half of caregivers are between 45-65 years of age, in the peak of their earning years. They often take time off work to take their loved ones to appointments, and some must leave work early when the health of their loved one worsens. Out-of-pocket expenses for equipment, medications and parking can also be expensive.

Research shows that caregivers spent $12.6 million in one year on expenses related to their roles.

Nova Scotia is the only province in Canada that has a monthly income or allowance for caregivers, known as the Caregiver Benefit Program. Financial assistance from the government for caregivers in other parts of Canada mainly take the form of federal tax credits and insurance benefits.

And yet caregivers make vitally important but often unrecognized contributions to our society. It is estimated that they contribute $25 billion in unpaid labour.

Change is urgently needed to better support our caregivers.The Conversation

Jenny Ploeg, Professor, School of Nursing, McMaster University and Maureen Markle-Reid, Associate Professor and Canada Research Chair in Person Centred Interventions for Older Adults with Multimorbidity and their Caregivers, School of Nursing, McMaster University

This article was originally published on The Conversation. Read the original article.

If you develop Alzheimer’s, will your children get it too?

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Rebecca Sims, Cardiff University

The most common question I get asked is “Will my child get Alzheimer’s disease?” In my experience, this concern is one of the biggest worries for sufferers, and given the devastating effects of the disease, it is not hard to see why it is a difficult thought to contemplate.

For those people with a familial form of Alzheimer’s disease, the answer is quite straightforward. This type of disease is caused by one or more mutation(s) in one of three genes: the amyloid precursor protein (APP), Presenilin 1 (PSEN1) and Presenilin 2 (PSEN2). All of these genes are involved in the production of the amyloid protein. This protein accumulates to form sticky buildups known as plaques, which are found between the cells of the Alzheimer brain and are characteristic of disease.

Those of us who are concerned that they may be at risk from familial Alzheimer’s disease can get a definitive answer through one of the many genetic tests available. A single copy of the mutated gene inherited from an affected parent will ultimately cause disease, with symptoms likely to be noticed before the age of 65 and typically between 30 and 60 years of age. Anyone concerned that they may suffer from this form of Alzheimer’s should seek a referral to a genetic counsellor.

Fortunately, families with a familial form of disease represent less than 1% of all families afflicted by this debilitating disease. For the remaining Alzheimer’s disease families, the answer as to the inheritance of disease is much less clear, and disease onset is certainly not inevitable.

Influencing disease

A combination of both genetic and environmental factors, such as age and gender, contribute to non-familial (also known as sporadic) disease risk, but how these risk factors interact and how many risk factors are required to cause disease is still unknown.

The genetics of non-familial Alzheimer’s is complex: we know that nearly thirty genes, common in the general population, influence disease risk, with potentially hundreds more involved. Additionally, two genes of low frequency have consistently been identified, with an imminent publication by the International Genomics of Alzheimer’s Project, showing another two rare genes have a relatively large effect on disease risk.

Perhaps most excitingly for researchers, genetics scientists have shown that four biological processes in Alzheimer’s disease – that were not previously thought to play a casual role in disease onset – are actually involved. The first process is the immune response, in particular the actions of immune cells and how these potentially dysfunction, attacking the brain, which results in brain cell death.

The second is the transport of molecules into the cell, suggesting that there is a mechanism for the movement of damaging proteins into the brain. The third process that has a role in the onset of Alzheimer’s is the synthesis and breakdown of fatty molecules. And the fourth is the processing of proteins that alters protein breakdown, movement, activity and interactions – all of which are essential for normal protein function.

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Lifestyle risk

Age is the greatest risk factor for disease, with the likelihood of developing Alzheimer’s roughly doubling every five years over the age of 65. Women also have more chance of developing the disease than men, potentially due to a reduction in female hormones after menopause.

Medical conditions that increase risk for dementia include cardiovascular factors (type 2 diabetes, high blood pressure, cholesterol levels, and obesity), and depression. While lifestyle factors such as physical inactivity, a diet that increases cholesterol, smoking and excessive alcohol intake, have all been shown to influence disease risk.

Even for those with a high number of genetic, environmental and lifestyle risk factors, Alzheimer’s disease is not inevitable. Likewise, individuals with a low number of risk factors for disease are not precluded from developing Alzheimer’s.

Given this lack of certainty and the lack of effective treatments for Alzheimer’s, most experts don’t recommend genetic testing for non-familial disease. This thinking may well evolve in the future, however, when research identifies new risk genes and improves our understanding of the dysfunctional processes in Alzheimer’s disease.

The Conversation

Answering the burning question, whether you will pass Alzheimer’s disease on to your children, is therefore still a near impossibility. But, as early diagnostic techniques improve, and with the prospect of a number of vaccines and therapeutics currently in clinical trials, risk prediction for Alzheimer’s disease may become mainstream and part of a developing precision medicine culture.

Rebecca Sims, Research Fellow, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University

This article was originally published on The Conversation. Read the original article.

Older Adults Are Still Likely Underestimating Cognitive Impairment in Their Families

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News release

 Study Finds Racial Differences in Reporting and Overall Trend of Underreporting Cognitive Impairment

An increasing number of older adults are reporting cognitive impairment in their families over the past two decades, according to a new study led by researchers at NYU Rory Meyers College of Nursing and East Carolina University’s Brody School of Medicine.

The study, which also finds ethnic and racial differences in reporting cognitive impairment, is published in Preventing Chronic Disease, a journal of the Centers for Disease Control and Prevention.

The aging population in the U.S. is growing rapidly, with the number of people age 65 and over in 2010 (40.2 million) projected to more than double by 2050. With the rapid increase in the aging population, the size of the population with cognitive impairment and dementia will continue to accelerate, highlighting the importance of identifying cognitive changes.

“Cognitive impairment may serve as a precursor to future dementia. Early detection of cognitive impairment can facilitate timely medical treatments, appropriate care planning, and prevention efforts,” said Bei Wu, PhD, Dean’s Professor in Global Health and director of Global Health & Aging Research at NYU Meyers, co-director of NYU Aging Incubator, and the study’s senior author.

The study sought to examine the trends of self-reported cognitive impairment among five major racial/ethnic groups from 1997 to 2015 in the United States. The researchers used data from the National Health Interview Survey, including 155,682 individuals age 60 and above in their sample. The large sample included people of a variety of races and ethnicities, including Asian Americans,  Blacks, Hispanics, Native Americans, non-Hispanic Blacks, and non-Hispanic Whites.

Rather than using a screening test or clinical examination to evaluate cognitive impairment, respondents were asked to report if any family member was “limited in anyway because of difficulty remembering or because of experiencing periods of confusion.”

The researchers found an increasing trend in self-reported cognitive impairment: the overall rate increased from 5.7 percent in 1997 to 6.7 percent in 2015 among older adults in the U.S. This finding may suggest that awareness of cognitive impairment, perhaps from heightened public attention to and interest in Alzheimer’s disease, has improved to some extent.

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When looking at each racial/ethnic group, however, the increasing trend was significant only among White respondents. In Whites, the rate of self-reported cognitive impairment increased from 5.2 percent in 1997 to 6.1 percent in 2015. Asian American, Black, Hispanic, and Native American respondents had higher rates of self-reported cognitive impairment than Whites, but these rates did not significantly increase from 1997 to 2015.

Regardless of the overall increasing trend, the rates of self-reported cognitive impairment were still low, which may suggest underreporting. The researchers note that the rates of self-reported cognitive impairment are much lower than the estimated prevalence of cognitive impairment. For adults 65 years and older, the rate of self-reported cognitive impairment was 6.3 percent in 2000 and 7.5 percent in 2012, while the estimated prevalence of cognitive impairment in the same age group was 21.2 percent in 2000 and 18.8 percent in 2012.

These findings underscore the need to further promote awareness of cognitive impairment, especially in minority populations. Different cultures hold different beliefs and perceptions of disease and aging. For instance, research has found that compared to Whites, minorities are less likely to seek treatment for psychiatric symptoms because of lack of access to care or due to stigma.

“Culturally specific health education is needed in individuals, family members, and healthcare providers to improve awareness and knowledge of signs and early symptoms of Alzheimer’s and other dementia,” said Huabin Luo, PhD, of East Carolina University.

In addition to Wu and Luo, Gary Yu of NYU Meyers coauthored the study.