Wednesday, June 21, 2017

Where Alzheimer's Begins

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Columbia University Medical Center.

ROOTS OF ALZHEIMER'S: 

Columbia University researchers have pinpointed 3 discoveries about Alzheimer's:
  • Where it starts
  • Why it starts there
  • How it spreads.
Learn why this can help researchers treat Alzheimer's sooner and better. 



Using high-resolution functional MRI (fMRI) imaging in patients with Alzheimer's disease and in mouse models of the disease, Columbia University Medical Center (CUMC) researchers have clarified three fundamental issues about Alzheimer's: where it starts, why it starts there, and how it spreads. In addition to advancing understanding of Alzheimer's, the findings could improve early detection of the disease, when drugs may be most effective. The study was published today in the online edition of the journalNature Neuroscience.

Alzheimer's disease starts in the entorhinal cortex (yellow). Using fMRI in mouse (left) and human (right) brains, the researchers provide evidence that the disease spreads from the entohrinal cortex (yellow) to other cortical regions (red) -- the perirhinal cortex and posterior parietal cortex. (Credit: Usman Khan/lab of Scott A. Small, MD, Columbia University Medical Center.)

"It has been known for years that Alzheimer's starts in a brain region known as the entorhinal cortex," said co-senior author Scott A. Small, MD, Boris and Rose Katz Professor of Neurology, professor of radiology, and director of the Alzheimer's Disease Research Center. "But this study is the first to show in living patients that it begins specifically in the lateral entorhinal cortex, or LEC. The LEC is considered to be a gateway to the hippocampus, which plays a key role in the consolidation of long-term memory, among other functions. If the LEC is affected, other aspects of the hippocampus will also be affected."

The study also shows that, over time, Alzheimer's spreads from the LEC directly to other areas of the cerebral cortex, in particular, the parietal cortex, a brain region involved in various functions, including spatial orientation and navigation. The researchers suspect that Alzheimer's spreads "functionally," that is, by compromising the function of neurons in the LEC, which then compromises the integrity of neurons in adjoining areas.

A third major finding of the study is that LEC dysfunction occurs when changes in tau and amyloid precursor protein (APP) co-exist. "The LEC is especially vulnerable to Alzheimer's because it normally accumulates tau, which sensitizes the LEC to the accumulation of APP. Together, these two proteins damage neurons in the LEC, setting the stage for Alzheimer's," said co-senior author Karen E. Duff, PhD, professor of pathology and cell biology (in psychiatry and in the Taub Institute for Research on Alzheimer's Disease and the Aging Brain) at CUMC and at the New York State Psychiatric Institute.

In the study, the researchers used a high-resolution variant of fMRI to map metabolic defects in the brains of 96 adults enrolled in the Washington Heights-Inwood Columbia Aging Project (WHICAP). All of the adults were free of dementia at the time of enrollment.

"Dr. Richard Mayeux's WHICAP study enables us to follow a large group of healthy elderly individuals, some of whom have gone on to develop Alzheimer's disease," said Dr. Small. "This study has given us a unique opportunity to image and characterize patients with Alzheimer's in its earliest, preclinical stage."

The 96 adults were followed for an average of 3.5 years, at which time 12 individuals were found to have progressed to mild Alzheimer's disease. An analysis of the baseline fMRI images of those 12 individuals found significant decreases in cerebral blood volume (CBV) -- a measure of metabolic activity -- in the LEC compared with that of the 84 adults who were free of dementia.

A second part of the study addressed the role of tau and APP in LEC dysfunction. While previous studies have suggested that entorhinal cortex dysfunction is associated with both tau and APP abnormalities, it was not known how these proteins interact to drive this dysfunction, particularly in preclinical Alzheimer's.

To answer this question, explained first author Usman Khan, an MD-PhD student based in Dr. Small's lab, the team created three mouse models, one with elevated levels of tau in the LEC, one with elevated levels of APP, and one with elevated levels of both proteins. The researchers found that the LEC dysfunction occurred only in the mice with both tau and APP.

The study has implications for both research and treatment. "Now that we've pinpointed where Alzheimer's starts, and shown that those changes are observable using fMRI, we may be able to detect Alzheimer's at its earliest preclinical stage, when the disease might be more treatable and before it spreads to other brain regions," said Dr. Small. In addition, say the researchers, the new imaging method could be used to assess the efficacy of promising Alzheimer's drugs during the disease's early stages.

Monday, June 19, 2017

Western Diet Increases Alzheimer’s Pathology in Genetically Predisposed Mice

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Neuroscience News

summary: Diet and lifestyle changes could lower the risk of developing Alzheimer’s disease for those who are genetically predisposed, a new study suggests.
Source: SfN.
Obese mice with a particular version of a gene strongly associated with Alzheimer’s disease (AD) in humans show increased Alzheimer’s pathology, according to new research published in eNeuro. The study suggests lifestyle changes could reduce the likelihood of developing AD in individuals with this genetic predisposition.
Individuals who inherit the gene APOE4 — approximately 12 percent of the U.S. population — have an increased risk of late-onset AD, but not all carriers develop the disease. Although the role of APOE4 in AD is not known, environmental factors that also increase risk of dementia, such as obesity, may contribute to development of AD.
Christian Pike and Alexandra Moser investigated the interaction between APOE4 and obesity in a mouse model of AD, in which some male mice carry the human version of APOE4 and others carry the more common human version APOE3. The authors found that APOE4-carrying mice fed a Western-like diet high in saturated fat and sugars for 12 weeks had increased deposits of β-amyloid protein as well a greater number of glial cells, characteristic of AD. These changes were not observed in mice carrying APOE3, which could mean that carriers of APOE4 are more susceptible to the effects of obesity on AD.

The authors found that APOE4-carrying mice fed a Western-like diet high in saturated fat and sugars for 12 weeks had increased deposits of β-amyloid protein as well a greater number of glial cells, characteristic of AD. NeuroscienceNews.com image is for illustrative purposes only.
ABOUT THIS NEUROSCIENCE RESEARCH ARTICLE
Source: SfN
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: The study will appear in eNeuro.



Saturday, June 17, 2017

Study identifies potential biomarker for Alzheimer's disease

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Boston University Medical Center

(Boston)--In one of the largest studies to date to use metabolomics, the study of compounds that are created through various chemical reactions in the body, researchers have been able to identify new circulating compounds associated with the risk of developing dementia and Alzheimer's disease (AD).
The findings, which appear in the journal Alzheimer and Dementia, point to new biological pathways that may be implicated in AD and could serve as biomarkers for risk of the disease.
AD is the most common form of dementia responsible for a slow and progressive deterioration of memory and leads to frailty and dependence in elderly people. Despite ongoing research effort and improved knowledge about the disease, there is currently no effective preventive or curative treatment for AD, which could result in a public health crisis given the continuous aging of populations worldwide.
Using data from the Framingham Heart Study (FHS), researchers from Boston University School of Medicine (BUSM), observed an association specifically between levels of anthranillic acid measured in the plasma and a higher risk of developing dementia and AD after 10 years of follow-up.
Although the researchers are cautious about their results, they identify several findings they find promising. "First anthranilic acid is produced during the degradation of tryptophan, an essential amino acid. Interestingly, other compounds produced through the same reactions have been reported as protective or deleterious for neurons and could constitute valuable drug targets. Second, this potential marker could also be used to identify groups of persons at higher risk of developing dementia, which could improve the efficiency of clinical trials and in the future, detect persons that would benefit the most from a preventive treatment," explained co-corresponding author Sudha Seshadri, MD, professor of neurology at BUSM and FHS senior investigator.
From a methodological point of view, this study is one of the first to use a prospective cohort such as the FHS to search for compounds associated with the risk of developing AD and dementia. "As the field of AD epidemiology is only beginning to integrate the metabolomics approach, it is likely that fruitful collaborations and innovative ways to analyze these data will follow," said co-corresponding author Vincent Chouraki, MD, PhD, former research fellow from BUSM and now assistant professor in epidemiology at Lille University School of Medicine in France.
###
Funding for this study was provided by the National Heart, Lung, and Blood Institute's Framingham Heart Study (contracts no. N01-HC-25195 and HHSN268201500001I) and grants from the National Institute of Neurological Disorders and Stroke (NS17950 ), the National Institute on Aging (AG008122, AG016495, AG049505 , AG049607 and AG033193) and the National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK-HL081572).

Thursday, June 15, 2017

Alzheimer's communication

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University of York

Which words are easier and harder for people with dementia? When finding the right word or comprehending a complex phrase becomes difficult, helpful research gives clarity on which word types work best. 



Scientists say they have a better understanding of why people with Alzheimer's struggle to recognize and understand words - and their research has the potential to be developed into a test which could help clinicians make an early diagnosis.

Word Complaints

In the early stages, the two most common complaints from people with Alzheimer's disease are difficulty remembering events and understanding and producing words.

Academics from the Universities of York and Oviedo, Spain, wanted to look at whether a patient's ability to recognize words is impaired in the early stages of the disease, and if it is, what properties of words make them easier or harder for a patient to recognize.

The research, which was done in northern Spain with colleagues at the Hospital Cabueñes in Gijón, was published in theJournal of Neuropsychology.

Word Diagnosis

A test of word recognition based on the findings could contribute to diagnosis, Professor Andrew Ellis, from the Department of Psychology at York, said.

He added: "The biggest potential impact is in diagnosis. It might be a useful addition to the armory of clinicians trying to do diagnosis.

"Alzheimer's disease isn't easy to diagnose in the early stages. There are other forms of dementia that are relatively common and it can be hard to distinguish between them in the early stages. A word recognition test based on these findings could contribute to diagnosis, but more work would need to be done."

Real Words versus Invented Words

As part of the study, participants were shown real words on a computer screen mixed with invented words. On each trial of the experiment, there was one real word on the screen and three non-words. The participant's task was simply to point to the real word on the screen.

Researchers chose the task primarily because it assesses whether words look familiar or not and does not require the patients to explain the meanings of words, something they struggle to do.

They conducted the study in Spanish but an example in English would be to point to the word EAGLE when it appears on the screen with SLINT, OMPUL and CROOM. The researchers chose words which they expected healthy older people to be able to recognize.

Forty people with mild or moderate Alzheimer's disease aged 66 to 91 years took part in the study, and 25 healthy controls matched to the patients on age, gender and years of education. The healthy controls picked out the real words with little difficulty, from which the scientists infer that the patients would also have known these words before the onset of their dementia.

In contrast, the patients with Alzheimer's disease missed about one in five of the real words. When the researchers looked at which properties of the words made them easier or harder for patients to recognise, they found that:
  1. COMMON WORDS: Patients recognised common words better than less common words
  2. ABSTRACT WORDS: Patients understood words with concrete meanings better than words with abstract meanings
  3. CHILDHOOD WORDS: Patients grasped words learned early in life better than words learned in later childhood or adulthood.
  4. LONG WORDS: The length of the words did not affect performance.

Ability to Use Words

Professor Ellis added: "A lot of work has been done with Alzheimer patients using the task of naming pictures of objects.

"In this study we wanted to look instead at whether their ability to recognise words is impaired in the early stages of the disease. If word recognition is impaired, we wanted to know what properties of words make them easier or harder for Alzheimer patients to recognise.

"We speculate that the damage responsible for the problems in word recognition and production that we and other researchers have identified, stem particularly from loss of cells in an area at the front of the left temporal lobe that is crucially involved in processing the meanings of concepts and words.

"The study is fundamental rather than applied research. Its purpose is to teach us more about how Alzheimer's disease affects the ability to use words, but it also has the potential to inform the clinical assessment of dementia."

Tuesday, June 13, 2017

Oral Health for Older Adults

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Administration for Community Living

A new dental resource provides low-cost programs for American seniors. Also check out the website's free “how to” guide for communities. 



The U.S. Department of Health and Human Services (HHS), Administration for Community Living (ACL), and Office on Women’s Health (OWH) have launched their first website focused on helping communities to promote the oral health of older adults. 

Users will be able to find nearly 200 community-based oral health programs through the site’s searchable database, as well as an Oral Health Guide designed to help local organizations start or enhance their own programs. 

The need for maintaining good oral health and getting regular check-ups is widely recognized, but there are often large gaps in availability and accessibility of services for older adults, particularly for older women given their longevity and economic resources. Through this new resource, ACL and OWH aim to help close those gaps and assist communities, governments, and other organizations in improving access to high quality oral health care for older adults. 

The searchable database can help communities identify an ideal program for replication or enhancement based on diverse search criteria. A community considering the start of its own mobile dental unit, for example, could search for existing programs that fit this criterion and learn more about this type of program. 

The accompanying Oral Health Guide can further assist communities in launching or enhancing their own program. Key tips, case studies, external resources, and other sources of support are included in the Oral Health Guide. For communities that already have an oral health program in place for older adults, the Oral Health Guide can assist with expansion or enhancement. 

Both the database and Oral Health Guide are now available at https://oralhealth.acl.gov


Thursday, June 8, 2017

"Memory Lane TV" Soothes Anxiety & Agitation in Dementia

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SOURCE:
  • WCSH6

Calm comes in handy during dementia's anxiety-ridden times. See how Memory Lane TV alleviates sundowning, smooths transitioning between activities, and soothes the changes that bring on agitation. 

see video on the right



At "The Cedars", in the morning, before lunch and late in the afternoon, Alzheimer’s patients are shown a series of carefully crafted mini-movies. Their creator is celebrated documentary film maker Alban Maino.

Maino combines beautiful, cinematographic images with music of the era, then uses familiar, aromatic fragrances through a device similar to a “Scentsy.” The result is a three-pronged sensory experience that Alban claims brings recognition and a sense of calm to Alzheimer’s patients, who often combat agitation and confusion throughout their day. 

In one video, a clip from the movie “Singing in the Rain” plays, along with its signature theme song, while the scent of popcorn permeates the room. Alban Maino has designed each clip with expert precision. "We are using all sorts of video, soundscape, music, archival footage, and even senses, such as the olfactory stimulation. We're able to awaken people from the sense of smell." 

In another video, one that runs during the morning sessions, Maino uses sunrises, light orchestral music and the aroma of baking bread. Nick Viti says it works particularly well and is evocative with his patients. “It’s a sort of natural cue of morning time because that’s been a part of many people’s morning routines for decades, before they came to us here at The Cedars.” 

The key to the videos, Maino says, is beautiful shots that are held for much longer than traditional television. He describes these moments as dream scenes. “And a dream scene to me is a 3- to 5-minute scene that takes you and transports you through guided imagery and sort of passive meditation." 

That calm comes in handy during the more anxiety-ridden times at The Cedars, during transitions from one activity to another and particularly for patients suffering from Sundowner's Syndrome, or late-day confusion. 

Maino points out one patient, a woman who has to wear headphones with music to stay calm. Through the use of customized music and through specific films at the end of the day, those panic attacks can be managed well which, in the end, improves her quality of life. 

The program follows the natural progression of each day — three, 24-minute long videos mirror the circadian rhythm. “In the morning, we're going to use sunrises and sounds of birds and in the evening it will be sunsets over the beautiful ocean in Maine." 

And while I visited, one group was watching a Cedars' favorite right before lunch: scenes from the vibrant and familiar Fryeburg Fair. The scenery is designed to remind them or take them away and helps to keep them alert so they will eat their important, nutrition rich lunch. And the combination of beautiful fall colors, familiar farm animals and an upbeat parade has them all looking at the screen and one or two tapping their toes. 

I ask one patient how the video, music and aromas make her feel. She turns to me and says, a smile across her face, “wonderful." 

So the big question: does it work? Some of the feedback so far is that, yes, caretakers are noticing after using the Memory-Lane.TV system for a couple of weeks, Alzheimer’s patients sleep better. And the added positive feedback is they are less agitated and easier to take care of. 

Full article at: WCSH6 - Alzheimer's: Breaking through to memory





Monday, June 5, 2017

Can vitamin E help those with Alzheimer's and related dementias

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Vitamin E may slow down Alzheimer's and ease caregiving, according to a JAMA report. See how vitamin E improved daily activities in dementia, including shopping, preparing meals, planning and traveling. 




Difficulty with activities of daily living often affect Alzheimer's patients. Disruption to daily routine is one of the hardest burdens for caregivers. New research suggests that Vitamin E may slow functional decline in patients with mild-to-moderate Alzheimer's disease. This includes problems with daily activities such as:

  • Shopping
  • Preparing meals
  • Planning
  • Traveling
It appears to also decrease caregiver burden. There was no added benefit for memory and cognitive testing with the vitamin.

Vitamin E may slow down Alzheimer's and ease caregiving, according to a JAMA report. See how vitamin E improved daily activities in dementia, including shopping, preparing meals, planning and traveling. 



he research was performed by the faculty of Icahn School of Medicine at Mount Sinai working with Veterans Administration Medical Centers. The study is published online in the Journal of the American Medical Association.

The researchers investigated vitamin E as α-Tocopherol, an important fat-soluble antioxidant. Mary Sano, PhD, was the trial co-investigator, and professor in the department of psychiatry, Icahn School of Medicine at Mount Sinai, and director of research at the James J. Peters Veteran's Administration Medical Center, Bronx, New York. She said,

"Since the cholinesterase inhibitors [Aricept/donepezil, galantamine, rivastigmine], we have had very little to offer patients with mild-to-moderate dementia."

"This trial showed that vitamin E delays progression of functional decline by 19% per year, which translates into 6.2 months benefit over placebo."
The finding is valuable because vitamin E is easy to purchase at local drugstores and it is also inexpensive. The clinical trial investigators believe it can be recommended as a treatment strategy, based on the double-blind randomized controlled trial.

The Veteran's Administration Cooperative Randomized Trial of Vitamin E and memantine in Alzheimer's Disease (TEAM-AD examined the effects of vitamin E 2,000 IU/d, 20 mg/d of memantine, the combination, or placebo on Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS-ADL) Inventory Score. Cognitive, neuropsychiatric, functional, and caregiver measures were secondary outcomes. A group of 613 patients with mild to moderate Alzheimer's disease were in the study, which was launched in August 2007 and finished in September 2012 at 14 Veterans Affairs Medical Centers. 

Dr. Sano previously led a study on Vitamin E in patients with moderately severe Alzheimer's disease. She found that the vitamin slowed disease progression in this group of patients as well.
.

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