Exercise for People with Dementia Improves Balance and Reduces Dependence

(Umeå University, Sweden) Regular exercise improves balance for people with dementia and can reduce dependence on assistance. This according to new research on healthcare for people suffering from dementia conducted at Umeå University, which has now been published in the Journal of the American Geriatrics Society.

In a unique study on people with dementia living in residential care facilities, researchers from Umeå University have found that regular functional exercise, similar to everyday activities and performed at high intensity, can improve balance and reduce dependence on assistance in activities of daily living, such as for instance mobility or toilet visits. Training sessions lasting 45 minutes, two to three times per week, can lead to an improved quality of life for individuals suffering from dementia – a progressive illness leading to gradual reduction in cognitive and physical function.

In 2012, the number of individuals with dementia in Sweden stretched to 150,000 according to the National Board of Health and Welfare (Socialstyrelsen). This is a number expected to reach at least 250,000 in 2050 at the speed of population ageing. Having an increased proportion of individuals with dementia in society increases the demand and costs for healthcare. At present, the cost of dementia in Sweden reaches around SEK 60 billion per annum, according to the National Board of Health and Welfare.

“Regular exercise has a positive effect on people with dementia and therefore, be included in the care in residential care facilities. Studies such as the present one are rare, but provide important knowledge to further build upon in order to develop care of people with dementia as a cost-effective means of meeting future challenges, and help individuals to maintain independence longer,”

says Annika Toots, PhD student at the Department of Community Medicine and Rehabilitation at Umeå University, and first author of the article.

The study, described in the article Effects of a high-intensity functional exercise program on dependence in activities of daily living and balance in older adults with dementia, is a part of the greater Umeå Dementia and Exercise Study (UMDE, performed involving people with dementia in residential care facilities.

As a next step, research groups at the Unit of Physiotherapy and Geriatric medicine will analyse which effect exercise has on for instance ability to walk and cognitive ability in the target group, as well as how participants and physiotherapists experienced the exercise programme.

The published study involved 186 people with dementia in 16 different residential care facilities in the Umeå area. All participants were 65 years of age or above and in need of personal care. The participants were randomly allocated into two groups, where one group undertook a high-intensive, functional exercise programme led by physiotherapists.

The programme included various functional exercises that aimed to improve leg strength, balance and walking, which are part of everyday activities. The workout covered 45 minutes, two to three times per week for a duration of four months.

Instead of training, the sedentary control group took part in stimulating activities of group conversations, singing and reading aloud sessions. The purpose of this was to control the positive effects that stimulation through togetherness and attention have. All participants were tested before, as well as four and seven months after the completion of the programme.

Due to the progressive course of dementia, a deterioration was noted in all participants’ abilities to independently manage everyday activities. The deterioration occurred at a slower pace in the exercise group and they showed an improved balance.

The effects of the exercise varied depending on the type of dementia, where the group with vascular dementia experienced better effects of exercising than participants with Alzheimer’s disease. To better plan and carry out exercise for people with dementia, it can, therefore, be of importance to identify the type of dementia.



Journal Reference:

Annika Toots, Håkan Littbrand, Nina Lindelöf, Robert Wiklund, Henrik Holmberg, Peter Nordström, Lillemor Lundin-Olsson, Yngve Gustafson, Erik Rosendahl. Effects of a High-Intensity Functional Exercise Program on Dependence in Activities of Daily Living and Balance in Older Adults with Dementia. Journal of the American Geriatrics Society, 2016; 64 (1): 55 DOI: 10.1111/jgs.13880


Estrogen Supplements May Protect Against Dementia

(Norwegian University of Science and Technology) Women who take estrogen supplements from before or at the start of menopause and continue with them for a few years have better preserved brain structure, which may reduce the risk of dementia.

Globally, one new person is affected by dementia every four seconds. In 2010, 36 million people were estimated to have dementia.

Now, findings in a doctoral thesis from the Norwegian University of Science and Technology (NTNU) show that estrogen supplements can reduce the risk of dementia in women.

“estrogen supplements can have a positive effect against dementia if women start early enough with treatment,” says Carl Pintzka, a medical doctor and PhD candidate at NTNU.

The finding has been just published in the journal Neurobiology of Aging.

A sample of 80 women who had used estrogen supplements through menopause was compared with 80 women who had never used estrogen supplements. All had participated in the Nord-Trøndelag Health Study (HUNT), a general population-based study in mid-Norway.

The brain shrinks with less estrogen

Following menopause, womens’ estrogen levels drop significantly compared to levels before menopause.

MRIs of the brains of the women in the study showed that those who had taken estrogen supplements throughout menopause had a larger hippocampus. The hippocampus is one of the most important structures for memory and sense of place, and is one of the structures that is affected early in the progression of Alzheimer’s disease.

“We also examined the shape of the hippocampus and found that areas where hormone therapy had the greatest effect are the same areas that are affected by Alzheimer’s disease in its early stages,” says Pintzka.

Other studies have shown that women who start estrogen supplements several years after menopause do not benefit from the same positive effect on the hippocampus.

Must start estrogen from the late 40s

Pintzka’s findings show that boosting estrogen levels increases the volume of the hippocampus. As of yet there are no drugs that stop or prevent the course of Alzheimer’s disease, and the focus has shifted towards strategies to prevent or delay the onset of dementia.

Successful strategies are thought to be those that increase brain volume, and that in particular preserve the hippocampus. The risk of dementia may therefore be reduced for women taking estrogen supplements around the time of menopause, according to Asta Håberg, a Professor of Neuroscience at NTNU and Pintzka’s supervisor.

Until 2002, many women in Norway and internationally took estrogen supplements during and after menopause. The reasons for boosting estrogen levels are to reduce hot flashes and osteoporosis and to prevent cardiovascular disease. Then the number of women taking supplements fell dramatically.

The studies that scared women

Pintzka points to two specific studies as the reason for the steep decline in the use of estrogen supplements. In the summer of 2002, a large study of menopausal women conducted by the “Womens Health Initiative” was published.

This study landed like a bombshell in professional circles and the media. The conclusion was that the disadvantages of long-term treatment with estrogen far outweighed the benefits.

The study included 16,000 women and showed that the combination of estrogen and progestin increased the risk of both heart disease and breast cancer. Furthermore, the study showed that those who took estrogen supplements had poorer memory and greater risk for dementia than the control group.

Soon after, The Journal of the American Medical Association published another study, which had followed 44,000 women for 20 years. This study showed that estrogen therapy increased the risk of ovarian cancer if treatment persisted for over 10 years.

Some risks increase, others drop

“It’s true that the risk of some cancers increases with estrogen supplements, but we also know, for example, that the risk of hip fractures and colorectal cancer drops with their use,” says Pintzka.

According to Håberg, it’s a big question whether the findings of the American studies can be transferred to Norwegian women, because women [in the American studies] started using estrogen at a later age. “estrogen supplements used in the United States are also different from the ones used in Europe,” she says.

More recent studies suggest that boosting estrogen levels has protective effects on the brain if started around menopause, but that the same treatment could be harmful for women if they start supplements later than a few years after menopause.

“The women who participated in the Women’s Health Initiative study started with estrogen supplementation 15-30 years after menopause. This was probably too late to expect a positive effect,” Pintzka says.

More and more people will be affected by dementia

According to Norway’s 2014 Public Health Report, Norway has approximately 70,000 people with dementia, and that number is anticipated to increase greatly in the coming years due to a growing population and higher average age.

Norway is not alone in facing this development, which is associated with the increasing average age of the population.

The World Health Organization has identified the fight against neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases, as some of the biggest health challenges society faces in the coming years.

Women should start early with estrogen if they decide to use it

Håberg believes that positive effects on the brain from using estrogen supplements are highly probable, but whether supplements eventually protect against dementia remains unclear.

“Women who want to take estrogen supplements should start early to benefit from the positive effect on the brain,” says Håberg.

Pintzka points out that none of the participants in his doctoral thesis had dementia at the start of the study, nor have any developed the disease since the MRIs were taken. He adds that neither he nor his supervisor know how many participants may develop dementia as they continue to age. An NTNU research group plans to follow up on this question in the next HUNT study.

Pintzka is now employed by St. Olav’s University Hospital in Trondheim as a researcher for the National Competence Service for Functional MRI.



Story Source:

The above post is reprinted from materials provided by The Norwegian University of Science and Technology (NTNU). Note: Materials may be edited for content and length.

The Norwegian University of Science and Technology (NTNU). (2016, January 22). Estrogen supplements may protect against dementia.ScienceDaily. Retrieved January 25, 2016 from www.sciencedaily.com/releases/2016/01/160122083802.htm


Chronic Stress and Anxiety Can Damage the Brain, Increase the Risk of Major Psychiatric Disorders

(Baycrest.org) A scientific review paper warns that people need to find ways to reduce chronic stress and anxiety in their lives or they may be at increased risk for developing depression and even dementia.

Led by the Rotman Research Institute at Baycrest Health Sciences, the review examined brain areas impacted by chronic anxiety, fear and stress in animal and human studies that are already published. The authors concluded that there is “extensive overlap” of the brain’s neurocircuitry in all three conditions, which may explain the link between chronic stress and the development of neuropsychiatric disorders, including depression and Alzheimer’s disease.

The paper is posted online this month in the journal Current Opinion in Psychiatry.

Experiencing anxiety, fear and stress is considered a normal part of life when it is occasional and temporary, such as feeling anxious and stressed before an exam or a job interview. However, when those acute emotional reactions become more frequent or chronic, they can significantly interfere with daily living activities such as work, school and relationships.

Chronic stress is a pathological state that is caused by prolonged activation of the normal acute physiological stress response, which can wreak havoc on immune, metabolic and cardiovascular systems, and lead to atrophy of the brain’s hippocampus (crucial for long-term memory and spatial navigation).

“Pathological anxiety and chronic stress are associated with structural degeneration and impaired functioning of the hippocampus and the prefrontal cortex (PFC), which may account for the increased risk of developing neuropsychiatric disorders, including depression and dementia,”

said Dr. Linda Mah, clinician scientist with Baycrest’s Rotman Research Institute and lead author of the review.

The review paper examined recent evidence from studies of stress and fear conditioning in animal models, and neuroimaging studies of stress and anxiety in healthy individuals and in clinical populations.

Dr. Mah and colleagues looked specifically at key structures in the neurocircuitry of fear and anxiety (amygdala, medial prefrontal cortex, hippocampus) which are impacted during exposure to chronic stress. The researchers noted similar patterns of abnormal brain activity with fear/anxiety and chronic stress – specifically an overactive amygdala (associated with emotional responses) and an under-active PFC (thinking areas of the brain that help regulate emotional responses through cognitive appraisal). This see-saw relationship was first identified in a landmark study by world-renowned neurologist and depression researcher Dr. Helen Mayberg over a decade ago.

Dr. Mah, an assistant professor of Psychiatry in the Department of Geriatric Psychiatry at the University of Toronto, concluded her review on a hopeful note by suggesting that stress-induced damage to the hippocampus and PFC is “not completely irreversible.” Anti-depressant treatment and physical activity have both been found to increase hippocampal neurogenesis, she said.

“Looking to the future, we need to do more work to determine whether interventions, such as exercise, mindfulness training and cognitive behavioural therapy, can not only reduce stress but decrease the risk of developing neuropsychiatric disorders,” said Dr. Mah

The scientific review paper follows on the heels of a major study Dr. Mah published in the American Journal of Geriatric Psychiatry (first posted online in October 2014), which found some of the strongest evidence yet that anxiety may accelerate conversion to Alzheimer’s disease in people diagnosed with mild cognitive impairment.

Dr. Alexandra Fiocco, a psychologist with the Institute for Stress and Wellbeing Research, Ryerson University, contributed to the review paper in Current Opinion in Psychiatry. The work was supported in part by the Ministry of Health and Long-Term Care AFP Innovation Fund.



Journal Reference:

Linda Mah, Claudia Szabuniewicz, Alexandra J. Fiocco. Can anxiety damage the brain? Current Opinion in Psychiatry, 2016; 29 (1): 56 DOI: 10.1097/YCO.0000000000000223


Living with Aging: Alzheimer’s, the Disease of Our Time

(Journal of Alzheimer’s Disease) When George Perry began studying Alzheimer’s disease less than 30 years ago, few scientists knew of the condition, let alone the public, which now cannot have a day pass without new revelations in the press.

Dr. Perry is a neuroscientist and Dean of the College of Sciences and Professor of Biology at the University of Texas at San Antonio. Perry is recognized in the field of Alzheimer’s disease research particularly for his work on oxidative stress.

Here is his TEDxAlamo talk from YouTube. It is worth a look.




Journal of Alzheimer’s Disease is published by IOS Press

Copyright © 2016



Alzheimer’s Diagnosis Complicated by History of Reading Problems

(Journal of Alzheimer’s Disease) Correctly diagnosing Alzheimer’s disease remains a challenge for medical professionals. Now, a new study published in the current issue of the Journal of Alzheimer’s Disease reveals a new clue to possible misdiagnosis.

The study found that older adults with a history of reading problems perform similarly on some neuropsychological tests to those who show signs of mild cognitive impairment (MCI) associated with early Alzheimer’s disease.

The finding, based on the results of a Stony Brook University-led research team in collaboration with Boston University School of Medicine, emphasizes the need for professionals to take into account developmental history and have a broad understanding of neuropsychological testing when interpreting the meaning of low memory test scores.

MCI is a term used to identify individuals with memory complaints and poor neuropsychological test performance but who otherwise functional normally. Having MCI has been identified as a risk factor for subsequent diagnosis of Alzheimer’s disease.

In the paper, titled “Lifelong Reading Disorder and Mild Cognitive Impairment: Implications for Diagnosis,” lead author Brian K. Lebowitz, PhD, Clinical Assistant Professor of Neurology at Stony Brook Medicine, and Research Associate in the Department of Psychiatry at Harvard Medical School, and colleagues assessed the relationship between MCI classification and suspected reading disorder in 1,804 community living adults followed by the Framingham Heart Study from 1999 to 2005. On average, participants were 62 years of age. Individuals with previous dementia, stroke and other neurological disorders were excluded from the study.

“We found a strong relationship between poor reading ability and low memory test scores,” said Dr. Lebowitz.

One key example from the findings is that individuals with evidence of lifelong reading difficulty were two to three-and-one-half times more likely than their peers to score at a level suggestive of possible memory decline on two tests commonly used to evaluate memory complaints in older adults.

The study assessed memory recall, reading, visual processing, and executive functioning using tests frequently employed in the assessment of cognitive complaints in older adults. Specific areas of memory analyzed included recall of previously presented short stories and word pairs, and the ability to draw from memory previously presented visual figures.

Dr. Lebowitz said that because memory complaints are extremely common in older adults, a lot of weight is placed on memory test scores when assessing the clinical significance of a patient’s memory concerns. However, memory tests are often given alone, without a comprehensive battery of neuropsychological tests that includes reading ability, and without a clear understanding of a patient’s lifelong pattern of cognitive strengths and weaknesses.

“Identifying the clinical significance of our finding is our next challenge,” Dr. Lebowitz said.

“It could mean that a reading or learning disorder history may increase the misdiagnosis of neurodegenerative disease, including Alzheimer’s disease. Alternatively, a reading disorder may represent a risk factor for the development of Alzheimer’s disease in later life.”

Dr. Lebowitz and colleagues emphasize that the findings highlight the need for individuals evaluating older adults for memory complaints to take a careful history and to consider alternative reasons why memory test scores may be low for a given individual.

The research was supported by grants from the National Heart, Lung and Blood Institute, the National Institute of Neurological Disorders and Stroke, and the National Institute on Aging.



Journal of Alzheimer’s Disease is published by IOS Press

Copyright © 2016


Dementia: New Insights into Causes of Loss of Orientation

(University of Exeter Medical School) New research has revealed how disease-associated changes in two interlinked networks within the brain may play a key role in the development of the symptoms of dementia.

The University of Exeter Medical School led two studies, each of which moves us a step closer to understanding the onset of dementia, and potentially to paving the way for future therapies. Both studies, part-funded by Alzheimer’s Research UK, are published in the Journal of Neuroscience and involved collaboration with the University of Bristol.

Both studies shed light on how two parts of the brain’s ‘GPS’ navigation system malfunctions in dementia, and point to likely underpinning causes for loss of orientation that is commonly experienced by people living with the condition.

In the first study, the team studied a part of the brain called the entorhinal cortex. Located near the base of the brain, this region is associated with functions including memory formation and navigation, and contains so-called “grid cells”. These nerve cells fire electrical discharges in a grid-like pattern, much like the grid on an Ordnance Survey map.

Paralleling the different scales employed by different maps, the grid firing patterns in the entorhinal cortex also have different scales, with cells at the top of the cortex having a more tightly packed grid pattern than those at the bottom. Scientists believe that this top-to-bottom gradient of different grid scales contributes pivotally to our sense of spatial location.

The team compared the activity in the entorhinal cortex of healthy mice and mice with dementia. They found that top-to-bottom gradients in electrical activity in the entorhinal cortex are not present in mice with dementia. Their findings suggest that the fine navigational detail, such as you would find on a large-scale map, is not correctly represented in patients with dementia.

Dr Jon Brown at the University of Exeter Medical School led the studies, as part of his Alzheimer’s Research UK Senior Fellowship. He said:

“This is an exciting discovery because it is the first time grid cell activity has been linked to the onset of disease. We now need further research to better establish how these findings translate to dementia in humans.”

In the second study, researchers examined “place cells” located in the hippocampus, a brain structure known to be critical in processing learning and memory, both affected by dementia. Place cells help us to identify where we are within a certain space.

The team found that the hippocampus of mice with dementia was associated with specific disturbances in synaptic, cellular, and network-level function, meaning that spatial information was wrongly encoded and spatial memory was impaired.

Dr Brown said:

“Dementia is one of the greatest health challenges of our time, and we still have so much to learn about its causes, as well as about how our brains work. This research makes progress in both areas, and is another small step along the road to earlier diagnoses and finding new treatments and therapies.”

Professor Andrew Randall, who co-supervised much of the work, said:

“This has been a fascinating experimental journey for our research teams, and much of the pivotal work was carried out by talented PhD students. We look forward to producing much more work of this nature as members of Exeter’s growing dementia research community.”

Dr Laura Phipps from Alzheimer’s Research UK, said:

“There are 850,000 people in the UK with dementia and a tenth of those are living in the South West. It is vital that researchers explore the complexities of the brain, to understand more about the causes of the condition and how we can tackle it. Dementia is not just a synonym for forgetfulness – these findings in mice highlight the impact that diseases like Alzheimer’s can have on spatial orientation. It will now be important to build on this research, to understand whether this chain of events can be targeted in the hunt for new treatments.”

The University of Exeter forms part of the Alzheimer’s Research UK South West Research Network – a community of dementia researchers in Exeter and Plymouth, working collaboratively to accelerate progress in dementia research.



Copyright University of Exeter


Anavex Announces Positive Dose-Response Data for ANAVEX 2-73 in Alzheimer’s Patients

(Anavex) Anavex Life Sciences Corp., a clinical-stage biopharmaceutical company developing differentiated therapeutics for the treatment of neurodegenerative diseases including Alzheimer’s disease, other central nervous system (CNS) diseases, pain and various types of cancer, today reported a positive dose-response relationship has been observed in a pre-planned interim analysis of data from the ongoing Phase 2a trial of ANAVEX 2-73 for treatment of mild to moderate Alzheimer’s disease.

The change in Mini Mental State Examination score (MMSE-△) (MMSE difference recorded for every single study subject at the beginning and the end of the five week period) from baseline to 5 weeks as a function of ANAVEX 2-73 dose was examined using linear regression analysis.

Among 32 patients treated with doses of ANAVEX 2-73 ranging from 3mg to 50mg/day, the MMSE-△ data showed a positive slope with confidence intervals not including the zero-value, consistent with a dose dependent improvement in MMSE scores over 5 weeks. The effect was unidirectional and also positive on another pharmacodynamic readout, the ERP-△ P300 amplitude.

The dose-response results were robust to statistical resampling (bootstrap analysis x 10,000 resamples). Analysis of variance and post hoc tests as well as Bayesian hierarchal analysis further confirmed that the higher doses achieved a statistical significant improvement in the MMSE-△ score over 5 weeks compared to the lower doses.

Based on these findings, it was estimated that an oral dose of 30 mg ANAVEX 2-73 had approximately 80% probability of achieving a +2 points or higher improvement in MMSE score over 5 weeks of treatment. Doses in this range have thus far been well tolerated by the study’s subjects, with no adverse events reported above grade one.

“While we remain cautious about interpreting the results of an interim analysis, evidence of ANAVEX 2-73’s positive dose response at 5 weeks on the MMSE is a welcome signal”, said Dr. Norman Relkin, MD, PhD, an Alzheimer clinical trialist and an advisor to Anavex.

“Evidence of a dose-response relationship is one of the factors taken into account by regulatory agencies when ultimately considering medications for approval.”

Christopher U. Missling, PhD, President and Chief Executive Officer of Anavex stated, “Our team is encouraged by these findings and we look forward to advancing ANAVEX 2-73 into a larger Phase 2/3 study for Alzheimer’s as well as initiating a double-blinded, randomized, placebo-controlled Phase 2 trial for ANAVEX 2-73 in an additional indication associated with cognitive impairment.”

Detailed information on the results will be provided in an upcoming scientific meeting.

About the ANAVEX 2-73 Phase 2a Study

The multicenter Phase 2a clinical trial of ANAVEX 2-73 consists of two parts and a total of 32 mild-to-moderate Alzheimer’s patients. PART A is a simple randomized, open-label, two-period, cross-over between oral (30mg/50mg) and IV (3mg/5mg) administration, adaptive trial lasting up to 5 weeks for each patient. PART B is an open-label extension for an additional 52 weeks. Initially planned for 26 weeks, PART B was extended to 52 weeks as a result of requests from patients and caregivers.

The primary endpoint of the Phase 2a trial is evaluation of safety and tolerability of ANAVEX 2-73, which had shown potential in preclinical studies to prevent, halt and/or reverse the course of the disease. Secondary endpoints were dose response, bioavailability, and exploratory cognitive effects using electroencephalographic (EEG) activity and event-related potentials (ERP), Cogstate battery, Mini Mental State Examination (MMSE), and evaluation of Alzheimer’s Disease Co-operative Study – Activities of Daily Living Inventory (ADSC-ADL) as well as the exploration of ANAVEX 2-73 as a potential add-on therapy to donepezil, the current standard of care.

Additional information regarding the ongoing Phase 2a clinical trial is available from the U.S. National Institutes of Health (NIH) clinical trials database at www.clinicaltrials.gov.



© 2007-2016 Anavex Life Sciences Corp. – All Rights Reserved.


Cancer Drug Improves Memory in Mouse Models of Alzheimer’s Disease

(MedicalNewsToday) An immune system-activating cancer medication improves cognitive performance and memory and reduces pathology in mouse models of Alzheimer’s disease, reports a new paper published online in Nature Medicine. The study identifies immune-checkpoint blockade as a potential therapeutic approach for Alzheimer’s disease and, possibly, for other neurodegenerative diseases.

Immune checkpoints are pathways in immune cells that can either activate or suppress immune responses. Programmed death-1 (PD-1) blockers are a class of cancer medications, recently approved by the US Food and Drug Administration, that block the PD-1 immune-checkpoint pathway. This activates immune cells and enables them to attack cancer cells.

In the study, Michal Schwartz and colleagues treated small groups of transgenic mice that develop hallmarks of Alzheimer’s disease, including the deposition of toxic amyloid-beta (Aβ) plaques in the brain and progressive memory impairment.

They find that mice treated twice with PD-1 blockers over three days show improved memory performance, reduced brain pathology and reduced inflammation one month after treatment, compared to transgenic mice that received either placebo or no treatment. They observed an even more pronounced improvement in learning, memory and pathology in mice that received two treatment sessions over two consecutive months.

The authors suggest that PD-1 blockade promotes the recruitment of protective immune cells into the brain, which may subsequently promote clearance of toxic Aβ plaques.


Journals, N. (2016, January 18). “Cancer drug improves memory in mouse models of Alzheimer’s disease.” Medical News Today. Retrieved from

Nature Medicine  doi:10.1038/nm.4022. PD-1 immune checkpoint blockade reduces pathology and improves memory in mouse models of Alzheimer’s disease. Kuti Baruch, Aleksandra Deczkowska, Neta Rosenzweig, Afroditi Tsitsou-Kampeli, Alaa Mohammad Sharif, Orit Matcovitch-Natan, Alexander Kertser, Eyal David, Ido Amit & Michal Schwartz.

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