Changes in Humour May Be an Early Sign of Dementia

(Journal of Alzheimer’s Disease) Researchers at University College London (UCL) have revealed that a change in sense of humour could be an early sign of dementia. The findings could help improve dementia diagnosis, by highlighting changes not commonly thought to be linked to the condition. The study was funded by Alzheimer’s Research UK, the Wellcome Trust, Medical Research Council (MRC) and NIHR Queen Square Dementia Biomedical Research Unit. The research was published in the Journal of Alzheimer’s Disease on 10 November 2015.

The research team was particularly interested in how sense of humour can change in frontotemporal dementia (FTD) and Alzheimer’s disease. While Alzheimer’s disease is the leading cause of dementia, frontotemporal dementia is the most common cause of dementia in the under-55s. Unlike in Alzheimer’s, memory difficulties are not an early indicator of FTD. Rather, people tend to experience behaviour and personality changes before they develop problems with memory. The research team wanted to explore these behavioural symptoms, to reveal early clues of underlying brain changes and aid diagnosis.

Because sense of humour is such an important part of our personalities and our dealings with other people, the research team focused on shifting preferences in comedy genre in people with dementia. Using a series of questionnaires, they asked friends or relatives of 48 people with different forms of FTD and Alzheimer’s to rate their loved one’s liking for different kinds of comedy. This included slapstick comedy such as Mr Bean, satirical comedy such as Yes, Minister or absurdist comedy such as Monty Python.

The researchers also asked those completing the questionnaire to say whether they had noticed instances of inappropriate humour. As well as collecting data about current humour preferences, the team asked the friends and relatives to reflect on the past 15 years – well before any of the study volunteers received a diagnosis – to identify any shifts in preference.

The team found that people with behavioural variant FTD – a particular form of FTD associated with behavioural changes – had an altered sense of humour compared to those with Alzheimer’s disease and healthy individuals. This included laughing at events others would not find funny such as a badly parked car or barking dog. The questionnaires and anecdotes revealed that people with bvFTD frequently laughed inappropriately at tragic events on the news or in their personal life. This did not happen in people with Alzheimer’s.

The researchers found that people with both bvFTD and Alzheimer’s tended to prefer slapstick humour to satirical and absurdist humour when compared with healthy people of a similar age. In fact, friends and relatives reported seeing these changes an average at least nine years before the start of more typical dementia symptoms. This highlights that changes in humour are not only an early feature of FTD, but may also occur in Alzheimer’s.

Dr Camilla Clark who led the research at the Dementia Research Centre, UCL, said:

“As sense of humour defines us and is used to build relationships with those around us, changes in what we find funny has impacts far beyond picking a new favourite TV show. We’ve highlighted the need to shift the emphasis from dementia being solely about memory loss.

These findings have implications for diagnosis – personality and behaviour changes should be prompts for further investigation, and clinicians themselves need to be more aware of these symptoms as a potential early sign of dementia. As well as providing clues to underlying brain changes, subtle differences in what we find funny could help differentiate between the different diseases that cause dementia.

Humour could be a particularly sensitive way of detecting dementia because it puts demands on so many different aspects of brain function, such as puzzle solving, emotion and social awareness.”

Dr Simon Ridley, Director of Research at Alzheimer’s Research UK, said:

“While memory loss is often the first thing that springs to mind when we hear the word dementia, this study highlights the importance of looking at the myriad different symptoms that impact on daily life and relationships. A deeper understanding of the full range of dementia symptoms will increase our ability to make a timely and accurate diagnosis.

We need to see larger studies, following people for extended periods of time, to understand how and when changes in humour could act as a red flag for underlying brain changes. Dementia diagnosis poses multiple challenges, but through research we will be able to improve diagnosis and ultimately find treatments that tackle the specific causes of the condition. Anyone who is concerned about changes in their behaviour should speak to their GP.”

Lee Pearse, from Sheffield, a Champion of Alzheimer’s Research UK, lost his much loved mum Valerie to frontotemporal dementia in March, she was just 67. He said:

“We first noticed changes in Mum’s behaviour when she was 55 but it took four years before she received the correct diagnosis of frontotemporal dementia. S

he’d always been very loving and family focused but became increasingly uninvolved and emotionless. As she had a history of depression, we put it down to that and her doctor agreed.

“Mum’s behaviour became more and more erratic and we began to question the diagnosis. She’d forget family birthdays, laugh if someone had an accident or heard someone was unwell and was even sacked from her job – all completely out of character.

I still feel distraught about what happened to Mum but proud to be supporting Alzheimer’s Research UK in its efforts to fund research to improve diagnosis and find the dementia treatments so urgently needed.”

Dr Rob Buckle, Director of Science Programmes at the MRC, said:

“As we come to understand more about the symptoms of dementia we realise that the complex condition is about much more than memory loss. Such insights will allow us to build up a full picture of the changes that people experience in the early stages of dementia and as the condition progresses, guiding both improved and earlier diagnosis and the delivery of care.

Recognising the behavioural patterns the condition follows will also help researchers discern different forms of the condition and identify suitable people for clinical trials to test new interventions.”


Ref: Altered sense of humor in dementia by C Clark et al. was published in the Journal of Alzheimer’s Disease on 10 November 2015

  • Alzheimer’s Research UK is the UK’s leading charity specialising in finding preventions, treatments and a cure for dementia.
  • We rely on donations to fund our vital dementia research. To help us defeat dementia, donate today by visiting or calling 0300 111 5555.
  • We are currently supporting dementia research projects worth over £26 million in leading Universities across the UK.
  • Our Defeat Dementia campaign, a pledge to raise £100 million in five years to grow the research field and accelerate progress towards new treatments and preventions, was announced by the Prime Minister at the G8 legacy event on 19 June 2014. For more information visit

Journal of Alzheimer’s Disease is published by IOS Press

Copyright © 2015



Obesity at Midlife May Speed Alzheimer’s Onset

(The Fisher Center for Alzheimer’s Research Foundation) Various studies suggest that being overweight at midlife increases your risk of developing Alzheimer’s in old age. Now, a new study found that people who are obese at age 50 may get Alzheimer’s at a younger age.

The study, from researchers at the National Institutes of Health, looked at 1,394 men and women who were part of the Baltimore Longitudinal Study of Aging, a large and ongoing study of Baltimore residents as they age. Their average age was around 60.

None had Alzheimer’s disease or other serious memory problems at the start of the study. They got regular checks of memory and thinking skills, for an average of about 14 years. During that time, 142 were diagnosed with Alzheimer’s disease.

The researchers found that people with the highest body mass index, or BMI, at age 50 were much more likely to develop Alzheimer’s disease. BMI is a formula doctors use that takes into account both height and weight to estimate body fat and the likelihood of developing health problems due to excess weight. People at a healthy weight generally have a BMI under 25. Those with a BMI of 25 to 30 are considered to be overweight, while those with a BMI over 30 are considered obese.

A man who is 5 foot 11 and weighs 180 pounds, for example, has a BMI just over 25, while a 5 foot 4 woman who weighs 145 would have a similar BMI on the healthy-overweight border. You can calculate your BMI at various online sites, including at NIH:

The researchers found that the higher someone’s BMI at midlife, the earlier they tended to get the disease. Each one-point increase in BMI was associated with getting Alzheimer’s six to seven months earlier. Someone with a BMI of 30, for example, might develop Alzheimer’s two-and-a-half years earlier than someone with a BMI of 25. Those with the highest BMIs also tended to have more brain changes typical of Alzheimer’s, even if they didn’t have symptoms of the disease.

Do those with higher BMI at midlife tend to stay that way? Or can the effects of BMI at midlife be changed for those who lower their BMI? These questions were not made clear by the current study, but answers to these questions could allow people to make more lifestyle changes that would reduce their risk of developing Alzheimer’s disease at an earlier age.

“As we try to cure Alzheimer’s disease, we also want to delay the onset of symptoms,” said study author Dr. Madhav Thambisetty, a neurologist at the NIH’s National Institute on Aging. “Maintaining a healthy BMI at midlife is likely to have long-lasting protective effects.” The findings appeared in the journal Molecular Psychiatry.

Increasingly, doctors believe that what’s good for the heart is good for the brain. Carrying excess weight has been closely linked with a variety of diseases that affect the heart and blood vessels, including heart disease, high blood pressure and diabetes. Being “apple-shaped,” with excess belly fat, as opposed to “pear-shaped,” with large thighs, may be a particular risk factor for heart disease – as well as Alzheimer’s.

Scientists also speculate that fat cells may produce harmful chemicals that promote inflammation in blood vessels throughout the body, including in the brain. People who are overweight may also tend to have diets low in “good” fats, such as those found in fish, and to get less exercise than those who are of normal weight.

Additional study is needed to determine how weight and body fat might affect brain health. Many factors go into determining who ultimately gets Alzheimer’s disease, including what genes you inherit. But anything that delays the onset of Alzheimer’s could have significant impacts on the costs – both human and financial — of caring for the disease.

By, The Alzheimer’s Information Site. Reviewed by William J. Netzer, Ph.D., Fisher Center for Alzheimer’s Research Foundation at The Rockefeller University.


Source: Y-F Chuang, Y An, M Bilgel, et al: “Midlife Adiposity Predicts Earlier Onset of Alzheimer’s Dementia, Neuropathology and Presymptomatic Cerebral Amyloid Accumulation.” Molecular Psychiatry, Sept. 1, 2015

Copyright © 2015 The Fisher Center for Alzheimer’s Research Foundation


Low Vitamin D Tied to Memory Problems

(The Fisher Center for Alzheimer’s Research Foundation) Low levels of vitamin D may play a role in memory problems and the onset of Alzheimer’s disease and other forms of dementia in the elderly, according to a new report. The findings underscore the importance of identifying vitamin D deficiency in older men and women, say the researchers, from the University of California, Davis, and Rutgers University.

The researchers found that memory skills declined two to three times faster in those with low blood levels of the vitamin compared to those with adequate vitamin D levels. “This work, and that of others, suggests that there is enough evidence to recommend that people in their 60s and older discuss taking a daily vitamin D supplement with their physicians,” said study author Joshua Miller, now at Rutgers.

For the study, the researchers followed 382 men and women living in northern California for about five years. Their mean age was 75. Some had dementia or mild cognitive impairment, a serious form of memory loss that may eventually lead to a diagnosis of Alzheimer’s disease.

The researchers found that about 60 percent of the study participants were low in vitamin D. A healthy vitamin D level is general defined as about 20 to 25 nanograms of the vitamin per milliliter of blood.

Seniors who had low levels of vitamin D tended to score worse on tests of episodic memory, which is the ability to recall personal experiences that occurred at a particular time and place. They also performed worse on tests of executive function, or the ability to plan ahead and solve problems. Both aspects of memory are severely impaired by Alzheimer’s disease.

They also found that seniors in the study who had dementia had lower vitamin D levels than those with mild cognitive impairment or normal cognitive function.

The authors didn’t study whether vitamin D supplements might slow the rate of cognitive decline. But they plan to continue research to see if taking vitamin D supplements might slow or prevent the onset of Alzheimer’s or dementia in those getting supplements of the vitamin. “Even if doing so proves to not be effective, there’s still very low health risk to doing it,” Dr. Miller said.

Vitamin D, which promotes bone health, is sometimes called the sunshine vitamin because it is produced in the skin upon exposure to sunlight. People living in northern latitudes may be particularly prone to vitamin D deficiency during the winter months, when sunlight levels are low.

Certain ethnic groups are also particularly prone to vitamin D deficiency, including African-Americans and Hispanics, who are less able to absorb sunlight through the skin. Among those groups and other darker-skinned individuals, low vitamin D should be considered a risk factor for dementia, the authors note. The findings were published in JAMA Neurology, a journal from of the American Medical Association.

“This is a vitamin deficiency that could easily be treated and that has other health consequences,” said Charles DeCarli, a study author and the director of the Alzheimer’s Disease Center at UC Davis.

“We need to start talking about it. And we need to start talking about it, particularly for people of color, for whom vitamin D deficiency appears to present an even greater risk,” he said.

Vitamin D is found naturally in some foods like fish, and it is also added to foods like milk. But the best way to raise blood levels of the vitamin is to spend at least 15 minutes in the sun each day.

Some doctors recommend taking vitamin D supplements, but the effects of taking very high doses are unknown. Vitamin D remains in the body, stored in fat, and getting excessive doses can produce side effects that can include digestive problems, headaches, irregular heartbeats and extreme fatigue.

By, The Alzheimer’s Information Site. Reviewed by William J. Netzer, Ph.D., Fisher Center for Alzheimer’s Research Foundation at The Rockefeller University.


Source: Joshua W. Miller, PhD; Danielle J. Harvey, PhD; Laurel A. Beckett, PhD; et al: “Vitamin D Status and Rates of Cognitive Decline in a Multiethnic Cohort of Older Adults.” JAMA Neurology, Sept. 14, 2015

Copyright © 2015 The Fisher Center for Alzheimer’s Research Foundation


Brain’s Immune System Could Be Harnessed to Fight Alzheimer’s

(University of Rochester Medical Center) A new study appearing in the Journal of Neuroinflammation suggests that the brain’s immune system could potentially be harnessed to help clear the amyloid plaques that are a hallmark of Alzheimer’s disease.

“This research confirms earlier observations that, when activated to fight inflammation, the brain’s immune system plays a role in the removal of amyloid beta,” said M. Kerry O’Banion, M.D., Ph.D., a professor in the University of Rochester Department of Neurobiology and Anatomy, the Del Monte Neuromedicine Institute, and the lead author of the study.

“We have also demonstrated that the immune system can be manipulated in a manner that accelerates this process, potentially pointing to a new therapeutic approach to Alzheimer’s disease.”

The findings are the culmination of years of investigation that were triggered when O’Banion and his colleagues made a surprising discovery while studying mouse models of Alzheimer’s disease.  They observed that amyloid beta plaques – which scientists believe play a major role in the disease – were being cleared in animals with chronic brain inflammation.

At the time, the mechanism by which the plaques were being removed was not clear.  O’Banion and his colleagues eventually set their sights on microglia, native cells that serve as one the central nervous system’s first lines of defense against infection and injury.  Microglia are present throughout the brain and spinal cord, are constantly monitoring their environment, and can be switched on or activated to perform different functions such as control inflammation, destroy pathogens, clean up the debris from dead or damaged cells, and seal off the site of an injury.

The researchers conducted a series of experiments to see if they could replicate the phenomenon of amyloid beta clearance absent brain inflammation.  This required that they “trick” the microglia into action which was accomplished by injecting a specific protein molecule, a cytokine, into the brain.  Cytokines play important roles in cell signaling and the researchers were able to replicate the mechanisms that instruct the microglia to activate an anti-inflammatory response.

Once the microglia were mobilized in mouse models of Alzheimer’s disease, the researchers observed a more than 60 percent reduction in amyloid beta in the brain.

“While we still need to fully understand the complexity and potential unintended consequences of this approach, it is clear that microglia play an important role in the removal of amyloid beta from the brain and may represent a novel approach to treating this disease,” said O’Banion.

Additional co-authors of the study include Jonathan Cherry, a Pathology graduate student now at Boston University, and John Olschowka with the University of Rochester.  The research was supported by the National Institute of Aging.


Journal Reference:

Jonathan D. Cherry, John A. Olschowka, M. Kerry O’Banion. Arginase 1 microglia reduce Aβ plaque deposition during IL-1β-dependent neuroinflammation. Journal of Neuroinflammation, 2015; 12 (1) DOI: 10.1186/s12974-015-0411-8

©2015 University of Rochester Medical Center Rochester, NY


Scientists Say Alzheimer’s is Probably a Collection of Diseases that Should be Classified and Treated Separately

(Hebrew University of Jerusalem) Deciphering the mechanism that underlies the development of Alzheimer’s disease in certain families but not in others, researchers at the Hebrew University of Jerusalem’s Faculty of Medicine have proposed that the malady is actually a collection of diseases that probably should be treated with a variety of different approaches.

Neurodegenerative diseases are incurable and debilitating conditions that result in degeneration or death of cells in the nervous system. Conditions such as prion disorders (the most famous of which is “Mad Cow Disease”), Alzheimer’s Disease and Parkinson’s Disease share two key features: they emerge as a result of aberrant protein folding and aggregation, and their onset is late in life. These maladies emerge either sporadically or as familial, mutation-linked illnesses (certain prion disease can be also infectious).

Most sporadic cases are diagnosed during the patient’s seventh decade of life or later, while familial cases typically manifest during the fifth or sixth decade. Despite their relative rareness, mutation-linked cases are very important, as they provide hints that can help decipher the mechanisms that underlie the development of the disease.

The late onset feature typical to distinct neurodegenerative diseases, and the common temporal emergence patterns of these maladies, raise key questions: first, why do individuals who carry disease-linked mutation show no clinical signs until their fifth or sixth decade of life? In addition, why do apparently distinct disorders share a common temporal emergence pattern?

One possible explanation is that as people age, the efficiency of the mechanisms that protect younger people from the toxic aggregation of proteins declines, thus exposing them to disease. Indeed, previous studies clearly indicate that the aging process plays key roles in enabling neurodegenerative disorders to onset late in life.

These finding raised the question of what mechanisms are negatively regulated by aging, allowing the emergence of neurodegeneration in the elderly.

Since neurodegenerative disorders stem from aberrant protein folding, an international research team, led by Prof. Ehud Cohen and Dr. Tziona Ben-Gedalya at The Institute for Medical Research Israel — Canada (IMRIC) in the Hebrew University’s Faculty of Medicine, postulated that an aging-associated decline in the activity of proteins that assist other proteins to fold properly, may be one mechanism that exposes the elderly to neurodegeneration.

To identify such mechanisms, they searched for similar mutational patterns in different proteins that are linked to the development of distinct neurodegenerative disorders. Their research showed that the development of Alzheimer’s disease in certain families, and of a familial prion disorder in other families, originate from very similar mutational patterns.

Based on this discovery, they identified that the malfunction of the protein “cyclophilin B,” which helps nascent proteins to attain their proper spatial structures, is responsible for the manifestation of both maladies. They also comprehensively characterized the mechanism that underlies the development of Alzheimer’s disease in individuals who carry these mutations, and found that it has no relevance to the emergence of the disease in patients who carry other Alzheimer’s-linked mutations.

According to Prof. Ehud Cohen:

“This study provides important new insights: first, it shows that the development of distinct neurodegenerative disorders stems from a similar mechanism.

More importantly, it indicates that Alzheimer’s disease can emanate from more than one mechanism, suggesting that it is actually a collection of diseases that should be classified.”

The new insights derived from this study may reinforce the efforts to develop novel therapies to the different subtypes of Alzheimer’s disease, providing new hope to those who suffer from this incurable disorder and to their families.

Prof. Ehud Cohen added:

“Our study proposes that the failure to develop efficient Alzheimer’s therapy emanates from the pooling, in clinical experiments, of patients who suffer from distinct disorders that eventually lead to Alzheimer’s symptoms.

Therefore it is essential to carefully characterize and classify the mechanisms that underlie Alzheimer’s disease, in order to allow for the development of novel therapies that can be prescribed to the individual patient according to their relevant disease subtype.”


Journal Reference:

T. Ben-Gedalya, L. Moll, M. Bejerano-Sagie, S. Frere, W. A. Cabral, D. Friedmann-Morvinski, I. Slutsky, T. Burstyn-Cohen, J. C. Marini, E. Cohen. Alzheimer’s disease-causing proline substitutions lead to presenilin 1 aggregation and malfunction. The EMBO Journal, 2015; DOI: 10.15252/embj.201592042

The paper’s co-authors include researchers at the Institute for Dental Sciences, Faculty of Dental Medicine, Hebrew University of Jerusalem; Dept. of Physiology and Pharmacology at the Sackler Faculty of Medicine at Tel Aviv University; Dept. of Biochemistry and Molecular Biology, Wise Faculty of Life Sciences, Tel Aviv University; and Bone and Extracellular Matrix Branch, NICHD, National Institutes of Health (NIH), USA.

The study was supported by the Rosalinde and Arthur Gilbert Foundation (AFAR), the European Research Council, the National Institute for Psychobiology in Israel (NIPI), and the Israel Science Foundation.

The Institute for Medical Research-Israel Canada (IMRIC), in the Hebrew University of Jerusalem’s Faculty of Medicine, is one of the most innovative biomedical research organizations in Israel and worldwide. IMRIC brings together the most brilliant scientific minds to find solutions to the world’s most serious medical problems, through a multidisciplinary approach to biomedical research. More information at The Hebrew University of Jerusalem is Israel’s leading academic and research institution, producing one-third of all civilian research in Israel. For more information, visit

Copyright Hebrew University of Jerusalem


Potential Solution for Side Effect of Alzheimer’s Immunotherapy Treatment

(University of Southhampton) It is estimated that 46.8 million people worldwide are living with dementia, with Alzheimer’s disease the most common form.

Now researchers from the University of Southampton have discovered a possible solution for side effects seen in immunotherapy treatment for Alzheimer’s.

Immunotherapy is a promising strategy for the treatment of Alzheimer’s that uses antibodies to stimulate the immune system to remove pieces of a protein called amyloid beta which accumulates in the brain (in deposits known as plaques) and is thought to be a major factor driving Alzheimer’s neurodegenerative effects.

Antibodies directed against amyloid beta have been able to successfully clear plaques and reverse cognitive deficits in mouse models. However, despite this success, clinical trials using these antibodies caused inflammatory side effects in the brain of Alzheimer’s patients, in particular amyloid-related imaging abnormalities (ARIA), which results in small bleeds and dangerous brain swelling.

The multidisciplinary Southampton team, led by Dr Jessica Teeling, and in collaboration with Lundbeck (a multinational pharmaceutical company based in Denmark), engineered three antibodies to change the way they engage cells in the immune system. They found that small but precise changes in the anti-amyloid antibodies preserved the immunotherapeutic activity without the inflammatory side effects.

Dr Teeling, Associate Professor in Immunology at The Centre for Biological Sciences, said:

“New antibodies are entering the clinic for Alzheimer’s disease; therefore, it is important to learn all we can from research into these novel interventions and use antibody engineering technology to optimise their effects.”

While these results underline the potential of antibodies to destroy disease-causing plaques in patients and provide possible future treatments, they also indicate that further work is needed to increase antibody potency, but without increasing inflammatory side effects.

Dr Stavenhagen, Head of Biologics at Lundbeck, said:

“These studies provide a roadmap of how to apply the advances in antibody engineering to antibody therapeutics that target neurodegenerative diseases. The next generation of antibody drugs to enter the clinic will contain new technologies and enhancements to improve the properties required to clear plaques, while keeping the rest of the brain safe.”

The study was published in the journal Acta Neuropathologica and was funded by the Medical Research Council (MRC).


Journal Reference:

James P. Fuller, Jeffrey B. Stavenhagen, Søren Christensen, Fredrik Kartberg, Martin J. Glennie, Jessica L. Teeling. Comparing the efficacy and neuroinflammatory potential of three anti-abeta antibodies. Acta Neuropathologica, 2015; 130 (5): 699 DOI: 10.1007/s00401-015-1484-2

© 2015 University of Southampton


This Drug May Not Help Women With Alzheimer’s

(WebMD) Researchers find no benefits from raloxifene in those with mild to moderate dementia.

The drug raloxifene doesn’t help the declining memory and thinking skills of women who have mild to moderate dementia due to Alzheimer’s disease, a small study suggests.

“We found no effect,” said study researcher Dr. Victor Henderson, professor of health research and policy and neurology and neurological sciences at Stanford University in California.

Raloxifene is a complex drug. It acts like the female hormone estrogen in some parts of the body, while it blocks the effects of estrogen in the breasts and uterus, the study authors explained.

The researchers decided to look at the drug after another study of raloxifene, which is also used to treat the bone-thinning disease osteoporosis, found that the drug reduced the risk of healthy women developing impairments in their thinking and memory, Henderson said.

The new study, published online Nov. 4 in Neurology, included 42 women who were recruited between 2006 and 2009 from several sites across the United States. The study participants, aged 68 to 84, all had late-onset Alzheimer’s disease that was in the mild to moderate stages.

The women were randomly assigned to take raloxifene or an inactive placebo pill for a year. The researchers tested the women’s memory and other mental functions at the start of the study and every three months after that.

Test scores didn’t differ significantly between the two groups, the investigators found. The scores didn’t differ for memory and thinking skills, or how well the women could perform activities of daily living such as dressing themselves and other routines.

However, because the number of women in the study was so small, with only 21 women receiving treatment with raloxifene, “this study can’t exclude a small effect,” Henderson said.

In addition, the findings don’t rule out that other drugs similar to raloxifene might have a benefit on thinking and memory, Henderson said. Raloxifene belongs to a class of drugs known as SERMs (selective estrogen receptor modulators). “The SERMs don’t all act in the same way,” he said.

“What this study shows,” said Heather Snyder, senior director of medical and scientific operations for the Alzheimer’s Association, “is that in this population, they don’t see a big benefit” with raloxifene.

However, she added, scientists are still trying to understand the genetic and biological reasons for Alzheimer’s, including hormonal pathways.

“I think there are a lot of things we don’t understand about the underlying biology and the role of these different pathways for Alzheimer’s disease,” she said.

About 5 million Americans are living with Alzheimer’s disease, according to the Alzheimer’s Association, although not all are diagnosed. Of those, two-thirds are women, Snyder said, “but we don’t know why.”

Women’s generally longer life expectancy may be one factor, but there may also be biological and genetic reasons, Snyder said.

Some of Henderson’s co-researchers report serving as consultants or speakers for Eli Lilly, which provided the study drug, and other pharmaceutical companies. The U.S. National Institutes of Health supported the study.


By Kathleen Doheny
SOURCES: Victor Henderson, M.D., professor of health research and policy and neurology and neurological sciences, Stanford University, Stanford, Calif.; Heather Snyder, Ph.D., senior director of medical and scientific operations, Alzheimer’s Association, Chicago; Nov. 4, 2015, Neurology, online.

Copyright © 2013-2015 HealthDay. All rights reserved.


Lifestyle Change Could Reduce Risk of Alzheimer’s

(Heidelberg, Universität) Heidelberg ageing researchers study connection between cholesterol level and cognitive decline in old age.

Changes in lifestyle could reduce the risk of developing Alzheimer’s disease. That was the conclusion of a study conducted by researchers of Heidelberg University’s Network Aging Research (NAR), who examined the data from two independent epidemiological studies.

Carriers of the ApoE4 genetic risk factor for Alzheimer’s may be able to reduce their increased risk of cognitive decline by reducing their cholesterol level, especially if they also suffer from cardiovascular disease. In Germany, approximately 20 percent of the population carries the ApoE4 risk factor. The results of the research were published in Dementia and Geriatric Cognitive Disorders.

ApoE stands for apolipoprotein E, a protein that plays a critical role in the metabolism of blood lipids. Among other things, it transports cholesterol to nerve cells which the latter require for signal exchange. There are three different genetic variants, or alleles, of the ApoE gene, which contains the blueprint for the ApoE protein. Carriers of the E4 allele, i.e. the ApoE4 genetic variant, have an increased risk of developing Alzheimer’s.

Cognitive deficits such as memory lapses can be harbingers of dementia and Alzheimer’s but can also occur independently, according to Prof. Dr. Hermann Brenner, Deputy Director of the Network Aging Research (NAR). In the NAR study led by Prof. Brenner at the German Cancer Research Center (DKFZ), epidemiologists Dr. Laura Perna and Dr. Ute Mons investigated the extent to which carriers of the E4 allele have a higher risk of cognitive deficits as they age compared to carriers of the other genetic variants.

The scientists were particularly interested in the interaction between ApoE4 and cholesterol levels. For their analyses they used blood samples and medical data from two DKFZ epidemiological studies on older adults who also took cognitive tests for memory and concentration capacity. The ESTHER Study included 1,434 individuals over the age of 70, and the KAROLA Study had 366 participants over 50.

The Heidelberg researchers found that the relationship between the ApoE4 risk factor and cognitive deficits, especially memory, was strongest in those with high cholesterol and heart disease.

“One possible explanation for the results could be that the brain is especially sensitive to the effects of ApoE4 once it has already been affected by cardiovascular disease and high cholesterol,” explains Laura Perna.

It is most likely a complex interaction between the various factors. The ApoE4 allele not only increases the risk of Alzheimer’s, but is also associated with an increased risk of arteriosclerosis. Arteriosclerosis, a narrowing of the arteries due to fatty deposits, can cause serious cardiac problems but also supports the development of dementia. It is assumed to be caused by a high level of “bad” LDL cholesterol in the blood, which often occurs in ApoE4 carriers. High cholesterol, in turn, is an independent risk factor for Alzheimer’s.

In spite of the fact that the relationships are not completely understood, the researchers emphasize the clinical relevance of their findings.

“Both high cholesterol and cardiovascular disease are potentially avoidable, and in many cases a healthy diet and lifestyle can reduce high cholesterol,” explains Prof. Brenner.

Regular exercise and a diet rich in vegetables and fruit and low in animal fat help keep cholesterol levels down. “What’s good for the heart is also good for the brain and memory. This appears to be especially important for carriers of the ApoE4 risk factor.”


Journal Reference:

Laura Perna, Ute Mons, Dan Rujescu, Matthias Kliegel, Hermann Brenner. Apolipoprotein E e4 and Cognitive Function: A Modifiable Association? Results from Two Independent Cohort Studies. Dementia and Geriatric Cognitive Disorders, 2015; 35 DOI: 10.1159/000440697

© Copyright Heidelberg University