USC Study Links Sugary Beverages to Memory Problems

(University of Southern California) Consumption of high-fructose corn syrup leads to brain inflammation in adolescent rats. Studying rats as model subjects, scientists found that adolescents were at an increased risk of suffering negative health effects from sugar-sweetened beverage consumption.

Adolescent rats that freely consumed large quantities of liquid solutions containing sugar or high-fructose corn syrup (HFCS) in concentrations comparable to popular sugar-sweetened beverages experienced memory problems and brain inflammation, and became pre-diabetic, according to a new study from USC. Neither adult rats fed the sugary drinks nor adolescent rats that did not consume sugar had the same issues.

“The brain is especially vulnerable to dietary influences during critical periods of development, like adolescence,” said Scott Kanoski, corresponding author of the study and assistant professor at the USC Dornsife College of Letters, Arts and Sciences.

Kanoski collaborated with USC’s Ted Hsu, Vaibhav Konanur, Lilly Taing, Ryan Usui, Brandon Kayser and Michael Goran. The study, which tested a total of 76 rats, was published online by the journal Hippocampus on Sept. 23.

Soft drinks, sodas, sugar

About 35 to 40 percent of the rats’ caloric intake was from sugar or HFCS. For comparison, added sugars make up about 17 percent of the total caloric intake of teens in the United States on average, according to the U.S. Centers for Disease Control and Prevention.

The rats were then tested in mazes that probe their spatial memory ability. Adolescent rats that had consumed the sugary beverages, particularly HFCS, performed worse on the test than any other group, which may be the result of the neuroinflammation detected in the hippocampus, Kanoski said.

The hippocampus is a part of the temporal lobe located deep within the brain that controls memory formation. People with Alzheimer’s and other dementias often suffer damage to the hippocampus.

“Consuming a diet high in added sugars not only can lead to weight gain and metabolic disturbances, but can also negatively impact our neural functioning and cognitive ability,” said Kanoski, whose team next plans to see how different monosaccharides (simple sugars) and HFCS affect the brain.

The research was funded by USC institutional support.

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Feeding Tubes Not Recommended in Advanced Dementia

(MedicalNews Today) Based on current scientific literature, gastrostomy tube (G-tube) placement or other long-term enteral access devices should be withheld or withdrawn in patients with advanced dementia or other near end-of-life conditions, according to a special report published in the OnlineFirst version of Nutrition in Clinical Practice (NCP), the official journal of the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.).

Written by the International Clinical Ethics Section of A.S.P.E.N., the report suggests that advanced dementia be seen by health care providers as a terminal illness. And that view and what it means should be communicated to the patient’s family and loved ones for patient-centered care decision making.

The report states,

“Numerous articles have been published about advanced dementia and use of feeding tubes, yet there remains a high consistency in finding a lack of efficacy in tube feeding in this population. Current scientific evidence suggests that the potential benefits of tube feeding do not outweigh the associated burdens of treatment in persons with advanced dementia. Studies consistently demonstrate a very high mortality rate in older adults with advanced dementia who have feeding tubes.”

Based on its findings, the authors conclude that a thorough discussion should take place with the patient, family, significant others, caregivers, and/or surrogate decision makers, touching on the risks, burdens, and benefits, as well as the most updated evidence-based findings.

They also stress that the final informed decision should be reached by all members of the healthcare team using a patient-centered approach, which respects the patient’s autonomy, self-determination and dignity. Recognizing the role health care institutions play in end-of-life planning, the authors of the report recommend that hospitals and long-term care facilities develop a process to promote advance directives to provide health care based on the patient’s wishes and best interest.

While the report focuses on patients with advanced dementia or near end of life conditions, the authors of the report believe the findings may be applicable to other patients if used in conjunction with scientific information about that defined patient population.

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MRI Technique Detects Evidence of Cognitive Decline Before Symptoms Appear

(Radiological Society of North America) A magnetic resonance imaging (MRI) technique can detect signs of cognitive decline in the brain even before symptoms appear, according to a new study published online in the journal Radiology. The technique has the potential to serve as a biomarker in very early diagnosis of preclinical dementia.
Brain PerfusionThis image shows brain perfusion. Red indicates low perfusion, yellow indicates high perfusion. Overall, the brain perfusion is similar between all three groups. The most prominent difference is present in the posterior cingulate cortex (indicated by the arrow), a region close to the midline in the superior and posterior part of the brain. Control participants who remain stable have higher perfusion as compared to deteriorating controls and MCI. Credit: Radiological Society of North America

The World Health Organization estimates that dementia affects more than 35 million people worldwide, a number expected to more than double by 2030. Problems in the brain related to dementia, such as reduced blood flow, might be present for years but are not evident because of cognitive reserve, a phenomenon where other parts of the brain compensate for deficits in one area. Early detection of cognitive decline is critical, because treatments for Alzheimer’s disease, the most common type of dementia, are most effective in this early phase.

Researchers recently studied arterial spin labeling (ASL), a promising MRI technique that doesn’t require injection of a contrast agent. ASL measures brain perfusion, or penetration of blood into the tissue.
Comparison with ControlThis image illustrates the direct comparison between the different groups. The biggest difference is present between stable controls and MCI, indicated in red-yellow, notably in the posterior cingulate cortex. The comparison of stable versus deteriorating controls (blue) shows differences in the same region yet less pronounced. The comparison between deteriorating controls and MCI revealed no significant differences. Credit: Radiological Society of North America

“ASL MRI is simple to perform, doesn’t require special equipment and only adds a few minutes to the exam,” said study author Sven Haller, M.D., from the University of Geneva in Geneva, Switzerland.

The study group included 148 healthy elderly participants and 65 people with mild cognitive impairment (MCI). The participants underwent brain MRI and a neuropsychological assessment, a common battery of tests used to determine cognitive ability.

Of the 148 healthy individuals, 75 remained stable, while 73 deteriorated cognitively at 18 months clinical follow-up. Those who deteriorated had shown reduced perfusion at their baseline ASL MRI exams, particularly in the posterior cingulate cortex, an area in the middle of the brain that is associated with the default mode network, the neural network that is active when the brain is not concentrating on a specific task. Declines in this network are seen in MCI patients and are more pronounced in those with Alzheimer’s disease.

The pattern of reduced perfusion in the brains of healthy individuals who went on to develop cognitive deficits was similar to that of patients with MCI.

“There is a known close link between neural activity and brain perfusion in the posterior cingulate cortex,” Dr. Haller said. “Less perfusion indicates decreased neural activity.”

The results suggest that individuals with decreased perfusion detected with ASL MRI may temporarily maintain their cognitive status through the mobilization of their cognitive reserve, but will eventually develop subtle cognitive deficits.

Previous research done with positron emission tomography (PET), the current gold standard for brain metabolism imaging, found that patients with Alzheimer’s disease had reduced metabolism in the same area of the brain where the perfusion abnormalities were found using ASL MRI. This points to a close link between brain metabolism and perfusion, according to Dr. Haller.

ASL MRI has potential as a standalone test or as an adjunct to PET for dementia screening, Dr. Haller said. While PET can identify markers of Alzheimer’s disease in the brain and cerebrospinal fluid, it exposes the patient to radiation. ASL does not expose the patient to radiation and is easy to perform in routine clinical settings.

“ASL might replace the classic yet unspecific fluordesoxyglucose PET that measures brain metabolism. Instead, PET could be done with the new and specific amyloid PET tracers,” Dr. Haller said.

The results also support a role for ASL MRI as an alternative to neuropsychological testing.

The researchers plan to perform follow-up studies on the patient group to learn more about ASL and long-term cognitive changes.

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Researchers Corroborate Neuroprotective Effects of Sirtuin 1 Activation on Mice with Alzheimer’s Disease

(Journal of Alzheimer’s Disease) A study coordinated by the University of Barcelona (UB) has described a mechanism that plays a key role in the evolution of Alzheimer’s disease. According to the paper published in the Journal of Alzheimer’s Disease, the activation of the protein Sirtuin 1 in a murine model with familial Alzheimer’s disease has neuroprotective effects.

The study, based on the PhD thesis developed by the researcher David Porquet (UB), first describes Sirtuin 1 pathway in this murine model. Mercè Pallàs, from the Department of Pharmacology and Therapeutic Chemistry at the Faculty of Pharmacy of UB, coordinates the study. The Bellvitge Biomedical Research Institute (IDIBELL) and the August Pi i Sunyer Biomedical Research Institute (IDIBAPS) also collaborate in the study.

A group of mice was fed with resveratrol, a natural polyphenolic compound found in grapes and red wine. Mice were modified to develop familial Alzheimer’s disease, an inherited neurodegenerative disorder that represents 5% of dementia cases and normally has an early onset. Resveratrol dose was equivalent to dietary supplementation and administered for 10 months. Then, its effects on cognitive function and neuronal tissues were compared with a control group that did not receive any supplementation.

“Results showed that resveratrol ameliorated short-term memory and stopped the accumulation of senile plaques and the development of tau protein, the two most important characteristics of the disease”,

explains Mercè Pallàs, researcher from the Research Group on Aging and Neurodegeneration of UB and the Centre for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED).

Researchers studied which mechanisms are activated in this process. Particularly, they focused their attention on Sirtuin 1, a protein involved in ageing.

“We used resveratrol because it is thought that one part of its beneficial effects is due to an increase in sirtuin activity”. “Although sirtuin proteic levels decreased —she adds—, its activity was increased”.

Surprisingly, the study showed an increase in other intracellular mechanisms.

Therefore, “resveratrol’s beneficial action increases these other mechanisms and mitochondrial function”, concludes the researcher.

According to Pallàs,

“sirtuin pathway may be a good Alzheimer’s disease treatment target. The study proves that if this pathway is regulated, in this case with resveratrol, the evolution of Alzheimer’s disease in this murine model of familial Alzheimer’s disease is modified”.

A previous study developed by the research group had already proved the important role that Sirtuin 1 plays in ageing.

“We administered the same type of resveratrol treatment to mice with accelerated senescence —modified to get older quicker— and we observed an increase of their life expectancy which was related to sirtuin activation”, points out Pallàs.

Further studies need to be conducted to elucidate whether or not resveratrol is also able to protect against mitochondrial dysfunction.

“If we corroborate the key role played by mytochondria-sirtuin interaction, the activation of sirtuin with resveratrol might have protective effects on high-fat diet–fed mice, which are supposed to suffer mitochondrial dysfunction”, says the researcher.

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National Dementia Association Launches Awareness Month

(NewsWise) In an effort to drive awareness of a common but little known dementia, Lewy body dementia (LBD) families are hosting events nationwide to help raise support for those affected by the disease. Greater public awareness is desperately needed, as LBD is the most misdiagnosed form of dementia.

Lewy Who?

LET’S CLEAR UP THE CONFUSION.

LBD is the second most common form of dementia, afflicting 1.4 million Americans. Symptoms resemble Alzheimer’s and Parkinson’s disease, but treatment may not. Correct early diagnosis can protect patients from receiving meds and treatments that could make symptoms worse.

LBD is the most misdiagnosed form of dementia. Most people are not diagnosed until at moderate or severe states. It takes on average over 18 months and three doctor visits to receive a correct diagnosis. That’s a missed opportunity that can leave people and their families unprepared and vulnerable.

The timing of these events aligns with the October National Lewy Body Dementia Awareness Month, driven by the Lewy Body Dementia Association (LBDA). Events are being organized across the country to help increase awareness. Educating the public about LBD symptoms to report to the doctor is a vital step in decreasing the time it takes to receive a diagnosis.

LBDA encourages people and organizations to host or attend local events to learn more about the disease, how it impacts those diagnosed, their caregivers and families. Participants will better be able to answer the question, “Lewy Who?” and help spread awareness of this devastating disease.

Proceeds raised will be donated to LBDA, the only organization in the United States that provides comprehensive education and support for the 1.4 million people and the families affected by LBD.

“Hosting or attending Awareness Movement events across the country during the month of October will help not only to spread the word about LBD but also to increase the base of support for LBD families,” says Michael Koehler, president of Lewy Body Dementia Association. “It takes a united front to make an impact and to provide vital information and outreach to those affected by this condition.”

To learn how you can help spread awareness, or find an event near you, visit lbda.org.

About Lewy Body Dementia Association

The Lewy Body Dementia Association (LBDA) is a 501(c)(3) national nonprofit health organization dedicated to raising awareness of Lewy body dementia (LBD), promoting scientific advances, and supporting people with LBD, their families and caregivers. LBD, a complex disease that can present with a range of physical, cognitive, and behavioral symptoms, is a “family disease.”

It dramatically affects not only the person diagnosed but also the primary caregiver. LBDA supports all those affected by Lewy body dementia through outreach, education and research. To learn more about LBD and LBDA, please visit www.lbda.org/lewywho.

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Memory Concerns Presage Cognitive Decline and Aβ Pathology

(AlzForum) A perceived slip in memory could signal future cognitive decline, suggests a paper in the October 7 Neurology. Researchers led by Richard Kryscio, University of Kentucky, Lexington, found that ostensibly normal volunteers who reported a subjective memory complaint were nearly three times likelier than non-complainers to meet criteria for mild cognitive impairment (MCI) or dementia over the next 10 years.

They also had more amyloid in their brains. Alzforum reported on these findings when they were presented at a conference last year (see Jul 2013 conference story). The study was covered by CBSCNN, and The Los Angeles Times.

“This is one of the few studies that chronicles the transition from subjective memory complaint to impairment,” said Frank Jessen, German Center for Neurodegenerative Diseases, Bonn.

Subjective cognitive decline, also known as subjective memory complaint (SMC), was recently defined as “self-experienced persistent decline in cognitive capacity in comparison with a previously normal status and unrelated to an acute event” (see Jessen et al., 2014). This can be rooted in depression, lack of vitamin B12, certain medications, or normal aging processes, but it may also reflect early Alzheimer’s disease.

“Not everyone who complains develops an impairment,” Kryscio told Alzforum.

His group wanted to determine how many people progress from SMC to MCI or dementia, what they term an “impaired state” in this study, and how fast, and how that correlated with AD pathology.

In 1989, Kryscio and colleagues began studying 531 cognitively healthy people, average age 73, from the Biologically Resilient Adults in Neurological Studies (BRAiNS) cohort, a longitudinal observational study and brain donation program at the University of Kentucky.

Yearly psychological tests assessed memory, language, executive and visuospatial function, and whether the subject had progressed to MCI or dementia. Before each round of testing, researchers asked the participants if they had noticed any change in memory since their last visit. If they answered yes, they were tagged as reporting an SMC. They donated their brain after death to be examined for signs of plaques or neurofibrillary tangles, the two hallmarks of Alzheimer’s pathology.

Of 296 people who declared an SMC, 114 progressed to MCI or dementia over about nine or 12 years, respectively. Having an ApoE4 allele doubled a person’s risk of becoming impaired, and smokers progressed to MCI almost three years faster. Interestingly, women on hormone replacement therapy progressed more slowly.

Research conflicts about whether supplemental estrogen protects from dementia or enhances risk (see Nov 2011 news story). Because the time to impairment varied depending on environmental factors, the study suggests that interventions could target the disease during this period, the authors wrote. Jessen agreed. “I predict these will be the subjects we treat in the future,” he told Alzforum.

Almost half of the original participants have come to autopsy. About a quarter of those who died without SMC or impairment had moderate to severe Aβ pathology in the brain, as did roughly a third of those who declared an SMC but did not progress to MCI or dementia. Of the 50 with SMC who became impaired, three-quarters accumulated abundant plaques and tangles. That amyloid built up in the SMC group but neurofibrillary tangles only appeared at impairment suggests that amyloid has an effect on cognition, said Jessen.

The researchers have not scanned the living volunteers to see if they have brain amyloid because PET amyloid ligands were not available when this study started, said Kryscio. He has no plans to add it at this point.

The study agrees with several others that use postmortem evidence or PET to correlate SMC with elevated amyloid build-up (see Barnes et al., 2006Perrotin et al., 2012Amariglio et al., 2012). It also jibes with a recent meta-analysis that found older people with SMC are twice as likely to develop dementia as people with no complaint (see Mitchell et al., 2014).

Researchers have yet to agree on a standard way to measure SMC, said Ron Petersen, Mayo Clinic, Rochester, Minnesota. The single survey question used in the Kryscio study captures some element of subjective concern but is quite basic, he said. Predicting whether an SMC could lead to dementia may depend on the type of memory change, suggested one study (see Amariglio et al., 2011).

Results imply that getting lost in familiar places or being unable to follow a group conversation predict future cognitive decline better than forgetting things from one second to the next.

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Jealous, Moody Women and Alzheimer’s Risk

(WebMD) Middle-aged women with a neurotic personality style and prolonged stress may have a heightened risk of developing Alzheimer’s disease, new research suggests.

Tracking 800 women over nearly four decades, Swedish scientists found that those who were most anxious, jealous and moody — which they defined as neurotic — and experienced long-standing stress had double the risk of developing Alzheimer’s compared to women scoring lowest in these traits.

“No other study has shown that [one style of] midlife personality increased the risk of Alzheimer’s disease over a period of nearly 40 years,” said study author Lena Johansson, a researcher at University of Gothenburg.

Outside experts cautioned, however, that the study results don’t prove that neuroticism triggers Alzheimer’s, but they do suggest an association between the two.

The study is published online Oct. 1 in the journal Neurology.

The most common type of dementia, Alzheimer’s disease causes profound memory loss and impairments in language, focus, judgment and visual perception, according to the Alzheimer’s Association. About 5.2 million Americans have been diagnosed with Alzheimer’s, which is progressive, incurable and ultimately fatal.

Johansson said she believes the results would also be true for men. But study data — pulled from research that began in the 1960s — happened to include only women in an era when few medical studies focused on females.

In the new study, participants with an average age of 46 were tracked for 38 years and given memory tests and personality tests measuring their levels of neuroticism and extraversion (defined as being outgoing) and introversion (defined as reserved or shy).

Study authors defined neuroticism as being easily distressed and exhibiting personality traits such as anxiety, jealousy or moodiness. People with this personality style are more likely, they said, to express guilt, anger, envy, worry and depression.

The women were also asked if they had experienced any period of prolonged stress lasting one month or longer and to rate their stress on a scale from zero to five, which represented constant stress during the previous five years. Stress responses included nervousness, sleep disturbances, fearfulness, irritability and tension.

Being introverted or extroverted alone didn’t seem to affect dementia risk, but women who were both easily distressed and withdrawn (introverted) had the highest risk of Alzheimer’s among all women analyzed. One-quarter of them developed the disease, compared to only 13 percent of those considered outgoing (extroverted) and not easily distressed.

“We know genetics drives personality and disease itself, but there’s very little understanding of how personality drives disease,” said Dean Hartley, director of science initiatives for the Alzheimer’s Association, who was not involved in the research. “We need more data.”

Just how might personality influence the risk for dementia? By influencing a person’s behavior, lifestyle or stress reactions, all of which affect overall health, Johansson said. Also, prior research has indicated that neuroticism and stress are associated with changes in the hippocampus, a brain structure affected early in Alzheimer’s disease.

Hartley said the new research was limited in its ability to measure participants’ actual stress levels, since it did so by asking them a single question about stress every five years instead of measuring specific biochemical responses to stress.

“Future studies should examine . . . whether this [neurotic] group responds well to interventions,” Johansson said. “It remains to be seen whether neuroticism could be modified by medical treatment or through lifestyle changes.”

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Protein that Causes Frontotemporal Dementia also Implicated in Alzheimer’s Disease

(Gladstone Institutes) Researchers at the Gladstone Institutes have shown that low levels of the protein progranulin in the brain can increase the formation of amyloid-beta plaques (a hallmark of Alzheimer’s disease), cause neuroinflammation, and worsen memory deficits in a mouse model of this condition. Conversely, by using a gene therapy approach to elevate progranulin levels, scientists were able to prevent these abnormalities and block cell death in this model.

Progranulin deficiency is known to cause another neurodegenerative disorder, frontotemporal dementia (FTD), but its role in Alzheimer’s disease was previously unclear. Although the two conditions are similar, FTD is associated with greater injury to cells in the frontal cortex, causing behavioral and personality changes, whereas Alzheimer’s disease predominantly affects memory centers in the hippocampus and temporal cortex.

Earlier research showed that progranulin levels were elevated near plaques in the brains of patients with Alzheimer’s disease, but it was unknown whether this effect counteracted or exacerbated neurodegeneration. The new evidence, published today in Nature Medicine, shows that a reduction of the protein can severely aggravate symptoms, while increases in progranulin may be the brain’s attempt at fighting the inflammation associated with the disease.

plaquesPlaques

According to first author S. Sakura Minami, PhD, a postdoctoral fellow at the Gladstone Institutes, “This is the first study providing evidence for a protective role of progranulin in Alzheimer’s disease. Prior research had shown a link between Alzheimer’s and progranulin, but the nature of the association was unclear. Our study demonstrates that progranulin deficiency may promote Alzheimer’s disease, with decreased levels rendering the brain vulnerable to amyloid-beta toxicity.”

In the study, the researchers manipulated several different mouse models of Alzheimer’s disease, genetically raising or lowering their progranulin levels. Reducing progranulin markedly increased amyloid-beta plaque deposits in the brain as well as memory impairments. Progranulin deficiency also triggered an over-active immune response in the brain, which can contribute to neurological disorders. In contrast, increasing progranulin levels via gene therapy effectively lowered amyloid beta levels, protecting against cell toxicity and reversing the cognitive deficits typically seen in these Alzheimer’s models.

These effects appear to be linked to progranulin’s involvement in phagocytosis, a type of cellular house-keeping whereby cells “eat” other dead cells, debris, and large molecules. Low levels of progranulin can impair this process, leading to increased amyloid beta deposition. Conversely, increasing progranulin levels enhanced phagocytosis, decreasing the plaque load and preventing neuron death.

“The profound protective effects of progranulin against both amyloid-beta deposits and cell toxicity have important therapeutic implications,” said senior author Li Gan, PhD, an associate investigator at Gladstone and associate professor of neurology at the University of California, San Francisco. “The next step will be to develop progranulin-enhancing approaches that can be used as potential novel treatments, not only for frontotemporal dementia, but also for Alzheimer’s disease.”

Other authors on the study include Sang-Won Min, Grietje Krabbe, Chao Wang, Yungui Zhou, Rustam Asgarov, Yaqiao Li, Lauren Martens, Lisa Elia, Michael Ward, Lennart Mucke, and Robert Farese. Funding for the research was provided by the Consortium for Frontotemporal Dementia, National Institutes of Health, and the S. D. Bechtel, Jr. Foundation.

About the Gladstone Institutes

To ensure our work does the greatest good, the Gladstone Institutes focus on conditions with profound medical, economic, and social impact – unsolved diseases of the brain, the heart, and the immune system. Affiliated with the University of California, San Francisco, Gladstone is an independent, nonprofit life science research organization that uses visionary science and technology to overcome disease.

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