New Research Advances from the Alzheimer's Association International Conference on Alzheimer's Disease 2010

This week, nearly 4,000 scientists from around the world gathered to report and discuss the latest advances in research on treatments, risk factors, and diagnosis for the health epidemic of the 21st century – Alzheimer's disease – at the Alzheimer's Association's 2010 International Conference on Alzheimer's Disease (AAICAD 2010) in Honolulu.

"With an aging baby boomer generation, the Alzheimer's disease crisis will continue to touch more lives and create an unsustainable fiscal toll on the nation's healthcare system – particularly Medicare and Medicaid," said William Thies, PhD, Chief Medical and Scientific Officer at the Alzheimer's Association.

"This week we saw promising investigations being pursued on a variety of fronts – avenues that could very well lead to significant changes in Alzheimer diagnosis and treatment. However, the chronic underinvestment in Alzheimer research continues to be the greatest obstacle to bringing new, more effective therapies to people," Thies said.

"Every day, researchers go to work with the sole purpose of advancing our understanding and knowledge about Alzheimer's, which is the defining disease of the baby boomer generation. We need a government response that shows equal commitment by providing the level of funding for research that will get us better diagnostic tests, treatments, and a cure," Thies added.

Highlights from the AAICAD 2010 included:

• The Alzheimer's Association announced the launch of Alzheimer's Association TrialMatchTM, a confidential, free, and interactive tool that provides comprehensive clinical trial information and an individualized trial matching service for people with Alzheimer's disease and related dementias. The Internet (www.alz.org/trialmatch) and phone-based (800-272-3900) program provides a first-of-its-kind service in Alzheimer's by delivering individualized matches to clinical trials for people with Alzheimer's, their healthcare professionals, caregivers, and healthy volunteers.
  
• The Dementia Demonstration Project (DDP), an interdisciplinary effort led by the Geriatric Research, Education and Clinic Center at the Minneapolis Veterans (VA) Medical Center, found that early detection, diagnosis and care management for people newly diagnosed with cognitive impairment and dementia can reduce outpatient costs by almost 30 percent. Veterans in the study who were diagnosed in the DDP clinics saw their average outpatient healthcare costs decline by an average of $1,991 in the year after diagnosis of cognitive impairment compared with the year before diagnosis. In the DDP clinics, following evaluation, the dementia care team met with the patient and family to review the results, discuss the diagnosis, and outline treatment recommendations. Informational material, assistance in identifying needed services, and direct support and training from team members was provided, as needed.
  
• Evidence from three long-term, large-scale studies (Framingham Study, Cardiovascular Health Study, NHANES III) supports the association of physical activity and certain dietary elements (tea, vitamin D) with possibly maintaining cognitive ability and reducing dementia risk in older adults. Plus, a new study in an animal model of Alzheimer's reported today at AAICAD 2010 suggests that an antioxidant-rich diet with walnuts may benefit brain function. Research has pointed towards a number of factors that may impact our risk of Alzheimer's and cognitive decline, the strongest being reducing cardiovascular risk factors. The Alzheimer's Association and others have repeatedly called for longer-term, larger-scale research studies to clarify the roles that these factors play in the health of the aging brain. These studies from AAICAD 2010 are some of the first reports of this type in Alzheimer's, and that is encouraging, but it is not yet definitive evidence.
  
• Scientists at AAICAD 2010 presented the first draft reports from three workgroups – covering Alzheimer's disease dementia, mild cognitive impairment (MCI) due to Alzheimer's disease, and preclinical Alzheimer's disease – convened by the National Institute on Aging (NIA) and the Alzheimer's Association to update the diagnostic criteria for Alzheimer's disease for the first time in 25 years. The proposals would change the existing criteria by better reflecting the various stages of the disease and the inclusion of Alzheimer's disease biomarkers. While the role of biomarkers differs in each of the three stages, much remains to be understood concerning their reliability and validity in diagnosis. This makes it critical that any new recommendations be thoroughly tested. Further input will be solicited by the NIA and the Association through a website launched immediately after the AAICAD presentations at www.alz.org/research/diagnostic_criteria.
  
• The primary therapeutic target in Alzheimer's disease has been the beta amyloid peptide, which clusters outside cells in the brain to form sticky clumps known as plaques. Recently, more attention has been given to the tau protein, which aggregates inside the brain cells of people with Alzheimer's, forming neurofibrillary tangles. Four new, though very preliminary, research studies reported at AAICAD 2010 described experimental immunotherapies for Alzheimer's – two of which target tau directly and two of which may reduce tau even though their primary target was beta amyloid. Importantly, these studies teach us more not only about tau-targeted therapies but also about the progression of Alzheimer's disease. It may be that amyloid changes in the brain happen early in Alzheimer's, and tau-related changes happen "downstream" where they have a more direct effect on cognitive function. Thus, immunotherapy treatments targeting amyloid may also alter neurodegenerative processes that occur later in the disease. However, this is still to be determined.
  
• In an early finding reported at AAICAD 2010, a gene known as FTO, which appears to be correlated with obesity in humans, may also increase risk of Alzheimer's disease and dementia. When a person has certain variants of both FTO and a recognized Alzheimer's risk gene known as APOE, the risk of Alzheimer's could be doubled. FTO has previously been shown to affect body mass index (BMI) and the risk for diabetes. These vascular risk factors have also been associated with risk of Alzheimer's disease. However, the researchers found that the increased risk was independent of these traits, suggesting that there is a different mechanism by which FTO is associated with an increased risk for Alzheimer's. We need to see these results confirmed by other researchers. In fact, we need to know more, in general, about the genetics and other causes of Alzheimer's so that we have additional targets for therapies and preventions.
  
• Last minute scientific submissions to AAICAD 2010, known as "hot topics," suggested that (1) a newly-discovered risk gene for Alzheimer's may have early impact on memory skills and brain volume, (2) intranasal insulin may be beneficial in Alzheimer's, and (3) beta amyloid deposits in the brains of people with Alzheimer's disease may take different shapes based on a known Alzheimer's risk gene.
  
  
  • Two studies reported at AAICAD 2010 give us more information about the TOMM40 gene – a newly identified risk gene for Alzheimer's. They found that healthy, middle aged people who have the high risk version of TOMM40 (a) did worse on memory tests and (b) had reduced brain volume in two regions affected early in Alzheimer's.
    
  • A short-term (4 months) clinical trial of intranasal insulin in Alzheimer's and mild cognitive impairment (MCI) showed statistically significant benefits on certain tests of memory and functioning, but no changes on others. In those who showed benefits on memory tests, there were also positive changes in Alzheimer's biomarkers in spinal fluid. Larger, longer-term studies are planned.
    
  • Researchers using a new imaging tool suggest that there are different shapes of beta amyloid deposits in the Alzheimer brain based on which version a person has of a well-established Alzheimer's risk gene, known as APOE. This may be especially important because in some recent drug trials the therapy provided benefits in people who had certain types of APOE but were less effective or not effective in others.
  
  
  
• Two new studies from AAICAD 2010 suggest that having Alzheimer's disease may increase the risk of getting other potentially disabling health conditions, including seizures and anemia. Researchers in one study found that that the rate of seizures, per 1,000 people per year, in a study population that included 14,838 people with Alzheimer's aged 50 years or older and 14,838 randomly-selected, age- and sex-matched people without Alzheimer's, was 9.1 among patients with Alzheimer's compared with 1.4 for those without Alzheimer's – an incidence rate that was 6.4 times higher. In a second study of 1,112 older adults (768 healthy controls, 133 MCI, 211 Alzheimer's), people with anemia were found to have an increased risk of Alzheimer's (odds ratio: 2.56). And people with Alzheimer's in the study were found to have an increased risk of being anemic (odds ratio: 2.61). If Alzheimer's also increases risk of other disabling conditions, then its impact may be more devastating than we've envisioned as the global population ages and as more countries become westernized in their habits and lifest
  
• Racially and ethnically diverse older adults are one of the fastest growing population segments in the United States. New research presented AAICAD 2010 revealed that older African-Americans and Latinos with significant cognitive impairment have a lower likelihood of nursing home placement and longer survival than White older adults in the study. These results have significant implications for caregiver burden and community resources. There is a greater than anticipated need for culturally-appropriate dementia care resources and home and community- based services for these populations.
  
  
  • These findings are particularly compelling since African-Americans are about two times more likely and Latinos about one and one-half times more likely to develop Alzheimer's and dementia than Whites, according to the Alzheimer's Association's 2010 Alzheimer's Disease Facts and Figures report.
    
  • Another study reported at AAICAD 2010 suggests that the bereavement process and mourning experience for Alzheimer caregivers after the death of their loved one varies greatly among different racial and ethnic groups.
    
  • A third research report suggested that cultural and spiritual beliefs of African-Americans, American Indians and Whites greatly influence how long it takes for a family to seek a medical diagnosis of Alzheimer's.

Please visit alz.org for more information.

"Hot Topics" from the Alzheimer's Association International Conference on Alzheimer's Disease 2010

-New Alzheimer's Risk Gene May Affect Memory Scores and Brain Atrophy in Middle Age
-Clinical Trial of Intranasal Insulin Shows Benefits in Alzheimer's and MCI
-Known Alzheimer's Risk Gene May Change Shape of Brain Deposits

Last minute scientific submissions to the Alzheimer's Association International Conference on Alzheimer's Disease 2010 (AAICAD 2010) in Honolulu, HI, known as "hot topics," suggest that (1) a newly-discovered risk gene for Alzheimer's may have early impact on memory skills and brain volume, (2) intranasal insulin may be beneficial in Alzheimer's, and (3) beta amyloid deposits in the brains of people with Alzheimer's disease may take different shapes based on a known Alzheimer's risk gene.

• Two studies reported at AAICAD 2010 give us more information about the TOMM40 gene – a newly identified risk gene for Alzheimer's. They found that healthy, middle aged people who have the high risk version of TOMM40 (a) did worse on memory tests and (b) had reduced brain volume in two regions affected early in Alzheimer's.
  
• A short-term trial of intranasal insulin in Alzheimer's and MCI showed statistically significant benefits on certain tests of memory and functioning, but no changes on some others. In those who showed benefits on memory tests, there were also positive changes in Alzheimer's biomarkers in spinal fluid.
  
• Researchers using a new imaging tool suggest that there are different shapes of beta amyloid deposits in the Alzheimer brain based on which version a person has of a well-established Alzheimer's risk gene, known as APOE. This may be especially important because in some recent drug trials the therapy provided benefits in people who had certain types of APOE but were less effective or not effective in others.

"These are some of the fantastic findings from this year's AAICAD, full of potential to move the field forward," said William Thies, PhD, Alzheimer's Association Chief Medical and Scientific Officer. "But there is too little happening in the field, and no plan in place from the federal government to stem the massive wave of Alzheimer's coming with the aging of the Baby Boomers."

"Alzheimer's is clearly the #1 public health challenge of the 21st century and research is the only way to solve this problem," Thies added. "There are more than 5 million Americans with the disease and about 11 million caregivers supporting them. Reliable estimates say that by 2050 those numbers could triple. Government must make an investment in Alzheimer research that proves they understand what's at stake – for individuals, families, the healthcare system, and the nation as a whole."

New Risk Gene for Alzheimer's is Associated with Poorer Memory Function and Grey Matter Loss in Middle Aged Persons Without Dementia

The TOMM40 gene has very recently been shown to influence age of onset in Alzheimer's disease. Two studies reported at AAICAD 2010 give us more information about this newly identified risk gene for Alzheimer's; they found that middle aged people without dementia who have the high risk version of the TOMM40 gene did worse on tests of memory and learning and had reduced brain volume in two regions that are often affected early in the course of Alzheimer's.

"These are exciting, initial results, but the exact role that TOMM40 plays in Alzheimer's remains to be determined," said William Thies, PhD, Chief Medical and Scientific Officer at the Alzheimer's Association. "The story of TOMM40 is evolving and may give us new insights into Alzheimer's disease."

"We desperately need to know more about the causes of Alzheimer's, and the factors that affect our risk of getting or not getting the disease. This kind of research will provide more targets for therapies and prevention strategies," Thies said.

In one study, Mark Sager, MD, of the University of Wisconsin Medical School, and colleagues studied a total of 726 people in middle-age with a family history of Alzheimer's from the Wisconsin Registry for Alzheimer's Prevention who were genotyped for TOMM40 and APOE, the latter of which is a well-established risk gene for Alzheimer's. Of these, 129 had the low risk version of TOMM40 and 229 had the high risk version. The average age of the study population was 54.

The researchers found that the group with the high risk version of the TOMM40 gene performed significantly worse on the tests of learning and memory (Rey Auditory Verbal Learning Test) than the group with the low risk version. These results remained significant regardless of APOE gene type.

"The deficits shown by the high risk group are similar to the kinds of changes in memory and learning that are seen in very early Alzheimer's," Sager said. "In this study population, TOMM40 genotyping is allowing us to find evidence of very early Alzheimer's disease at least 20 years before people begin to show the outward symptoms. This is a step forward in Alzheimer's prevention research."

In a second study, Sterling Johnson, PhD, also of the University of Wisconsin School of Medicine and Public Health, and colleagues found that among healthy, middle aged adults (mean age 57) who have the APOE e3/e3 gene type, those with the high risk version of the TOMM40 gene had significantly less gray matter volume in two brain regions affected early in Alzheimer's disease than those with the low risk version of the gene.

According to the researchers, the study suggests that there is a connection between TOMM40 and brain cell loss in people who are relatively young and currently not symptomatic.

"This is the first study to associate TOMM40 to brain imaging in people at risk for Alzheimer's disease," Johnson said. "The brain differences between TOMM40 groups were very similar but less severe that what is observed in full-blown Alzheimer's. It may be that the TOMM40 gene will be a useful measure of Alzheimer's risk in middle-age, but additional research with longitudinal follow-up is needed."

Allen Roses, MD, and colleagues at Duke University first discovered that the TOMM40 gene helped explain differences in age of onset among people with sporadic Alzheimer's disease.

Clinical Trial of Intranasal Insulin Shows Some Benefits in Alzheimer's and MCI

Previous research has strongly suggested that Alzheimer's and diabetes/insulin resistance are closely related. For example, Alzheimer's is associated with reduced brain insulin signaling and low levels of insulin in cerebrospinal fluid (CSF).

"These deficiencies may reduce or eliminate insulin's beneficial roles in the brain," said Suzanne Craft, PhD, of VA Puget Sound Health Care System/University of Washington in Seattle. "We believe that restoring normal insulin function in the brain may provide therapeutic benefits to adults with Alzheimer's. Intranasal administration enables insulin to access brain regions that are compromised in Alzheimer's."

Craft and colleagues had previously shown enhanced cognition and daily functioning in adults with MCI and early Alzheimer's using intranasal insulin treatment for 21 days. This new study expanded the time frame to four months, during which 109 participants with MCI or Alzheimer's received either placebo, or 20 or 40 IU daily intranasal insulin treatment.

The researchers found that in the 20 IU dose group (10 IU twice daily) results on a test of delayed story recall significantly improved compared with those who received placebo, as did functional status measured by the Dementia Severity Rating Scale. Improvements in delayed memory recall persisted for two months after the insulin treatment ended. However, memory and learning on the ADAS-Cog and ability to do activities of daily living measured by the ADCS-ADL scores were unchanged.

For 15 of the insulin-treated participants who agreed to have a spinal tap, improved memory and functional status were associated with an improved Alzheimer's biomarker profile as reflected by a lowered CSF tau/Aβ42 ratio.

"These results provide encouraging support for further study of intranasal insulin as a therapy for Alzheimer's," Craft said. "We are currently planning a large, multi-center clinical trial."

New Imaging Compounds for Alzheimer's Protein Deposits in the Brain Show that Different Forms of the APOE Risk Gene Create Different Shapes of Beta Amyloid

A new class of biomarkers has been discovered that can stick to protein structures in the body and emit colors reflecting the different shapes or forms of the proteins. They are called luminescent conjugated oligothiophenes (LCOs) or luminescent conjugated polymers (LCPs). Among other uses, they are currently being employed in test tubes, animal models and autopsied Alzheimer's brains to study the structure of proteins deposits caused by the disease. The new markers bind to the two well-established hallmarks of Alzheimer's – beta amyloid plaques and tau tangles – and glow different colors depending on which forms of the deposits they "stick" to (e.g., plaques often "glow" orange, while tangles "glow" yellowish green).

In this study reported at AAICAD 2010, Sam Gandy, MD, PhD, of Mount Sinai School of Medicine, New York, and colleagues used LCOs/LCPs to investigate the possibility that the shape of brain protein deposits in people with Alzheimer's who have the APOE ε4/ε4 gene type (highest risk) is different from those having APOE ε3/ε3 (neutral risk).

Frozen brain sections from people who died with Alzheimer's were stained using two LCPs/LCOs: pentamer formyl thiophene acetic acid (pFTAA) and polythiophene acetic acid (PTAA). Using PTAA, the researchers observed that Alzheimer patients with APOE ε4/ε4 had core and cerebrovascular amyloid of different shapes, while in people with APOE ε3/ε3 the two amyloid structures had the same shape. Using pFTAA revealed that tau tangle densities in ε4/ε4 Alzheimer patients that were apparently greater than those with ε3/ε3.

"The findings support our hypothesis that APOE genotype changes amyloid structure," Gandy said. "This is important because the different shapes might respond differently to treatments that attempt to clear amyloid deposits from the brain."

In some recent drug trials, the experimental therapy provided benefits in people who had a certain type of the APOE gene (known as ε3) but were less or not effective in another type (ε4).

LCOs/LCPs were pioneered by Peter Nilsson of the Department of Chemistry, Linköping University, Sweden. The study also involved collaborating teams from Charité – Universitätsmedizin Berlin, Germany (led by Frank Heppner), Washington University, St Louis (led by David Holtzman), and other labs at Mount Sinai (led by Patrick Hof and Dara Dickstein).

Please visit alz.org for more information.

Alzheimer's Disease may Increase Risk of Anemia and Seizures

Global Impact Could Multiply As The Population Continues to Age

Having Alzheimer's disease may increase the risk of getting other potentially disabling health conditions, including seizures and anemia, according to new research presented today at the Alzheimer's Association International Conference on Alzheimer's Disease 2010 (AAICAD 2010) in Honolulu, HI.

"Alzheimer's disease is a global health crisis with devastating effects on individuals, families, and national healthcare systems," said William Thies, PhD, Chief Medical and Scientific Officer at the Alzheimer's Association. "If, in fact, Alzheimer's also increases risk of other disabling conditions, then its impact may be more devastating than we've envisioned as the global population ages and as more countries become westernized in their habits and lifestyles."

According to the 2009 World Alzheimer Report from Alzheimer's Disease International, a London-based nonprofit, international federation of 71 national Alzheimer organizations including the Alzheimer's Association, the number of people with Alzheimer's or another dementia, currently 35 million, is expected to nearly double every 20 years, to 65.7 million in 2030 and 115.4 million in 2050.

Worldwide, the economic cost of dementia has been estimated as $315 billion annually. (Wimo, et al. "An Estimate of the Total Worldwide Societal Costs of Dementia in 2005." Alzheimer's & Dementia: The Journal of the Alzheimer's Association. Vol. 3, Issue 2, April 2007.)

Alzheimer's is Associated with Increased Incidence of Seizures

Some small studies have shown Alzheimer's to be a risk factor for seizures. H. Michael Arrighi, PhD, of Janssen Alzheimer Immunotherapy Research & Development; Nicole Baker, MPH, Pfizer; and colleagues conducted an observational study to estimate the incidence rate of seizures among a large cohort of people with Alzheimer's. The researchers used anonymized electronic medical records from nearly 400 primary medical practices in the United Kingdom. The study population included 14,838 people with Alzheimer's aged 50 years or older and a comparison cohort of 14,838 randomly-selected, age- and sex-matched patients without Alzheimer's. People with Alzheimer's were followed for an average of 2.3 years; non-Alzheimer's patients were followed for an average of 3.4 years.

Over that time period, the researchers found that the rate of seizures, per 1,000 people per year, was 9.1 among patients with Alzheimer's disease compared with 1.4 for those without Alzheimer's – an incidence rate that was 6.4 times higher. In addition, they found that the incidence rate of seizures was highest among the youngest Alzheimer's patients, and that it decreased with age. Incidence among non-Alzheimer's patients increased slightly with age.

"The increased risk of seizures among patients with Alzheimer's disease was seen in all age groups, but there was a substantial increase among the youngest patients. It is especially important for these patients and their caregivers to be aware of this risk," Baker said.

"The connection between Alzheimer's and seizures provides additional avenues for research into the basic biology of both diseases, and possibly interventions and therapies to respond to the overall impact of Alzheimer's disease" Arrighi said.

Alzheimer's is Associated with Lower Hemoglobin Levels and Anemia

Studies suggest that iron accumulates in the tau tangles in the brains of people with Alzheimer's, and that overall levels of iron are elevated in both Alzheimer's and Mild Cognitive Impairment (MCI) brains. However, it is not clear from the scientific literature if this altered brain iron profile is reflected in plasma iron levels.

Noel Faux, PhD, of the Mental Health Research Institute, Parkville, Australia, and colleagues examined hemoglobin, iron and other blood-based measurements in the 1,112 participants (768 healthy controls, 133 MCI, 211 Alzheimer's) of the Australian Imaging Biomarkers and Lifestyle (AIBL) study of Ageing. Participants also completed questionnaires on diet and medication intake (including supplements). Results were then correlated with measures of short-term, long-term and total memory, and global cognition.

The researchers found that people with Alzheimer's in the study had significantly lower levels of hemoglobin, mean cell hemoglobin concentration (MCHC), and packed cell volume compared with healthy controls, after adjustment for age and gender. Consistent with these data, the erythrocyte sedimentation rate (ESR) was significantly higher in Alzheimer's compared to healthy controls.

Participants with anemia in the study were found to have an increased risk of Alzheimer's (odds ratio: 2.56). And people with Alzheimer's in the study were found to have an increased risk of being anemic (odds ratio: 2.61). Self reported iron intake was not different in the two groups.

"In our population, we found that people with Alzheimer's disease were more likely to be anemic, and this was not explained by dietary iron deficiency," Faux said. "This suggests that hemoglobin production is deficient in Alzheimer's patients."

"Alzheimer's had not previously been recognized as a risk factor for anemia, which is a common clinical problem for the elderly and can contribute to problems such as heart failure and renal failure," Faux continued. "The cause of anemia in Alzheimer's is still uncertain, but we speculate that Alzheimer's is a disease that affects both brain and blood. We are currently investigating this intriguing possibility."

Please visit alz.org for more information.

New Study: A gene known as FTO, which appears to be correlated with obesity in humans, may also increase risk of Alzheimer's disease and dementia

- When Combined with a Known Alzheimer's Gene, Your Alzheimer's Risk may be Doubled -

A gene known as FTO, which appears to be correlated with obesity in humans, may also increase risk of Alzheimer's disease and dementia, according to new research presented today at the Alzheimer's Association International Conference on Alzheimer's Disease 2010 (AAICAD 2010) in Honolulu, HI. And when a person has certain variants of both FTO and a recognized Alzheimer's risk gene known as APOE, the risk of Alzheimer's could be doubled.

"While scientists know Alzheimer's involves progressive brain cell failure, they have not yet identified any single reason why cells fail," said Maria Carrillo, PhD, senior director of Medical and Scientific Relations at the Alzheimer's Association. "However, there is evidence about certain factors that may increase the likelihood of developing Alzheimer's."

"Some of these factors we can't control, such as age, family history, and genetics," Carrillo said. "Others we may be able to influence, including heart health, tobacco and alcohol use, and head injury."

FTO has previously been shown to affect body mass index (BMI), leptin levels (a protein hormone that plays a key role in appetite and metabolism), and the risk for diabetes. These vascular risk factors have also been associated with risk of Alzheimer's disease.

In the study reported at AAICAD 2010, Caroline Graff, MD, PhD, and colleagues at the Karolinska Institutet, Sweden, explored the direct role of the FTO gene on Alzheimer's and dementia risk in old age. In addition, a possible interaction of FTO with the APOE gene, a well-established genetic risk factor for Alzheimer's, was assessed. The researchers followed 1,003 people aged 75 years and older without dementia from the Kungsholmen project, Sweden, for nine years to detect new cases of Alzheimer's and dementia. All participants had been genotyped for FTO and APOE on DNA sampled at the beginning of the study.

They found that people in the study population who carried the AA gene-variant in the FTO gene had a 58 percent increased risk for developing Alzheimer's and a 48 percent increased risk for developing dementia compared with those who did not have this genetic variant, after adjustment for age, gender, education, and APOE genotype.

The findings also suggest that the risk-effect of FTO-AA on dementia is further elevated to 100 percent increased risk in the presence of APOE ε4, which is the highest risk variant of the APOE gene. The effect of the FTO-AA genotype on Alzheimer's and dementia risk remained after additional adjustment for diabetes, BMI, cardiovascular disease and physical inactivity.

"One of the intriguing aspects of the results is that the increased risk was independent of the traits previously associated with FTO, such as obesity and diabetes measured at baseline," Graff said. "Our results suggest that the mechanism by which FTO is associated with an increased risk for Alzheimer's and dementia may be different from how it increases the risk for obesity."

"This is a fascinating early finding, which fits with the known connections between heart health and brain health," Carrillo said. "However we do need to see these results confirmed by other researchers. In fact, we desperately need to know more, in general, about the genetics and other causes of Alzheimer's so that we have additional targets for therapies and preventions. One major positive step in that direction would be for the federal government to address its chronic underfunding of Alzheimer's disease research."

Please visit alz.org for more information.

Large-Scale, Long-Term Studies Support Roles of Physical Activity and Diet in Dementia and Cognitive Decline

- Also, Antioxidant–Rich Diet Improves Memory and Learning in Alzheimer's Mice -



Honolulu, Hawaii, July 11, 2010 – Evidence from three long-term, large-scale studies supports the association of physical activity and certain dietary elements (tea, vitamin D) with possibly maintaining cognitive ability and reducing dementia risk in older adults, according to new research presented today at the Alzheimer's Association International Conference on Alzheimer's Disease 2010 (AAICAD 2010) in Honolulu, HI.

Plus, a new study in an animal model of Alzheimer's reported today at AAICAD 2010 suggests that an antioxidant-rich diet with walnuts may benefit brain function.

"Research has pointed us towards a number of factors that may impact our risk of Alzheimer's and cognitive decline, the strongest being reducing cardiovascular risk factors," said William Thies, PhD, Chief Medical and Scientific Officer at the Alzheimer's Association. "The Alzheimer's Association and others have repeatedly called for longer-term, larger-scale research studies to clarify the roles that these factors play in the health of the aging brain."

"These are some of the first reports of this type in Alzheimer's, and that is encouraging, but it is not yet definitive evidence," Thies continued. "Longitudinal studies and clinical trials are expensive, and I'm deeply concerned that the trials we need will not happen because of the chronic underfunding of Alzheimer research by the federal government."

Framingham Study Shows Physical Activity Lowers Risk of Dementia, Especially in Men

Several long-term epidemiological studies have related physical activity and cognitive decline, dementia and/or Alzheimer's disease, although the results of published research studies thus far are not entirely consistent and several large studies failed to show an association. Most of these studies followed participants for less than six years or had significant loss to follow-up. Still needed are studies including long-term follow-up in older persons in age brackets at higher risk of incident Alzheimer's to elucidate the true relationship.

One such long-term trial is the Framingham Study, a population-based study that has followed participants residing in the town of Framingham, Massachusetts since 1948 for cardiovascular risk factors, and is now also tracking cognitive performance. Framingham is widely acknowledged as a premier longitudinal study; it has continued to yield valuable information for more than 40 years.

Zaldy Tan, MD, MPH, of Brigham and Women's Hospital, GRECC, VA Boston, and Harvard Medical School, and colleagues estimated the levels of 24-hour physical activity of more than 1,200 elderly participants from the Framingham Study (742 female; age 76 +\-5) during the study's 20th examination cycle (1986-87) and followed them for the development of dementia. They divided the participants into five groups based on level of physical activity, from lowest (Q1) to highest (Q5).

Over two decades of follow-up (mean 9.9 +/-5 years), 242 participants developed dementia (of which 193 were Alzheimer's). The researchers found that participants who performed moderate to heavy levels of physical activity had about a 40 percent lower risk of developing any type of dementia. Further, people who reported the lowest levels of physical activity were 45 percent more likely to develop any type of dementia compared to those who reported higher levels of activity. Similar results were seen when analyses were limited to Alzheimer's alone. Analyses showed that the observed associations were largely evident in men in the study.

"This is the first study to follow a large group of individuals for this long a period of time," Tan said. "It suggests that lowering the risk for dementia may be one additional benefit of maintaining at least moderate physical activity, even into the eighth decade of life."

Tea Consumption Slows Cognitive Decline in the Cardiovascular Health Study

Observational studies have shown associations between consumption of either tea or coffee and cognitive function in older adults, but data including long-term follow-up and rate of change in cognitive function are lacking.

Lenore Arab, PhD, of UCLA, and colleagues used data on more than 4,800 men and women aged 65 and older from the Cardiovascular Health Study to examine the relationship between consumption of tea, coffee, and change in cognitive function over time. Study participants were followed up for up to 14 years for naturally-occurring cognitive decline using the Mini-Mental State Examination (3MSE) administered at baseline and annually up to 8 times. People scored on the average 1.17 points less per year. Tea and coffee drinking were assessed using a food frequency questionnaire.

The researchers found that people who consumed tea at a variety of levels had significantly less cognitive decline (17-37 percent) than non-tea drinkers. More specifically, study participants who drank tea 5-10 times/year, 1-3 times/month, 1-4 times/week, and 5+ times/week had average annual rates of decline 17 percent, 32 percent, 37 percent, and 26 percent lower, respectively, than non-tea drinkers.

According to the scientists, coffee consumption did not show any effect except at the very highest level of consumption – where it was associated with significantly decreased decline of 20 percent.

"The suggestion of a positive effect of tea consumption in slowing cognitive decline requires further investigation," Arab said. "Interestingly, the observed associations are unlikely to be related to caffeine, which is present in coffee at levels 2-3 times higher than in tea."

Vitamin D Deficiency Increases Risk of Cognitive Impairment

Recent European studies suggest vitamin D deficiency is associated with increased odds of cognitive impairment and dementia in later life, although previous findings from the U.S. have been mixed. Interest in vitamin D has intensified recently as research has suggested that it may play a role in a variety of age-associated diseases.

David Llewellyn, PhD, of the University of Exeter Peninsula Medical School (UK), and colleagues examined information from 3,325 adults aged 65 years and older from the Third National Health and Nutrition Examination Survey (NHANES III), a study that was carefully designed to accurately represent the U.S. non-institutionalized population. Vitamin D levels were measured from blood samples and compared with performance on a measure of general cognitive function that incorporated tests of memory, orientation in time and space, and ability to maintain attention.

The researchers classified participants as being cognitively impaired if they scored in the worst 10 percent of older adults in the study. They found that the odds of cognitive impairment were about 42 percent higher in those people who were deficient in vitamin D, and 394 percent higher in people who were severely deficient.

"It appears that the odds of cognitive impairment increase as vitamin D levels go down, which is consistent with the findings of previous European studies," Llewellyn said. "Given that both vitamin D deficiency and dementia are common throughout the world, this is a major public health concern."

According to Llewellyn, the majority of older U.S. adults have insufficient vitamin D levels because skin becomes less efficient at producing vitamin D with age and sunlight (UVB radiation) levels are limited for much of the year.

"Vitamin D supplements have proven to be a safe, inexpensive and effective way to treat deficiency. However, few foods contain vitamin D and levels of supplementation in the U.S. are currently inadequate. More research is urgently needed to establish whether vitamin D supplementation has therapeutic potential for dementia," Llewellyn said.

Antioxidant–Rich Diet with Walnuts Improves Memory and Learning in Alzheimer's Mice

It has been suggested that oxidative stress may have a key role in Alzheimer's disease. Oxidative stress occurs when the production of free radicals exceeds the antioxidant capacity of a cell. Reports have suggested that beta amyloid can increase oxidative stress leading to brain cell death.

Walnuts are source of -linolenic acid (a plant-based omega-3 fatty acid) and have high content of antioxidants. In March 2004, the U.S. Food and Drug Administration said that "Supportive but not conclusive research shows that eating 1.5 ounces of walnuts per day, as part of a low saturated fat and low-cholesterol diet, and not resulting in increased caloric intake, may reduce the risk of coronary heart disease."

Abha Chauhan, PhD, and colleagues at the New York State Institute for Basic Research in Developmental Disabilities, examined the effect of diet containing 6 percent or 9 percent walnuts (equivalent to 1 oz. and 1.5 oz. daily intake of walnuts in people) on the cognitive, emotional and motor functions in a transgenic mouse model of Alzheimer's. The mice were fed custom-mix diets from the age of four months for nine to 15 months. Control mice were fed diet without walnuts. The experimental and control mice were examined at the age of 13 to 14 months and 18 to 19 months for spatial memory and learning ability, position discrimination learning ability, motor coordination, and anxiety-related behavior.

The researchers found that Alzheimer's transgenic mice on the diet without walnuts at both testing periods showed memory deficits, anxiety-related behavior, and severe impairment in spatial learning ability, position discrimination learning ability and motor coordination. The Alzheimer's transgenic mice on 6 percent walnuts diet and 9 percent walnuts diet showed significant improvement in learning, memory, emotional regulation and motor coordination compared to transgenic mice that did not eat walnuts. The effects of 6 percent and 9 percent walnuts diets were similar.

"Our results suggest protective effects of walnuts in the Alzheimer's mice," Chauhan said. "Dietary supplementation of walnuts may have beneficial effect on brain function, and deserves further study."

Four Researchers Given Lifetime Achievement Awards by the Alzheimer's Association

Honolulu, Hawaii; July 11, 2010 – The Alzheimer's Association recognized four scientists for their extraordinary achievements in advancing Alzheimer research at the Alzheimer's Association International Conference on Alzheimer's Disease 2010 (AAICAD 2010) in Honolulu, Hawaii.

Honorees for their professional and scientific contributions to Alzheimer research are:

•Takeshi Iwatsubo, MD, Department of Neuropathology, Graduate School of Medicine at the University of Tokyo.
•Karen H. Ashe, MD, PhD, Department of Neurology and Neuroscience Director at the University of Minnesota.
•Marsel Mesulam, MD, Dunbar Professor of Neurology and Psychiatry and Director of the Cognitive Neurology and Alzheimer's Disease Center at Northwestern University.
•Marilyn Albert, PhD, Director of the Division of Cognitive Neuroscience in the Department of Neurology at Johns Hopkins University School of Medicine.

"We are beginning to reap the benefits of Alzheimer's scientific advancements made in the last two decades, including a robust pipeline of anti-dementia drug therapies and advances in early detection," said William Thies, PhD, Chief Medical and Scientific Officer at the Alzheimer's Association. "These leading researchers, who have been in the vanguard of scientific advancements in Alzheimer's disease, have devoted their professional careers to greater understanding of this disease. Their dedication and commitment will help us defeat Alzheimer's – the public health threat of the 21st century – and create a world where future generations will not have to experience this progressive and fatal disease."

Lifetime Achievement Awards in Alzheimer's Disease Research
Henry Wisniewski, MD, PhD; Khalid Iqbal, PhD; and Bengt Winblad, MD, PhD, founded AAICAD in 1988. Lifetime Achievement Awards named in their honor are given to three outstanding scientists who have dedicated their careers to helping millions around the world through their research.

At AAICAD 2010, the 2010 Henry Wisniewski Lifetime Achievement Award was presented to Dr. Takehsi Iwatsubo, whose significant research with the Japanese Alzheimer's Disease Neuroimaging Initiative (J-ADNI) is creating a longitudinal workup of standardized neuroimaging, biomarker and clinico-psychological surveys. Designed to maximize compatibility with US-ADNI, it is hoped that this work along with other global ADNI efforts will establish rigorous, quantitative descriptions of the natural course of Alzheimer's in its very early stages.

The 2010 Khalid Iqbal Lifetime Achievement Award was presented to Dr. Karen Ashe, whose research focuses on animal and cellular models of Alzheimer's. These transgenic animal models enhance understanding of how amyloid and tau proteins – thought to be the keys to the cause and progression of Alzheimer's – impact memory and cognition. Transgenic mice have been a mainstay in the preclinical investigation of new treatments for Alzheimer's.

The 2010 Bengt Winblad Lifetime Achievement Award was presented to Dr. Marsel Mesulam. His research addresses the connectivity of the monkey brain, the organization of human cholinergic pathways, the representation of cognitive functions by large-scale neurocognitive networks, and the neurobiology of dementias. Dr. Mesulam's work on cholinergic pathways has been groundbreaking in understanding Alzheimer's. He is a world expert in Primary Progressive Aphasia.

Zaven Khachaturian Award
In addition to these three awards, Dr. Marilyn Albert was recipient of the 2010 Zaven Khachaturian Award at AAICAD. Named in honor of noted scientist, administrator, consultant, lecturer and author, Zaven Khachaturian, PhD, this award recognizes an individual whose compelling vision, selfless dedication, and extraordinary achievement has significantly advanced the field of Alzheimer science.

Dr. Albert's distinguished career includes more than two decades as a faculty member at Harvard University Medical School. Her research has primarily focused on the cognitive and brain changes associated with aging and Alzheimer's. The scope has also encompassed investigating potential methods of early identification of Alzheimer's and lifestyle factors that may maintain mental abilities with advancing age.

About AAICAD
The Alzheimer's Association International Conference on Alzheimer's Disease (AAICAD) is the world's largest conference of it's kind, bringing together researchers from around the world to report and discuss groundbreaking research and information on the cause, diagnosis, treatment and prevention of Alzheimer's disease and related disorders. As a part of the Alzheimer's Association's research program, AAICAD serves as a catalyst for generating new knowledge about dementia and fostering a vital, collegial research community.

About the Alzheimer's Association
The Alzheimer's Association is the leading voluntary health organization in Alzheimer care, support and research. Our mission is to eliminate Alzheimer's disease through the advancement of research, to provide and enhance care and support for all affected, and to reduce the risk of dementia through the promotion of brain health. Our vision is a world without Alzheimer's. Visit www.alz.org or call 800-272-3900.