Research Advances From 2014 Alzheimer's Association International Conference

COPENHAGEN, Denmark, July 16, 2014 /PRNewswire-USNewswire/ -- Results from four research studies reported as "developing topics" at the Alzheimer's Association International Conference^® 2014 (AAIC^® 2014) in Copenhagen include significant advances in evidence regarding treatment and early detection of Alzheimer's disease and dementia, as well as new ideas in the basic brain science of dementia that may lead to new diagnostic and treatment targets.

"Developing topics" at AAIC are authorized late submissions to the conference and often include last-minute calculations and data analyses. More than 150 developing topics abstracts were accepted this year out of the 2,431 total scientific presentations at AAIC 2014.  Following are four particularly noteworthy submissions:

• A two-year clinical trial in Finland of a multi-component lifestyle intervention in 1,260 older adults at risk for cognitive impairment and Alzheimer's showed that physical activity, nutritional guidance, cognitive training, social activities and management of heart health risk factors improved cognitive performance, both overall and in separate measures of executive function, such as planning abilities, and the relationship between cognitive functions and physical movement.
• A randomized trial in the U.K. involving family caregivers of people with dementia tested a short psychological support program delivered by graduate students. The intervention significantly reduced caregivers' anxiety and depression, and this impact lasted for two years. At AAIC 2014, the scientists also will report on the impact of the program on costs of care.
• In a post-mortem study of more than 340 brains of people identified after death as having Alzheimer's disease-related changes, researchers identified that a third abnormal protein, known as TDP-43, may play an important role in Alzheimer's along with well-known beta-amyloid and tau proteins. People with TDP-43 were 10 times more likely to have been cognitively impaired at death than those without it.
• A study in which cognitively normal seniors were measured for brain tau protein levels using positron emission tomography (PET) scans showed that memory decline was linked with higher levels of tau buildup in several brain regions, demonstrating the potential value of these scans in early detection of dementia and in identifying participants for research studies.

"AAIC is the premiere Alzheimer's and dementia research conference, and this year's developing topics are exciting both in their scope and in their findings," said Keith Fargo, Ph.D., Alzheimer's Association director of Scientific Programs & Outreach. "The science covers a lot of ground -- from the first large-scale, long-term clinical trial of a lifestyle-based treatment regimen, to an early detection technology that tracks well with cognitive decline, to a possible new target for therapy, which also is a possible explanation of why some people have Alzheimer's brain changes but no dementia. The study on the brain protein TDP-43 clearly demonstrates the value of basic research to feed the front end of the drug pipeline."

With the support of the Alzheimer's Association and the Alzheimer's community, the United States created its first National Plan to Address Alzheimer's Disease in 2012. The plan includes the critical goal, which was adopted by the G8 at the Dementia Summit in 2013, of preventing and effectively treating Alzheimer's by 2025. It is only through strong implementation and adequate funding of the Plan, including an additional $200 million in fiscal year 2015 for Alzheimer's research, that we'll meet that goal. For more information and to get involved, visit www.alz.org.

Lifestyle Changes Improve Memory and Thinking in At-Risk Older Adults in Two-Year Clinical Trial

Researchers have observed a number of modifiable risk factors associated with increased risk of late-life cognitive impairment and Alzheimer's disease, but recent short-term prevention trials focusing on single, isolated risk factors have had modest results, at best. Longer, larger, better controlled trials looking at modifying multiple risk factors have been needed.

At AAIC 2014, Miia Kivipelto, M.D., Ph.D., Professor at the Karolinska Institutet, Sweden and the National Institute for Health and Welfare, Helsinki, Finland, and colleagues reported on the results of the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), a two-year randomized controlled trial of 1,260 participants age 60 to 77 with modifiable risk factors for cognitive impairment and Alzheimer's. Randomized controlled clinical trials are considered the "gold standard" for demonstrating treatment efficacy and safety.

Participants were divided into two groups; one received an intervention that included nutritional guidance, physical exercise, cognitive training, social activities, and management of heart health risk factors, while the control group received regular health advice. After two years, the intervention group performed significantly better on a comprehensive cognitive examination. In addition to performing better overall, the intervention group did significantly better on specific tests of memory, executive function (complex aspects of thought such as planning, judgment, and problem-solving), and speed of cognitive processing.

"This is the first randomized control trial showing that it is possible to prevent cognitive decline using a multi-domain intervention among older at-risk individuals. These results highlight the value of addressing multiple risk factors in improving performance in several cognitive domains," said Kivipelto. "Participants told us their experience was very positive, and dropout rate only 11 percent after two years."

The researchers say an extended, 7-year follow up study is planned, and will include measures of dementia/Alzheimer's incidence and biomarkers including brain imaging with MRI and PET.

Psychological Intervention for Family Dementia Caregivers Reduces Anxiety, Depression, and Costs

Two-thirds of people with dementia live at home, with family members providing most of their care. About 40 percent of family caregivers have clinical depression or anxiety. At AAIC 2014, Gill Livingston, M.B.Ch.B., M.D., F.R.C.Psych. and colleagues at University College London reported on the effectiveness of START (STrAtegies for RelaTives), a standardized, manual-based psychological intervention delivered to dementia caregivers and family members by psychology graduate students.

The START program included education about dementia, caregiver stress, and where to get emotional support. Also included were techniques for managing challenging behaviors of the person with dementia, changing unhelpful thoughts, promoting acceptance, assertive communication, relaxation, planning for the future, increasing pleasant activities, and maintaining learned skills.

In a randomized controlled trial, 260 family caregivers were assigned in a two-to-one ratio to either START intervention or standard treatment. The intervention consisted of eight sessions given over two to four months. Upon examination after 16 to 24 months, the START group caregivers showed significantly better results than the control group on measures of depression, anxiety, and costs of care. 

"Family caregivers for people with Alzheimer's or another dementia require tailored, affordable interventions to enable them to cope without becoming depressed, which is bad for the caregiver and also for the person they are caring for," said Livingston. "START can be taught to psychology graduates rapidly and delivered relatively inexpensively, making it potentially a highly useful model for techniques that enable caregivers to manage better. This may help them to stay in that role longer and provide better and more consistent care, which may reduce or delay placement into a nursing home or assisted living."

Researchers Identify Additional Abnormal Protein, TDP-43, in Brains of People with Alzheimer's

Abnormal build-up of beta-amyloid and tau proteins are considered the primary indicators of Alzheimer's disease in the brain. Amyloid "plaques" and tau "tangles" form and increase for years in the brains of people with the disease, usually well before symptoms such as memory loss become apparent.

Little is known about the role in memory loss and dementia of another protein, TAR DNA binding protein of 43kDa (TDP-43), which is seen in ALS. Keith Josephs, M.D. of the Mayo Clinic and colleagues conducted a study to determine whether TDP-43 has an effect, independent of amyloid and tau, on the course and symptoms of Alzheimer's. The results were reported at AAIC 2014.

The researchers conducted post-mortem examinations on the brains of 342 people who were determined to have Alzheimer's disease based on the extent of tau tangles in the cortex. The subjects' brains were screened for the presence, amount, and distribution of TDP-43, and these findings were correlated with the results of tests of memory and cognition taken when the subjects were alive. The researchers also used MRI to assess atrophy in several brain regions.

After controlling for other factors including age at death, amyloid deposition, genetic risk for Alzheimer's, and vascular disease, the scientists concluded that the 195 study subjects with TDP-43 were 10 times more likely to have been cognitively impaired at death than subjects without TDP-43. They found that the "third protein" had strong correlations with cognition, memory loss, and shrinkage of the hippocampus, an area of the brain that is important to memory and is especially damaged in Alzheimer's.

The scientists speculate that absence of TDP-43 may help explain why some people have plaques and tangles in their brain, but do not experience dementia.

"These findings show that TDP-43 amplifies memory loss and hippocampal atrophy in Alzheimer's disease, and also appears to overpower what has been termed 'resilient cognition' in Alzheimer's, where subjects remain cognitively normal in spite of high levels of Alzheimer's brain changes," said Josephs. "This suggests that TDP-43 is a key player in the Alzheimer's neurodegenerative process, and should be considered a potential therapeutic target for treatment of the disease."

Tau Protein Found through PET Scans in Living Normal Older Adults Linked to Memory Decline

The presence of tangles of abnormal tau protein in the brain is one of the defining characteristics of Alzheimer's disease. The detection of brain tau deposits in living people has only recently become possible through advances in positron emission tomography (PET), an imaging technology that uses a radioactive imaging agent to highlight areas of interest inside the body.

In previous research, levels of tau in the brain have been found to be more closely associated with cognitive decline in Alzheimer's than levels of the other characteristic Alzheimer's protein, known as beta amyloid. Identifying the early buildup of these proteins in the brain, even before memory and thinking symptoms are present, is considered a strong candidate for early detection and diagnosis of Alzheimer's and for identifying volunteers for prevention studies.

In the largest study of its type to be reported, Keith Johnson, M.D. of Massachusetts General Hospital and colleagues conducted a study to determine if tau found in the brains of normal adults through PET imaging was associated with changes in memory. Johnson reported the results at AAIC 2014.

Using an imaging agent (F18 T807, Lilly) that binds with tau in the brain, the researchers conducted PET scans of 56 cognitively normal individuals with a median age of 72 who had undergone annual memory testing over the previous three years. They found that higher levels of tau in areas of the brain important to memory (entorhinal cortex and temporal neocortex) were associated with worsening on the memory test.

"These preliminary data suggest that tau in these brain areas is related to memory decline in normal older individuals," said Johnson. "This study demonstrates the potential for PET technology to be used for early detection, and to help pick participants for prevention trials and treatment trials that target tau."

About AAIC
The Alzheimer's Association International Conference (AAIC) is the world's largest gathering of leading researchers from around the world focused on Alzheimer's and other dementias. As a part of the Alzheimer's Association's research program, AAIC serves as a catalyst for generating new knowledge about dementia and fostering a vital, collegial research community. Scientists leading the advancement of research gather to report and discuss the most current data on the cause, diagnosis, treatment and prevention of Alzheimer's disease and related disorders. 

About the Alzheimer's Association
The Alzheimer's Association is the world's leading voluntary health organization in Alzheimer's 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.

SOURCE Alzheimer's Association