Alzheimer's Association Update

Results from interventional studies 

Docosahexaenoic acid (DHA) is the most abundant omega 3 fatty acid in the brain and has long been of interest as a potential treatment for Alzheimer's disease. Study results presented at ICAD showed mixed results for DHA. An 18-month study of 402 volunteers with mild to moderate AD conducted by the Alzheimer's Disease Cooperative Study found that DHA did not slow the rate of change on tests of mental function, global dementia severity, activities of daily living, or behavioral symptoms. However, a six-month study of 485 healthy older adults with mild memory complaints found that those in the treatment group performed significantly better on a visuospatial test of episodic memory than those in the placebo group.

In a surprising discovery, the experimental drug dimebolin (Dimebon; Medivation, Inc., San Francisco, CA) now in phase III clinical trials, was found to increase levels of the protein beta-amyloid in mouse models of AD. Beta-amyloid is thought to be a key player in the development and progression of AD. Said study co-author Samuel Gandy, MD, PhD, of the Mount Sinai School of Medicine, New York:

This result is highly unexpected in what may prove to be a clinically beneficial Alzheimer's drug. A number of ideas need to be pursued. It may turn out that the drug works by getting toxic amyloid out of brain nerve cells. Or, the effects of dimebolin on other brain systems may override its effect on increasing beta amyloid. Finally, the drug's beneficial actions might have nothing to do with amyloid, which, if true, indicates the existence of important therapeutic targets independent of beta-amyloid.

The role of risk factors 

Numerous study results shared at ICAD shed new light on risk factors for AD. Several garnered media attention across the globe, including a study examining whether post-traumatic stress disorder (PTSD) influences one's risk of developing dementia. Researchers Kristine Yaffe, MD, and colleagues studied 181,093 veterans age 55 and older without dementia, following up on their cognitive function over seven years. Of the total study participants, 53,155 had been diagnosed with PTSD when enrolled. Researchers found that veterans with PTSD were nearly twice as likely to develop dementia as veterans without PTSD.

Also gaining the spotlight were results of a study indicating that moderate alcohol intake may significantly decrease one's risk of developing dementia. Kaycee Sink, MD, MAS, and colleagues studied alcohol intake and development of dementia in 3,069 community-dwelling adults age 75 and older without dementia. Nearly 500 of the participants had mild cognitive impairment (MCI). Participants were examined every six months for up to six years for changes in memory or thinking abilities. Researchers found that consuming one to two alcoholic beverages per day was associated with a 37 percent lower risk of dementia in participants with normal cognitive function at baseline. However, this was not the case for those with MCI. Any amount of alcohol consumption among those with MCI at baseline was associated with faster rates of cognitive decline.

The potential role of diet and exercise in influencing one's risk of developing dementia was a much discussed topic at ICAD. Researchers reported that following the Dietary Approaches to Stop Hypertension (DASH) diet was associated with higher scores for cognitive function and that four food groups from the diet—whole grains, vegetables, low-fat dairy foods, and nuts and beans—may be especially beneficial for cognitive function in later life. Other researchers found that that maintaining or increasing physical activity throughout life may slow cognitive decline with age. In one study, older adults who were sedentary had the lowest levels of cognitive function at the beginning of the study and the fastest rate of decline. In an intriguing twist, a study of post-menopausal women found that those who regularly participated in moderate-intensity physical activity had improved cognitive function in later life, while those who regularly participated in strenuous physical activity were at increased risk of cognitive impairment later in life.

Clinical diagnosis and study recruitment 

Studies estimate that between 2000 and 2005 less than 35 percent of people living with AD or related dementias had a diagnosis of the condition in their medical record. To address obstacles to early diagnosis, Australian researchers interviewed more than 100 general practitioners looking for insights into which physicians are more likely to diagnose AD early in its clinical course. An interim analysis of data from 25 physicians was presented at ICAD. In this interim analysis, a physician's positive attitude toward dementia diagnosis and treatment was the most common factor in an early diagnosis. Having trusting, personal relationships with individuals who provide support services was also linked to a greater chance of early diagnosis. The most cited barriers to early diagnosis included the physician's dependence on patients and family members to alert them to possible memory loss, challenges with the timing of referral and support services, and fear of damaging the patient-physician relationship.

Study results presented at ICAD suggest that physicians play an important role not only in early diagnosis of AD but also in recruitment of volunteers for clinical trials. Tamara Markgraf, MBA, and colleagues from the Wisconsin Alzheimer's Disease Research Center (ADC) interviewed 22 administrators and outreach staff members from 20 ADCs about recruitment strategies and outcomes. Partnering with local physicians, working with local clinics, and conducting educational seminars and health fairs were the most effective recruitment tools, while patient registries and internet recruitment efforts were much less successful.

Biomarkers 

Using data from the Alzheimer's Disease Neuroimaging Initiative, Susan Landau, PhD, and colleagues investigated which biomarkers best predicted decline in cognitive function in those with MCI and which predicted those individuals with MCI who would go on to develop AD. Their data showed that decreased glucose metabolism in the brain, combined with poor memory recall, was the most effective predictor of conversion from MCI to AD. People with MCI who fared poorly in these tests were 15 times more likely to go on to develop AD than those with normal results on these tests.

Glucose metabolism also was a key focus of research conducted by investigators at the Center for Brain Health at New York University School of Medicine. The investigators developed an automated scanning method that rapidly samples glucose metabolism in 32 brain regions. Study participants were divided into seven subgroups based upon their initial diagnosis and results of subsequent memory and thinking tests performed up to three years after their original scan. Investigators found a significant correlation between glucose metabolism in several brain regions and the progression from “stable normal” to “normal with subsequent clinical decline” and to subcategories of MCI and AD. They also found that glucose metabolism in the hippocampus was a sensitive predictor of decline and a discriminator between disease stages. Compared with people whose cognitive function was classified as “stable normal,” hippocampal glucose metabolism was 5 percent lower in those classified as “normal with subsequent clinical decline,” 12 percent lower in those classified as “stable MCI,” 14 percent lower in those classified as “MCI with subsequent clinical decline,” and 24 percent lower in those with AD.

In the area of potential genetic biomarkers for AD, Allen Roses, MD, shared results of a small study in which inheriting the long-repeat version of the Tomm40 gene, in addition to the ɛ3 form of the apolipoprotein E (APOE) gene, was associated with an increased risk of developing AD and an increased risk of developing it at an earlier age. Individuals in the study carrying both genes developed AD an average of seven years earlier—at about age 70—than individuals who inherited the APOE ɛ3 gene but not the Tomm40 gene. If this association is confirmed in larger studies, the presence of both genes could prove a tool for identifying those at increased risk of AD.

In addition to presenting the latest in AD research, ICAD recognized several leaders in the field. Lifetime Achievement Awards named in honor of ICAD founders Henry Wisniewski, MD, PhD, Khalid Iqbal, PhD, and Bengt Winblad, MD, PhD, were given to Richard Mayeux, MD, MS, Columbia University; Virginia M.-Y. Lee, PhD, MBA., University of Pennsylvania; and Martin Rossor, MD, University College London, respectively. The Zaven Khachaturian Award, honoring the noted Alzheimer researcher, lecturer, and author, was given to William Markesbery, MD, University of Kentucky.

Planning for ICAD 2010, which will be held July 10–15, 2010, in Honolulu, Hawaii, is well under way.