Submitted by the Alzheimer's Association, Georgia Chapter
New studies reported at the Alzheimer’s Association International Conference 2013 in Boston cover the spectrum of Alzheimer’s disease and dementia research, including novel treatment and prevention strategies, possible new risk factors, advances in early detection and diagnosis, and an updated model of disease progression.
The Alzheimer’s Association International Conference is the premier annual forum for presentation and discussion of the latest Alzheimer’s and dementia research. Celebrating 25 years of progress while shaping the future of dementia science, AAIC 2013 brought together nearly 5,000 leading experts and researchers from 66 countries around the world, and featured more than 1,800 scientific presentations.
Potential Alzheimer’s disease risk factors
Most kinds of cancer associated with decreased risk of Alzheimer’s; Chemotherapy adds additional decrease in Alzheimer’s risk
A study of the health records 3.5 million U.S. veterans indicated that most kinds of cancer are associated with a significantly decreased risk of Alzheimer’s disease. Results suggested that chemotherapy treatment for almost all of those cancers conferred an additional decrease in Alzheimer’s risk. The researchers found no association between cancer history and reduced risk of any other typical age-related health outcome; in fact, most cancer survivors were found to be at increased risk for non-Alzheimer’s dementia. The scientists concluded that the findings indicate that the protective relationship between most cancers and Alzheimer’s disease is not explained simply by increased mortality among cancer patients. More research is needed to determine the cause(s) of the reduced risk, and therefore identify potential new therapeutic avenues for Alzheimer’s.
Diabetes drug associated with reduced risk of dementia
Type 2 diabetes may double the risk of dementia. However, in a study of nearly 15,000 type 2 diabetes patients age 55 and older, patients who started on metformin, an insulin sensitizer, had a significantly reduced risk of developing dementia compared with patients who started other standard diabetes therapies. Trials are currently under way to evaluate metformin as a potential therapy for dementia and mild cognitive impairment.
Older age at retirement is associated with a reduced risk of dementia
An analysis of health and insurance records of more than 429,000 self-employed workers in France found that retirement at older age is associated with a reduced risk of dementia, with a lower risk for each added year of working longer. The researchers suggested that professional activity may contribute to higher levels of intellectual stimulation and mental engagement, which may be protective against dementia, though more research is needed in this area.
Socioeconomic factors may explain higher Alzheimer’s risk in African-Americans
In the United States, older African-Americans are about twice as likely to have Alzheimer’s and other dementias as older whites. But in a study of 3,075 black and white elders who were free of dementia at the beginning of the study, the risk difference was no longer statistically significant after researchers adjusted for socioeconomic factors including education level, literacy, income and financial adequacy. The authors urged that future studies investigating racial and ethnic dementia risk disparities should take a broad range of socioeconomic factors into account.
Alzheimer’s disease detection and diagnosis
Online tests for Alzheimer’s do not measure up
A panel of Canadian experts – including geriatricians, human-computer interaction specialists, neuropsychologists and neuroethicists – reviewed 16 freely accessible online tests for Alzheimer’s disease, and found that the tests scored poorly on scales of overall scientific validity, reliability and ethical factors. The experts found that most of the tests (12 of 16) scored “poor” or “very poor” for overall scientific validity and reliability, and concluded that these tests are not useful for the diagnosis of Alzheimer’s disease. All 16 tests scored “poor” or “very poor” on the evaluation criteria for ethical factors. Ethical issues included overly dense or absent confidentiality and privacy policies, failure to disclose commercial conflicts of interests, failure to meet the stated scope of the test and failure to word the test outcomes in an appropriate and ethical manner.
No evidence of benefit in population screening for dementia
UK researchers conducted a systematic review of studies that looked at population screening for dementia and compared outcomes with a routine pattern of care in the general population, among patients in general medical practice, and among patients in community care. The researchers found no evidence of the effect of screening on patient outcomes including cognitive, mental and emotional health, social function and planning, and no indication of its added value compared to current practice. They suggest that policymakers should be very cautious about adopting population screening for dementia without any evidence of benefits or risks. The Alzheimer’s Association recommends that people see their doctor for a thorough evaluation at the earliest signs of memory problems or changes. For the 10 Warning Signs of Alzheimer’s, visit www.alz.org.
Self-reported changes in memory may be earliest clinical markers of Alzheimer’s
Four studies supported increasing evidence that subjective cognitive decline (SCD) — the self-reported perception of memory or cognition problems — is a potentially valid early clinical marker of brain and cognitive changes that may indicate Alzheimer’s disease. One study cognitively normal older people showed a significant relationship between self-reported cognitive concerns and evidence of buildup of beta-amyloid protein, the main component of Alzheimer’s brain “plaques,” as revealed by PET scans. Another study of nearly 4,000 nurses age 70 and older indicated that a subjective concern about memory could be a marker of subsequent decline in objectively measured memory, especially among carriers of the ApoE4 gene, the strongest known genetic risk factor for Alzheimer’s. In a third study, older adults underwent annual cognitive assessments for an average of 10 years. Subjects who reported a change in memory since their last assessment were almost twice as likely to be diagnosed with mild cognitive impairment or dementia during follow-up than those who did not report such a change. Also at AAIC 2013, an international group of Alzheimer’s researchers announced the formation of the Subjective Cognitive Decline Initiative (SCD-I) to develop a new research framework for SCD, with a focus on preclinical Alzheimer’s.
Alzheimer’s disease therapies update
Preliminary results in studies of two new potential Alzheimer’s therapies
It has been suggested that amyloid plaques can stimulate microglia, the brain’s first-line immune cells, to produce inflammatory compounds that cause brain cell damage in Alzheimer’s patients. The experimental compound CHF5074 (Chiesi Pharmaceuticals), which is designed to inhibit inflammation by modifying microglial action, has been shown to prevent formation of brain plaques and reduce deficits in mouse models of Alzheimer’s. In a 90-week clinical trial of CHF5074 in people with mild cognitive impairment, powered only for safety and dosing, not for efficacy, an interim analysis of cognitive tests of 32 patients showed statistically significant, dose-dependent improvements in participants’ cognitive abilities. Study participants who carried one or two copies of the ApoE4 gene, which increases the risk of Alzheimer’s, performed significantly better than ApoE4 non-carriers on two of the cognitive tests.
Researchers reported results of an early-stage, randomized, double-blind, placebo-controlled, multiple-dose study of the experimental medication MK-8931 (Merck), which inhibits beta secretase - one of two enzymes that produce beta-amyloid - in people with mild-to-moderate Alzheimer’s. They found that the drug significantly lowered beta amyloid in cerebrospinal fluid at the highest dose; the average reduction from baseline was more than 80 percent. According to the researchers, the drug was generally well-tolerated.
Two Alzheimer’s drug studies with innovative approaches
Allopregnanolone, also known as Allo, is a neurosteroid found in the brain and bloodstream. In previous studies, it has shown promise as a potential regenerative therapy to promote brain cell creation and improve cognitive function in older animals and animal models of Alzheimer’s disease. Allo is naturally expressed in the brain and reaches relatively high levels during the third trimester of pregnancy. At AAIC 2013, researchers reported the design of a Phase 1, multiple ascending dose, clinical trial of Allo in participants diagnosed with MCI due to Alzheimer’s and mild Alzheimer’s, with doses administered once-per-week for 12 weeks to establish a safe and tolerated dose. Secondary goals of the trial include assessing potential short-term effects of Allo dosing on cognition and MRI indicators of Alzheimer’s, and informing a subsequent Phase 2 proof of concept trial.
Scientists at Zinfandel and Takeda Pharmaceuticals International, Inc., are initiating an international Phase 3 trial of low dose pioglitazone, a medication which at higher doses is approved for treatment of type 2 diabetes, as a therapy to delay onset of MCI due to Alzheimer’s. In earlier human studies, treatment with pioglitazone was associated with decreased markers of brain inflammation. For the first time, study participants will be cognitively normal individuals who carry genetic risk variations in the ApoE and TOMM40 genes that are associated with an increased Alzheimer’s risk and earlier onset of symptoms. The trial will begin enrollment in 2013. Additional study goals include validating the new NIA/Alzheimer’s Association diagnostic criteria for MCI due to Alzheimer’s and determining an appropriate set of cognitive tests that would work effectively in all study sites around the globe.
The Alzheimer’s Association International Conference (AAIC) is the world’s largest conference of its 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, AAIC 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 world’s 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. For more information, visit www.alz.org or call (800) 272-3900.