Alzheimer’s Research Advances from the AAIC 2012

New studies reported at the Alzheimer’s Association International Conference® 2012 (AAIC®2012), July 14-19, in Vancouver cover the spectrum of Alzheimer’s disease and dementia research, including causes, risk factors, detection and diagnosis, treatment, and prevention.

The good news at the Alzheimer’s Association International Conference is that we are making advances toward earlier detection of Alzheimer’s, greater knowledge of dementia risk factors, and better treatments and prevention,” said William Thies, PhD, Alzheimer’s Association Chief Medical and Scientific Officer. “These advances are critical in order to create a future where Alzheimer’s disease is no longer a death sentence but a manageable, treatable, curable, or preventable disease.”

The soaring global costs of Alzheimer’s and dementia care, the escalating number of people living with the disease, and the challenges encountered by affected families all demand a meaningful, aggressive and ambitious effort to solve this problem.

“The urgency is clear. By midcentury, in the U.S. alone, care for people with Alzheimer’s will cost more than $1 trillion. This will be an enormous and unsustainable strain on the healthcare system, families, and federal and state budgets. The first-ever U.S. National Plan to Address Alzheimer’s Disease was unveiled in May, and must be speedily and effectively implemented. An additional $100 million commitment is needed now for Alzheimer’s research, education, outreach and community support,” Thies said.

This August and September, the Alzheimer’s Association will be hosting town hall meetings in communities throughout the country. These events offer people the opportunity to share their views how best to implement the National Alzheimer’s Plan. Visit www.alz.org/plan for more information.

Alzheimer’s Therapies Update

IVIG stabilizes Alzheimer’s for Three Years in Extended Phase Two Clinical Trial

The first report of long-term (3-year) stabilization of Alzheimer’s disease symptoms with intravenous immunoglobulin (IVIG/Gammagard, Baxter), was presented at AAIC 2012. IVIG is being studied as an immunotherapy for Alzheimer’s. Participants in the original Phase 2 study received six months of treatment followed by a 12-month open-label extension; several doses were tested. Participants were then offered additional IVIG treatment at a single standardized dose (0.4mg/kg every two weeks) for an additional 18 months. Study participants who were treated with the standardized dose for the full 36 months (n=4) had the best outcome, with no decline on several standard measures of cognition, memory, daily functioning and mood at the three year endpoint. While the small number of participants may limit the reliability of the findings, the results are tantalizing. A Phase 3 trial is in progress and there will soon be more definitive data on the efficacy of IVIG treatment.

Upcoming Prevention Trials

At an AAIC 2012 Featured Research Session titled “Collaboration for Alzheimer’s Prevention: Common Issues Across Presymptomatic Treatment Trials,” updates were given on three new Alzheimer’s disease prevention trials that are beginning soon or in the planning stages.

Two of the studies – conducted by the Alzheimer’s Prevention Initiative and the Dominantly Inherited Alzheimer’s Network – will be conducted in families affected by younger onset genetic Alzheimer’s. The third study, proposed by the Alzheimer’s Disease Cooperative Study, is known as the Anti-Amyloid Treatment of Asymptomatic Alzheimer’s Disease (A4) trial. A4 scientists will study participants aged 70+ who have normal memory and thinking abilities, with evidence of Alzheimer’s changes in their brains shown on a PET scan using a special imaging dye.

“Improved imaging technologies and updated diagnostic guidelines are enabling the detection of early changes in the brain that are consistent with what is now known as presymptomatic (or preclinical) Alzheimer’s,” said Thies. “People in this stage of the disease are an ideal population for prevention trials to delay the onset or slow the progression of cognitive decline. These studies are among the most exciting current and upcoming Alzheimer’s therapy trials.”

New Symptomatic Drug Shows Cognitive Benefits in Phase 2 Trial

A six-month, Phase 2b trial of EVP-6124 (EnVivo Pharmaceuticals), a selective, partial, alpha-7 nicotinic agonist, in 409 people with mild to moderate Alzheimer’s showed statistically significant benefits on two well-established measures of memory, language, attention and other cognitive abilities. EVP-6124 is an experimental symptomatic drug with a different mechanism of action than the current FDA- and EMA-approved Alzheimer’s drugs. Alpha-7 nicotinic agonists amplify the effects of acetylcholine, a brain chemical that is essential for normal brain and memory function.

Alzheimer’s Early Warning Signs and Risk Factors

Late-Life Drinking, Binge Drinking, and Cognitive Decline

Light to moderate alcohol consumption has generally been considered to have some health benefits. However, two studies reported at AAIC 2012 in Vancouver suggest that moderate alcohol use in late-life, heavier use earlier in life, transitioning to drinking in late-life, and “binge” drinking in late-life increase risk of cognitive decline.

In one study, researchers followed more than 1,300 women aged 65 and older for 20 years. They measured frequency of current and past alcohol use at the beginning, midpoint and late phases of the study; participants were assessed for cognitive impairment and dementia. They found that:

  • Women who reported drinking more in the past than at the beginning of the study were at 30% increased risk of developing cognitive impairment.
  • Moderate drinkers at baseline or at midpoint had similar risk of cognitive impairment to non-drinkers; however, moderate drinkers in the late phase of the study were roughly 60% more likely to develop cognitive impairment.
  • Women who changed from nondrinking to drinking over the course of the study had a 200% increased risk of cognitive impairment.

Binge drinking is a pattern of alcohol consumption in which someone who is not otherwise a heavy drinker consumes several drinks on one occasion. In an analysis of data from more than 5,000 participants aged 65 and older in the Health and Retirement Study, binge drinking once a month or more was reported by 8.3% of men and 1.5% of women; binge drinking twice a month or more was reported by 4.3% of men and 0.5% of women. Those who reported binge drinking at least twice a month were more than twice as likely to have the greatest decline in both cognitive function and memory.

According to the researchers, doctors and other healthcare professionals should carefully assess their older patients for both how much they drink and any changes in patterns of alcohol use.

Clinical Trials of Exercise

Four studies reported at AAIC 2012 describe the ability of targeted exercise training to promote improved mental functioning and reduced risk for cognitive impairment and dementia in cognitively healthy older adults and those with mild cognitive impairment (MCI), an intermediate stage between the expected cognitive decline of normal aging and the more pronounced decline of dementia. MCI involves problems with memory, language, thinking and judgment that are greater than typical age-related changes.

The reports, from 6- and 12-month randomized controlled clinical trials, depict the beneficial effects of different types of exercise – resistance training, aerobic training, and balance-stretching training – on a variety of cognitive abilities, brain structure, and risk factors for cognitive decline such as depression and sleep quality.

These new studies begin to clarify exactly which types of physical activity are most effective, how much needs to be done, and for how long. In particular, where previous research showed positive associations between aerobic activity, particularly walking, and cognitive health, these reports suggest that resistance training is emerging as particularly valuable for older adults. It is generally accepted that regular physical activity is essential to healthy aging; it also may prove to be a strategy to delay or prevent the onset of cognitive impairment and dementia.

Gait Changes

Gait disturbances – such as a slowing of walking pace or a more variable stride – could indicate a decline in cognitive function, according to new research studies reported at AAIC 2012. In general, the scientists found that gait became slower and more variable as cognitive decline progressed.

  • One study in Switzerland followed 1,153 older participants who had a range of cognitive abilities from healthy cognition to severe Alzheimer’s. Results suggested that walking speed slowed as cognition worsened. Those with Alzheimer’s in the study walked slower than those with MCI, who in turn walked slower than those who were cognitively healthy.
  • A study from the Mayo Clinic Study of Aging explored the stride length, cadence and velocity of more than 1,341 participants through a computerized gait instrument at two or more visits 15 months apart. Participants with lower cadence, velocity and amplitude of the stride length experienced significantly larger declines in global cognition, memory and executive function.

“With an aging baby boomer generation advancing into greater risk for Alzheimer’s and dementia, it is important for physicians to be aware of the associations between gait and mental function. For busy doctors with limited time with patients, monitoring deterioration in a patient’s gait is ideal because it doesn’t require any expensive technology or take a lot of time to assess. It may provide early detection of fall risk and the earliest stages of cognitive impairment in older adults,” Thies said.

Sleep Patterns

Several studies reported at AAIC 2012 suggest a relationship between sleep quality and quantity and risk of cognitive decline. For example:

  • More than 15,000 participants in the Nurses’ Health Study who were age 70 or older at their first cognitive examination were followed for up to six years including questions about sleep duration and regular cognitive assessments.  The researchers found that extreme sleep durations (2 hours more or less per night than normal) and changes in sleep duration over time may contribute to cognitive decline and early Alzheimer’s changes in older adults.
  • A study of 1,300 women age 75+ enrolled in a large multi-center study and followed up to five years found that participants with sleep-disordered breathing or sleep apnea had more than twice the odds of developing MCI or dementia over the five years compared with those who did not have sleep-disordered breathing. Participants with greater nighttime wakefulness were more likely to score worse on tests of global cognition and verbal fluency than those without it.
  • The French Three-City Study is an ongoing, long-term, multisite study of the relationship between vascular disease and dementia in community-dwelling individuals age 65 or older. Nearly 4,900 nondemented study participants were followed for up to eight years. Scientists found that excessive daytime sleepiness, which was reported by 17.9% of participants, was associated with an increased risk of cognitive decline.

The researchers suggest that the public health implications of these findings could be substantial, as they may lead to the eventual identification of sleep-based strategies for reducing risk of cognitive impairment and dementia. In theory, interventions to normalize sleep duration and correct sleep disorders may not only improve quality of life, but have potential to reduce or prevent cognitive decline.

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