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A report at the International Conference on Prevention of Dementia sponsored by the Alzheimer's Association (Chicago) in Washington last week suggested that unexplained weight changes in late life have an impact on dementia risk and also may be useful, when combined with other factors such as biomarkers, as an indicator for early detection of dementia.

James Mortimer, PhD, professor of epidemiology and biostatistics at the University of South Florida (Tampa) and co-principal investigator of the Nun Study, and colleagues sought to determine whether there is an association of weight at baseline and rate of weight loss with the risk of developing dementia, and also whether there is an association of weight or weight loss with the severity of Alzheimer's disease (AD) changes in the brain seen at autopsy.

Some 537 non-demented Catholic nuns ages 75-102 who were participants in the Nun Study were followed for up to 10 years, with annual clinical assessments and determinations of weight. In a subset of 363 Catholic sisters who died during the study, the associations of weight at baseline and the final weight before death with Alzheimer's brain changes were assessed. In the same group, age- and education-adjusted associations of baseline weight and final weight with the final MMSE score before death were evaluated.

Lower initial weight and higher rate of weight loss were significantly associated with an increased risk of developing dementia, Mortimer said. "This is the first study to show that lower weight up to 10 years before death is specifically related to the severity of Alzheimer's disease. Given its very long duration prior to onset of dementia, it is likely that weight loss is specifically associated with the Alzheimer's disease process and not to a restriction in food intake due to cognitive decline."

He added that unexplained weight loss late in life coupled with other biomarkers "may help to identify those at risk of Alzheimer's more than a decade before symptoms start to show. Identification of people who are at high risk of Alzheimer's will be critical once agents become available that slow the disease course."

In other conference news:

A team of scientists has developed a new concept called "motivational reserve," similar to "cognitive reserve," that may be related to incidence and progression of Alzheimer's.

Simon Forstmeier, PhD, and Andreas Maercker, MD, PhD, of the University of Zurich in Switzerland, and colleagues have developed and are investigating the motivational reserve concept, which suggests that qualities such as will power, self-discipline, motivation and optimism may protect against cognitive decline and delay the manifestation of Alzheimer's.

The team is evaluating newly developed instruments for measuring premorbid motivational competence. Established instruments are considered insufficient because they rely mainly on self-report and refer to the present state.

In new research presented at the conference, cognitive functions were assessed in a sample of 120 non-demented individuals aged 60 to 95 years. Motivational and cognitive abilities were estimated using these new instruments and procedures based on the individual's occupational history. The researchers found that present cognitive abilities such as verbal fluency and working memory could be independently predicted by former motivational and cognitive abilities.

An ongoing study is investigating the predictive power of motivational reserve on the incidence of MCI and dementia.

"Previous research showed that motivational abilities such as self-motivation, goal setting, and emotion regulation can be trained in individuals with and without psychiatric disorders," Forstmeier said. "The next step is to apply these interventions in people at risk for Alzheimer's or in the early stages of the disease in order to test their ability to delay onset or progression."

Early results from the Alzheimer's Disease Neuroimaging Initiative (ADNI), a public-private research partnership organized by the National Institutes of Health (NIH; Bethesda, Maryland), indicate AD researchers may be able to reduce the time and expense associated with clinical trials.

Preliminary results from ADNI show how it might yield improved methods and uniform standards for imaging and biomarker analysis, so these techniques can be employed in the fight against Alzheimer's disease.

The ADNI study observes and tracks changes in normal individuals, in people with mild cognitive impairment — a condition that often precedes Alzheimer's — and in people with Alzheimer's. Researchers will use PET (positron emission tomography) and MRI scans to track changes in the brain, laboratory analyses of cerebrospinal fluid and blood to study biomarkers, and clinical interviews to track cognitive performance over time.

ADNI is expected to improve neuroimaging and biomarker measures and consequently allow faster and more efficient evaluation of potential therapies for Alzheimer's.

The $60 million, five-year study began recruiting in early 2006, and today about 800 older people at 58 sites in the U.S. and Canada participate in the effort. The project is supported primarily by the National Institute on Aging (NIA), a component of NIH, with private-sector support from pharmaceutical companies, other organizations and the Alzheimer's Association through the Foundation for NIH . In addition to NIA, other federal partners are the National Institute of Biomedical Imaging and Bioengineering , also part of NIH, and the FDA.

"New treatment options are urgently needed for the millions of people who have Alzheimer's and for those at risk as the population ages," said Richard Hodes, MD, director of the NIA. "This preliminary report on aspects of ADNI is quite encouraging."

ADNI principal investigator Michael Weiner, MD, of the Department of Veterans Affairs Medical Center and University of California, San Francisco gave a progress report and described the new ADNI database during the conference. Nine other ADNI researchers gave reports on early results and preliminary findings from various studies.

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