Study identifies potential biomarker for Alzheimer's disease

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Boston University Medical Center

 

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(Boston)--In one of the largest studies to date to use metabolomics, the study of compounds that are created through various chemical reactions in the body, researchers have been able to identify new circulating compounds associated with the risk of developing dementia and Alzheimer's disease (AD).

The findings, which appear in the journal Alzheimer and Dementia, point to new biological pathways that may be implicated in AD and could serve as biomarkers for risk of the disease.

AD is the most common form of dementia responsible for a slow and progressive deterioration of memory and leads to frailty and dependence in elderly people. Despite ongoing research effort and improved knowledge about the disease, there is currently no effective preventive or curative treatment for AD, which could result in a public health crisis given the continuous aging of populations worldwide.

Using data from the Framingham Heart Study (FHS), researchers from Boston University School of Medicine (BUSM), observed an association specifically between levels of anthranillic acid measured in the plasma and a higher risk of developing dementia and AD after 10 years of follow-up.

Although the researchers are cautious about their results, they identify several findings they find promising. "First anthranilic acid is produced during the degradation of tryptophan, an essential amino acid. Interestingly, other compounds produced through the same reactions have been reported as protective or deleterious for neurons and could constitute valuable drug targets. Second, this potential marker could also be used to identify groups of persons at higher risk of developing dementia, which could improve the efficiency of clinical trials and in the future, detect persons that would benefit the most from a preventive treatment," explained co-corresponding author Sudha Seshadri, MD, professor of neurology at BUSM and FHS senior investigator.

From a methodological point of view, this study is one of the first to use a prospective cohort such as the FHS to search for compounds associated with the risk of developing AD and dementia. "As the field of AD epidemiology is only beginning to integrate the metabolomics approach, it is likely that fruitful collaborations and innovative ways to analyze these data will follow," said co-corresponding author Vincent Chouraki, MD, PhD, former research fellow from BUSM and now assistant professor in epidemiology at Lille University School of Medicine in France.

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Funding for this study was provided by the National Heart, Lung, and Blood Institute's Framingham Heart Study (contracts no. N01-HC-25195 and HHSN268201500001I) and grants from the National Institute of Neurological Disorders and Stroke (NS17950 ), the National Institute on Aging (AG008122, AG016495, AG049505 , AG049607 and AG033193) and the National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK-HL081572).

Alzheimer's disease looks different in people over 80

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Medscape Today

Alzheimer's disease (AD) may be more difficult to detect in people older than 80 years, suggest results of a new study, because disease presentation may be different than that seen in the larger population of patients.

"The typical pattern of AD-related cognitive and morphometric changes seen in the young old appear to be less salient in the very old," first author Nikki H. Stricker, PhD, from the Veterans Affairs Boston Healthcare System and the Department of Psychiatry, Boston University School of Medicine, Boston, Massachusetts, and colleagues report.

"Thus, mild cases of AD in the very old may go undetected if one expects to see the prototypical pattern and severity of cognitive or brain changes that occur in the young old with AD," they conclude.

This study highlights "the importance of paying attention to age when reviewing cognitive test performances and in reviewing other possible biomarkers of Alzheimer's disease such as neuroimaging scans," coauthor Mark W. Bondi, PhD, from the Psychology Service, Veterans Affairs San Diego Healthcare System, San Diego, California, noted in comments to Medscape Medical News.

Their results are published online August 10 in Neurology.

Signs, Symptoms More Subtle in 80-Plus Group

The researchers compared hippocampal volume and cortical gray matter thickness in areas known to be affected by AD in 105 patients with AD and 125 healthy control participants. Participants between 60 and 75 years old made up the "young-old" group, whereas those 80 years and older made up the "very-old" group. Among the 105 participants with AD, 64 were young-old, and 41 were very-old.

Brain morphometric and cognitive scores of the patients with AD were standardized to their respective age-appropriate healthy control subgroup and then compared, the researchers explain.

In the very-old, compared with the young-old, there was less severe cortical thinning in the left posterior cingulate cortex, right lateral temporal cortex, and bilateral parietal cortex, as well as in overall cortical thickness.

This finding is, in part, because these brain areas decrease in thickness as a result of aging. Therefore, there are fewer differences between the healthy very-old brain and the very-old brain with AD, the researchers point out.

"Our results indicate that overlap between normal and AD-related brain changes seen on magnetic resonance imaging (MRI) scans is greater in the very-old than in the young-old," Dr. Bondi said. "For example, the typical pattern of brain changes seen in an 85-year-old person with AD is less salient than in a 70-year old person with AD."

Similarly, several cognitive domains, including executive function, immediate memory, and attention/processing speed, were less abnormal in the very-old patients with AD relative to their young-old peers.

Broad Clinical Implications

"Clarification of how the presentation of AD changes with age may enhance our ability to detect early AD in the very-old, one of the fastest growing segments of the population," Dr. Bondi commented.

"Enhanced detection will be crucial for early application of interventions that may slow the disease process, thus preserving cognitive status, functional independence, and quality of life," he added.

Reached for comment, Rhoda Au, PhD, from the Department of Neurology, Boston University School of Medicine in Boston, Massachusetts, said "the most important broader implications" of this study are "its recognition of the developmental continuum extending to the very last years of life (and) that the elderly population cannot be characterized as a single subset population."

Dr. Au was not involved in the study but authored a linked commentary in the journal.

"As more and more people live into the 8th and 9th decades and beyond, the diagnostic and treatment practices applied to the younger old may not apply or work as effectively with the oldest old," she told Medscape Medical News.

The study was supported primarily by the National Institutes of Health (NIH) and the Dana Foundation. Dr. Stricker receives or has received research support from the Rosalind and Arthur Gilbert Foundation/American Federation for Aging Research and the NIH. Dr. Bondi serves as an associate editor for the Journal of the International Neuropsychological Society and receives research support from the Alzheimer's Association and the NIH. A complete list of author disclosures is listed in the original article. Dr. Au receives research support from the National Institute on Aging, the National Institute of Neurological Disorders and Stroke, and the Fogarty International Center.