Standard tests may miss cognitive decline in older adults

By Steve Tokar

People whose mental abilities have declined according to their own judgment and that of a close friend or family member, but who do not have mild cognitive impairment (MCI) according to standardized tests of mental function, show changes in brain structure and function similar to those seen in people diagnosed with MCI, according to a new study.

The results are reported by researchers at the San Francisco VA Medical Center and the University of California, San Francisco.

People with MCI are considered to be at significant risk for developing Alzheimer’s disease

“This shows that standardized tests might not be identifying people who are at risk of becoming cognitively impaired and eventually developing Alzheimer’s disease,” says lead author Linda Chao, PhD, a radiology researcher at SFVAMC and an associate adjunct professor of radiology and psychiatry at UCSF. “This is important because when new drugs are developed that delay Alzheimer’s, we will want to know who to target.”

The study is currently available in the online In Press section of Neurobiology of Aging.

Using magnetic resonance imaging techniques, the researchers measured brain structure and function in 18 cognitively healthy participants, 13 participants diagnosed with MCI, and 17 participants who were classified as “pre-MCI” based on a score of 0.5 on the Clinical Dementia Rating (CDR) but who nonetheless scored normally on standardized tests of cognition.

Compared with the healthy controls, the brains of pre-MCI participants showed the same deficits as the brains of participants diagnosed with MCI: significantly lower volume in a number of brain areas and significantly lower levels of N-acetyl aspartate, a biochemical marker of neuronal health.

In the CDR exam, the subject and his or her family member or friend compare the subject’s own past and current cognitive and functional abilities. “The argument is that this exam is more sensitive than standardized tests, which measure results against a norm,” says Chao. “Rather than being compared with other people, you are tracking changes in yourself – whether you have declined compared to how you used to be.”

According to most clinicians, a CDR score of 0.5 shows some mental decline but not enough to merit a diagnosis of dementia, she says. A score of zero indicates no impairment, while a score of 1 or higher indicates dementia. The CDR scoring scale does not include a diagnosis of MCI, according to Chao.

“There are a lot of relatively high-functioning people who have subjective memory complaints yet who score normally on standard memory tests,” observes Chao. “This study suggests that when someone says that they’re not as sharp as they used to be, it warrants investigation.”

Chao emphasizes that a CDR score of 0.5 “does not at all mean that dementia and Alzheimer’s are inevitable. We are saying, though, that anyone who scores higher than zero should be looked at more closely.”

The senior author of the study is Michael Weiner, MD, director of the Center for the Imaging of Neurodegenerative Diseases at SFVAMC and professor of radiology, medicine, psychiatry and neurology at UCSF.

Co-authors are Susanne G. Mueller, MD, of SFVAMC and UCSF; Shannon T. Buckley, BA, Kristen Peek, BA, Sky Raptentsetseng, BS, and Jeremy Elman, BA, of SFVAMC; Kristine Yaffe, MD, of SFVAMC and UCSF; Bruce Miller, MD, and Joel Kramer, PsyD, of UCSF; Catherine Madison, MD, of California Pacific Medical Center; Dan Mungas, PhD, of University of California, Davis; and Norbert Schuff, PhD, of SFVAMC and UCSF.

The study was supported by a grant from the National Institute on Aging that was administered by the Northern California Institute for Research and Education.

NCIRE - the Veterans Health Research Institute - is the largest research institute associated with a VA medical center. Its mission is to improve the health and well-being of veterans and the general public by supporting a world-class biomedical research program conducted by the UCSF faculty at SFVAMC.

SFVAMC has the largest medical research program in the national VA system, with more than 200 research scientists, all of whom are faculty members at UCSF.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.