High Uric Acid Levels: A Possible New Dementia Biomarker
Researchers at Yale and at Johns Hopkins, led by Barry Gordon, M.D., Ph.D., a professor of Therapeutic Cognitive Neuroscience at Johns Hopkins, have found that a simple blood test to measure uric acid, a measure of kidney function, might reveal a risk factor for cognitive problems and dementia in old age. Of 96 adults age 60 to 92 years, those with uric-acid levels at the high end of the normal range had the lowest scores on tests of mental processing speed, verbal memory, and working memory.
Reporting recently in the journal Neuropsychology, Dr. Gordon and his colleagues noted that high-normal uric acid levels, defined in this study as 5.8 to 7.6 mg/dL for men and 4.8 to 7.1 mg/dL for women, were more likely to be associated with cognitive problems even when the researchers controlled for age, gender, weight, race, education, diabetes, hypertension, smoking, and alcohol abuse. These findings suggest that older people with serum (blood) uric-acid levels in the high end of the normal range are more likely to process information slowly and experience failures of verbal and working memory, as measured by the Wechsler Adult Intelligence Scale and other well-established neuropsychological tests.
The link between high-normal uric acid levels and dementia is sufficiently intriguing enough for the scientists to propose clinical studies of whether medicines that reduce uric acid, such as allopurinol, can help older people with high-normal uric acid levels avoid developing the mild cognitive deficits that often precede dementia.
For reasons that are not entirely clear, uric acid levels increase with age, says Dr. Gordon. Higher levels of uric acid are linked with known risk factors for dementia, including high blood pressure, atherosclerosis, type 2 diabetes, and the “metabolic syndrome” of abdominal obesity and insulin resistance. There is also mounting evidence that end-stage renal (kidney) disease increases the risk of cognitive dysfunction and dementia in elderly adults. Given this web of connections, uric acid could potentially become a valuable biological marker for very early cognitive problems and dementia in old age.
The researchers say that it’s unclear why mild cognitive problems appear with high normal uric acid levels. Paradoxically, uric acid also has anti-oxidant properties that are thought to be protective in other situations. Dr. Gordon and his colleagues are also researching links between uric acid and vascular damage in the brain and attempting to dissect which aspects of uric acid and its production help or hurt the nervous system.
This research update by Peter V. Rabins, M.D., editor of the Memory Bulletin, and co-director of the Division of Geriatric and Neuropsychiatry at the Johns Hopkins School of Medicine, comes from the Winter 2007 Memory Bulletin.
