Cholesterol Decline May Be Associated With Early Stages of Dementia

By Will Boggs, MD

NEW YORK (Reuters Health) Jan 19 - A decline in total cholesterol levels precedes the diagnosis of dementia by at least 15 years, according to an epidemiologic study reported in the January issue of the Archives of Neurology.

"Studies like this are extremely valuable because they can provide a 'window' on to processes going on early in dementia, allowing researchers to look back in time at people's health and other characteristics and compare these between people who develop dementia and those who do not," Dr. Robert Stewart from King's College London, UK told Reuters Health.

Dr. Stewart and colleagues used data from the Honolulu-Asia Aging Study to compare the natural history of cholesterol level change over a 26-year period between 56 men who were found to have dementia at examination 3 years after the last cholesterol measurement and 971 men who did not have dementia.

Total cholesterol levels at the beginning of the study did not differ by later dementia status, the authors report, but the decline in subsequent cholesterol levels was significantly steeper among men who went on to develop dementia.

Adjustment for potential confounding factors strengthened the association between cholesterol level decline and the development of dementia, the results indicate.

The cholesterol level decline was most marked in men with dementia and the APOE epsilon-4 allele and in those with dementia and worse self-reported general health at the final cholesterol measurement, the researchers note.

"The observed associations may not represent direct causal pathways," the investigators say. "Hypocholesterolemia is recognized to be associated with frailty and poor general health. It also has been found to be specifically associated with inflammatory markers and poor nutritional status."

Rather, they suggest, "It is possible that the decline in cholesterol levels is a marker for early processes that reflect neurodegenerative changes and also lead to a decline in general health status."

The drop in cholesterol was not a result of medication. "Very few of the participants in this study were receiving cholesterol lowering treatment at the time the decline in cholesterol levels was observed (there were few cholesterol lowering medications around at that time in the 1970s), so medication was not responsible for this," Dr. Stewart explained.

"The drop in cholesterol was instead probably caused by some other event and was a 'marker' of risk rather than actually increasing the risk itself," he concluded.

Arch Neurol 2007;64:103-107.