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Monday, January 22nd 2007

Cholesterol & Dementia

Could lower levels of “good” cholesterol contribute to the development of dementia? Two studies, back-to-back, provide circumstantial evidence.

“Good” cholesterol (HDL) scavenges and picks up cholesterol from other lipoproteins and returns it to the liver. A study at Albert Einstein looked at the very elderly and a specific gene encoding for cholesterol ester transfer protein. CETP, at least in part, moves cholesterol into the liver.

The variation of the CETP gene they looked at, actually increased the amount of HDL (which remained) in the blood.

The researchers found that in a group of 158 people age 95 and older, those with the variant were twice as likely to pass tests of mental agility as those with a different version of the gene: 61 percent of those with the protective variant had good cognitive function, compared with 30 percent of controls.

Here’s the abstract and the full text of the study if you want to pay for it.

Of course it is questionable what this knowledge actually offers us,

Drugs that mimic the effect of this genetic variation by lowering levels of CETP are already being tested as potential therapies for preventing heart disease. CETP inhibitors have been highly anticipated by cardiologists because they can raise the level of HDL cholesterol; current cholesterol drugs only lower the level of “bad” LDL cholesterol. However, Pfizer recently halted trials of its CETP inhibitor torcetrapib after the drug raised death rates in patients, which has prompted concerns that similar drugs will also fail.

But the implications of the study, that lower cholesterol (in this instance, specifically HDL) promotes cognitive decline, seem to be backed up by another recent study. This write up is on Medscape (free subscription required).

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.

So, okay it isn’t that impressive,

“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.”

“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.

But maybe he shouldn’t put his findings down so quickly, seeing as other studies (and I’m sure there are more than just the one I’ve cited) seem to show a relationship between cognitive function in old age and HDL levels (although, the Neurology study doesn’t even show that, I’m kind’ve extending the findings). Still, when I’m 75 I’d like my HDL to be stable (or increasing).