Could high HDL-cholesterol raise dementia risk?

A new study has added to data suggesting that HDL cholesterol (HDL-c) – sometimes called ‘good’ cholesterol, as it can help protect against heart disease – may be a risk factor for developing dementia.

A paper on the study published in The Lancet Regional Health – Western Pacific has found an association between HDL-c and dementia in a large sample of nearly 19,000 initially healthy older people, although, the authors stress it is too early to say there is a causal link.

Patients with very high levels of the biomarker of 80 mg/dL or more were found to have a 27% greater risk of developing dementia, with the association most pronounced among those aged 75 and over. The recommended range for HDL-c is currently 40 mg/dL in men and 50 mg/dL in women.

The link also appeared to be independent of traditional dementia risk factors, including physical activity level, alcohol intake, education, diabetes, or smoking.

The findings come a few weeks after another study published in Neurology, which looked at data from more than 184,000 adults with an average age of 70, also showed a correlation between HDL-c and dementia, with a 15% increased risk in people with levels above 65 mg/dL and a 7% increase in those with very low levels (11 to 41 mg/dL).

It’s worth noting that both those studies contradict a recently published meta-analysis of data from 100 studies suggesting that HDL-c levels were unrelated to Alzheimer’s dementia.

The authors of the latest study note that it has limitations, including a reliance on self-reported variables like alcohol intake and a lack of granularity on the HDL-c data. For example, the data did not cover genetic variations that can affect plasma HDL-c levels and could have revealed an underlying genetic contribution to the finding, and they acknowledge that, for now, there is no pathophysiological explanation.

Nevertheless, they conclude: “Given dementia is the third major cause of disability worldwide, these findings are timely and may suggest that identifying individuals with very high HDL-c could act as a new strategy for the early identification of high-risk individuals.”

Oxford University geratology specialist Professor Gordon Wilcock said the study was an important contribution to the data around the potential role of HDL-c in dementia, but added he “would not consider altering [...] lifestyle to adjust [...] HDL-c level until the evidence is more conclusive.”

“There are conflicting reports about the potential role of this type of cholesterol in relation to dementia and I think it might turn out to be a marker for something else, or not relevant at all,” said Prof Wilcock.

Professor David Curtis of the University College London (UCL) Genetics Institute is also sceptical that the study is demonstrating a real effect.

“The main claim is that very high HDL-c is associated with increased risk of dementia, but the confidence interval for the hazard ratio very nearly includes 1, implying that the results could quite easily have occurred by chance,” he said.

“This kind of association study, incorporating multiple variables as covariates, is always difficult to interpret, as different kinds of confounding can arise,” he added. “Even if the results do reflect some real biological effect, it is not clear that there are any important implications.”