Both high and low HDL cholesterol tied to slight increase in risk of dementia

ISLAMABAD, OCT 06 (ONLINE): New research, published today in the journal Neurology, reports that high levels as well as low levels of “good” HDL cholesterol were associated with a higher risk of developing dementia.
The study involved more than 184,000 participants with an average of 70 years who were followed for 17 years.

The researchers were seeking to understand the relationship between two types of cholesterol, HDL-C and LDL-C, and the likelihood of developing dementia in older age.
While there have been some studies on this topic, not many have considered the influence of statin medications or examined the possibility of more complex associations.

The researchers explored these connections using extensive data from both survey responses and electronic health records.
Tracking dementia
The study subjects were members of the Kaiser Permanente Northern California health plan who were 55 or older.

These members had taken a health survey between 2002 and 2007, did not have dementia before the survey, and had their cholesterol measured within two years after the survey.
The research team tracked these members until December 2020 to see if they developed dementia.

They used specific methods and models to understand the data, ensuring they considered various factors such as demographics and medications.
The researchers said the findings showed that both very low and very high levels of HDL-C were linked to a higher risk of developing dementia.
Relationship between HDL-C levels and dementia risk

The researchers reported that people with the highest HDL cholesterol levels had a 15% higher dementia risk compared to those with mid-range levels.
Those with the lowest HDL levels had a 7% higher dementia risk versus the mid-range group.

Researchers said these relationships held even after accounting for other factors such as alcohol use, hypertension, cardiovascular disease, and diabetes.
On the other hand, levels of “bad” LDL-C cholesterol didn’t show a clear link to dementia risk for everyone. However, for those who were using statins, a higher LDL-C level indicated a slightly higher dementia risk.
Age also seemed to play a role in the relationship between HDL-C and dementia risk but not with LDL-C.

While this large study shows associations, it cannot prove high or low HDL cholesterol levels directly cause dementia.
Erin Ferguson, MPH, a lead study author and a former Boston University SPH student currently affiliated with the University of California San Francisco, told Medical News Today that “we found a U-shaped relationship between HDL-C and dementia risk, such that people with either lower or higher HDL-C had a slightly elevated risk of dementia.”

“Overall, we found no association between LDL-C and dementia,” Ferguson added.
Clifford Segil, DO, a neurologist at Providence Saint John’s Health Center in Calilfornia who was not involved in this research, told Medical News Today that “studies looking into how to prevent dementia are appreciated as our treatments for dementia in 2023 continue to only provide modest clinical improvements.”

As a reminder, the three most common dementias are Alzheimer’s dementia, vascular or multi-infarct dementia, and Lewy-Body dementia or Parkinson’s dementia. Statin use, or medication used to lower cholesterol in our blood, has been proven to decrease a risk of second lifetime heart attack and stroke. Statin use needs to be studied specifically regarding decreasing the risk of multi-infarct of vascular dementia.

Dr. Clifford Segil
“This study looked at using cholesterol-lowering medications to decrease all dementia rather than statin use to decrease multi-infarct or vascular dementia,” Dr. Segil pointed out.
Further research needed to understand complex associations
Ferguson noted that “this work suggests that some lipoproteins (like HDL) may be modifiable risk factors of dementia, even in late life, but to take advantage of this we need to next evaluate whether these effects are causal and how to effectively modify HDL.”

While the magnitude of the association is fairly small, these results suggest that the relationship between HDL-C and dementia is complex. Our work supports a body of recent literature showing there are nonlinear relationships between HDL and other diseases (like cardiovascular disease and cancer) and mortality. The mechanisms for why these nonlinear relationships exist are still unknown.
Erin Ferguson, MPH
“Future studies will need to investigate causal relationships at play to confirm that there is clinical relevance,” Ferguson explained.
Segil agreed, saying, “more research should follow this study specifically looking at the role of using statins, or cholesterol-lowering medications, on the development of multi-infarct or vascular dementia.”

“Patients with memory loss often have MRI brain [findings consistent] with chronic ischemic changes and statins use may decrease these small silent strokes, but further research is needed to determine if this is the case,” she added.

Segil concluded by saying “elderly patients should not start taking statin medications to prevent dementia based on this study.”

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