Hypercholesterolemia in Midlife Raises Dementia Risk

Kathleen Louden

April 17, 2008

April 17, 2008 (Chicago, Illinois) — High serum total cholesterol levels in midlife increase the risk of developing Alzheimer's disease 3 decades later, new research shows.

Alzheimer's disease was 1.5 times more prevalent in men and women who had total cholesterol levels of 249 to 500 mg/dL when they were middle-aged than in people with normal cholesterol levels, according to a retrospective study that involved 9752 members of a Kaiser Permanente health plan in northern California.

The study results send a message to physicians, study coauthor Alina Solomon, MD, from the University of Kuopio, in Finland, who collaborated with researchers at Kaiser Permanente, told Medscape Neurology & Neurosurgery: "Minding heart health may protect the brain."

Dr. Solomon presented the results here at the American Academy of Neurology (AAN) 60th Annual Meeting.

Heart Health

In this multiethnic cohort, the patients were 40 to 45 years old when they had health evaluations between 1964 and 1973. They stayed with the health plan through at least 1994, so that the researchers were able to check their most recent medical records, from 1994 to 2007, for a documented diagnosis of Alzheimer's disease.

On retrospective chart review, the authors found that 504 patients had Alzheimer's disease, with a mean age at diagnosis of 68.8 years. High cholesterol increased Alzheimer's risk regardless of midlife diabetes, hypertension, and obesity; smoking; and late-life stroke, according to Dr. Solomon.

They found that subjects in the highest quartile for cholesterol level in their 40s had an increased risk for AD compared with those in the lowest quartile.

Even less severely elevated cholesterol was associated with an increased risk for dementia, said Dr Solomon. Patients whose total cholesterol levels were between 221 and 248 mg/dL were still more likely to have a diagnosis of Alzheimer's disease later in life compared with patients with cholesterol levels below 198 mg/dL.


Adjusted Risk for Alzheimer's Disease by Cholesterol Levels During Midlife

Quartile Hazard Ratio 95% CI
< 198 mg/dL reference
198 – 220 mg/dL 1.18 0.88 – 1.57
221 – 248 mg/dL 1.30 0.98 – 1.73
249 – 500 mg/dL 1.52 1.14 – 2.02

Possibly, the study underestimated the risk of Alzheimer's disease, Dr. Solomon said in an interview with Medscape Neurology & Neurosurgery. Some patients may have had the disease, but it was not yet diagnosed at the most recent visit, she theorized. In addition, she said, some patients may have received lipid-lowering medications when they became available, but the authors did not have this information.

Because the data from the 1960s and early 1970s did not have information on triglycerides and low-density-lipoprotein (LDL) cholesterol, the authors were unable to analyze whether these measures had an effect on Alzheimer's risk.

The researchers did observe a trend toward an increased risk for vascular dementia in this patient population, but the difference was not statistically significant, according to the abstract.

Based on their study findings, Dr. Solomon advised physicians not to delay in treating patients in their 40s who have high cholesterol levels. She said she would prescribe dietary and other lifestyle modifications first and, if necessary, medication. However, it is not yet clear whether statins will protect against the development of Alzheimer's disease, she stated.

A "Hot Topic"

A study published online January 16 in Neurology found that statin use did not lower the risk of Alzheimer's disease.

That study's principal author, Zoe Arvanitakis, MD, associate professor in the department of neurological sciences at Rush University Medical Center, in Chicago, Illinois, spoke to Medscape Neurology & Neurosurgery after viewing Dr. Solomon's poster at the AAN meeting. Their study had important differences from the new study in that it looked at patients in their late 70s, she said, and their follow-up was only for up to 13 years.

"It may be that you need to take statins a lot longer to benefit," said Dr. Arvanitakis, who had no relationship with Dr. Solomon's research. "This is a hot topic and an ongoing story."

Dr. Solomon reports no relevant financial disclosure.

American Academy of Neurology 60th Annual Meeting: Abstract P04.067. Presented April 16, 2008.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.