Dementia Tied to Fluctuations in Blood Lipids Over Time

Fluctuations in total cholesterol and triglyceride levels in people 60 and older were tied to a higher risk of incident dementia, including Alzheimer’s disease, a longitudinal study showed.

Over a median follow-up of 12.9 years, participants in the highest quintile of total cholesterol variability versus the lowest quintile had a 19% increased risk of incident Alzheimer’s or related dementias (HR 1.19, 95% CI 1.04-1.36, P=0.011), reported Suzette Bielinski, PhD, of the Mayo Clinic in Rochester, Minnesota, and co-authors.

Those in the highest quintile of triglycerides variability had a 23% increased risk compared with the lowest quintile (HR 1.23, 95% CI 1.08-1.41, P=0.002), the researchers wrote in Neurology.

“Routine screenings for cholesterol and triglyceride levels are commonly done as part of standard medical care,” Bielinski said in a statement. “Fluctuations in these results over time could potentially help us identify who is at greater risk for dementia, help us understand mechanisms for the development of dementia, and ultimately determine whether leveling out these fluctuations could play a role in reducing dementia risk.”

Vascular risk factors, including hyperlipidemia, have been linked with dementia but most studies have measured them at a single point in time, Bielinski and colleagues noted. Research about cholesterol variation over time has not evaluated relationships between dementia and fluctuations in high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides, they added.

The researchers studied 11,571 participants in the Rochester Epidemiology Project (REP), a medical records system that links researchers with data from community providers who care for residents of southern Minnesota and western Wisconsin.

Participants were age 60 and older, did not have a prior diagnosis of Alzheimer’s or dementia at the index date of Jan. 1, 2006, and had three or more lipid measurements including total cholesterol, triglycerides, LDL-C, or HDL-C in the 5 years before the index date.

The most recent lipid values before January 2006 were considered baseline measurements. Lipid variation was defined as any change in lipid levels over time, regardless of direction, and was measured using variability independent of the mean.

Alzheimer’s and dementia diagnoses were determined by ICD codes. The researchers did not differentiate by dementia type and included all dementia under the CMS definition of Alzheimer’s disease and Alzheimer’s disease-related dementia.

The study population was followed from baseline to incident dementia, death, or Dec. 31, 2018. Mean age was 71, 54% were women, and 96% were white.

Participant histories included stroke (13%), myocardial infarction (7%), diabetes (35%), or cancer (22%). Half of participants were on lipid-lowering treatment at baseline. Findings were adjusted for sex, race, education, and lipid-lowering treatments.

Over the follow-up period, a total of 2,473 (21%) individuals had a dementia diagnosis. No relationship between variations in LDL-C and HDL-C and dementia risk was seen.

It’s not clear why or how fluctuating levels of total cholesterol and triglycerides were related to dementia risk, Bielinski noted. Changes in BMI, which may occur as dementia develops, may be a factor. It’s possible variations in some lipid levels are biomarkers, not risk factors, for dementia, the researchers observed.

“Further studies looking at the changes over time for this relationship are needed in order to confirm our results and potentially consider preventative strategies,” Bielinski said.

The study had several limitations, the researchers acknowledged. People included in the study had more comorbidities than others. Dementia subtypes were not known, and ICD codes may have underdiagnosed incident dementia. Moreover, the cohort was predominantly white and the findings may not be representative of other populations.