Oslo, Norway—Patients with familial hypercholesterolemia (FH) do not face excess risk of dementia, according to a new study, which also verified that the use of statins does not affect that risk or lack thereof.

The study published in the Journal of the American Medical Association Network Open sought to determine if high-density lipoprotein (HDL) cholesterol caused by a genetic mutation was associated with any increased risk of dementia.

FH is an inherited disease caused by a mutation in the low-density lipoprotein-C (LDL-C) receptor gene. Worldwide, according to a recent meta-analysis, the prevalence of FH in the general population is one in 313 individuals. The authors pointed out that FH leads to high levels of plasma LDL-C from birth and excess risk of early atherosclerosis and premature cardiovascular disease (CVD).

The Norwegian cohort study included 3,520 participants with genetically verified FH; they were compared to 69,713 age-matched and sex-matched controls. Researchers from Oslo University Hospital identified no excess risk of dementia for those patients with FH versus matched controls. They also found no association between statin use and dementia.

Concerns have been raised that hypercholesterolemia, which is a cardiovascular risk factor, might also heighten dementia risk. At the same time, the benefits of statin therapy on dementia risk are controversial, the authors advised.

To help answer those concerns, the study team conducted a prospective cohort study from 2008 to 2018 in Norway, with statistical analysis performed from January 2021 to February 2022.

Over 10 years of follow-up, most dementia cases occurred among individuals aged 70 years—62.9% in FH patients and 67.2% in the control group.

"We found no excess risk of dementia in patients with FH vs. matched controls (HR for total dementia, 0.9; 95% CI, 0.7-1.2)," the researchers wrote. "There was no association between cumulative DDDs [defined daily doses] of statins and total dementia in patients with FH with HRs of 1.2 (95% CI, 0.4-3.8) for cumulative DDDs of 5,000 to 10,000 and 1.9 (95% CI, 0.7-5.0) for cumulative DDDs greater than 10,000."

The findings are significant, according to the authors, because CVD risk factors are important in the development of dementia. They suggested that a third of dementia cases might be associated with CVD risk factors and preventable.

"There is a positive association between levels of low-density lipoprotein cholesterol (LDL-C) and dementia risk. A high LDL-C level may be associated with AD [Alzheimer's disease] neurodegeneration," the authors wrote. "Statins may slow the conversion from mild cognitive impairment (MCI) to dementia. Recent research suggests a possible link between inflammation, dyslipidemia, atherosclerosis, and dementia."

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