Familial Hypercholesterolemia and Related Statin Use Not Linked to Dementia Risk

Patients with familial hypercholesterolemia (FH) have no increased risk of dementia, and there is no association between use of statins and dementia risk in this population, according to a study in JAMA Network Open.

The Norwegian registry-based, prospective cohort study compared the incidence of dementia, including total dementia, vascular dementia, and Alzheimer disease (AD)-dementia in AD, in patients with genetically verified FH and randomly selected age- and sex-matched control individuals in the Norwegian population from 2008 to 2018.

The patients with FH were genetically diagnosed from 1992 to 2014, and control patients were matched to the FH population in a 1:20 ratio.

Dementia was defined as total dementia according to International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10). Follow-up continued until the endpoint, death from other causes, or December 31, 2018, whichever occurred first, and January 1, 2008, was the earliest possible start of follow-up.

A total of 3520 patients with FH and 69,713 control patients were included. Overall, 53.0% of patients were women (52.9% with FH and 53.0% in the control group). Patients were aged mean 51.8±11.5 years in the FH group and 51.7±11.5 years in the control group at the beginning of follow-up. The mean age at diagnosis was 45.1±14.0 years in patients with FH.

During the study, 1356 patients, including 62 with FH (62.9% women) and 1294 control patients (61.9% women) developed dementia. AD-dementia in AD was the most common type (56.5% of all cases) in the patients with FH.

No overall excess risk for total dementia (hazard ratio [HR], 0.9; 95% CI, 0.7-1.2), vascular dementia (HR, 0.9; 95% CI, 0.5-1.6), or AD-dementia in AD (HR, 1.1; 95% CI, 0.8-1.6) was found in patients with FH compared with the control patients.

A majority of dementia cases were patients aged 70 years or older, including 62.9% of patients with FH and 67.2% of patients in the control group.

No association was observed between statin consumption measured as cumulative defined daily doses (DDDs) of statins and total dementia risk in patients with FH. The HR was 1.2 (95% CI, 0.4-3.8) for the cumulative DDD of 5000 to 10,000. For the highest cumulative DDD of statins more than 10,000, the HR was 1.9 (95% CI, 0.7-5.0). The HR for the highest cumulative dose decreased to 1.70 (95% CI, 0.57-5.12) after further adjustment for comorbidities and comedications. The median cumulative statin dose until the end of follow-up was 8798 DDDs (IQR, 4233-14,795) in the patients with FH.

Among several study limitations, the follow-up was too short to observe any differences in long-term dementia risk, and information was lacking on important confounders, such as lifestyle factors and low-density lipoprotein cholesterol levels. Also, the study results are based on the ICD-10 code.

“We found no excess risk of total dementia, vascular dementia, or AD-dementia in AD in individuals with genotyped FH compared with age-matched and sex-matched controls in the general Norwegian population during 10 years of follow-up,” wrote the study authors. “In addition, there was no association between statin use and dementia risk among individuals with FH.”

Reference

Mundal LJ, Igland J, Svendsen K, Holven KB, Leren TP, Retterstøl K. Association of familial hypercholesterolemia and statin use with risk of dementia in Norway. JAMA Netw Open. Published online April 19, 2022. doi:10.1001/jamanetworkopen.2022.7715