The Effect of Statins on Dementia Risk in Familial Hypercholesterolemia

Genetic mutation, conceptual 3D illustration. Double stranded DNA molecule with mutation in a gene. Concept for genetic disorder. Destroyed human genome. DNA destruction and gene mutation
Researchers sought to examine whether individuals with familial hypercholesterolemia are at a heightened risk for dementia and whether statin use is tied to dementia risk.

Dementia risk was not elevated among patients with familial hypercholesterolemia (FH), according to results of a prospective cohort study published in JAMA Network Open.

Dementia affects approximately 50 million people worldwide and by 2050, it is estimated that 1 in 85 persons will have dementia. A third of all cases of dementia can be linked with cardiovascular disease (CVD) risk factors, and as FH increases risk for premature CVD, individuals with FH may also be at elevated risk for dementia.

In order to evaluate whether FH associates with dementia, data were sourced from a prospective registry of age- and gender-matched individuals with FH (n=3520) and control individuals (n=69,713) recruited from the Oslo University Hospital and the general Norwegian population, respectively, between 2008 and 2018.

The cohorts of FH and control individuals were 47.1% and 47.0% men, aged mean 51.8 (SD, 11.5) and 51.7 (SD, 11.5) years, 6.3% and 1.0% had coronary heart disease (P <.001), 2.3% and 1.6% hypertension (P <.001), and 78.6% and 10.1% took statins (P <.001), respectively.

In general, the FH cohort was not associated with increased dementia risk (hazard ratio [HR], 0.93; 95% CI, 0.72-1.20).

Stratified by subgroups, women (HR, 0.95; 95% CI, 0.69-1.30), men (HR, 0.90; 95% CI, 0.60-1.37), those aged 40-59 years (HR, 1.17; 95% CI, 0.55-2.51), 60-69 years (HR, 1.04; 95% CI, 0.63-1.72), and 70 years and older (HR, 0.86; 95% CI, 0.62-1.19) were not at higher risk for dementia compared with control individuals.

Similar trends were observed when patients were stratified by dementia type, FH associated neither with Alzheimer disease (HR, 1.12; 95% CI, 0.80-1.59) nor vascular dementia (HR, 0.89; 95% CI, 0.49-1.62) risk. This trend was observed when genders were assessed separately.

There was also no evidence that the cumulative daily dose of statins affected dementia risk in FH.

A study limitation was the follow-up duration (10 years), the researchers acknowledged. It remains unclear whether FH is associated with long-term dementia risk.

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


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