Dementia is one of the major causes of disability worldwide, affecting approximately 50 million people, with nearly 10 million new cases yearly. Cardiovascular disease (CVD) risk factors are important in the development of dementia. Familial hypercholesterolemia (FH) may represent a model disease for studying atherosclerosis and the risk of dementia. A recent study suggests that individuals with FH have no excess risk of dementia and that there is no association between long-term high-intensity statin use and dementia risk. The study findings were published in the JAMA Network Open on April 19, 2022.

FH leads to high levels of plasma LDL-C from birth and excess risk of early atherosclerosis and premature CVD. People with FH are often put on statins at a young age to keep their genetic predisposition for high cholesterol in check. Prior studies have shown that early and prolonged statin exposure might prevent dementia, in particular vascular dementia. The role of statin treatment to prevent AD is, however, controversial. Therefore, Dr Liv J. Mundal and her team conducted a study to determine whether individuals with FH, who have been exposed to lifelong hypercholesterolemia, have an excess risk of dementia and whether statin use is associated with dementia risk.
In this prospective study, the researchers included 3,520 patients with FH and 69,713 age- and sex-matched controls from the general Norwegian population between 2008 and 2018. They determined dementia according to the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes F00-03 and G30. They assessed the data on the incident cases of total dementia, vascular dementia, Alzheimer's disease-associated dementia, and data on lipid-lowering medication were obtained from the Norwegian Patient Registry, Cause of Death Registry, and the Norwegian Prescription Database. They calculated hazard ratios (HRs) for the risk of dementia for individuals with FH vs matched controls using Cox regression.
Key findings of the study:
Upon 10 years of follow-up, the researchers found that 62 patients with FH and 1294 patients in the control group had developed dementia.
They noted that most dementia cases occurred among individuals aged 70 years and older (39 patients with FH [62.9%] and 870 patients [67.2%] in the control group).
They found no excess risk of dementia in patients with FH vs matched controls (HR for total dementia, 0.9).
They further observed no association between cumulative DDDs of statins and total dementia in patients with FH with HRs of 1.2 for cumulative DDDs of 5000 to 10 000 and 1.9 for cumulative DDDs greater than 10 000.
The authors concluded, "These findings suggest that individuals with FH have no excess risk of dementia compared with age-matched and sex-matched controls and that there is no association between use of statins and risk of dementia in patients with FH."
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DOI:10.1001/jamanetworkopen.2022.7715