People with familial hypercholesterolemia (FH), taking statins in most cases, were not prone to more dementia in a prospective cohort study from Norway.
There was no excess risk of total dementia — counting vascular dementia and Alzheimer’s disease (AD) — in FH patients versus matched controls (HR 0.9, 95% CI 0.7-1.2), according to Kjetil Retterstøl, MD, PhD, of the University of Oslo, and colleagues.
The researchers had followed the outcomes of over 3,500 FH patients from 2008 to 2018 using nationwide registries. The study was published in JAMA Network Open.
Statin therapy was used by 79% of FH patients, compared with 10% of controls. Greater consumption of statins, even high-intensity statins over several years, was not associated with any change in risk of dementia, according to Retterstøl’s team.
FH is an inherited disease that can be diagnosed by genetic testing. It is characterized by high levels of low-density lipoprotein (LDL) cholesterol starting in childhood and an excess risk of early atherosclerosis and premature cardiovascular disease.
Prior research had linked elevated LDL cholesterol and dementia. In the present study, it appeared that lipid-lowering therapy had no dementia-reducing benefits.
That is not to say that statins are definitely not helpful in FH, however.
“A systematic review of randomized placebo-controlled trials indicated that statins given late in life to individuals at risk of vascular disease have no effect in preventing AD or dementia. In the present study, the patients with FH had a high mean age (45.1 years) at the time of FH diagnosis, suggesting that the patients were not treated with statins before diagnosis, which may partly explain these findings,” Retterstøl and colleagues argued.
They also suggested that the study’s relatively short duration of follow-up precluded them from picking up any long-term differences in dementia between FH patients and controls, and statin users versus nonusers.
“Importantly, asymptomatic, neurodegenerative processes in the brain may develop several years ahead of dementia. Lowering LDL cholesterol levels by use of statins may slow a conversion from MCI [mild cognitive impairment] to dementia. In the current study, we did not include MCI, which may be a prodromal stage for dementia,” the investigators added.
Their study counted 3,520 individuals with FH confirmed on genetic testing (mean age 51.8 years, 52.9% women). This cohort was compared against 69,713 age-matched and sex-matched controls obtained from the general Norwegian population.
Over follow-up, 62 FH patients and 1,294 controls developed dementia.
The majority of cases occurred in people age 70 years and older. AD was the most common form of dementia in FH, accounting for 56.5% of cases.
“As the world’s population ages, we are facing a global epidemic of AD. A delay in the onset of dementia by 2 years could potentially lower the prevalence of AD by more than 22 million cases over the next 40 years,” the authors said.
They cautioned that their study relied on databases that lacked important variables (e.g., lifestyle factors and LDL cholesterol levels). Diagnostic codes were also subject to potential errors, given that different forms of dementia can present similarly, their underlying pathophysiology established only by autopsy.
The study was funded by South-Eastern Norway Regional Health Authority and The Throne Holst Nutrition Research Foundation, Norway.
Retterstøl and co-authors had no disclosures.