Cholesterol in middle-aged ‘linked to Alzheimer’s years later’

High levels of cholesterol in middle-age are associated with an increased risk of developing dementia and Alzheimer’s disease more than a decade later, new research suggests.

High levels of low-density lipoprotein (LDL) were linked to an increased risk of developing the conditions.

While elevated levels of total cholesterol were also associated with an increased risk, this link was weaker, suggesting it is largely driven by LDL cholesterol, researchers say.

The study provides the strongest evidence so far on the relationship between blood cholesterol and dementia and Alzheimer’s disease. It was led by the London School of Hygiene & Tropical Medicine (LSHTM) with the University of Tsukuba, Japan and OXON Epidemiology, London and Madrid.

Study lead Dr Nawab Qizilbash is senior clinical epidemiologist at OXON Epidemiology and honorary associate professor in pharmacoepidemiology at LSHTM.

He said: “While the link between LDL cholesterol and dementia and Alzheimer’s disease is modest and found in people followed up from middle age for over 10 years, any modifiable risk factor is welcome for this huge, burgeoning and devastating disease.

“Most of the known risk factors are difficult to modify and convincing evidence that their modification can prevent dementia or Alzheimer’s disease is scarce.

“Likewise, long term follow-up (more than 10 years) of randomised and non-randomised studies are needed to assess if the benefits of LDL cholesterol-lowering interventions – which greatly reduce coronary heart disease – may additionally reduce the risk of dementia or Alzheimer’s disease.”

Funded by Alzheimer’s UK, researchers used anonymised data from the UK Clinical Practice Research Database (CPRD) on more than 1.8 million UK adults.

They were all aged over 40 and had a blood cholesterol measurement taken between 1992 and 2009, with a follow-up period up to 23 years or until dementia diagnosis.

In what is believed to be the largest study of its kind, researchers were able to calculate the risks of subsequent dementia and Alzheimer’s disease for blood total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides, adjusting for other factors.

Researchers focused on blood cholesterol measurement taken in middle age (under 65s) who have less disease.

A follow-up period of more than ten years meant they could avoid bias resulting from a long silent period when the pathology was present but symptoms were clinically absent or vague.

In the 953,635 people in the study who had an LDL cholesterol recording, 2.3% (21,602) went on to be diagnosed with dementia or Alzheimer’s disease.

Of the more than 1.8 million people who had a first total cholesterol reading, nearly 50,000 (2.7%) had a subsequent diagnosis in the 23-year follow-up period, up to 2015.

The study found that the associations were weaker in people who had their blood cholesterol measured after the age of 65.

No consistent associations were observed for high-density lipoprotein (HDL) cholesterol or triglycerides.

Lead author Dr Masao Iwagami, assistant professor at the University of Tsukuba and honorary Associate Professor in Epidemiology and Population Health at LSHTM, said: “Our study dwarfs in size all previous studies and provides really precise results.

“In people with cholesterol measured below age 65 the risk of dementia being diagnosed more than 10 years later was about 60% higher in those with LDL cholesterol levels above 200 mg/dL (5.17 mmol/L) compared to those with levels less than 100 mg/dL (2.6mmol/L).

“The strength of this association is comparable with other modifiable risk factors such as alcohol consumption and greater than for blood pressure.”

The authors acknowledge limitations of the study including the lack of information on diet or physical activity, so it was not possible to assess the influence of these factors on blood cholesterol and how it might affect the observed associations.

The study is published in Lancet Healthy Longevity.