A low level of high-density lipoproteins (HDL), commonly known as “good” cholesterol, may raise the risk of developing Alzheimer’s disease say US researchers, who caution their findings still need to be confirmed by other studies.

The researchers, from Columbia University College of Physicians & Surgeons, New York, NY, report their investigation in a study published in the December issue of Archives of Neurology, a JAMA/Archives journal.

Low levels of high-density lipoproteins (HDL), a well-known risk factor for heart disease, are common in the US, said lead author Dr Christiane Reitz, assistant professor of neurology in the Sergievsky Center and Taub Institute at the University, in a press statement.

She and her colleagues also wrote in their background information that:

“Dyslipidemia [high total cholesterol and triglycerides] and late-onset Alzheimer’s disease are highly frequent in western societies.”

“More than 50 percent of the US adult population has high cholesterol. About 1 percent of people age 65 to 69 years develop Alzheimer’s disease, and the prevalence increases to more than 60 percent for people older than 95 years,” they added.

Previous studies of HDL and Alzheimer’s risk have either found no link or their findings have been unclear, but their new study followed participants for longer, resulting in a more accurate account of the numbers who went on to develop Alzheimer’s disease, the researchers told the press.

For this study, for an average of four years, they followed 1130 elderly people living in northern Manhattan. The participants came from a random sampling of Medicare recipients and were aged 65 and over. None had a history of dementia or cognitive impairment when they joined.

To collect their data, Reitz and colleagues studied medical, neurological and neuropsychological evaluations.

They assigned a diagnosis of “probable” Alzheimer’s disease when onset of dementia could not be explained by any other disorder and a diagnosis of “possible” Alzheimer’s disease when the most likely cause of dementia was Alzheimer’s disease but there was evidence that other disorders could have contributed to the dementia, such as stroke or Parkinson’s disease.

The researchers found that:

  • Over the follow up, 101 participants developed Alzheimer’s, of which 89 were “probable” and 12 were “possible”.
  • The mean age of participants who received either of these diagnoses was 83 years at onset.
  • They were also more often Hispanic and had a higher prevalence of diabetes at the start of the study than counterparts who did not develop dementia.
  • Higher blood levels of HDL (above 55 mg/dl) were linked with a decreased risk of both probable and possible Alzheimer’s, even after adjusting for vascular risk factors and lipid-lowering treatments.
  • Adjusting for vascular risk factors and lipid-lowering treatments eliminated any links between higher total cholesterol, non-HDL cholesterol and LDL cholesterol levels and risk of probable and possible Alzheimer’s disease.
  • There was a 40 per cent higher rate of developing Alzheimer’s among those with low HDL (below 55 mg/dl).

Reitz and colleagues concluded that in this study:

” … higher levels of HDL cholesterol were associated with a decreased risk of both probable and possible Alzheimer’s disease.”

They also noted it was important to consider, when interpreting these results, that the study was “conducted in an urban multiethnic elderly community with a high prevalence of risk factors for mortality and dementia.”

“Thus, our results may not be generalizeable to cohorts with younger individuals or to cohorts with participants with a lower morbidity [disease] burden,” they stressed.

Nonetheless, a distinguishing feature of this study is that unlike previous studies that included mostly white people, it included a large number of African Americans and Hispanics, suggesting the link between low HDL and higher risk of Alzheimer’s may apply in many different ethnic groups.

Speculating on their results, Reitz told the press it is not clear why HDL may be linked to higher risk of Alzheimer’s, but said there was some evidence to suggest two reasons:

“We know low HDL raises the risk of stroke and that stroke is associated with Alzheimer’s”, said Reitz, “so stroke may be the mediator”.

“But there’s also evidence that HDL works by itself to clear amyloid proteins from the brain,” she added.

Alzheimer’s is thought to be caused by two abnormal structures found in the brains of people who have died of the disease: plaques and tangles. The plaques are deposits of amyloid beta proteins that build up in the spaces between brain cells, tangles are twisted fibers of tau protein that build up inside cells.

According to the Alzheimer’s Association, there are 5.3 million Americans living with Alzheimer’s disease. From 2000 to 2006, Alzheimer’s disease deaths increased 46.1 per cent, while other major causes of death like prostate cancer, breast cancer, heart disease HIV-related illnesses, and stroke decreased.

The Association says strategic investments in other diseases have led to decline in deaths, and the same type of investment is urgently needed for Alzheimer’s.

“If raising HDL can lower a person’s risk of developing Alzheimer’s disease, that means we may be able to significantly reduce the rate of Alzheimer’s disease in the population.” said Reitz, adding that their findings now need to be confirmed by other studies.

Grants from the National Institute on Aging, the Charles S Robertson Memorial Gift for Research in Alzheimer’s Disease and the Blanchette Hooker Rockefeller Foundation helped pay for the study.

“Association of Higher Levels of High-Density Lipoprotein Cholesterol in Elderly Individuals and Lower Risk of Late- Onset Alzheimer Disease.”
Christiane Reitz; Ming-Xin Tang; Nicole Schupf; Jennifer J. Manly; Richard Mayeux; Jose A. Luchsinger.
Arch Neurol.Vol 67, No 12, pp 1491-1497, December 2010.
DOI:d10.1001/archneurol.2010.297

Additional sources: Columbia University College of Physicians & Surgeons press release, JAMA and Archives Journals, Alzheimer’s Association (US).

Written by: Catharine Paddock, PhD