A recent research study has indicated that high-density lipoprotein cholesterol (HDL-C) could be a high-risk factor for dementia, especially for people over the age of 75. Though high levels of HDL cholesterol — also known as good cholesterol — have always been equated with improved cardiac health, neurological experts are of the opinion that too much of it might not be optimal for your cognitive well-being. It’s being attributed as a cause that’s independent of traditional risk factors for dementia, which include smoking, diabetes, alcohol consumption and physical activity level.
“High HDL levels could be effectively used as an indicator for dementia risk, especially in Alzheimer risk prediction algorithms,” said Dr Sultana Monira Hussain, first author of the study and senior research fellow, School of Public Health and Preventive Medicine, Monash University, Australia, in her official statement.
The study published in The Lancet Regional Health – Western Pacific involved as many as 18,668 older adults. They were selected from the Aspirin in Reducing Events in the Elderly (ASPREE) trial of 2010 to 2014, and none of them had any diagnosed cardiovascular or cognitive impairments. These participants were further examined from October 2022 to January 2023, revealing that some of them, especially those with high HDL-C levels of over 80 mg/dL, were showing signs of dementia. They registered a 27% higher risk of developing the condition than those with lower levels of HDL-C.
The lipoprotein truck and its passengers
Dr Pawan Ojha, director, neurology, Fortis Hiranandani Hospital, Vashi, Mumbai, cites the example of a transport truck to explain the role of lipoproteins (molecules composed of lipids and proteins) that travel across the body carrying cholesterol, proteins and apolipoproteins (a class of proteins that bind to lipids to form lipoproteins) needed for multiple physiological functions. Cholesterol, being insoluble in blood, has to attach itself to proteins or amino acids to transport across the body. “Cholesterol, triglycerides, apolipoproteins, etc., are just passengers in these transport trucks [lipoproteins]. It should be noted that when it comes to the traditional definition of HDL and LDL, only the amount of cholesterol in these transport molecules changes,” he says. According to the American Heart Association (AHA), HDL carries only one-third to one-fourth of the total blood cholesterol; it’s not able to transport the entire amount of excess cholesterol to the liver to be expelled from the body.
Lipoproteins and cholesterol play a major role in determining vascular health and hence could be considered markers for dementia, opines Dr Balaji BS, consultant, neurology and epileptology, Aster Whitefield Hospital, Bangalore.
Cholesterol and cognitive health
Dr Ojha points out that as far as the link between HDL levels and brain health is concerned, we should take into account that HDL comprises more than just cholesterol. “When it comes to cholesterol and health, it is a different story for the heart and a totally different one in regard to brain health. As far as the brain is concerned, we have to forget the traditional ‘good’ and ‘bad’ classification of cholesterol when dealing with dementia,” he says. Conditions such as stroke and dementia develop due to different physiological dysfunctions. Stroke typically results from insufficient blood supply to the brain due to excess cholesterol deposition in the arteries, whereas dementia is caused by certain cognitive impairments resulting from a lack of proper relay and coordination involving various proteins and other molecules in neural cells.
“When we consider cognitive health, dementia or Alzheimer’s disease, we should be more concerned about apolipoproteins instead of cholesterol, especially apolipoprotein E (ApoE) and its role in the formation of neurofibrillary tangles and amyloid plaques, which are the main biomarkers for Alzheimer’s disease,” informs Dr Ojha. Neurofibrillary tangles refer to the abnormal deposition of proteins inside certain neurons that makes them tangled, hindering communication with other nerve cells. Amyloid plaques result from the excess deposition of certain beta-amyloids (a protein) between neurons, disrupting the optimal functioning of the brain.
Apolipoprotein E: The genetic risk factor for Alzheimer’s disease
ApoE is regarded as one of the key genetic factors that could increase the risk of Alzheimer’s disease. This protein molecule is being extensively researched across the world to understand its interaction with neurons and its overall impact on cognitive health. HDL molecules are likely to have more ApoE, including its E3 and E4 alleles (variants), which are known to increase the risk of Alzheimer’s disease. “HDL molecules will have ApoE; if its E3 and E4 alleles are there, then the individual is likely to have a higher risk of dementia later in life. In addition, high HDL levels can also be a sign of faulty lipid transport and metabolism,” says Dr Ojha.
Further research is required
“While we know that HDL cholesterol is important for cardiovascular health, this study suggests that we need further research to understand the role of very high HDL cholesterol in the context of brain health,” Dr Hussain added in her statement.
Interestingly, other studies also indicate that high and low levels of HDL in middle age could spike dementia risk later in life. A research article published in the journal Neurology found that high and low levels of HDL-C were associated with an elevated risk of dementia, with LDL-C having a modest impact.
Dr Ojha says that these studies can pave the way for developing new fronts in finding ways to control, manage or cure dementia (especially Alzheimer’s disease) in the near future. “Most of these studies are conducted on Caucasian participants or formulated using Caucasian health data. The results might be a bit different when it comes to Indians and Asians,” he adds.
Takeaways
While high-density lipoprotein (HDL) or good cholesterol is usually linked with improved cardiac health, high levels of it can be a risk factor for neurological conditions like dementia. The study involving 18,668 older adults found that those with high HDL levels had a 27% higher risk of developing dementia than those with lower levels of the same. Apolipoprotein E (a protein) is considered one of the key genetic factors that could increase the risk of Alzheimer’s disease. Further research is required to better understand the connection between high HDL levels and brain health.
