CardioExchange Archive

A recent study in Neurology found that cholesterol levels in mid-life were not linked to the development of Alzheimer’s disease in older age. In fact, the study by Michelle Mielke and colleagues found that large drops in cholesterol levels in old age were a harbinger of Alzheimer’s. CardioExchange asked Cynthia Carlsson, Assistant Professor and Alzheimer’s researcher at the University of Wisconsin School of Medicine and Public Health, to provide an expert perspective on this counterintuitive finding.

There has been a lot of controversy as to what role cholesterol plays in the development of dementia. To date, studies suggest that elevated midlife cholesterol increases the risk of Alzheimer’s disease. This idea is also supported by animal studies that show increased cholesterol triggers the development of the hallmark amyloid plaques in the brains of animals. In addition to Dr. Mielke’s study, other investigators have shown in longitudinal analyses that blood cholesterol levels tend to be higher in midlife and then drop later in life prior to the onset of dementia.

Some believe this reflects the subclinical disease process leading to either dietary changes or other inflammatory changes that alter the blood cholesterol levels. Because serum cholesterol is a negative, acute-phase reactant, with an increased inflammatory state (such as during acute or chronic illness) serum cholesterol levels decline. Alzheimer’s disease is associated with inflammatory changes; thus, it could theoretically trigger a decline in serum cholesterol.

Therefore, I am not too surprised that Dr. Mielke found that those individuals with the greatest cholesterol decline had the highest risk of Alzheimer’s disease: These results most likely reflect that the person is progressing to a disease state, rather than the low-cholesterol levels triggering the dementia.