How is heart disease linked to Alzheimer's development?

• There is a known association between Alzheimer’s disease and cardiovascular disease.
• Past research shows there may be a possible genetic link between these two conditions.
• Researchers from Edith Cowan University in Australia have found a potential genetic connection between Alzheimer’s disease and several coronary artery disease-related disorders and lipids such as cholesterol.

For some time now, researchers have known there is a connection between Alzheimer’s disease and cardiovascular disease .

Previous studies have linked heart conditions like high blood pressure , dyslipidemia , coronary artery disease , and atrial fibrillation to an increased risk of developing Alzheimer’s disease and other forms of dementia .

Past research has also discussed a possible genetic link between Alzheimer’s disease and heart disease. For example, a study published in November 2018 found that both conditions shared common genetics in some people.

“Observational studies share strong genetic evidence supporting a link between coronary artery disease and the risk of dementia, as well as an increased risk of late-onset Alzheimer’s disease with a genetically determined risk of coronary artery disease,” Artika Kirby , a PhD candidate at the Centre for Precision Health at Edith Cowan University in Australia told Medical News Today .

“There is also strong evidence of shared genes, particularly the apolipoprotein E ( APOE ) gene , a well-established risk gene for Alzheimer’s disease, evidenced in the shared genetic architecture between coronary artery disease and late-onset Alzheimer’s disease,” she added.

“Alzheimer’s disease and coronary artery disease — or cardiovascular diseases more widely — also share other genes including GPBP1 , SETDB2 , DAB2IP , and DNM2 ; however, the underlying biological mechanisms between Alzheimer’s disease and coronary artery disease — or heart disease or cardiovascular diseases, more widely — remains unresolved,” Kirby noted.

Kirby is the lead author of a new study recently published in the International Journal of Molecular Science that has found a potential genetic link between Alzheimer’s disease and several coronary artery disease-related disorders and lipids , such as cholesterol .

What are the traits of coronary artery disease?

For this study, Kirby and her colleagues focused on seven traits of coronary artery disease, which occurs when plaque build-up inside the arteries supplying blood to the heart:

• angina pectoris
• cardiac dysrhythmias
• coronary arteriosclerosis
• ischemic heart disease
• myocardial infarction (heart attack)
• nonspecific chest pain
• coronary artery disease.

Scientists also focused on 13 different lipids associated with coronary artery disease, including lipoproteins , triglycerides , and cholesterol.

“During our literature search, we evidenced a lack of evidence for Alzheimer’s disease and coronary artery disease traits,” Kirby explained.

“Given the significant risk of Alzheimer’s disease and cardiovascular diseases — including coronary artery disease traits — globally, we were motivated to investigate potential genetic links between Alzheimer’s disease and coronary artery disease traits,” she added.

Genetic link between Alzheimer’s and coronary artery disease

The researchers used a three-way cross-traits genetic analysis for their study.

At the study’s conclusion, they found a notable genetic connection between all of the seven coronary artery disease traits assessed, as well as triglycerides.

“A positive global genetic correlation refers to, at the very least, the potential for some individuals with a genetic predisposition to elevated levels of triglycerides or any of the seven coronary artery disease traits assessed in our study to a potentially increased risk of Alzheimer’s disease,” KIrby said.

Additionally, the scientists discovered a genetic overlap between Alzheimer’s disease and three more lipid measurements — high-density lipoproteins (HDLs), low-density lipoproteins (LDLs), and total cholesterol — and also identified genome-wide significant genes shared across Alzheimer’s disease, several lipids, and coronary artery disease traits.

“Investigating gene overlap, especially whether there is gene overlap more than by chance, sheds light on the possibility of shared (overlapping) genes across multiple diseases such as Alzheimer’s disease, several lipids, and coronary artery disease traits,” Kirby said.

According to the researcher, “[t]hese findings can improve our understanding of the underlying biological mechanisms, and interconnectedness at the gene level, between Alzheimer’s disease, select lipids, and coronary artery disease traits.”

“Further genetic studies can help us better understand the genetic underpinnings of Alzheimer’s disease and coronary artery disease— and cardiovascular diseases more widely — in how the diseases may interact at the gene level,” she added. “This can allow us to better understand the onset and progression of Alzheimer’s disease, and potentially work towards finding therapeutic targets for both Alzheimer’s disease and cardiovascular diseases.”

Is there a causal relationship between heart disease and Alzheimer’s?

After reviewing this study, Cheng-Han Chen, MD , a board certified interventional cardiologist and medical director of the Structural Heart Program at MemorialCare Saddleback Medical Center in Laguna Hills, CA, told MNT he found it interesting.

“Some studies have shown a connection between Alzheimer’s and some other cardiovascular disease risk factors, such as hyperlipidemia , but this study is interesting in that it digs down to the underlying genetics for each of these separate conditions,” Chen said.

Nevertheless, he cautioned that: “It definitely is a large leap, I should say, to make this connection, as the genes that they identified are not really understood in their functions and their actual connections to each of those conditions were either Alzheimer’s or cardiovascular disease.“

“So it’s a long way to go to say that they’re actually causative or dependency related to each of the conditions. This is more of an association study, just to say that there may be some sort of genetic association that is common to both conditions,” he added.

MNT also spoke with Heather M. Snyder, PhD , senior vice president of medical and scientific operations of the Alzheimer’s Association, about this study.

Snyder, who was not involved in the research, commented that:

“This is an interesting paper taking a unique lens to understanding the connection between the brain and the heart — specifically the genetics that may link coronary artery disease and Alzheimer’s disease. The study found a number of shared genes of interest, but did not find a shared causal link between the two diseases through the genes.”

“For researchers, discovery of these shared genes may provide clues into areas of biology that these diseases ‘share,’ which may — with further investigation — provide insights into possible treatment methods or targets, including repurposed drugs,” she added.

Better understanding of the heart-brain link needed

Readers may wonder how a neurological condition and a heart condition could possibly share genetics. “Assuming that there is a relationship, it currently is not very well understood,” Chen told MNT .

“It could either be that there are shared genetic risk factors for each of the conditions, such that if you have those genes, you’re more prone to have some traits that will predispose you to both heart disease and Alzheimer’s. The other possibility is there really is a genetic connection that we do not even understand at all. So the short answer is ‘we don’t know’.”

– Cheng-Han Chen, MD

“This is just the beginning,” he continued. “There will be a lot of future research that will need to build upon these identified genes to see, number one, what they do, number two, how exactly they’re related and what potential mechanisms could be involved between those gene products and eventual risk for developing either Alzheimer’s or cardiovascular disease. And so there’s a lot of research in between that needs to be done.”

Snyder commented that there are numerous lines of research that make the connection between our heart health and brain health.

“For instance, individuals with cardiovascular disease are at an increased risk for Alzheimer’s and other diseases that cause cognitive decline,” she explained.

“A large study known as SPRINT-MIND , which recently reported long-term follow up data at AAIC 2024, continues to show that an intervention aimed to aggressively reduce systolic blood pressure can reduce the likelihood of mild cognitive impairment (MCI) alone and MCI and dementia prevalence together, but not dementia alone, in study participants,” added Snyder.

“For clinicians, this study reinforces the importance of regularly including discussion about brain health, as we do about heart health, in their interactions with patients,” said Snyder. “A next step for this work is to further advance an understanding of the linking biological underpinnings with further investigation of the common mechanisms and pathways that may link coronary artery disease, lipids, and Alzheimer’s.”