Multiple cardiovascular disease (CVD) subtypes are associated with an increased risk for Alzheimer’s disease (AD), with hypotension showing the strongest link.

Results of a cross-sectional study, which included nearly 800,000 adults from the UK Biobank and the All of Us Research Program, showed significant associations between AD and several cardiovascular conditions.

In both cohorts, hypotension emerged as a significant risk factor for AD, with affected adults nearly three times more likely to develop the disease in the UK Biobank and nearly twice as likely in the All of Us cohort. Hypertension, cerebral infarction, cardiac arrhythmias, heart failure, and chronic ischemic heart disease were also linked to an elevated risk for AD.

“By examining different types of heart disease individually, we identified which adults with heart disease might have the highest risk for cognitive decline. This highlights the importance of optimal cardiovascular health to possibly prevent [AD],” lead investigator Aili Toyli, a student at Michigan Technological University in Houghton, Michigan, said in a press release.

The study was published online on June 10 in the Journal of the American Heart Association.

Heart-Brain Connection

CVD and AD share several established risk factors, including diabetes, obesity, smoking, and hypertension. Vascular injury may contribute to cognitive decline by disrupting the blood-brain barrier and reducing cerebral blood flow, while AD-related pathology may also impair cardiovascular function.

Although previous studies have tied individual cardiovascular conditions to cognitive impairment, less is known about how specific CVD subtypes compare in their relationship with AD.

The investigators sought to examine these associations using data from two large, demographically distinct cohorts: the UK Biobank cohort comprising 502,133 participants (mean age, 56.5 years; 54.4% women; 94.1% White) and the All of Us cohort comprising 287,011 participants (mean age, 58 years; 60.1% women; 52.4% White, 19.9% Black, and 16.6% Hispanic). They also explored potential shared genetic mechanisms.

Associations between AD and 10 cardiovascular conditions and risk factors, including hypertension, hypotension, angina pectoris, acute myocardial infarction (AMI), pulmonary embolism, cardiac arrhythmias, heart failure, chronic rheumatic heart disease, chronic ischemic heart disease, and cerebral infarction were assessed.

Hypotension Tops the List

After adjusting for demographic, lifestyle, and clinical factors, hypotension showed the strongest link to AD in both cohorts.

In the UK Biobank, hypotension was associated with the highest odds of AD (odds ratio [OR], 2.74; 95% CI, 2.52-2.98), followed by hypertension (OR, 1.57; 95% CI, 1.46-1.68), cardiac arrhythmias (OR, 1.52; 95% CI, 1.41-1.63), and cerebral infarction (OR, 1.49; 95% CI, 1.30-1.71).

In All of Us, hypotension showed the strongest association with AD (OR, 1.97; 95% CI, 1.57-2.23), followed by cerebral infarction (OR, 1.85; 95% CI, 1.50-2.30) and hypertension (OR, 1.65; 95% CI, 1.37-1.99).

AMI was not significantly associated with AD in either cohort. Chronic rheumatic heart disease did not show a significant association.

Notably, associations between CVD and AD varied by race and ethnicity. In stratified analyses, hypertension showed a stronger association with AD among Black and Hispanic participants than with White participants. The investigators reported that CVD-AD associations were generally stronger in Black and Hispanic populations.

In genetic analyses, the investigators identified 164 proximal single nucleotide variant pairs shared between AD and CVD traits, with the strongest overlap seen in genomic regions containing APOE, MAPT, and genes involved in myocardial structure and vascular function.

“These results should be interpreted as hypothesis generating rather than evidence of causal genetic mechanisms, but they suggest a potentially shared genetic basis between heart and brain pathology,” the investigators wrote.

Limitations of the study include the cross-sectional design, which prevented causal inference; reliance on International Classification of Diseases, 10th Revision, diagnostic codes; and the frequent co-occurrence of multiple cardiovascular conditions that made it difficult to isolate the effects of individual CVD subtypes.

Maintaining Optimal Blood Pressure

The findings of the study reinforce the importance of maintaining optimal blood pressure throughout life, Elisabeth Marsh, MD, professor of neurology at Johns Hopkins University School of Medicine in Baltimore who was not involved in the study, said in press release.

“We’ve known for a long time that high blood pressure can have damaging long-term effects on the brain,” said Marsh, who is also the director of the Johns Hopkins Bayview Stroke Center in Baltimore. “This study shows us that blood pressure can also become a problem when it is too low for long periods of time.”

While scientists are still investigating the mechanisms that lead to neurodegeneration and cognitive decline with aging, Marsh said, it is not surprising that prolonged hypotension may impair brain function because “the brain is not getting what it needs.”

Vascular health and brain health are closely linked, and hypotension warrants further attention in future dementia research and prevention strategies.

Disclosure information for study authors is available in the original study publication. Marsh reported no relevant financial disclosures.