Tracking the Heart-Brain Connection

A new study based on data from the National Alzheimer’s Coordinating Center (NACC) reveals that high blood pressure is linked to developing Alzheimer’s disease, but only in specific patient groups: those with a history of stroke and those experiencing cognitive impairment. The correlation doesn’t hold in other groups of patients, though. The findings, published in the journal Neurology in March, address a longstanding controversy about the connection between blood pressure and dementia, and suggest a possible strategy for reducing patients’ risk of Alzheimer’s disease.

High blood pressure increases the risk of many health problems, but previous work has yielded contradictory results about whether it’s linked to Alzheimer’s disease. “We know midlife hypertension is a risk factor for dementia, but for late life blood pressure, it’s sometimes associated with a higher risk of dementia in some studies, while others don’t find any association,” says Yuan Ma, Assistant Professor of Epidemiology at Harvard’s T.H. Chan School of Public Health and senior author on the new study.

Ma and her colleagues hypothesized that the confusion might come from different studies looking at different populations of patients, since the health of older people varies widely. “An older adult in their eighties, they could be very healthy and physically active, or they could have some functional limitations, or cognitive impairment, so we feel like we are not examining one group of people, it’s people with different characteristics,” she says.

To test that theory, the researchers needed data from a huge group of patients. The NACC database was the obvious place to find them. “The NACC dataset is really a unique data resource to address this, because it has a large sample size of patients [followed] over the years,” says Ma. This allowed her group at Harvard, working with an international team of collaborators at several other institutions, to select a population of more than 2,000 NACC participants, all with extensive clinical and pathological records. They chose the sample to encompass several different subgroups, including those with cognitive impairment, stroke history, and carriership of the APOE ε4 gene, which is considered a major Alzheimer’s disease risk factor.

Through an extensive series of analyses, Ma’s team found that high systolic blood pressure - the top number in a blood pressure reading - is a risk factor for Alzheimer’s disease, but only in patients with a history of stroke or cognitive impairment. It doesn’t seem to be connected in people without any of the risk factors studied, or those who only carried the APOE ε4 gene but lacked the other characteristics.

From Correlation to Causation

The results help resolve the contradictions in earlier findings and point toward possible clinical interventions. “An important finding for us to further confirm in future studies is to see if we can identify high-risk participants who may benefit more from optimal blood pressure management to prevent Alzheimer’s pathology,” says Ma. However, she cautions that at this point, the data only point to a correlation between high blood pressure and dementia, and do not prove that hypertension causes Alzheimer’s disease directly.

New technologies could help address that question and other limitations of the current work. “This study is based on the neurological postmortem pathology data, so basically we only know [Alzheimer’s disease] happened during their lifetime, but exactly when it happened, we don’t know that, and also the blood pressure was only measured at certain time points,” says Ma.

She adds that the specific optimal blood pressure may also vary from one person to another. “Should we have a personalized blood pressure management regimen for different individuals based on their characteristics, especially those factors we saw from the current study, if they have stroke, if they have some cognitive impairment?” she says.

Despite these limitations, the results open a promising new avenue for addressing the rising health burden of dementia. “This is a really big deal, given how prevalent vascular cardiometabolic conditions are in the population… if this is a trigger, we probably could reduce Alzheimer’s pathology and future risk of Alzheimer’s disease,” says Ma.

Ma emphasizes that the power of the NACC dataset comes from enabling researchers to get relatively fast answers and generate new hypotheses. “This dataset offered this opportunity, where we didn’t need to collect data from scratch to test some hypotheses… this is a way to generate the next hypothesis,” she says.