Hypertension, white matter hyperintensities, and dementia: What’s the link?

LOS ANGELES – While uncontrolled hypertension is an established risk factor for dementias including Alzheimer’s disease, the pathways by which it might lead to dementia remain poorly understood.

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In research presented at the Alzheimer’s Association International Conference, Jérémie Lespinasse, PharmD, an investigator with the University of Bordeaux and INSERM U1219 in Bordeaux, France, presented data showing that hypertension-linked increases in the brain’s load of white matter hyperintensities – an imaging biomarker linked to small-vessel disease – was associated with cognitive decline independent of amyloid cascade biomarkers.

“We know that hypertension is related to cognitive decline and dementia, including Alzheimer’s dementia,” Carole Dufouil, PhD, the study’s last author and the research director at INSERM U1219, said in an interview. “But we didn’t know the pathway. It could go through what’s more typical of vascular pathology or it could go through what’s more typical of AD – and that’s what we wanted to test.”

The researchers found that the impact of hypertension on cognition doesn’t “go through amyloid,” Dr. Dufouil said, but rather a typically vascular pathway of white matter hyperintensities and neurodegeneration. “This is a big difference from other brain markers for which you know they exist, but you don’t know how to treat them,” she said. “This one is treatable.”

For their research, Dr. Lespinasse, Dr. Dufouil, and colleagues used a cross-sectional sample of data from the MEMENTO study, a 5-year observational cohort of 2,323 patients recruited at 26 memory centers in France between 2011 and 2014. Of the patients in MEMENTO, 62% were women, and the mean age was 71. All patients were deemed free of dementia and had isolated cognitive complaints or mild cognitive impairment at baseline. A total of 60% had hypertension, and 17% had uncontrolled hypertension defined as above 140/90 mm Hg despite treatment. Cognitive testing and MRI was conducted on all patients, while 60% also had ¹⁸F-fluorodeoxyglucose PET scanning and a minority, 18%, had cerebrospinal fluid samples.

The investigators found in using a structural equation model that the uncontrolled hypertension subjects had significantly lower cognition when compared against those without (P = .001). About half of the harmful effect of uncontrolled hypertension on brain functions was mediated by white matter hyperintensities load (P = .021) and neurodegeneration (P = .024) but not by cerebrospinal fluid biomarkers for amyloid-beta 42/40 ratio or tau.

The study’s main limitation was its use of cross-sectional data, the investigators said, while its strength was in a multifactorial model that allowed for a more integrative look at the relationships among hypertension, Alzheimer’s biomarkers, white matter hyperintensities, and cognition.

The investigators stressed the importance of controlling hypertension generally – and for all clinicians to be more aware of its cognitive impacts. Dr. Dufouil said that memory clinics should make blood pressure monitoring a key part of their workups, and should ensure that people are well controlled. “Up until recently it hasn’t been obvious” that control of hypertension has a key role in dementia prevention.

“It’s now obvious,” she said.

Dr. Lespinasse and Dr. Dufouil disclosed no industry relationships.