A new study connects elevated pulse pressure (PP) with Alzheimer's disease (AD) biomarkers in cognitively normal persons, specifically those aged 55 to 70 years.
The new finding suggests a direct link with Alzheimer's pathophysiology.
"This is one of the few studies to show an actual association with AD pathophysiology where people didn't have any vascular disease, so there was no reason to think that was playing a role," the study's lead author, Daniel A. Nation, PhD, Veterans Affairs San Diego Healthcare System, California, told Medscape Medical News.
The study was published online November 13 in Neurology.
Increased AD Markers
The study included 177 cognitively normal, stroke-free participants (mean age, 69.4 years) who were enrolled at 3 centers: University of California at San Diego, University of Washington, and Oregon Health and Sciences Center. None of the participants had clinically significant abnormalities.
Researchers measured P-tau and amyloid-β (Aβ) proteins from central nervous system (CNS) samples. They calculated PP (systolic minus diastolic blood pressure) from the average of 2 recordings of blood pressure.
The study found that PP elevation was associated with Aβ1-42 levels (P = .01), increased P-tau concentrations (P = .002), and increased P-tau to Aβ1-42 ratio (P < .001).
After controlling for age, sex, APOE genotype, and body mass index, the relationship between PP and P-tau remained (P = .044), as did the relationship with the Ptau to Aβ ratio (P = .001), but the correlation between PP and Aβ1-42 was no longer present (P = .35).
Although the researchers initially thought this might indicate that P-tau was a more important marker than Aβ, post hoc analysis found that the relationship between PP was present with both biomarkers.
This analysis also showed that the association existed only for participants aged 55 to 70 years.
"We were able to observe that in a group of people who were otherwise totally healthy this association between pulse pressure and CSF biomarkers," said Dr. Nation. "It suggests a direct connection or direct link between this vascular measure and the actual AD pathophysiology at an early time point."
But according to Dr. Nation, this may not be the end of the story. "I wouldn't rule out the possibility that this association will emerge in people in the older age range; it just happened that in our particular sample, most or all of the signal in the association was within a younger age group," he said.
He found it "interesting" that this relationship that's exclusive to the fifth and sixth decades of life is consistent with earlier findings that midlife blood pressure evaluation is more predictive of later neurodegeneration and cognitive decline than is late-life blood pressure elevation, However, he stressed that this was a secondary analysis where "we were sort of exploring the data."
He also noted that the study included participants with a wide age range (55 to 100 years), which could be considered a limitation.
Dr. Nation and his colleagues are already exploring samples from other large data sets to see whether they can replicate the results.
Commenting on this new study, Douglas W. Scharre, MD, director, Division of Cognitive Neurology, associate professor of neurology and psychiatry, and director, Memory Disorders Research Center, Ohio State University, Columbus, noted that the findings don't prove cause and effect.
He found it "curious" that the relationship was not found in those over age 70, a group in whom both AD and increased PP are more prevalent.
"It has long been noted that cerebrovascular and cardiovascular disease are also risk factors for Alzheimer's disease and this may play into that story," said Dr. Scharre.
The study was supported by the Alzheimer's Association, National Institutes of Health, University of Washington, and Oregon Health Sciences University. Dr. Nation has disclosed no relevant financial relationships.
Neurology. Published online November 13, 2013. Abstract
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Cite this: Pulse Pressure Linked to AD Biomarkers - Medscape - Nov 21, 2013.
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