Cardio Stress Response Reduced in Preclinical Alzheimer's

Nancy A. Melville

October 27, 2016

BALTIMORE — Patients in the earliest stages of Alzheimer's disease show significant decreases in cardiovascular response to stress compared with those who don't have the disease, new research suggests.

"To our knowledge, this is the first time that such an observation has been made — specifically — in older adults who are known to be within the preclinical stage of Alzheimer's disease," senior author Peter J. Snyder, PhD, told Medscape Medical News.

"The findings show that, even in the earliest preclinical stage of the disease, there are subtle effects on peripheral cardiac control," said Dr Snyder, who is a professor of neurology at Alpert Medical School of Brown University and senior vice president and chief research officer of the Lifespan Hospital System, Providence, Rhode Island.

Their findings were presented here at the American Neurological Association (ANA) 2016 Annual Meeting.

The study involved 63 adults, with a mean age of 62 years (range, 55 - 75 years), who were determined to have preclinical Alzheimer's disease, with a self-reported first-degree family history of the disease, reports of memory problems, and positron emission tomography findings indicating elevated cortical burden of β-amyloid, a pathological hallmark of Alzheimer's disease.

The patients were evaluated with electrocardiography for changes in vagal tone at rest and then during performance on the Groton Maze Learning Test, a computer-administered hidden maze learning test designed to induce mild cognitive stress for approximately 190 seconds.

Measures evaluated at baseline and 18-month follow-ups included respiratory sinus arrhythmia (RSA) and heart rate variability (HRV).

The results showed that patients who did not have preclinical Alzheimer's disease (β-amyloid negative) had normal vagal ratios, with normal increases in HRV while exposed to cognitive stress (P = .0061) and subsequent decreases at rest (P < .0001).

Similar responses were observed with RSA — the β-amyloid–negative patients showed increases while exposed to cognitive stress in relation to the pre- and post-stress conditions (P < .0001).

In contrast, the β-amyloid–positive patients failed to show alterations in HRV or RSA in response to cognitive stress at any point during the testing.

"β-Amyloid–positive subjects showed no change in RSA at any point during testing," the authors said.

"Not only were [the β-amyloid–positive patients'] responses less than those of patients without elevated β-amyloid, but they were so dampened as to fail to be statistically significantly different from either pre- or post-test," they added.

"Both measures were expected to show modest increases, reflecting heightened autonomic arousal, during completion of a neuropsychological test."

The vagal ratio between high- and low-frequency components of HRV and RSA typically becomes less reactive with normal aging as the result of declines in parasympathetic tone; however, the greater changes in early Alzheimer's are notable, the authors explained.

In a previous study published in the Journal of Alzheimer's Disease, they found evidence of increases in resting cardiac workload among patients with preclinical Alzheimer's disease.

The changes in vagal tone observed in the new study may be indicators of the changes slowly taking place in the brain during early-stage Alzheimer's disease, Dr Snyder speculated.

"We believe that this may suggest that patients in the preclinical stage of the disease are experiencing prodromal changes in the brain's control of autonomic functions, most likely impacting vagal control of the heart," he said.

Much more needs to be understood about the relationship, he added.

"These findings point to a complex relationship between Alzheimer's disease and the autonomic nervous system's control of the heart," Dr Snyder said.

"The bidirectional relationship between the cardiovascular system and this neurodegenerative disease is confusing and not well understood at this point.

"We are working hard to understand the neurochemistry and physiologic bases for these effects. This work will hopefully lead to increased efforts to tease apart this complex relationship."

The study was supported with an unrestricted grant from Pfizer Inc. The authors have disclosed no relevant financial relationships.

American Neurological Association (ANA) 2016 Annual Meeting. Abstract M122. Presented October 18, 2016.

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