Why Standing Up Could Worsen Cognition in Parkinson's Patients with Orthostatic Hypotension

February 16, 2017

ARTICLE IN BRIEF

Parkinson's disease patients with orthostatic hypotension experienced more cognitive decline, according to a new study. The results suggest that routine blood pressure monitoring should be a part of cognitive assessment in Parkinson's disease, and point toward treatment of orthostatic hypotension as a promising approach to improving cognitive function in some patients.

Cognitive impairment is associated with orthostatic hypotension, and both are common in Parkinson's disease (PD). But does orthostatic hypotension contribute to cognitive impairment in PD? A new study published in the January 3 edition of Neurology indicates it does.

The simple but important conclusion from the study is that “when a Parkinson's disease patient with orthostatic hypotension is sitting down, he or she is going to be cognitively different than when standing up,” said the senior co-author Roy L. Freeman, MD, professor of neurology at Harvard Medical School and director of the Center for Autonomic and Peripheral Nerve Disorders at Beth Israel Deaconess Hospital in Boston.

That raises several critical issues for assessing patients, for treating them, and for advising them about remaining active in the community, he said. The results suggest that routine blood pressure monitoring should be a part of cognitive assessment in PD, Dr. Freeman added, and point toward treatment of orthostatic hypotension as a promising approach to improving cognitive function in some patients.

Little is known about the cognitive effects of orthostatic hypotension, even outside of PD, Dr. Freeman noted. Yet it is the most common autonomic disturbance in PD, affecting as many of half of patients. Cognitive impairment is similarly common in advanced disease, “but it has been difficult to disentangle the underlying disease, which itself drives cognitive impairment, from the effects of orthostatic hypotension,” Dr. Freeman said.

STUDY DESIGN

DR. ROY L. FREEMAN said the simple but important conclusion from the study is that “when a Parkinson's disease patient with orthostatic hypotension is sitting down, he or she is going to be cognitively different than when standing up.”

To address that issue, Dr. Freeman and colleagues, including first author Justin Centi, PhD, a neuropsychologist, studied 37 non-demented PD patients (18 with orthostatic hypotension and 19 without) with an average disease duration of about six years, along with 18 healthy controls. All subjects were given a battery of neuropsychological tests, first while supine, then while tilted up at 60 degrees, then again while supine, and again while upright.

Systolic blood pressure in those with orthostatic hypotension fell an average of 30 mm Hg when tilted up, compared to a decline of 5 mm Hg in PD patients without hypostatic hypotension and 2 mm Hg in controls.

PD patients as a whole performed somewhat worse on cognitive tests than controls while supine, specifically on semantic fluency, Stroop color naming, memory encoding, and delayed recall. There were no significant differences between patients with and without orthostatic hypotension on any test while in the supine position.

Upon upright tilt, the cognitive abilities of patients with and without orthostatic hypotension worsened, but the effect in those with orthostatic hypotension was much greater. On nine of the 18 individual tests performed, patients with orthostatic hypotension performed significantly worse than those without OH while tilted upright.

“What was astonishing to me was the magnitude of the deficit,” Dr. Freeman said. Even patients whose classical orthostatic hypotension symptoms were relatively mild “still had a quite profound increase in cognitive impairment, which was reversible when they returned to the supine position.”

For patients with orthostatic hypotension, “we need to be aware that the symptoms we all think of, such as presyncope, lightheadedness, and dizziness, may not encompass the entire symptom complex.” Consideration of cognitive impairment should be part of taking the full history, he said.

“We also need to think about the possibility that, in patients complaining about attention, concentration, or executive function deficits, orthostatic hypotension may be contributing to that,” even if they are not complaining about the more classical symptoms. It is also possible, though not yet tested, that treatment of orthostatic hypotension in such patients may improve their cognition.

Because cognitive testing in the clinic, which is usually performed while seated, may underestimate the degree of impairment the patient experiences while upright, it calls into question the so-called “ecological validity” of the tests — that is, how well the results predict how the patient performs on similar tasks in their daily life.

“When a patient is standing up and functioning in the world,” whether making change or crossing a street or shopping for dinner, “the degree of competency may not be predictable from the clinical results,” Dr. Freeman said. Performance is unlikely to improve, and may continue to decline the longer the patient remains upright. Over prolonged periods of standing, blood pressure may continue to fall, or at best stabilize, and “there is no reason to expect that cognition will improve when the blood pressure does not.”

EXPERTS COMMENT

DR. CHRISTOPHER HESS said assuming the results are replicated in a larger study, “clinicians need to consider the possibility that even in our patients who are not experiencing presyncope or syncopal episodes, in those patients with cognitive impairment, it may be reasonable to be more aggressive in treating their orthostatic hypotension in order to try to improve their cognitive function.”

“Although this is a small study, the results indicate it is reasonable to think that orthostatic hypotension might be a factor in cognitive impairment in a subset of PD patients, which we had not considered before,” said Christopher Hess, MD, assistant professor of neurology at the University of FloridaCollege of Medicine in Gainesville. “This could potentially represent a variable that is not being controlled for.”

Assuming the results are replicated in a larger study, he said, “clinicians need to consider the possibility that even in our patients who are not experiencing presyncope or syncopal episodes, in those patients with cognitive impairment, it may be reasonable to be more aggressive in treating their orthostatic hypotension in order to try to improve their cognitive function.”

In the same way that a complete exam includes querying about other non-motor symptoms such as depression and constipation, he added, “I think it is reasonable for all neurologists to measure a sitting and standing blood pressure in all patients, regardless of whether they are reporting symptoms.”

[Indeed, the American College of Physicians and the American Academy of Family Physicians recommend that clinicians initiate treatment in adults aged 60 years or older with systolic blood pressure persistently at or above 150 mm Hg to achieve a target systolic blood pressure of less than 150 mm Hg to reduce the risk for mortality, stroke, and cardiac events. Both organizations recommend that clinicians select the treatment goals for adults aged 60 years or older based on a periodic discussion of the benefits and harms of specific blood pressure targets with the patient.]

DR. MARIO MASELLIS said the clinical implication, pending confirmation in larger studies, “is that we should be changing our practice to check for orthostatic hypotension more routinely. Unless you check for drops in blood pressure, you may miss it, because patients may not be able to tell you they are having symptoms,” and may not associate cognitive symptoms with postural changes.

“This is an important study,” commented Mario Masellis, MD, PhD, associate scientist at Sunnybrook Research Institute in Toronto, Canada, “because it is one of the first to show a definitive association between postural changes and changes in cognitive impairment in Parkinson's disease.”

The results provide a rationale for a trial targeting orthostatic hypotension in PD patients as a way to improve cognitive impairment, he said.

The clinical implication, pending confirmation in larger studies, “is that we should be changing our practice to check for orthostatic hypotension more routinely,” he said. “Unless you check for drops in blood pressure, you may miss it, because patients may not be able to tell you they are having symptoms,” and may not associate cognitive symptoms with postural changes.

In his own practice, Dr. Masellis asks caregivers to perform supine and standing blood pressure readings at home, twice a day for a week, in order to check for orthostatic hypotension that may not manifest as clearly in the clinic.

http://journals.lww.com/neurotodayonline/Fulltext/2017/02160/Why_Standing_Up_Could_Worsen_Cognition_in.7.aspx