Article In Brief
A new study found that patients with type 2 diabetes mellitus with orthostatic hypertension had transient, posture-mediated cognitive deficits compared with those who did not have orthostatic hypertension.
Diabetic patients with orthostatic hypotension (OH) may experience measurable declines in cognitive function when they move from lying down to standing, according to a new study from China.
The study, published August 9 online in Annals of Neurology, enrolled two groups of patients with type 2 diabetes, one with OH and the other without it, and then evaluated their performance on neuropsychological tests administered first while the patients were supine and then while standing. The group with OH performed worse on the cognitive tests in the upright position than did those without OH.
Although the cognitive deficits were transient, they suggest that diabetic patients with OH may routinely be experiencing cognitive changes that aren’t necessarily evident and may be overlooked during a typical checkup.
Understanding the effects of OH on cognition due to autonomic failure is important, particularly as clinical assessments and neuroimaging data are collected only in the seated or supine positions, said the researchers from Weihai Municipal Hospital in China.
The study authors noted that OH, characterized by a marked drop in blood pressure following a transition from a supine to a standing position, occurs in about 28 to 30.5 percent of elderly people with diabetes mellitus. Common symptoms of OH included lightheadedness, blurred vision, drowsiness, and other signs of cerebral hypoperfusion. In some cases, patients who experience sudden drops in blood pressure may fall, which might bring it to the attention of their health providers.
“OH is one clinical manifestation of autonomic neuropathy in diabetes mellitus and it is also an important risk factor for cognitive impairment,” the researchers wrote.
Type 2 diabetes itself has been linked with cognitive deficits, accelerated age-related cognitive decline, cognitive impairment, and dementia.
“DM [diabetes mellitus] is a risk factor for orthostatic hypotension due to arterial wall stiffness, which, in turn, reduces the vasoreactivity of the vascular bed to compensate for blood pressure changes,” the study authors noted.
The Chinese researchers said in their report that, to their knowledge, their study was the first to examine the acute effects of hypotension on cognitive performance in patients with type 2 diabetes mellitus.
The study was conducted at Weihai Municipal Hospital from January to December 2017. A total of 299 patients without dementia were enrolled, including 97 with diabetes and neurogenic OH and 107 normotensive patients with diabetes but not OH. There were also 95 controls in the study.
OH was defined as a reduction in systolic blood pressure (BP) of at least 20 mmHg and/or a reduction in diastolic BP of at least 10 mm/Hg during the first three minutes of standing or being positioned with a head-up tilt on a 60-degrees tilt table. Blood pressure, neuropathy, and general cognitive function were assessed at baseline.
Patients were given a battery of neuropsychological and memory tests in the supine position, followed by a second round of testing after they stood.
Compared with controls, the diabetic patients with or without OH had lower scores on cognitive testing, but the group with OH had the worst performance.
“Standing posture exacerbated and broadened cognitive deficits in the DMOH [diabetes mellitus orthostatic hypotension] group for all measures in different domains of cognition, including executive functioning, memory, visuospatial skills, information processing speed, and attention,” the researchers reported. They said the findings aligned with previous studies of Parkinson’s disease patients and patients with pure autonomic failure or autoimmune autonomic neuropathy that found posture-related cognitive deficits.
One of the study’s authors, Zhenguang Li, MD, said in an email to Neurology Today that “it seems reasonable to modify assessment methodology in diabetes mellitus patients to include testing in a variety of postures.”
“There are also implications for functional neuroimaging studies, as imaging data are collected in the supine position and thus without consideration of the influence of posture change on hemodynamics,” Dr. Li said.
He and his team said more attention needs to be paid to OH as it relates to diabetes.
“Orthostatic hypotension, as a clinical manifestation of diabetic autonomic neuropathy, is a significant risk factor for syncope, cognitive decline, falls, cardiovascular disease, stroke, and all-cause mortality,” Dr. Li said. “It seems reasonable to test OH and cognitive deficits in diabetes mellitus patients.”
Janice Gilden, MD, professor of medicine and chief of the diabetes, endocrinology and metabolism division at Chicago Medical School of Rosalind Franklin University of Medicine and Science, said that clinicians often only take blood pressure while the patient is on the examining table, which means they could be overlooking valuable information, especially if the patient is diabetic.
“I would say that in diabetes care, autonomic neuropathy is a forgotten complication,” said Dr. Gilden, whose research focuses on diabetes and autonomic neuropathy. She said the fact that a patient could be experiencing OH-related cognitive lapses when transitioning to standing could impact their ability to follow through on self-care instructions they get at a checkup. Last-minute advice is often given as a patient is getting ready to leave the office.
“They may not be able to remember what is said or comprehend what needs to be done,” she said, whether it’s how to best to take a medication or dietary recommendations.
Dr. Gilden said identifying OH is also key to helping patients adopt strategies to prevent a fall, such as standing up slowly.
“We have patients who fall who don’t know why they fall,” she said. “Patients may have symptoms (of OH) and not know they have symptoms.”
Andreea M. Rawlings, PhD, a biostatistician at Kaiser Permanente in Portland, OR, who has done research on the long-term implications of OH, said the new findings from China add “to the growing body of literature on the impact of orthostatic hypotension on cognitive function.”
She said that there are two key possible explanations for the connection between OH and cognitive decline.
“The first is that there is a biological mechanism by which orthostatic hypotension itself leads to cognitive impairment,” perhaps due to hypoxia of the brain when blood pressure drops.
Alternatively, she said the cognitive impairment associated with OH may be due to vascular changes. OH “may be a biomarker for elevated vascular risk,” Dr. Rawlings said, so those patients may benefit from closer monitoring of vascular risk factors that have been associated with dementia, such as diabetes and hypertension.
“We need long-term prospective studies to understand disease progression in people with OH,” she said. “If we treat or prevent OH do we improve cognitive outcomes?”
Dr. Rawlings was the lead author of a Neurology study published in 2018 by researchers at Johns Hopkins University, where she used to work, that followed more than 11,000 patients for up to 25 years and found that those who had OH at the start were more likely than those who didn’t to develop dementia and ischemic stroke.
Among the strategies doctors suggest to patients to prevent drops in blood pressure is to stay well hydrated, stand up slowly, and limit alcohol consumption, Dr. Rawlings said. Physicians may also adjust a patient’s medications if that seems to be the cause.
Horacio C. Kaufmann, MD, FAAN, professor of neurology and medicine at NYU Langone Health, said the new study on diabetes and OH confirms “studies done in Parkinson’s disease and aging in general that orthostatic hypotension affects cognition.”
But he said the study also raises questions. For example, he said, in the study, the average fall in systolic blood pressure was 25 mmHg or 30 mmHg, with a standard deviation of 10 mmHg, so is there a threshold below which a drop in blood pressure becomes deleterious to cognitive function? Are more modest dips problematic, or is cognition only affected with big drops? Also, what are the implications of repeated drops in blood pressure day after day? Will preventing the fall prevent cognitive impairment?
“If you assume that the cognitive impairment is due to ischemia, not enough oxygen getting to the brain, having long periods of low cerebral perfusion is likely a bad thing for you,” said Dr. Kaufmann, who specializes in autonomic disorders.
He said adjusting medication to raise blood pressure only when standing is not always possible because available drugs also increase blood pressure when supine, and “we know in fact that raising blood pressure is also associated with increased risk of dementia.”
Dr. Kaufmann said on a practical level, patients identified with OH should not make important decisions or sign documents while standing.
Drs. Zhang, Rawlings, and Kaufmann had no disclosures.