Orthostatic Hypotension Affects Cognition in Parkinson’s

Pauline Anderson

December 15, 2016

Having Parkinson's disease (PD) itself affects cognition, but new research shows that adding orthostatic hypotension (OH) has an even greater impact on cognitive function in patients with PD.

A new study shows patients with PD and those with PD plus OH had similar mild cognitive impairment compared with matched controls while in the supine position, but there was a significant adverse effect on cognition only in the PDOH group when patients were in the upright position.

"Patients with Parkinson's disease need to be screened for orthostatic hypotension regardless of whether or not they are reporting symptoms," said lead author, clinical neuropsychologist Justin Centi, PhD, Department of Psychological and Brain Sciences, Boston University, Massachusetts (now working for a private practice in Boston).

"The presence of orthostatic hypotension on clinical examination should alter the approach to management to include consideration for postural effects on cognition."

When possible, added Dr Centi, clinicians should consider referrals for neuropsychological testing with a battery that includes repeat assessment in a variety of postures.

And, because the cognitive deficits that emerged in the study included problems with visuospatial processing, clinicians should consider nonmotor factors as possibly contributing to problems, such as gait instability and falls, he said.

Their findings were published online November 30 in Neurology.

The study included 55 patients without dementia. Among them were 18 normotensive PD patients with OH and a group of 19 normotensive PD patients without OH, matched for disease duration, motor symptom severity, and levodopa equivalent dosages. The study also included 18 controls matched for age, sex, and education.

None of the study participants met criteria for dementia. There were no baseline differences in blood pressure or heart rate.

OH was defined as a sustained reduction in systolic blood pressure of at least 20 mm Hg or a reduction in diastolic blood pressure of at least 10 mm Hg during the first 3 minutes of standing or while on a tilt table.

Many of the patients with OH were asymptomatic, and none reported severe symptoms of OH.

Researchers tested patients on neuropsychological performance while supine, then upright (60 degrees from flat), and then supine again. They looked at attention/executive function, memory, and visuospatial skills, which are domains that are typically problematic for patients with PD.

Compared with controls, both PD groups showed impaired cognition while supine and were impaired on several executive measures and had poorer memory encoding while tilted upright.

This pattern, said the authors, is seen in as many as 55% of patients with PD and is most likely the result of functional disconnection.

Deficit Patterns

Following the tilt, PD patients with OH showed a greater posture-mediated impairment than controls on several tests, including Arithmetic, Symbol Search, Phonemic Fluency, the Stroop test (color-word condition), memory encoding (P < .01), and Visual Dependence (P = .01).

Compared with patients with PD without OH, PD patients with OH showed a significantly greater effect of postural change on Symbol Search (P < .01), CERAD (Consortium to Establish a Registry for Alzheimer's Disease) total score (P < .01), and Visual Dependence (P < .01).

"The pattern of deficits was reflective of an exacerbation of already vulnerable domains, including information processing speed, working memory, learning, verbal fluency, and visuospatial processing," noted Dr Centi.

The cognitive declines were reversed when patients were returned to the supine position.

Because this transient change was not seen in patients with PD —without OH or in controls, the results imply "a direct effect of OH," the authors conclude.

Worsening cognition as a result of OH has a significant impact on daily living — for example, it makes shopping, counting change, and tracking conversations a challenge, they note.

The findings are important because they suggest that neuropsychological testing in PD, and perhaps all conditions where OH is frequently concomitant, has failed to effectively capture the full nature of cognitive deficits, Dr Centi said.

"This has major implications for both clinical and research-related endeavors. Moreover, studies that rely on functional neuroimaging — for example, fMRI [functional MRI] and PET [positron emission tomography] — which is conducted only in the supine position, may need to consider a more limited scope when interpreting their findings."

Dr Centi stressed that because none of the study patients rated symptoms as moderate or severe when tilted, reliance on their self-report would likely fail to identify many cases of OH in the clinical setting.

Dr Centi and his colleagues recommend that, at a minimum, all patients with PD be screened regardless of whether or not they report common symptoms, for example, lightheadedness.

And as some patients may have delayed-onset OH, clinicians should consider a more comprehensive autonomic evaluation if they don't have the time or resources to fully assess for this presentation in the office setting, said Dr Centi.

Implication "Far-Reaching"

In an accompanying editorial, Laura S. Boylan, MD, Department of Neurology, New York University School of Medicine, New York, and Lambros Messinis, PhD, Neuropsychology Section Department of Neurology, University of Patras Medical School, Greece, agreed that If the study findings are found to be generalizable, "the implications are potentially far-reaching."

An improved understanding of underlying mechanisms between systemic blood pressure and cognitive function is needed and should span subspecialty disciplines of clinical and basic research, but this would be "a challenge in an age of silos," Dr Boylan and Dr Messinis note.

They noted that limitations of the study included its sample size, use of repeated measures, and use of cognitive tests of unknown ecologic validity/applicability to daily life.

While all patients were normotensive at baseline, some were receiving blood pressure medication, which may be confounding, they said. They also pointed out that tilt-table positioning is not equivalent to standing up.

The study was "interesting" and the research methods and statistical analysis "appear appropriate and reasonable," said Christopher Hess, MD, assistant professor, neurology, and co-director, Movement Disorders Fellowship, University of Florida Center for Movement Disorders and Neurorestoration, Gainesville, when asked to comment for Medscape Medical News.

"This is an important study which suggests that focusing on the treatment of orthostatic hypotension might improve cognition in patients with PD," said Dr Hess.

"The findings reinforce the need to do sitting and standing blood pressure measurements in patients with PD as not all patients in the study described the symptoms of orthostatic hypotension."

Further studies with larger sample sizes would help to determine whether the results of the study are more generalizable to routine cognitive screening and neuropsychiatric testing, added Dr Hess.

The study was funded by a National Research Service Awards training grant (National Institutes of Health, National Institute of Neurological Disorders and Stroke) as part of Dr Centi's doctoral dissertation. Dr Centi, Dr Boylan, and Dr Messinis have disclosed no relevant financial relationships.

Neurology. Published online November 30, 2016. Abstract, Editorial

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