The absence of orthostatic heart rate increase is associated with cognitive impairment in Parkinson's disease.

Ryota Tanaka,Atsushi Umemura,Takashi Ogawa,Kazuo Yamashiro,Genko Oyama,Kenya Nishioka,Yasushi Shimo,Nobutaka Hattori,Pasquale Abete

doi:10.1371/journal.pone.0240491

Abstract

Orthostatic hypotension (OH) frequently accompanies autonomic dysfunction and is an important risk factor for cognitive impairment in Parkinson's disease (PD). While OH is usually diagnosed based on an orthostatic blood pressure drop, the association between the heart rate response and cognitive impairment remains unclear. We retrospectively analyzed 143 cases of clinically diagnosed PD to determine the association between the absence of a heart rate response and cognitive impairment in PD with OH. Among the patients with OH, neurogenic OH was diagnosed in cases without a heart rate increase, while all other patients were diagnosed with non-neurogenic OH. Dementia was found in 23 of 143 PD cases (16.1%) in this cohort. The presence of OH was an independent risk factor for dementia in PD in addition to the disease severity, years of education and beta-blockers use. Neurogenic OH was significantly associated with dementia compared to the no OH group (hazard ratio [HR] 7.3, 95% confidence interval [CI] 2.2-24.6, P<0.01), an association that was preserved after adjusting for age, gender and other covariant factors. However, no such association was observed for non-neurogenic OH (HR 2.9, 95%CI 0.8-10.9, P = 0.12). While the cognitive impairment was significantly worse in the neurogenic OH group than the no-OH group, the groups were otherwise similar. The blood pressure decrease was significantly lower in both OH groups than in the no-OH group, despite no significant differences between the OH groups. Our finding showed that OH without a heart rate response was an important predictor of cognitive impairment in PD.

Highlights

Parkinson’s disease (PD) is a neurodegenerative disorder with a middle-age onset, and it manifests as progressive motor symptoms, including bradykinesia, muscular rigidity, tremor at rest, and postural or gait disturbance [1, 2]
We noted no significant differences in dementia between the non-neurogenic Orthostatic hypotension (OH) group and the no-OH group; there was a significant association after adjusting for beta-blocker use
The association between OH and cognitive decline has been inconclusive, a recent meta-analysis of prospective cohort data showed the OH increased the risk of dementia, and this trend was preserved in two subtypes of dementia: Alzheimer’s disease and vascular dementia [18]

Summary

Introduction

Parkinson’s disease (PD) is a neurodegenerative disorder with a middle-age onset, and it manifests as progressive motor symptoms, including bradykinesia, muscular rigidity, tremor at rest, and postural or gait disturbance [1, 2]. Non-motor symptoms, such as cognitive decline and autonomic dysfunction, are important factors that affect the prognosis of PD [3, 4]. 30% of PD patients develop dementia, and OH has been consider an independent risk factor for cognitive decline, along with one’s age, an older age at onset, akinetic-rigid subtypes, and non-motor symptoms such as visual hallucination and, rapid eye movement sleep behavior disorders in PD [12]. While OH is usually diagnosed based on a decrease in BP within 3 minutes after rising from a supine position, the absence of a heart rate increase is an important response for discriminating neurogenic OH from non-neurogenic OH [13]. Few studies have assessed the association between the presence or absence of heart rate response and cognitive decline in cases of PD with OH.

Material and methods

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