Orthostatic Hypotension Is Associated With Cognitive Decline in Parkinson Disease

Katherine Longardner, Ece Bayram, Irene Litvan, Katherine Longardner, Ece Bayram, Irene Litvan

Abstract

Introduction: Cognitive impairment and orthostatic hypotension (OH) are common, disabling Parkinson disease (PD) symptoms that are strongly correlated. Whether the relationship is causative or associative remains unknown. OH may occur without classic orthostatic symptoms of cerebral hypoperfusion (i.e., lightheadedness or dizziness). Whether longitudinal differences in cognition occur between symptomatic and asymptomatic OH patients has not been explored. Objectives: We characterized the prevalence of OH, orthostatic symptoms, and cognitive impairment among PD patients and compared cognition between patients with and without OH, and between patients with symptomatic and asymptomatic OH. Methods: Our cross-sectional, retrospective, observational study included 226 clinically diagnosed PD patients who underwent repeated standardized evaluations. Among these, 62 had longitudinal follow-up of > 3.5 years. We compared longitudinal Montreal Cognitive Assessment (MoCA) scores between patients remaining OH-free (n = 14) and those without baseline OH that developed OH (n = 28), matched for age, sex, education, and PD duration. We also compared MoCA scores between groups with asymptomatic OH (n = 13) and symptomatic OH (n = 13) matched for the same factors. Results: In the cross-sectional analysis, OH patients had worse cognition. In the longitudinal analysis (mean follow-up = 5.3 years), OH patients had worse cognitive decline (p = 0.027). Cognitive impairment was similar between asymptomatic and symptomatic OH patients in the cross-sectional and longitudinal analyses. Conclusions: OH is associated with cognitive impairment in PD. Further studies are needed in larger cohorts to expand our findings and to determine whether treating OH can prevent or delay cognitive dysfunction.

Keywords: Parkinson disease; cognition; dysautonomia; movement disorders; orthostatic hypotension.

Copyright © 2020 Longardner, Bayram and Litvan.

Figures

Figure 1
Figure 1
Flow diagram of Parkinson disease (PD) patients with orthostatic hypotension (OH+) and without OH (OH–) included in the longitudinal comparisons.
Figure 2
Figure 2
Change in Montreal Cognitive Assessment (MoCA) scores over time in Parkinson disease patients without orthostatic hypotension (OH–) and with orthostatic hypotension (OH+) (graph depicts least square regression lines and 95% confidence intervals).

References

    1. Antonini A, Barone P, Marconi R, Morgante L, Zappulla S, Pontieri FE, et al. . The progression of non-motor symptoms in Parkinson's disease and their contribution to motor disability and quality of life. J Neurol. (2012) 259:2621–31. 10.1007/s00415-012-6557-8
    1. Litvan I, Aarsland D, Adler CH, Goldman JG, Kulisevsky J, Mollenhauer B, et al. . MDS Task Force on mild cognitive impairment in Parkinson's disease: critical review of PD-MCI. Mov Disord. (2011) 26:1814–24. 10.1002/mds.23823
    1. Pigott K, Rick J, Xie SX, Hurtig H, Chen-Plotkin A, Duda JE, et al. . Longitudinal study of normal cognition in Parkinson disease. Neurology. (2015) 85:1276–82. 10.1212/WNL.0000000000002001
    1. Hely MA, Reid WG, Adena MA, Halliday GM, Morris JG. The Sydney multicenter study of Parkinson's disease: the inevitability of dementia at 20 years. Mov Disord. (2008) 23:837–44. 10.1002/mds.21956
    1. Palma JA, Kaufmann H. Epidemiology, diagnosis, and management of neurogenic orthostatic hypotension. Mov Disord Clin Pract. (2017) 4:298–308. 10.1002/mdc3.12478
    1. Gibbons CH, Schmidt P, Biaggioni I, Frazier-Mills C, Freeman R, Isaacson S, et al. . The recommendations of a consensus panel for the screening, diagnosis, and treatment of neurogenic orthostatic hypotension and associated supine hypertension. J Neurol. (2017) 264:1567–82. 10.1007/s00415-016-8375-x
    1. Claassen DO, Adler CH, Hewitt LA, Gibbons C. Characterization of the symptoms of neurogenic orthostatic hypotension and their impact from a survey of patients and caregivers. BMC Neurol. (2018) 18:125. 10.1186/s12883-018-1129-x
    1. Merola A, Coon EA. Dysautonomia in early Parkinson disease: a window into the determinants of functional disability and an opportunity for early intervention. Clin Auton Res. (2020) 30:191–2. 10.1007/s10286-020-00684-3
    1. Udow SJ, Robertson AD, MacIntosh BJ, Espay AJ, Rowe JB, Lang AE, et al. . 'Under pressure': is there a link between orthostatic hypotension and cognitive impairment in α-synucleinopathies? J Neurol Neurosurg Psychiatry. (2016) 87:1311–21. 10.1136/jnnp-2016-314123
    1. McDonald C, Newton JL, Burn DJ. Orthostatic hypotension and cognitive impairment in Parkinson's disease: causation or association? Mov Disord. (2016) 31:937–46. 10.1002/mds.26632
    1. Espay AJ, LeWitt PA, Kaufmann H. Norepinephrine deficiency in Parkinson's disease: the case for noradrenergic enhancement. Mov Disord. (2014) 29:1710–9. 10.1002/mds.26048
    1. Fanciulli A, Jordan J, Biaggioni I, Calandra-Buonaura G, Cheshire WP, Cortelli P, et al. . Consensus statement on the definition of neurogenic supine hypertension in cardiovascular autonomic failure by the American Autonomic Society (AAS) and the European Federation of Autonomic Societies (EFAS) : Endorsed by the European Academy of Neurology (EAN) and the European Society of Hypertension (ESH). Clin Auton Res. (2018) 28:355–62. 10.1007/s10286-018-0529-8
    1. Kim JS, Oh YS, Lee KS, Kim YI, Yang DW, Goldstein DS. Association of cognitive dysfunction with neurocirculatory abnormalities in early Parkinson disease. Neurology. (2012) 79:1323–31. 10.1212/WNL.0b013e31826c1acd
    1. Espay AJ, LeWitt PA, Hauser RA, Merola A, Masellis M, Lang AE. Neurogenic orthostatic hypotension and supine hypertension in Parkinson's disease and related synucleinopathies: prioritisation of treatment targets. Lancet Neurol. (2016) 15:954–66. 10.1016/S1474-4422(16)30079-5
    1. Merola A, Romagnolo A, Rosso M, Lopez-Castellanos JR, Wissel BD, Larkin S, et al. . Orthostatic hypotension in Parkinson's disease: does it matter if asymptomatic? Parkinsonism Relat Disord. (2016) 33:65–71. 10.1016/j.parkreldis.2016.09.013
    1. Freeman R, Illigens BMW, Lapusca R, Campagnolo M, Abuzinadah AR, Bonyhay I, et al. . Symptom Recognition is impaired in patients with orthostatic hypotension. Hypertension. (2020) 75:1325–32. 10.1161/HYPERTENSIONAHA.119.13619
    1. Centi J, Freeman R, Gibbons CH, Neargarder S, Canova AO, Cronin-Golomb A. Effects of orthostatic hypotension on cognition in Parkinson disease. Neurology. (2017) 88:17–24. 10.1212/WNL.0000000000003452
    1. Sforza M, Assogna F, Rinaldi D, Sette G, Tagliente S, Pontieri FE. Orthostatic hypotension acutely impairs executive functions in Parkinson's disease. Neurol Sci. (2018) 39:1459–62. 10.1007/s10072-018-3394-2
    1. Merola A, Romagnolo A, Rosso M, Suri R, Berndt Z, Maule S, et al. . Autonomic dysfunction in Parkinson's disease: a prospective cohort study. Mov Disord. (2018) 33:391–7. 10.1002/mds.27268
    1. Anang JB, Nomura T, Romenets SR, Nakashima K, Gagnon JF, Postuma RB. Dementia predictors in parkinson disease: a validation study. J Parkinson's Dis. (2017) 7:159–62. 10.3233/JPD-160925
    1. Hiorth YH, Pedersen KF, Dalen I, Tysnes OB, Alves G. Orthostatic hypotension in Parkinson disease: a 7-year prospective population-based study. Neurology. (2019) 93:e1526–34. 10.1212/WNL.0000000000008314
    1. Nasreddine ZS, Phillips NA, Bédirian V, Charbonneau S, Whitehead V, Collin I, et al. The montreal cognitive assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. (2005) 53:695–9. 10.1111/j.1532-5415.2005.53221.x
    1. Postuma RB, Berg D, Stern M, Poewe W, Olanow CW, Oertel W, et al. MDS clinical diagnostic criteria for Parkinson's disease. Mov Disord. (2015) 30:1591–601. 10.1002/mds.26424
    1. Roheger M, Kalbe E, Liepelt-Scarfone I. Progression of cognitive decline in Parkinson's disease. J Parkinsons Dis. (2018) 8:183–93. 10.3233/JPD-181306
    1. Lessig S, Nie D, Xu R, Corey-Bloom J. Changes on brief cognitive instruments over time in Parkinson's disease. Mov Disord. (2012) 27:1125–8. 10.1002/mds.25070
    1. Krishnan K, Rossetti H, Hynan LS, Carter K, Falkowski J, Lacritz L, et al. . Changes in montreal cognitive assessment scores over time. Assessment. (2017) 24:772–7. 10.1177/1073191116654217
    1. Goetz CG, Tilley BC, Shaftman SR, Stebbins GT, Fahn S, Martinez-Martin P, et al. . Movement disorder society-sponsored revision of the unified Parkinson's disease rating scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov Disord. (2008) 23:2129–70. 10.1002/mds.22340
    1. Hoehn MM, Yahr MD. Parkinsonism: onset, progression and mortality. Neurology. (1967) 17:427–42. 10.1212/WNL.17.5.427
    1. Dalrymple-Alford JC, MacAskill MR, Nakas CT, Livingston L, Graham C, Crucian GP, et al. . The MoCA: well-suited screen for cognitive impairment in Parkinson disease. Neurology. (2010) 75:1717–25. 10.1212/WNL.0b013e3181fc29c9
    1. Aiken LS, West SG, Reno RR. Multiple Regression: Testing and Interpreting Interactions. Newbury Park, CA: Sage; (1991).
    1. Cohen J. A power primer. Psychol Bull. (1992) 112:155–9. 10.1037/0033-2909.112.1.155
    1. Yoo SW, Kim JS, Oh YS, Ryu DW, Lee KS. Trouble concentrating is an easily overlooked symptom of orthostatic hypotension in early Parkinson's disease. J Parkinson's Dis. (2019) 9:405–41. 10.3233/JPD-191578
    1. Phillips AA, Warburton DE, Ainslie PN, Krassioukov AV. Regional neurovascular coupling and cognitive performance in those with low blood pressure secondary to high-level spinal cord injury: improved by alpha-1 agonist midodrine hydrochloride. J Cereb Blood Flow Metab. (2014) 34:794–801. 10.1038/jcbfm.2014.3
    1. Ten Harmsen BL, van Rumund A, Aerts MB, Bergkamp MI, Esselink RAJ, Richard E, et al. . Clinical correlates of cerebral white matter abnormalities in patients with Parkinson's disease. Parkinsonism Relat Disord. (2018) 49:28–33. 10.1016/j.parkreldis.2017.12.029
    1. Pilleri M, Facchini S, Gasparoli E, Biundo R, Bernardi L, Marchetti M, et al. . Cognitive and MRI correlates of orthostatic hypotension in Parkinson's disease. J Neurol. (2013) 260:253–9. 10.1007/s00415-012-6627-y
    1. Aarsland D, Creese B, Politis M, Chaudhuri KR, Ffytche DH, Weintraub D, et al. . Cognitive decline in Parkinson disease. Nat Rev Neurol. (2017) 13:217–31. 10.1038/nrneurol.2017.27
    1. Riley DE, Espay AJ. Cognitive fluctuations in Parkinson's disease dementia: blood pressure lability as an underlying mechanism. J Clin Mov Disord. (2018) 5:1. 10.1186/s40734-018-0068-4
    1. Hohler AD, Amariei DE, Katz DI, DePiero TJ, Allen VB, Boyle S, et al. . Treating orthostatic hypotension in patients with Parkinson's disease and atypical Parkinsonism improves function. J Parkinsons Dis. (2012) 2:235–40. 10.3233/JPD-2012-012101
    1. Norcliffe-Kaufmann L, Kaufmann H. Is ambulatory blood pressure monitoring useful in patients with chronic autonomic failure? Clin Auton Res. (2014) 24:189–92. 10.1007/s10286-014-0229-y

Source: PubMed

3
Sottoscrivi