Multicenter Study

. 2021 Aug 24;97(8):e814-e824.

doi: 10.1212/WNL.0000000000012342. Epub 2021 Jun 7.

Association of Orthostatic Hypotension With Cerebral Atrophy in Patients With Lewy Body Disorders

Andrea Pilotto¹, Alberto Romagnolo², Andrea Scalvini², Mario Masellis², Yasushi Shimo², Laura Bonanni², Richard Camicioli², Lily L Wang², Alok K Dwivedi², Katherine Longardner², Federico Rodriguez-Porcel², Mark DiFrancesco², Joaquin A Vizcarra², Elisa Montanaro², Simona Maule², Alessandro Lupini², Carmen Ojeda-López², Sandra E Black², Stefano Delli Pizzi², Myrlene Gee², Ryota Tanaka², Kazuo Yamashiro², Taku Hatano², Barbara Borroni², Roberto Gasparotti², Maria C Rizzetti², Nobutaka Hattori², Leonardo Lopiano², Irene Litvan², Alberto J Espay², Alessandro Padovani², Aristide Merola²

Affiliations

¹ From the Neurology Unit (A. Pilotto, A.S., B.B., A.L., A. Padovani), Department of Clinical and Experimental Sciences, and Neuroradiology Unit (R.G.), Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia; Parkinson's Disease Rehabilitation Centre (A. Pilotto, M.C.R.), FERB ONLUS-S. Isidoro Hospital, Trescore Balneario, Bergamo; Department of Neuroscience "Rita Levi Montalcini" (A.R., E.M., L.L.) and Autonomic Unit (S.M.), Department of Medical Sciences, University of Turin, Italy; Department of Medicine (Neurology) (M.M., C.O.-L., S.E.B.), University of Toronto; Hurvitz Brain Sciences Program (M.M., C.O.-L., S.E.B.), Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Department of Neurology (Y.S., R.T., K.Y., T.H., N.H.), Juntendo University Graduate School of Medicine, Tokyo, Japan; Department of Neuroscience Imaging and Clinical Sciences (L.B., S.D.P.), University G. d'Annunzio of Chieti-Pescara, Chieti, Italy; Department of Medicine and Neuroscience and Mental Health Institute (R.C., M.G.), University of Alberta, Edmonton, Canada; Department of Radiology (L.L.W.), and Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E.), Department of Neurology, University of Cincinnati, OH; Department of Molecular and Translational Medicine (A.K.D.), Texas Tech University Health Sciences Center, El Paso; Parkinson and Other Movement Disorders Center (K.L., I.L.), Department of Neurosciences, University of California, San Diego, La Jolla; Department of Neurology (F.R.-P.), Medical University of South Carolina, Charleston; Imaging Research Center (M.D), Department of Radiology, Cincinnati Children's Hospital Medical Center; University of Cincinnati College of Medicine (M.D.), OH; Department of Neurology (J.A.V.), Emory University, Atlanta, GA; ASST Spedali Civili Hospital (R.G.), Brescia, Italy; and Department of Neurology (A.M.), The Ohio State University, Columbus . pilottoandreae@gmail.com.
² From the Neurology Unit (A. Pilotto, A.S., B.B., A.L., A. Padovani), Department of Clinical and Experimental Sciences, and Neuroradiology Unit (R.G.), Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia; Parkinson's Disease Rehabilitation Centre (A. Pilotto, M.C.R.), FERB ONLUS-S. Isidoro Hospital, Trescore Balneario, Bergamo; Department of Neuroscience "Rita Levi Montalcini" (A.R., E.M., L.L.) and Autonomic Unit (S.M.), Department of Medical Sciences, University of Turin, Italy; Department of Medicine (Neurology) (M.M., C.O.-L., S.E.B.), University of Toronto; Hurvitz Brain Sciences Program (M.M., C.O.-L., S.E.B.), Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Department of Neurology (Y.S., R.T., K.Y., T.H., N.H.), Juntendo University Graduate School of Medicine, Tokyo, Japan; Department of Neuroscience Imaging and Clinical Sciences (L.B., S.D.P.), University G. d'Annunzio of Chieti-Pescara, Chieti, Italy; Department of Medicine and Neuroscience and Mental Health Institute (R.C., M.G.), University of Alberta, Edmonton, Canada; Department of Radiology (L.L.W.), and Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E.), Department of Neurology, University of Cincinnati, OH; Department of Molecular and Translational Medicine (A.K.D.), Texas Tech University Health Sciences Center, El Paso; Parkinson and Other Movement Disorders Center (K.L., I.L.), Department of Neurosciences, University of California, San Diego, La Jolla; Department of Neurology (F.R.-P.), Medical University of South Carolina, Charleston; Imaging Research Center (M.D), Department of Radiology, Cincinnati Children's Hospital Medical Center; University of Cincinnati College of Medicine (M.D.), OH; Department of Neurology (J.A.V.), Emory University, Atlanta, GA; ASST Spedali Civili Hospital (R.G.), Brescia, Italy; and Department of Neurology (A.M.), The Ohio State University, Columbus .

PMID: 34099524
PMCID: PMC8397588
DOI: 10.1212/WNL.0000000000012342

Multicenter Study

Association of Orthostatic Hypotension With Cerebral Atrophy in Patients With Lewy Body Disorders

Andrea Pilotto et al. Neurology. 2021.

. 2021 Aug 24;97(8):e814-e824.

doi: 10.1212/WNL.0000000000012342. Epub 2021 Jun 7.

Authors

Affiliations

¹ From the Neurology Unit (A. Pilotto, A.S., B.B., A.L., A. Padovani), Department of Clinical and Experimental Sciences, and Neuroradiology Unit (R.G.), Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia; Parkinson's Disease Rehabilitation Centre (A. Pilotto, M.C.R.), FERB ONLUS-S. Isidoro Hospital, Trescore Balneario, Bergamo; Department of Neuroscience "Rita Levi Montalcini" (A.R., E.M., L.L.) and Autonomic Unit (S.M.), Department of Medical Sciences, University of Turin, Italy; Department of Medicine (Neurology) (M.M., C.O.-L., S.E.B.), University of Toronto; Hurvitz Brain Sciences Program (M.M., C.O.-L., S.E.B.), Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Department of Neurology (Y.S., R.T., K.Y., T.H., N.H.), Juntendo University Graduate School of Medicine, Tokyo, Japan; Department of Neuroscience Imaging and Clinical Sciences (L.B., S.D.P.), University G. d'Annunzio of Chieti-Pescara, Chieti, Italy; Department of Medicine and Neuroscience and Mental Health Institute (R.C., M.G.), University of Alberta, Edmonton, Canada; Department of Radiology (L.L.W.), and Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E.), Department of Neurology, University of Cincinnati, OH; Department of Molecular and Translational Medicine (A.K.D.), Texas Tech University Health Sciences Center, El Paso; Parkinson and Other Movement Disorders Center (K.L., I.L.), Department of Neurosciences, University of California, San Diego, La Jolla; Department of Neurology (F.R.-P.), Medical University of South Carolina, Charleston; Imaging Research Center (M.D), Department of Radiology, Cincinnati Children's Hospital Medical Center; University of Cincinnati College of Medicine (M.D.), OH; Department of Neurology (J.A.V.), Emory University, Atlanta, GA; ASST Spedali Civili Hospital (R.G.), Brescia, Italy; and Department of Neurology (A.M.), The Ohio State University, Columbus . pilottoandreae@gmail.com.
² From the Neurology Unit (A. Pilotto, A.S., B.B., A.L., A. Padovani), Department of Clinical and Experimental Sciences, and Neuroradiology Unit (R.G.), Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia; Parkinson's Disease Rehabilitation Centre (A. Pilotto, M.C.R.), FERB ONLUS-S. Isidoro Hospital, Trescore Balneario, Bergamo; Department of Neuroscience "Rita Levi Montalcini" (A.R., E.M., L.L.) and Autonomic Unit (S.M.), Department of Medical Sciences, University of Turin, Italy; Department of Medicine (Neurology) (M.M., C.O.-L., S.E.B.), University of Toronto; Hurvitz Brain Sciences Program (M.M., C.O.-L., S.E.B.), Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Department of Neurology (Y.S., R.T., K.Y., T.H., N.H.), Juntendo University Graduate School of Medicine, Tokyo, Japan; Department of Neuroscience Imaging and Clinical Sciences (L.B., S.D.P.), University G. d'Annunzio of Chieti-Pescara, Chieti, Italy; Department of Medicine and Neuroscience and Mental Health Institute (R.C., M.G.), University of Alberta, Edmonton, Canada; Department of Radiology (L.L.W.), and Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E.), Department of Neurology, University of Cincinnati, OH; Department of Molecular and Translational Medicine (A.K.D.), Texas Tech University Health Sciences Center, El Paso; Parkinson and Other Movement Disorders Center (K.L., I.L.), Department of Neurosciences, University of California, San Diego, La Jolla; Department of Neurology (F.R.-P.), Medical University of South Carolina, Charleston; Imaging Research Center (M.D), Department of Radiology, Cincinnati Children's Hospital Medical Center; University of Cincinnati College of Medicine (M.D.), OH; Department of Neurology (J.A.V.), Emory University, Atlanta, GA; ASST Spedali Civili Hospital (R.G.), Brescia, Italy; and Department of Neurology (A.M.), The Ohio State University, Columbus .

PMID: 34099524
PMCID: PMC8397588
DOI: 10.1212/WNL.0000000000012342

Abstract

Objective: To evaluate whether orthostatic hypotension (OH) or supine hypertension (SH) is associated with brain atrophy and white matter hyperintensities (WMH), we analyzed clinical and radiologic data from a large multicenter consortium of patients with Parkinson disease (PD) and dementia with Lewy bodies (DLB).

Methods: Supine and orthostatic blood pressure (BP) and structural MRI data were extracted from patients with PD and DLB evaluated at 8 tertiary-referral centers in the United States, Canada, Italy, and Japan. OH was defined as a systolic/diastolic BP fall ≥20/10 mm Hg within 3 minutes of standing from the supine position (severe ≥30/15 mm Hg) and SH as a BP ≥140/90 mm Hg with normal sitting BP. Diagnosis-, age-, sex-, and disease duration-adjusted differences in global and regional cerebral atrophy and WMH were appraised with validated semiquantitative rating scales.

Results: A total of 384 patients (310 with PD, 74 with DLB) met eligibility criteria, of whom 44.3% (n = 170) had OH, including 24.7% (n = 42) with severe OH and 41.7% (n = 71) with SH. OH was associated with global brain atrophy (p = 0.004) and regional atrophy involving the anterior-temporal (p = 0.001) and mediotemporal (p = 0.001) regions, greater in severe vs nonsevere OH (p = 0.001). The WMH burden was similar in those with and without OH (p = 0.49). SH was not associated with brain atrophy (p = 0.59) or WMH (p = 0.72).

Conclusions: OH, but not SH, was associated with cerebral atrophy in Lewy body disorders, with prominent temporal region involvement. Neither OH nor SH was associated with WMH.

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Conflict of interest statement

Andrea Pilotto received speaker honoraria and travel grants from AbbVie Pharmaceuticals BioMarin Pharmaceutical, Chiesi Pharmaceuticals, Nutricia Pharmaceuticals, UCB Pharma, and Zambon Pharmaceuticals. Alberto Romagnolo has received grant support and speaker honoraria from AbbVie, speaker honoraria from Chiesi Farmaceutici, and travel grants from Lusofarmaco, Chiesi Farmaceutici, Medtronic, and UCB Pharma. Andrea Scalvini has no financial conflict to disclose. Mario Masellis receives salary support from the Department of Medicine at Sunnybrook Health Sciences Centre and the University of Toronto, as well as the Sunnybrook Research Institute. He has received grants/research support from Parkinson Canada, Canadian Institutes of Health Research, Teva, Early Researcher Award–Ministry of Economic Development and Innovation, C5R, Weston Brain Institute, Ontario Brain Institute, Sunnybrook AFP Innovation Fund, Novartis, Washington University, Roche, Alzheimer's Drug Discovery Foundation, Brain Canada, and Heart and Stroke Foundation Centre for Stroke Recovery. He has received consulting fees from Ionis, Wave Life Sciences, Alector, and Arkuda Therapeutics, as well as royalties from Henry Stewart Talks Ltd. Yasushi Shimo was funded by grants from the Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research and received speaker honoraria from Medtronic, Boston Scientific, Otsuka Pharmaceutical, Takeda Pharmaceutical Co, Sumitomo Dainippon Pharma, Novartis Pharma, MSD, FP Pharmaceutical Corp, Kyowa Hakko Kirin, and AbbVie, Inc. Laura Bonanni has no financial conflict to disclose. Richard Camicioli acknowledges funding from Canadian Institutes of Health Research, Brain Canada, the Michael J. Fox Foundation, the University of Alberta Hospital Foundation, and Parkinson Canada. Data included in the current study were obtained through a Canadian Institutes of Health Research operating grant. He is funded by the Canadian Consortium on Neurodegeneration in Aging as lead of the Lewy Body Team. Lily Wang has no financial conflict to disclose. Alok K. Dwivedi is supported as a coinvestigator by the NIH grants 1R01HL125016-01, 1 R21 HL143030-01, and 1R21 AI133207 and as a collaborator in NIH R21 AI118228 grant. He has been also serving as a statistician in Cancer Prevention and Research Institute of Texas grants (PP180003, PP170068, PP170004, PP140164, 140211, PP110156, PP150031, and PP130083), Center for Clinical and Translational Science and Training K12 (consultant) award, Coldwell (coinvestigator), and TMF (coinvestigator). He is a director of Biostatistics & Epidemiology Consulting Lab at the Texas Tech University Health Sciences Center El Paso. Katherine Longardner, Federico Rodriguez-Porcel, Mark DiFrancesco, Joaquin A. Vizcarra, Elisa Montanaro, Simona Maule, Alessandro Lupini, Carmen Ojeda-Lopez, Sandra E. Black, Stefano Delli Pizzi, and Myrlene Gee have no financial conflicts to disclose. Ryota Tanaka received honoraria from Takeda Pharmaceutical Co, Ltd, Nippon Behringer Ingelheim Co, Ltd, Dai-Nippon Sumitomo Pharma Co Ltd, and Otsuka Pharmaceutical Co, Ltd. Kazuo Yamashiro has no financial conflict to disclose. Taku Hatano received grant support from the Agency for Medical Research and Development under grant 19dm0107156 and the Setsuro Fujii Memorial Osaka Foundation for Promotion of Fundamental Medical Research; speaker honoraria from Takeda Pharmaceutical Co Lid, Dai-Nippon Sumitomo Pharma Co, Ltd, Otsuka Pharmaceutical Co, Ltd, Eisai Co, Ltd, Abbvie Inc, and Ono Pharmaceutical, Co, Ltd; and publishing royalties from Nankodo. Barbara Borroni, Roberto Gasparotti, and Maria Cristina Rizzetti have no financial conflicts to disclose. Nobutaka Hattori has received speaker honoraria from Dai-Nippon Sumitomo, Otsuka, Takeda, Kyowa-Kirin, GSK, Nippon, Boehringer Ingelheim, FP, Eisai, Kissei, Nihon Medi-physics, Novartis, Biogen Idec Japan, AbbVie, Astellas, Boston Scientific Japan, Sanofi, Pfizer Japan, Alexion, Mylan N.V, MSD, Daiichi Sankyo, and MDS. He has received consultancies and subcontracting from Dai-Nippon Sumitomo, Biogen Idec, Otsuka, Takeda, Kyowa-Kirin, Meiji Seika, Hisamitsu, and Kao. Leonardo Lopiano has received honoraria for lecturing and travel grants from Medtronic, UCB Pharma, and AbbVie. Irene Litvan’s research is supported by the NIH grants 2R01AG038791-06A, U01NS090259, U01NS100610, U01NS80818, R25NS098999, P20GM109025, U19 AG063911-1, and1R21NS114764-01A1; Parkinson Study Group, Michael J. Fox Foundation, Parkinson Foundation, Lewy Body Association, Roche, Abbvie, Biogen, EIP-Pharma, and Biohaven Pharmaceuticals. She was a member of the Scientific Advisory Board of Lundbeck and Corticobasal Degeneration Solutions. She receives her salary from the University of California San Diego and as chief editor of Frontiers in Neurology. Alberto Espay has received grant support from the Michael J. Fox Foundation and the NIH; personal compensation as a consultant/advisory board member for Abbvie, Neuroderm, Neurocrine, Amneal, Acadia, Acorda, Kyowa Kirin, Sunovion, Lundbeck, and USWorldMeds; publishing royalties from Lippincott Williams & Wilkins, Cambridge University Press, and Springer; and honoraria from USWorldMeds, Acadia, and Sunovion. Alessandro Padovani received grant support from the Ministry of Health and Ministry of Education, Research and University and the CARIPLO Foundation, as well as personal compensation as a consultant/advisory board member for Avanir, Lundbeck, Eli-Lilly, Biogen, Neuraxpharma, and GE Health. Aristide Merola is supported by the NIH (KL2 TR001426) and has received speaker honoraria from Theravance BioPharma, Medtronic, CSL Behring, Cynapsus Therapeutics, Lundbeck, AbbVie, and Abbott. He has received grant support from Lundbeck and Abbott. Go to Neurology.org/N for full disclosures.

Figures

**Figure 1. Study Flowchart**
DLB = dementia with Lewy bodies; PD = Parkinson disease.

**Figure 2. Atrophy and WMH Rating According to OH and SH Subgroups**
OH = orthostatic hypotension; SH = supine hypertension; WM = white matter; WMH = white matter hyperintensities. Post hoc analyses (*significance set with Bonferroni correction at α = 0.016).

See this image and copyright information in PMC

References

1. Jain S, Goldstein DS. Cardiovascular dysautonomia in Parkinson disease: from pathophysiology to pathogenesis. Neurobiol Dis. 2012;46(3):572-580. - PMC - PubMed
1. Fanciulli A, Jordan J, Biaggioni I, 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. Clin Auton Res. 2018;28(4):355-362. - PMC - PubMed
1. Pilotto A, Romagnolo A, Tuazon JA, et al. Orthostatic hypotension and REM sleep behaviour disorder: impact on clinical outcomes in α-synucleinopathies. J Neurol Neurosurg Psychiatry. 2019;90(11):1257-1263. - PubMed
1. Udow SJ, Robertson AD, Macintosh BJ, et al. “Under pressure” : is there a link between orthostatic hypotension and cognitive impairment in α -synucleinopathies? J Neurol Neurosurg Psychiatry. 2016;87:1311-1321. - PubMed
1. Kim J-S, Oh Y-S, Lee K-S, Kim Y-I, Yang D-W, Goldstein DS. Association of cognitive dysfunction with neurocirculatory abnormalities in early Parkinson disease. Neurology. 2012;79(13):1323-1331. - PMC - PubMed

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Association of Orthostatic Hypotension With Cerebral Atrophy in Patients With Lewy Body Disorders

Affiliations

Association of Orthostatic Hypotension With Cerebral Atrophy in Patients With Lewy Body Disorders

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous