Andrew D Robertson1, Michelle A Messner2, Zahra Shirzadi1, Galit Kleiner-Fisman3, Joyce Lee4, Julia Hopyan5, Anthony E Lang6, Sandra E Black7, Bradley J MacIntosh1, Mario Masellis8. 1. Hurvitz Brain Sciences Program, Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada. 2. Cognitive & Movement Disorders Clinic, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. 3. Neurology, Baycrest Centre for Geriatric Care, Toronto, Ontario, Canada. 4. Elder Care Program, North York General Hospital, Toronto, Ontario, Canada. 5. Hurvitz Brain Sciences Program, Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada; Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada. 6. Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada; Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada. 7. Hurvitz Brain Sciences Program, Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada; Cognitive & Movement Disorders Clinic, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; L.C. Campbell Cognitive Neurology Research Unit, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada. 8. Hurvitz Brain Sciences Program, Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada; Cognitive & Movement Disorders Clinic, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; L.C. Campbell Cognitive Neurology Research Unit, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada. Electronic address: mario.masellis@sunnybrook.ca.
Abstract
BACKGROUND: Orthostatic hypotension and cognitive impairment are two non-motor attributes of Lewy body spectrum disorders that impact independence. This proof-of-concept study examined cerebral blood flow (perfusion) as a mediator of orthostatic hypotension and cognition. METHODS: In fifteen patients with Lewy body disorders, we estimated regional perfusion using pseudo-continuous arterial spin labeling MRI, and quantified orthostatic hypotension from the change in systolic blood pressure between supine and standing positions. Executive, visuospatial, attention, memory, and language domains were characterized by neuropsychological tests. A matching sample of non-demented adults with cerebral small vessel disease was obtained to contrast perfusion patterns associated with comorbid vascular pathology. RESULTS: Compared to the vascular group, patients with Lewy body disorders exhibited lower perfusion to temporal and occipital lobes than to frontal and parietal lobes (q < 0.05). A greater orthostatic drop in systolic pressure was associated with lower occipito-parietal perfusion in these patients (uncorrected p < 0.005; cluster size ≥ 20 voxels). Although orthostatic hypotension and supine hypertension were strongly correlated (r = -0.79, p < 0.001), the patterns of association for each with perfusion were distinct. Specifically, supine hypertension was associated with high perfusion to anterior and middle cerebral arterial territories, as well as with low perfusion to posterior regions. Perfusion within orthostatic hypotension-defined regions was directly related to performance on visuospatial and attention tasks, independent of dementia severity (p < 0.05). CONCLUSIONS: These findings provide new insight that regional cerebral hypoperfusion is related to orthostatic hypotension, and may be involved in domain-specific cognitive deficits in Lewy body disorders.
BACKGROUND:Orthostatic hypotension and cognitive impairment are two non-motor attributes of Lewy body spectrum disorders that impact independence. This proof-of-concept study examined cerebral blood flow (perfusion) as a mediator of orthostatic hypotension and cognition. METHODS: In fifteen patients with Lewy body disorders, we estimated regional perfusion using pseudo-continuous arterial spin labeling MRI, and quantified orthostatic hypotension from the change in systolic blood pressure between supine and standing positions. Executive, visuospatial, attention, memory, and language domains were characterized by neuropsychological tests. A matching sample of non-demented adults with cerebral small vessel disease was obtained to contrast perfusion patterns associated with comorbid vascular pathology. RESULTS: Compared to the vascular group, patients with Lewy body disorders exhibited lower perfusion to temporal and occipital lobes than to frontal and parietal lobes (q < 0.05). A greater orthostatic drop in systolic pressure was associated with lower occipito-parietal perfusion in these patients (uncorrected p < 0.005; cluster size ≥ 20 voxels). Although orthostatic hypotension and supine hypertension were strongly correlated (r = -0.79, p < 0.001), the patterns of association for each with perfusion were distinct. Specifically, supine hypertension was associated with high perfusion to anterior and middle cerebral arterial territories, as well as with low perfusion to posterior regions. Perfusion within orthostatic hypotension-defined regions was directly related to performance on visuospatial and attention tasks, independent of dementia severity (p < 0.05). CONCLUSIONS: These findings provide new insight that regional cerebral hypoperfusion is related to orthostatic hypotension, and may be involved in domain-specific cognitive deficits in Lewy body disorders.
Authors: Joseph Classen; Jiri Koschel; Christian Oehlwein; Klaus Seppi; Peter Urban; Christian Winkler; Ullrich Wüllner; Alexander Storch Journal: J Neural Transm (Vienna) Date: 2017-07-12 Impact factor: 3.575
Authors: Julius S Ngwa; Thomas V Fungwe; Oyonumo Ntekim; Joanne S Allard; Sheree M Johnson; Chimene Castor; Lennox Graham; Sheeba Nadarajah; Richard F Gillum; Thomas O Obisesan Journal: Dement Geriatr Cogn Disord Date: 2018-04-25 Impact factor: 2.959
Authors: Andrew D Robertson; Sean J Udow; Alberto J Espay; Aristide Merola; Richard Camicioli; Anthony E Lang; Mario Masellis Journal: Neuropsychiatr Dis Treat Date: 2019-08-02 Impact factor: 2.570
Authors: Elena M Christopoulos; Jennifer Tran; Sarah L Hillebrand; Peter W Lange; Rebecca K Iseli; Carel G M Meskers; Andrea B Maier Journal: Int J Cardiol Hypertens Date: 2020-12-08
Authors: Leroy L Cooper; Jayandra J Himali; Alyssa Torjesen; Connie W Tsao; Alexa Beiser; Naomi M Hamburg; Charles DeCarli; Ramachandran S Vasan; Sudha Seshadri; Matthew P Pase; Gary F Mitchell Journal: J Am Heart Assoc Date: 2017-08-17 Impact factor: 5.501