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The vascular hypothesis proposes that recurrent episodic hypotension results in cerebral hypoperfusion, in turn causing anoxic damage to vulnerable areas of the brain and impaired cognitive function. Support for this hypothesis has come from brain MRI studies showing an association between white matter hyperintensities and a postural drop in blood pressure among PD patients. Alternatively, the association between orthostatic hypotension and cognitive decline in PD may reflect shared underlying synuclein\u2010related pathology affecting common neuroanatomical and neurochemical substrates. Cardiac imaging studies demonstrate noradrenergic denervation early in PD, and cardiac denervation has been associated with poorer cognition. Neurogenic orthostatic hypotension occurs as a result of defective norepinephrine release from sympathetic terminals upon standing. Neuropathological studies have also demonstrated Lewy body pathology in the locus coeruleus; the main source of noradrenaline in the brain. Locus coeruleus norepinephrine levels are reduced in PD patients with dementia when compared with PD patients without. In this review, we examine the evidence for an association between orthostatic hypotension and cognitive impairment in PD. We evaluate the literature supporting the hypothesis that progressive noradrenergic denervation underlies both orthostatic hypotension and cognitive impairment, and we examine studies suggesting that recurrent cerebral hypoperfusion results in cognitive decline in PD. Finally, we explore how modulation of blood pressure and the noradrenergic nervous system may improve cognition in PD. \u00a9 2016 International Parkinson and Movement Disorder Society<\/jats:p>","DOI":"10.1002\/mds.26632","type":"journal-article","created":{"date-parts":[[2016,4,19]],"date-time":"2016-04-19T03:41:17Z","timestamp":1461037277000},"page":"937-946","source":"Crossref","is-referenced-by-count":138,"title":["Orthostatic hypotension and cognitive impairment in Parkinson's disease: Causation or association?"],"prefix":"10.1002","volume":"31","author":[{"given":"Claire","family":"McDonald","sequence":"first","affiliation":[{"name":"Institute of Cellular Medicine Newcastle University Newcastle upon Tyne UK"},{"name":"Newcastle upon Tyne Hospitals NHS Foundation Trust Newcastle UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia L.","family":"Newton","sequence":"additional","affiliation":[{"name":"Institute of Cellular Medicine Newcastle University 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