Cognitive fluctuations in Parkinson's disease dementia: blood pressure lability as an underlying mechanism

Abstract

Background: Cognitive fluctuations refer to alterations in cognition, attention, or arousal occurring over minutes to hours, most commonly in patients with dementias associated with advanced Lewy body pathology. Their pathophysiologic underpinning remains undetermined.

Case presentation: We documented serial blood pressure (BP) measurements in an 86-year-old man with Parkinson's disease dementia experiencing cognitive fluctuations during an office visit. This patient's associated dysautonomia included labile BP with orthostatic hypotension and nocturnal hypertension. A spontaneous episode of unresponsiveness occurred while his BP was 72/48. His mental status began to recover immediately as his BP increased to 84/56 when he was placed in a recumbent position; it fully returned to baseline when it reached 124/66 within 1 min. His heart rate remained in the mid-to-high 60s throughout. Subsequent treatment with midodrine markedly reduced the frequency of cognitive fluctuations.

Conclusions: Paroxysmal hypotension may represent an explanatory mechanism for cognitive fluctuations, a common clinical feature in patients with Parkinson's disease dementia and dementia with Lewy bodies.

Keywords: Cognitive fluctuations; Dementia with Lewy bodies; Dysautonomia; Orthostatic hypotension; Parkinson’s disease dementia.

Conflict of interest statement

Not applicable (no identifying information included)Not applicableThe authors declare that they have no competing interests relevant to this case report. DER has received honoraria from Allergan and Merz. AJE has received grant support from the NIH, Great Lakes Neurotechnologies and the Michael J Fox Foundation; personal compensation as a consultant/scientific advisory board member for Abbvie, TEVA, Impax, Merz, Acadia, Cynapsus/Sunovion, Lundbeck, and USWorldMeds; publishing royalties from Lippincott Williams & Wilkins, Cambridge University Press, and Springer; and honoraria from Abbvie, UCB, USWorldMeds, Lundbeck, Acadia, the American Academy of Neurology, and the Movement Disorders Society. He serves as Associate Editor of the Journal of Clinical Movement Disorders and on the editorial board of Parkinsonism and Related Disorders.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1

Theoretical relationship between blood pressure lability and cognitive fluctuations according to burden of Lewy body pathology. The undulating red line represents the erratic ambulatory blood pressure recording of a patient with a Lewy body disorder and dysautonomia over the waking hours of a single day, with BP wandering between and over thresholds of hypotension and hypertension. The blue panels represent mild, moderate, and severe Lewy body pathology. As the BP lability increases with disease progression so does the frequency of hypotension-induced cerebral hypoperfusion episodes, which may correlate with cognitive fluctuations. Although this has not been directly examined, we propose that with severe cortical pathology (right-most panel), the cognitive fluctuations may become subclinical, obscured by a higher baseline dementia, which precludes inter-episode lucidity