Abnormal circadian blood pressure regulation and cognitive impairment in α-synucleinopathies

Circadian blood pressure (BP) rhythm is important for the maintenance of healthy daily life, and its disruption is associated with poor outcomes. Cardiovascular autonomic failure is often observed in older populations but has a greater impact on neurodegenerative disorders such as α-synucleinopathies. These BP abnormalities include orthostatic hypotension (OH), supine hypertension (SH), and a loss of nocturnal BP fall. OH not only causes falls or syncope but is also related to cognitive impairment in α-synucleinopathies. For example, OH doubles or triples the risk for the development of cognitive impairment in Parkinson's disease (PD). The diffuse central and peripheral neuropathology of α-synuclein may contribute to both OH and cognitive impairment. Moreover, repeated cerebral hypoperfusion in OH is thought to be related to cerebrovascular and neuronal damage, which may cause cognitive impairment. SH, which often coexists with OH, is also associated with cognitive impairment through cerebrovascular damage, such as white matter lesions and cerebral microbleeds. The reverse-dipping (riser) pattern on ambulatory BP monitoring is commonly observed in PD (∼56%), regardless of disease duration and severity. It is also related to cognitive impairment and more pronounced when coexisting with OH. These abnormal circadian BP profiles may be synergistically associated with cognitive impairment and poor outcomes in α-synucleinopathies. Although evidence for aggressive control of BP dysregulation improving cognitive impairment and outcomes is limited, regular BP monitoring appears to be important for total management of α-synucleinopathies.