Blood Pressure Variability and Cognitive Function in Older Adults: A New Look

High blood pressure (BP), especially in midlife, has long been associated with an increased risk of cognitive decline and dementia. While previous research has predominantly focused on hypertension and mean BP, recent studies have shed light on the significance of BP variability (BPV). BPV is now recognized as a crucial predictor of adverse cardiovascular outcomes, such as stroke and myocardial infarction, and even mortality, regardless of mean BP levels. Moreover, high BPV has been linked to adverse structural brain changes, including reduced hippocampal volume and increased white matter hyperintensities. Recent meta-analyses have also revealed a stronger association between increased BPV, particularly in older individuals, and a higher risk of developing dementia, surpassing the relationship with mean BP.

Short-Term and Mid-Term BPV: Unveiling the Circadian Patterns

While most studies have focused on long-term BPV and cognitive impairment, the connection between short-term (across 24 hours) and mid-term (across days) BPV and cognitive functioning remains underexplored and inconclusive. Short-term BPV provides valuable insights into the circadian patterns of BP, including the nocturnal BP drop and the morning BP surge. Typically, during sleep, systolic and diastolic BP exhibit a decline of 10-20%, known as 'dipping'. However, some individuals exhibit abnormal nocturnal BP changes, falling into three categories: 'extreme-dippers' (>20%), 'non-dippers' (<10%), and 'reverse-dippers' (showing an increase instead of a decrease in nocturnal BP). While abnormal nocturnal BP patterns and an exaggerated morning BP surge are associated with an increased risk of cardiovascular events, the connection between circadian BPV patterns and cognition remains a subject of uncertainty.

Arterial Stiffness: A Key Player

One essential factor in understanding the link between BPV and cognitive function is arterial stiffness. Arterial stiffness, reflecting reduced arterial elasticity and compliance, increases with age and can be measured using parameters such as the pulse wave velocity (PWV) and the augmentation index (AIx). Arterial stiffness is a well-established cardiovascular risk factor for cognitive impairment and exhibits a strong bidirectional relationship with hypertension. The link between arterial stiffness and cognitive decline is likely mediated by cerebral vascular functioning, including cerebral pulsatility. Studies suggest that changes in vascular functioning, such as a decline in cerebral blood flow, occur before structural neuroanatomical changes, such as hippocampal atrophy. Recent research has linked increased systolic short-term BPV with higher arterial stiffness in hypertensive patients. Additionally, abnormal circadian BP patterns, including an exaggerated morning BP surge, have been independently associated with increased arterial stiffness in hypertensive individuals. Notably, non-dippers have significantly higher arterial stiffness, as assessed via PWV, compared to dippers. However, the relationship between short-term BPV and arterial stiffness in non-hypertensive individuals remains unclear, and there is a dearth of studies examining mid-term BPV and arterial stiffness.

Unveiling the Findings

Study findings underscore the link between higher BPV, independently of mean BP, and lower cognitive performance, especially in sustained attention and overall cognition. Contrary to expectations, study found no significant associations between short-term (awake or sleep) or day-to-day BPV (morning or evening) and cerebrovascular pulsatility. However, higher systolic short-term sleep BPV was linked with increased arterial stiffness (PWV), while higher diastolic day-to-day evening BPV was linked with lower arterial stiffness. The varying patterns of associations between BPV categories, such as short-term vs. mid-term BPV, emphasize that specific BPV categories likely reflect distinct underlying biological mechanisms, each playing a unique role in cognitive decline. These findings underscore the potential of systolic and diastolic BPV as early clinical markers or treatment targets for cognitive decline.

BPV and Cognition: Unraveling the Complexity

Study results suggest that fluctuations in BP throughout the day and night are more crucial for cognitive health than mean BP or circadian BP patterns, especially in community-dwelling older adults. Conflicting findings in the existing literature may be attributed to variations in BPV metrics, cognition assessment methods, and the studied population. In this study, wake and sleep BPV, as well as circadian BP patterns, were assessed within the same participant sample, revealing diverse associations with cognition. Higher wake and sleep-time BPV were significantly associated with lower cognitive test performance, while no significant associations were found between night-time dipping or the morning blood pressure surge and cognitive measures. These results are in line with similar studies in older community-dwelling participants that reported no significant associations between night-time dipping status and cognitive functioning. Further research is needed, particularly to explore the impact of night-time dipping patterns in different age groups and populations.

The Role of Diastolic and Systolic BPV

Study findings emphasize the significance of considering both diastolic and systolic day and night-time BPV and suggest that individual sleep BPV measurements are more sensitive indicators than generic night-time BPV. Systolic awake short-term BPV was significantly negatively associated with sustained attention and general cognition (3MS). In contrast, for BPV during sleep, no significant associations were found for systolic BPV, but increased diastolic BPV was significantly associated with reduced psychomotor speed. These findings align with previous research in community-dwelling older adults, indicating that increased systolic BPV during the day is associated with reduced overall cognitive functioning but not during the night. Notably, while our results found a significant association between sleep diastolic BPV and psychomotor speed, it did not reach statistical significance when examining night-time BPV. Thus, future BPV studies should classify day/night based on the participants' sleep status rather than pre-selected generic times. Variations in predictive values between night-time and day-time blood pressure variability (BPV) are commonly observed in the existing literature that has investigated the clinical significance of short-term BPV for cardiovascular events.

Factors Influencing BPV

Daytime BPV is influenced by BP changes in response to environmental factors, such as physical activity levels, regulated by intrinsic cardiovascular mechanisms like arterial compliance and reflexes. On the other hand, night-time BPV may be indicative of sympathetic drive and could signal sleep apnea, which is associated with a sympathetic overactivity leading to increased peripheral vascular resistance and changes in cardiac output. While this study excluded participants with obstructive sleep apnea, no clinical assessments were conducted to screen participants for sleep-related disorders.

Day-to-Day BPV and Executive Functioning

Both morning and evening day-to-day BPV were significantly associated with executive functioning. Prior research had primarily focused on morning measures of day-to-day BPV. Study findings demonstrate that both morning and evening day-to-day BPV are associated with executive functioning, although morning measures showed stronger associations and effect sizes. This aligns with previous studies, which have found links between increased day-to-day systolic and diastolic BPV and cognitive decline and an elevated risk of dementia.

Diastolic BPV in Focus

Systolic and diastolic BP are affected differently by age. Systolic BP generally increases with age, while diastolic BP follows an increasing trend in middle age but then decreases in later life, often due to age-related arterial stiffening. Recent research indicates that diastolic BPV, particularly in the short- and mid-term, plays an independent role in cognitive decline, especially in individuals above the age of 60. However, further research is necessary to fully understand the role of diastolic BPV in cognitive decline.

BPV and Vascular Stiffness

Study results demonstrate that increased short-term systolic sleep BPV is linked with increased arterial stiffness (PWV), while increased evening diastolic BPV is negatively associated with arterial stiffness. This aligns with previous research that has reported a significant positive association between systolic BPV (across 24 hours) and arterial stiffness (PWV) in hypertensive individuals. Systolic BPV appears to exhibit stronger associations with arterial stiffening than diastolic BPV, whether in the short or long term.

Exploring the Mechanisms

The precise pathophysiological differences between systolic and diastolic BPV and cognitive decline, as well as adverse cardiovascular outcomes, remain unclear. Study hypothesis suggests that high systolic BPV reflects vascular stiffness, while high diastolic BPV may be linked with autonomic dysfunctions.

Focus on BPV for Intervention

Study findings suggest that intervention efforts should primarily target blood pressure variability rather than circadian BP patterns. While past research has indicated associations between decreased BP dipping during the night and increased arterial stiffness in hypertensive samples, our study found no such connection. However, our results indicate that extreme dippers are negatively associated with the pulsatility of the middle cerebral artery. The role of extreme BP dipping in predicting cardiovascular risk remains subject to debate, but recent research suggests that it may not play a pivotal role in the development of hypertension-mediated organ damage. Furthermore, the positive relationship between morning BP surge and arterial stiffness disappears after accounting for systolic short-term BPV.

The Mechanistic Link

The proposed mechanism linking increased BPV with cognitive decline is that high BPV leads to excessive fluctuations in cerebral blood flow, exposing the brain to hyper- and hypotensive episodes, ultimately promoting cerebrovascular impairments. As individuals age, cerebrovascular autoregulatory mechanisms, which protect the cerebral microvasculature against BP fluctuations and ensure sufficient blood flow, become less efficient. BPV becomes particularly significant in older adults. Previous research has connected increased BPV with white matter hyperintensities, reduced cortical thickness, and lower cerebrovascular reactivity. Arterial stiffening may intensify these effects, as stiffened vessels transmit aortic BP to brain arterioles with less dampening. Increased cerebrovascular pulsatility may mediate the relationship between BPV, cerebrovascular damage, and dementia.

The Takeaway

In summary, the study demonstrates that systolic and diastolic short- and mid-term BPV are negatively associated with cognitive functioning, independently of mean BP. Short-term BPV appears to be particularly associated with attention and psychomotor speed, while day-to-day BPV is primarily linked with executive functioning. BPV seems more sensitive in detecting associations with lower cognitive performance and arterial stiffening than circadian BP measures in a cognitively unimpaired older adult population. This study underscores the importance of considering the variable nature of systolic and diastolic BP when addressing BP as a risk factor for dementia.

Reference Article

Gutteridge DS, Tully PJ, Smith AE, Loetscher T, Keage HA. Cross-sectional associations between short and mid-term blood pressure variability, cognition, and vascular stiffness in older adults. Cereb Circ Cogn Behav. 2023 Sep 1;5:100181. doi: 10.1016/j.cccb.2023.100181. PMID: 37711969; PMCID: PMC10497990.

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