Tau pathologies mediate the association of blood pressure with cognitive impairment in adults without dementia: The CABLE study

Abstract

Introduction:This study delineated the interrelationships among blood pressure (BP), cerebrospinal fluid (CSF) core biomarkers of Alzheimer's disease (AD), and cognition. Methods:The linear regression analyses were conducted in 1546 non-demented participants (mean age of 61.58 years, range 40 to 89 years; 40% female; average days of BP measurement, 9.10 days). Mediation analyses with 10,000 bootstrapped iterations were used to explore the mediation effects.Results: A clear age-related pattern of BP was delineated. Mid-life hypertension (especially systolic BP), late-life lower diastolic BP, as well as mid-and late-life higher pulse pressure were associated with cognitive impairment and tau-related biomarkers. BP variability was associated only with cognition but not with CSF biomarkers. Overall, the associations between BP and cognition were partially mediated (proportion: 11% to 30%) by tau pathologies, independently of amyloid pathology.Discussion: Tau pathologies might play important roles in the relationship between BP and cognition, with significant age-and BP-type dependences.

Visit-to-Visit Blood Pressure Variability and Longitudinal Tau Accumulation in Older Adults

“…One prior study failed to detect any relationship between BPV and cerebral spinal fluid tau levels. 20 It is unclear why the present study found a different pattern of results, but it could be that cerebral spinal fluid tau levels are less sensitive to regional tau deposition within specific brain areas affected in the earliest stages of AD (eg, the entorhinal cortex) where robust relationships between BPV and tau were observed. This particular study examined day-to-day BPV over an average of 9.1 days, 20 suggesting mechanisms underlying BPV may differ by timespan of BP measurement.…”

“…20 It is unclear why the present study found a different pattern of results, but it could be that cerebral spinal fluid tau levels are less sensitive to regional tau deposition within specific brain areas affected in the earliest stages of AD (eg, the entorhinal cortex) where robust relationships between BPV and tau were observed. This particular study examined day-to-day BPV over an average of 9.1 days, 20 suggesting mechanisms underlying BPV may differ by timespan of BP measurement. 22 The findings of the present study could suggest vascular dysfunction represented by increased BPV contributes to pathological tau accumulation; however, replication of the present study finding is needed to further support a role for increased BPV in cerebral tau changes.…”

“…The only study to examine BPV in relation to AD biomarkers showed no relationship with cerebral spinal fluid amyloid-beta or tau levels. 20 To our knowledge, no studies have evaluated the relationship between BPV and regional tau accumulation by tau-PET scans. The present study examined the longitudinal relationship between BPV and later tau accumulation in older adults, focusing on temporal regions affected during early-stage AD.…”

“…The role of BP in cerebrovascular disease is well established, [12][13][14][15] but fewer studies have examined whether BP is related to Alzheimer disease (AD) pathophysiology. Findings to date have suggested that elevated BP may be associated with cerebral spinal fluid biomarkers and positron emission tomography (PET) markers of both cerebral amyloidosis and tau-mediated neurodegeneration, [16][17][18][19][20] as well as AD pathology at autopsy. 13 More recent studies have particularly emphasized specific links between BP elevation and pathophysiological markers of hyperphosphorylated tau, 13,16,17,21 as links between BP and amyloid-beta markers have been less consistent.…”

“…15,17 At least one study has suggested tau specific changes may mediate relationships between BP and cognitive impairment, independent of amyloid-beta. 20 Beyond average BP and the associated treatment strategies of aggressive BP lowering, other aspects of BP may be important for cognitive decline with potential implications for specific therapeutic approaches. Recent interest in BP variability (BPV) over months to years (eg, visit-to-visit BPV) has emerged as a vascular risk factor for cerebrovascular disease and cognitive decline, independent of average BP levels.…”