Visit-to-visit blood pressure variability and regional cerebral perfusion decline in older adults

Sible, Isabel J.; Yew, Belinda; Dutt, Shubir; Bangen, Katherine J.; Li, Yanrong; Nation, Daniel A.

doi:10.1016/j.neurobiolaging.2021.04.009

Cited by 27 publications

(42 citation statements)

References 33 publications

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“…The current investigation adds to ongoing work detailing relationships between BPV and AD. 6 , 10 , 11 , 13 , 16 - 18 , 38 In addition, patterns of CSF change were observed predominantly in APOE ε4 carriers, consistent with recent work relating BPV and APOE ε4 to other important markers of AD (e.g., medial temporal volume loss). 18 …”

Section: Discussionsupporting

confidence: 88%

Visit-to-Visit Blood Pressure Variability and CSF Alzheimer Disease Biomarkers in Cognitively Unimpaired and Mildly Impaired Older Adults

Sible

Nation

2022

Neurology

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Background and Objectives:Blood pressure variability is an emerging risk factor for cognitive decline and dementia, but mechanisms remain unclear. The current study examined whether visit-to-visit blood pressure variability is related to CSF Alzheimer’s disease biomarker levels over time, and whether associations differed by APOE ϵ4 carrier status.Methods:In this retrospective analysis of a prospective cohort study, cognitively unimpaired or mildly impaired older adults from the Alzheimer’s Disease Neuroimaging Initiative underwent 3-4 blood pressure measurements over a 12-month period and ≥ 1 lumbar puncture for the evaluation of CSF phosphorylated tau, total tau, and amyloid-beta levels at follow-up (6-108 months later). APOE ϵ4 carriers were defined as having ≥ 1 ϵ4 allele. Visit-to-visit blood pressure variability was determined over 12 months as variability independent of mean. Only CSF samples collected after the final blood pressure measurement were analyzed. Bayesian linear growth modeling investigated the role of blood pressure variability, APOE ϵ4, and the passage of time on CSF biomarker levels after controlling for several variables, including average blood pressure and baseline hypertension.Results:466 participants (mean 76.7 (7.1 SD) years of age) were included in the study. Elevated blood pressure variability was associated with increased CSF phosphorylated tau (ß: .81 [95% CI .74, .97]), increased total tau (ß: .98 [95% CI .71, 1.31]), and decreased amyloid-beta levels (ß: -1.52 [95% CI -3.55, -.34]) at follow-up. APOE ϵ4 carriers with elevated blood pressure variability had the fastest increase in phosphorylated tau levels (ß: 9.03 [95% CI 1.67, 16.36]). Blood pressure variability was not significantly related to total tau or amyloid-beta levels over time based on APOE ϵ4 carrier status.Discussion:Older adults with elevated blood pressure variability exhibit increased CSF phosphorylated tau, increased total tau, and decreased amyloid-beta over time, suggesting blood pressure variability may correlate with alterations in Alzheimer’s disease biomarkers. Findings warrant further study of the relationship between blood pressure variability and the development of Alzheimer’s disease. APOE ϵ4 carrier status moderated relationships between blood pressure variability and CSF phosphorylated tau but total tau or not amyloid-beta, consistent with other studies relating hemodynamic factors to tau changes.

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Section: Discussionsupporting

confidence: 88%

Visit-to-Visit Blood Pressure Variability and CSF Alzheimer Disease Biomarkers in Cognitively Unimpaired and Mildly Impaired Older Adults

Sible

Nation

2022

Neurology

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“…Seated BP measurements were obtained from participants 3-4 times between study screening and 12-months followup using a calibrated mercury sphygmomanometer, as described elsewhere (Sible et al, 2020(Sible et al, , 2021b. Intraindividual BPV was calculated for each participant using the 3-4 BP measurements collected over the 12 month period as variation independent of mean (VIM), a commonly used index of visit-to-visit BPV that is uncorrelated with average BP levels across visits (de Heus et al, 2019;Rothwell et al, 2010;Rouch et al, 2020;Sible et al, 2020Sible et al, , 2021aSible et al, , 2021b. VIM was calculated as: VIM = SD/mean x , where the power x was derived from non-linear curve fitting of BP SD against average BP using the nls package in R (R Core Team, 2018), as described elsewhere (Rothwell et al, 2010;Yano, 2017).…”

Section: Bp Assessmentmentioning

confidence: 99%

“…Chronic large fluctuations in BP may stress arterial walls and promote microvascular injury and arterial remodeling (Nagai et al, 2017). These vascular changes may convey vulnerability to cerebral hypoperfusion injury (Sible et al, 2021b) and subsequent neuronal injury, especially in regions highly sensitive to BPrelated hypoxic-ischemic injury, such as the hippocampus (Iadecola, 2004;Ma et al,. 2020b;Vikner et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Blood pressure variability and medial temporal atrophy in apolipoprotein ϵ4 carriers

Sible

Nation

Initiative³

2021

Brain Imaging and Behavior

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Blood pressure variability is an emerging risk factor for dementia but relationships with markers of neurodegeneration and Alzheimer’s disease risk are understudied. We investigated blood pressure variability over one year and follow-up medial temporal brain volume change in apolipoprotein ϵ4 carriers and non-carriers, and in those with and without Alzheimer’s disease biomarker abnormality. 1051 Alzheimer’s Disease Neuroimaging Initiative participants without history of dementia or stroke underwent 3–4 blood pressure measurements over 12 months and ≥ 1 MRI thereafter. A subset (n = 252) underwent lumbar puncture to determine Alzheimer’s disease cerebral spinal fluid amyloid-beta and phosphorylated tau biomarker abnormality. Blood pressure variability over 12 months was calculated as variability independent of mean. Longitudinal hippocampal and entorhinal cortex volume data were extracted from serial brain MRI scans obtained after the final blood pressure measurement. Apolipoprotein ϵ4 carrier status was defined as at least one ϵ4 allele. Bayesian growth modelling revealed a significant interaction of blood pressure variability by ϵ4 by time on hippocampal (ß: -2.61 [95% credible interval -3.02, -2.12]) and entorhinal cortex (ß: -1.47 [95% credible interval -1.71, -1.17]) volume decline. A similar pattern emerged in subsets with Alzheimer’s disease pathophysiology (i.e., abnormal levels of both amyloid-beta and phosphorylated tau). Findings suggest that elevated blood pressure variability is related to medial temporal volume loss specifically in ϵ4 carriers, and in those with Alzheimer’s disease biomarker abnormality. Findings could implicate blood pressure variability in medial temporal neurodegeneration observed in older ϵ4 carriers and those with prodromal Alzheimer’s disease.

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“…However, this autoregulation mechanism is affected by aging and chronic hypertension, with a rightward shift of the plateau stage, rendering the brain frailer to low BP levels [ 73 ], and is associated with hypoperfusion leading to ischemic brain injury [ 74 ]. Recently, high BPV with extreme high and low BP levels has been reported to hamper cerebral perfusion, causing recurrent episodes of cerebral hypoperfusion in older adults [ 75 ]. Cerebral hypoperfusion contributes to cognitive decline and the progression and severity of dementia in the general population [ 76 ].…”

Section: Potential Mechanisms Underlying the Relationship Between Blo...mentioning

confidence: 99%

“…Studies assessing sex differences in cerebral hypoperfusion caused by BPV are lacking. One study reported no statistical differences in the relationship between BPV and cerebral hypoperfusion after adjusting the sex [ 75 ].…”

Section: Potential Mechanisms Underlying the Relationship Between Blo...mentioning

confidence: 99%

The impact of blood pressure variability on cognition: current limitations and new advances

Sun

2023

Journal of Hypertension

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Dementia is the most common neurodegenerative disease in the aging population. Emerging evidence indicates that blood pressure (BP) variability is correlated with cognitive impairment and dementia independent of mean BP levels. The state-of-the-art review summarizes the latest evidence regarding the impact of BP variability on cognition in cognitively intact populations, patients with mild cognitive impairment, and different dementia types, focusing on the important confounding factors and new advances. This review also summarizes the potential mechanisms underlying the relationship between BP variability and cognitive impairment, and dementia, briefly discussing sex differences in the relationship. At last, current limitations and future perspectives are discussed to optimize BP management in preventing cognitive impairment and dementia.

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Visit-to-visit blood pressure variability and regional cerebral perfusion decline in older adults

Cited by 27 publications

References 33 publications

Visit-to-Visit Blood Pressure Variability and CSF Alzheimer Disease Biomarkers in Cognitively Unimpaired and Mildly Impaired Older Adults

Visit-to-Visit Blood Pressure Variability and CSF Alzheimer Disease Biomarkers in Cognitively Unimpaired and Mildly Impaired Older Adults

Blood pressure variability and medial temporal atrophy in apolipoprotein ϵ4 carriers

The impact of blood pressure variability on cognition: current limitations and new advances

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