Abstract
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.
Highlights
Blood pressure (BP) is among the most studied vascular risk factors linked to cognitive impairment, neuropathological change, and dementia (Lane et al, 2019; Zlokovic, 2011)
252 participants confirmed to have Alzheimer’s disease (AD) pathophysiology contributed to 595 MRI scans and the median time interval between BP variability (BPV) measurement and MRI scan was 12 months (IQR: 30 months)
Primary analyses revealed a significant interaction of systolic BPV by time on hippocampal (ß: -0.51 [95% credible interval (CI) -0.63, -0.30]) and entorhinal cortex volume (ß: -0.28 [95% CI -0.34, -0.22]), indicating that participants with elevated systolic BPV were observed to have the fastest hippocampal and entorhinal cortex volume decline at follow-up (Fig. 1a)
Summary
Blood pressure (BP) is among the most studied vascular risk factors linked to cognitive impairment, neuropathological change, and dementia (Lane et al, 2019; Zlokovic, 2011). Recent work suggests that elevated BPV is associated with cerebrovascular disease (Ma, et al, 2020a) and predictive of cognitive impairment and dementia, including AD and vascular dementia (Ma et al, 2020b; Rouch et al, 2020; Yoo et al, 2020), even in healthy older adults with wellcontrolled average BP (Cho et al, 2018). 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 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)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
