scholarly journals Blood pressure variability and medial temporal atrophy in apolipoprotein ϵ4 carriers

2021 ◽  
Author(s):  
Isabel J. Sible ◽  
Daniel A. Nation ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Blood Pressure ◽  
Alzheimer's Disease ◽  
Entorhinal Cortex ◽  
Amyloid Beta ◽  
Blood Pressure Variability ◽  
Credible Interval ◽  
Carrier Status ◽  
Phosphorylated Tau ◽  
Disease Biomarker

AbstractBlood 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.

scholarly journals Visit-to-visit Blood Pressure Variability and Regional Cerebral Perfusion Decline in Older Adults

2020 ◽  
Author(s):  
Isabel Sible ◽  
Belinda Yew ◽  
Shubir Dutt ◽  
Katherine J. Bangen ◽  
Yanrong Li ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Blood Pressure ◽  
Older Adults ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Blood Pressure Variability ◽  
Cerebral Perfusion ◽  
Cerebral Spinal Fluid ◽  
Spinal Fluid ◽  
Phosphorylated Tau

Abstract Background: Blood pressure variability has been linked to dementia risk, independent of average blood pressure levels. It has been hypothesized that dysregulated blood pressure may challenge autoregulatory mechanisms and risk cerebral hypoperfusion. The current study examined whether visit-to-visit blood pressure variability over one year is related to concurrent regional cerebral perfusion decline over the same period in older adults.Methods: Sixty-three older adults without history of dementia or stroke underwent repeated blood pressure measurement and arterial spin-labelling magnetic resonance imaging over the same one year period. Fluorodeoxyglucose-positron emission tomography determined cerebral metabolism at baseline. A subset underwent lumbar puncture to detect cerebral spinal fluid amyloid-beta (n=18) and phosphorylated tau (n=21) abnormalities. Visit-to-visit blood pressure variability and change in regional cerebral perfusion were both calculated over 12 months. Multiple linear regression examined relationships between blood pressure variability and change in regional perfusion after controlling for age, sex, average blood pressure, antihypertensive medication use and cerebral metabolism. Exploratory analyses were repeated in participant subsets with abnormal cerebral spinal fluid amyloid-beta and phosphorylated tau.Results: Elevated blood pressure variability was related to perfusion decline in medial orbitofrontal cortex (ß = -.36; p = .008), hippocampus (ß = -.37; p = .005), entorhinal cortex (ß = -.48; p < .001), precuneus (ß = -.31; p = .02), inferior parietal cortex (ß = -.44; p < .001) and inferior temporal cortex (ß = -.46; p < .001). Elevated blood pressure variability was similarly related to perfusion decline in some regions among participant subsets showing abnormal cerebral spinal fluid amyloid-beta and phosphorylated tau.Conclusions: Older adults with elevated visit-to-visit blood pressure variability exhibit concurrent regional cerebral perfusion decline in areas vulnerable to cerebrovascular dysfunction in Alzheimer’s disease, independent of cerebral hypometabolism. Similar findings are observed in exploratory analyses of older adults with Alzheimer’s disease biomarker abnormalities. The study is limited by the small sample size, particularly the subset of participants with Alzheimer’s disease biomarker abnormalities. Findings may have therapeutic implications, given that certain antihypertensive medications have differential effects on variability of blood pressure independent of average levels.

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

Hypertension ◽  
2021 ◽  
Author(s):  
Isabel J. Sible ◽  
Daniel A. Nation ◽  
Michael Weiner ◽  
Paul Aisen ◽  
Ronald Petersen ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Older Adults ◽  
Alzheimer Disease ◽  
Entorhinal Cortex ◽  
Blood Pressure Variability ◽  
Credible Interval ◽  
Brain Regions ◽  
Carrier Status ◽  
Average Blood Pressure

Background: Elevated blood pressure variability (BPV) is predictive of dementia, independent of average blood pressure levels, but neuropathological mechanisms remain unclear. We examined whether BPV in older adults is related to tau accumulation in brain regions vulnerable to Alzheimer disease and whether relationships are modified by apoϵ4 carrier status. Methods: Two hundred eighty-six Alzheimer’s Disease Neuroimaging Initiative participants without history of dementia underwent 3 to 4 blood pressure measurements over 12 months and ≥1 tau positron emission tomography thereafter. BPV was calculated as variability independent of mean. Each scan determined tau burden (standardized uptake value ratio) for a temporal meta–region of interest, including burden from entorhinal cortex, amygdala, parahippocampus, fusiform, inferior temporal, and middle temporal. Bayesian linear growth modeling examined the role of BPV, apolipoprotein ϵ4 carrier status, and time on regional tau accumulation after controlling for several variables, including baseline hypertension. Results: Elevated BPV was related to tau accumulation at follow-up in a temporal meta-region, independent of average blood pressure levels (ß, 0.89 [95% credible interval, 0.86–0.92]) and especially in entorhinal cortex (ß, 2.57 [95% credible interval, 2.15–2.99]). Apoϵ4 carriers with elevated BPV had the fastest tau accumulation at follow-up (ß, 1.73 [95% credible interval, 0.47–3.03]). Conclusions: BPV is related to tau accumulation in brain regions vulnerable to Alzheimer disease, independent of average blood pressure. APOEϵ4 modified this relationship. Bidirectionality of findings is possible. BPV may represent a marker of vascular dysfunction related to early-stage tau pathology contributing to Alzheimer disease.

scholarly journals Prediction of Alzheimer’s disease biomarker status defined by the ‘ATN framework’ among cognitively healthy individuals: results from the EPAD longitudinal cohort study

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Catherine M. Calvin ◽  
◽  
Casper de Boer ◽  
Vanessa Raymont ◽  
John Gallacher ◽  
...  
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Blood Pressure ◽  
Alzheimer's Disease ◽  
Family History ◽  
Risk Scores ◽  
Healthy Individuals ◽  
Disease Biomarker ◽  
Composite Risk ◽  
Composite Scores

Abstract Background The Amyloid/Tau/Neurodegeneration (ATN) framework has been proposed as a means of evidencing the biological state of Alzheimer’s disease (AD). Predicting ATN status in pre-dementia individuals therefore provides an important opportunity for targeted recruitment into AD interventional studies. We investigated the extent to which ATN-defined biomarker status can be predicted by known AD risk factors as well as vascular-related composite risk scores. Methods One thousand ten cognitively healthy older adults were allocated to one of five ATN-defined biomarker categories. Multinomial logistic regression tested risk factors including age, sex, education, APOE4, family history of dementia, cognitive function, vascular risk indices (high systolic blood pressure, body mass index (BMI), high cholesterol, physical inactivity, ever smoked, blood pressure medication, diabetes, prior cardiovascular disease, atrial fibrillation and white matter lesion (WML) volume), and three vascular-related composite scores, to predict five ATN subgroups; ROC curve models estimated their added value in predicting pathology. Results Age, APOE4, family history, BMI, MMSE and white matter lesions (WML) volume differed between ATN biomarker groups. Prediction of Alzheimer’s disease pathology (versus normal AD biomarkers) improved by 7% after adding family history, BMI, MMSE and WML to a ROC curve that included age, sex and APOE4. Risk composite scores did not add value. Conclusions ATN-defined Alzheimer’s disease biomarker status prediction among cognitively healthy individuals is possible through a combination of constitutional and cardiovascular risk factors but established dementia composite risk scores do not appear to add value in this context.

[P2-221]: COGNITIVE CORRELATES OF BLOOD PRESSURE VARIABILITY IN ALZHEIMER's DISEASE

2017 ◽  
Vol 13 (7S_Part_14) ◽  
pp. P695-P695
Author(s):  
YongSoo Shim ◽  
Bora Yoon ◽  
San Jung ◽  
Dong Won Yang
Keyword(s):  
Alzheimer’S Disease ◽  
Blood Pressure ◽  
Alzheimer's Disease ◽  
Blood Pressure Variability ◽  
Cognitive Correlates

Blood pressure variability predicts cognitive decline in Alzheimer's disease patients

2014 ◽  
Vol 35 (10) ◽  
pp. 2282-2287 ◽  
Author(s):  
Simona Lattanzi ◽  
Simona Luzzi ◽  
Leandro Provinciali ◽  
Mauro Silvestrini
Keyword(s):  
Alzheimer’S Disease ◽  
Blood Pressure ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Blood Pressure Variability

scholarly journals Antemortem Visit-To-Visit Blood Pressure Variability Predicts Cerebrovascular Lesion Burden in Autopsy-Confirmed Alzheimer’s Disease

2021 ◽  
pp. 1-11
Author(s):  
Isabel J. Sible ◽  
Katherine J. Bangen ◽  
Anna E. Blanken ◽  
Jean K. Ho ◽  
Daniel A. Nation
Keyword(s):  
Alzheimer’S Disease ◽  
Blood Pressure ◽  
Alzheimer's Disease ◽  
Cerebrovascular Disease ◽  
Blood Pressure Variability ◽  
Cognitive Change ◽  
Elevated Blood Pressure ◽  
Elevated Blood ◽  
Cerebrovascular Lesion

Background: Blood pressure variability is linked to Alzheimer’s disease (AD) risk and MRI-based markers of cerebrovascular disease. Less is known about the role of blood pressure variability in postmortem evaluation of cerebrovascular disease and AD. Objective: To determine whether antemortem blood pressure variability predicts cerebrovascular and AD pathology and follow-up cognitive change in autopsy-confirmed AD. Methods: National Alzheimer’s Coordinating Center participants (n = 513) underwent 3-4 approximately annual blood pressure measurements and were confirmed to have AD at postmortem evaluation. A subset (n = 493) underwent neuropsychological evaluation at follow-up. Regression models examined relationships between blood pressure variability and cerebrovascular and AD pathological features and follow-up cognitive change. Results: Elevated blood pressure variability predicted increased postmortem cerebrovascular lesion burden (ß = 0.26 [0.10, 0.42]; p = 0.001; R 2 = 0.12). Increased blood pressure variability predicted specific cerebrovascular lesion severity, including atherosclerosis in the Circle of Willis (OR = 1.22 [1.03, 1.44]; p = 0.02) and cerebral arteriolosclerosis (OR = 1.32 [1.04, 1.69]; p = 0.03). No significant relationships were observed between blood pressure variability and AD pathological findings, including Braak & Braak stage, neuritic plaques or diffuse plaques, or cerebral amyloid angiopathy, or follow-up cognitive decline. Conclusion: Findings suggest that elevated blood pressure variability is related to postmortem cerebrovascular lesion burden in autopsy-confirmed AD, independent of average blood pressure and AD neuropathology. Blood pressure fluctuation may selectively promote atherosclerotic and arteriolosclerotic brain lesions with potential implications for cognitive impairment and dementia.

Sign in / Sign up

Export Citation Format

Share Document