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 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 Object-in-place Memory Predicted by Anterolateral Entorhinal Cortex and Parahippocampal Cortex Volume in Older Adults

2019 ◽  
Vol 31 (5) ◽  
pp. 711-729 ◽  
Author(s):  
Lok-Kin Yeung ◽  
Rosanna K. Olsen ◽  
Bryan Hong ◽  
Valentina Mihajlovic ◽  
Maria C. D'Angelo ◽  
...  
Keyword(s):  
Older Adults ◽  
Alzheimer Disease ◽  
Entorhinal Cortex ◽  
Spatial Information ◽  
Brain Regions ◽  
Spatial Relationships ◽  
Object Representations ◽  
Functional Connections ◽  
Place Memory ◽  
Parahippocampal Cortex

The lateral portion of the entorhinal cortex is one of the first brain regions affected by tau pathology, an important biomarker for Alzheimer disease. Improving our understanding of this region's cognitive role may help identify better cognitive tests for early detection of Alzheimer disease. Based on its functional connections, we tested the idea that the human anterolateral entorhinal cortex (alERC) may play a role in integrating spatial information into object representations. We recently demonstrated that the volume of the alERC was related to processing the spatial relationships of the features within an object [Yeung, L. K., Olsen, R. K., Bild-Enkin, H. E. P., D'Angelo, M. C., Kacollja, A., McQuiggan, D. A., et al. Anterolateral entorhinal cortex volume predicted by altered intra-item configural processing. Journal of Neuroscience, 37, 5527–5538, 2017]. In this study, we investigated whether the human alERC might also play a role in processing the spatial relationships between an object and its environment using an eye-tracking task that assessed visual fixations to a critical object within a scene. Guided by rodent work, we measured both object-in-place memory, the association of an object with a given context [Wilson, D. I., Langston, R. F., Schlesiger, M. I., Wagner, M., Watanabe, S., & Ainge, J. A. Lateral entorhinal cortex is critical for novel object-context recognition. Hippocampus, 23, 352–366, 2013], and object-trace memory, the memory for the former location of objects [Tsao, A., Moser, M. B., & Moser, E. I. Traces of experience in the lateral entorhinal cortex. Current Biology, 23, 399–405, 2013]. In a group of older adults with varying stages of brain atrophy and cognitive decline, we found that the volume of the alERC and the volume of the parahippocampal cortex selectively predicted object-in-place memory, but not object-trace memory. These results provide support for the notion that the alERC may integrate spatial information into object representations.

Getting to know a new protocol in hypertension care

2020 ◽  
Vol 16 (1) ◽  
Author(s):  
Mona Lundin
Keyword(s):  
Blood Pressure ◽  
Digital Technology ◽  
Interaction Analysis ◽  
Medical Discourse ◽  
Graphical Form ◽  
Graph Data ◽  
Average Blood Pressure ◽  
Infrastructure Design

This study explores the use of a new protocol in hypertension care, in which continuous patient-generated data reported through digital technology are presented in graphical form and discussed in follow-up consultations with nurses. This protocol is part of an infrastructure design project in which patients and medical professionals are co-designers. The approach used for the study was interaction analysis, which rendered possible detailed in situ examination of local variations in how nurses relate to the protocol. The findings show three distinct engagements: (1) teasing out an average blood pressure, (2) working around the protocol and graph data and (3) delivering an analysis. It was discovered that the graphical representations structured the consultations to a great extent, and that nurses mostly referred to graphs that showed blood pressure values, which is a measurement central to the medical discourse of hypertension. However, it was also found that analysis of the data alone was not sufficient to engage patients: nurses' invisible and inclusion work through eliciting patients' narratives played an important role here. A conclusion of the study is that nurses and patients both need to be more thoroughly introduced to using protocols based on graphs for more productive consultations to be established. 

Heritability analyses show visit-to-visit blood pressure variability reflects different pathological phenotypes in younger and older adults

2013 ◽  
Vol 31 (12) ◽  
pp. 2356-2361 ◽  
Author(s):  
Cristina Menni ◽  
Massimo Mangino ◽  
Feng Zhang ◽  
Gail Clement ◽  
Harold Snieder ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Older Adults ◽  
Blood Pressure Variability

Abstract WP218: Increased Systolic Blood Pressure Variability Among Diabetic Patients is Associated With Higher Risk of Incident Stroke: A Secondary Analysis of ACCORDION

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Adam H de Havenon ◽  
Ka-Ho Wong ◽  
Eva Mistry ◽  
Mohammad Anadani ◽  
Shadi Yaghi ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Pressure Variability ◽  
Proportional Hazards ◽  
Secondary Analysis ◽  
Cox Proportional Hazards ◽  
Diabetic Patients ◽  
Adjusted Risk ◽  
Cox Proportional Hazards Models ◽  
Increased Risk

Background: Increased blood pressure variability (BPV) has been associated with stroke risk, but never specifically in patients with diabetes. Methods: This is a secondary analysis of the Action to Control Cardiovascular Risk in Diabetes Follow-On Study (ACCORDION), the long term follow-up extension of ACCORD. Visit-to-visit BPV was analyzed using all BP readings during the first 36 months. The primary outcome was incident ischemic or hemorrhagic stroke after 36 months. Differences in mean BPV was tested with Student’s t-test. We fit Cox proportional hazards models to estimate the adjusted risk of stroke across lowest vs. highest quintile of BPV and report hazard ratios along with 95% confidence intervals (CI). Results: Our analysis included 9,241 patients, with a mean (SD) age of 62.7 (6.6) years and 61.7% were male. Mean (SD) follow-up was 5.7 (2.4) years and number of BP readings per patient was 12.0 (4.3). Systolic, but not diastolic, BPV was higher in patients who developed stroke (Table 1). The highest quintile of SBP SD was associated with increased risk of incident stroke, independent of mean blood pressure or other potential confounders. (Table 2, Figure 1). There was no interaction between SBP SD and treatment arm assignment, although the interaction for glucose approached significance (Table 2). Conclusion: Higher systolic BPV was associated with incident stroke in a large cohort of diabetic patients. Future trials of stroke prevention may benefit from interventions targeting BPV reduction.

scholarly journals Plasma tau correlates with basal forebrain atrophy rates in people at risk for Alzheimer disease

Neurology ◽  
2019 ◽  
Vol 94 (1) ◽  
pp. e30-e41 ◽  
Author(s):  
Enrica Cavedo ◽  
Simone Lista ◽  
Marion Houot ◽  
Andrea Vergallo ◽  
Michel J. Grothe ◽  
...  
Keyword(s):  
Older Adults ◽  
At Risk ◽  
Alzheimer Disease ◽  
Basal Forebrain ◽  
Large Scale ◽  
Carrier Status ◽  
Annual Percent Change ◽  
Β Amyloid ◽  
T Tau ◽  
Cognitively Intact

ObjectiveTo investigate whether baseline concentrations of plasma total tau (t-tau) and neurofilament light (NfL) chain proteins are associated with annual percent change (APC) of the basal forebrain cholinergic system (BFCS) in cognitively intact older adults at risk for Alzheimer disease (AD).MethodsThis was a large-scale study of 276 cognitively intact older adults from the monocentric INSIGHT-preAD (Investigation of Alzheimer's Predictors in Subjective Memory Complainers) cohort. Participants underwent baseline assessment of plasma t-tau and NfL concentrations as well as baseline and 24-month follow-up MRI scans. Linear models with and without influential observations (calculated using the Cook distance) were carried out to investigate the effect of plasma NfL and t-tau concentrations, and their interaction effect with β-amyloid status and APOE genotype, on the APC of the whole BFCS and its anterior (Ch1/2) and posterior (Ch4) subdivisions separately.ResultsHigher plasma t-tau concentrations at baseline were associated with higher BFCS rate of atrophy (model without influencers: n = 251, F value = 4.6815; p value = 0.031). Subregional analyses showed similar results for both the APC of the Ch1/2 (model without influencers: n = 256, F value = 3.9535, p corrected = 0.047) and Ch4 BFCS sectors (model without influencers: n = 253, F value = 4.9090, p corrected = 0.047). Baseline NfL, β-amyloid load, and APOE ε4 carrier status did not affect APC of the BFCS.ConclusionIncreased concentrations of baseline plasma t-tau may predict in vivo structural BFCS atrophy progression in older adults at risk for AD, independently of β-amyloid status and APOE genotype.

Blood Pressure Variability and Dementia Rating Scale Performance in Older Adults With Cardiovascular Disease

2007 ◽  
Vol 20 (1) ◽  
pp. 73-77 ◽  
Author(s):  
Therese Anne Keary ◽  
John Gunstad ◽  
Athena Poppas ◽  
Robert H. Paul ◽  
Angela L. Jefferson ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Older Adults ◽  
Blood Pressure Variability ◽  
Rating Scale ◽  
Dementia Rating Scale

scholarly journals Functional network integrity presages cognitive decline in preclinical Alzheimer disease

Neurology ◽  
2017 ◽  
Vol 89 (1) ◽  
pp. 29-37 ◽  
Author(s):  
Rachel F. Buckley ◽  
Aaron P. Schultz ◽  
Trey Hedden ◽  
Kathryn V. Papp ◽  
Bernard J. Hanseeuw ◽  
...  
Keyword(s):  
Older Adults ◽  
Functional Connectivity ◽  
Alzheimer Disease ◽  
Cognitive Decline ◽  
Cognitive Networks ◽  
Rate Of Change ◽  
Control Networks ◽  
Clinically Normal ◽  
And Control

Objective:To examine the utility of resting-state functional connectivity MRI (rs-fcMRI) measurements of network integrity as a predictor of future cognitive decline in preclinical Alzheimer disease (AD).Methods:A total of 237 clinically normal older adults (aged 63–90 years, Clinical Dementia Rating 0) underwent baseline β-amyloid (Aβ) imaging with Pittsburgh compound B PET and structural and rs-fcMRI. We identified 7 networks for analysis, including 4 cognitive networks (default, salience, dorsal attention, and frontoparietal control) and 3 noncognitive networks (primary visual, extrastriate visual, motor). Using linear and curvilinear mixed models, we used baseline connectivity in these networks to predict longitudinal changes in preclinical Alzheimer cognitive composite (PACC) performance, both alone and interacting with Aβ burden. Median neuropsychological follow-up was 3 years.Results:Baseline connectivity in the default, salience, and control networks predicted longitudinal PACC decline, unlike connectivity in the dorsal attention and all noncognitive networks. Default, salience, and control network connectivity was also synergistic with Aβ burden in predicting decline, with combined higher Aβ and lower connectivity predicting the steepest curvilinear decline in PACC performance.Conclusions:In clinically normal older adults, lower functional connectivity predicted more rapid decline in PACC scores over time, particularly when coupled with increased Aβ burden. Among examined networks, default, salience, and control networks were the strongest predictors of rate of change in PACC scores, with the inflection point of greatest decline beyond the fourth year of follow-up. These results suggest that rs-fcMRI may be a useful predictor of early, AD-related cognitive decline in clinical research settings.

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