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      Orthostatic Blood Pressure Recovery Is Associated With the Rate of Cognitive Decline and Mortality in Clinical Alzheimer’s Disease

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          Abstract

          Background

          Impaired recovery of blood pressure (BP) after standing has been shown to be related to cognitive function and mortality in people without dementia, but its role in people with Alzheimer’s disease (AD) is unknown. The aim of this study was to investigate the association of the orthostatic BP response with cognitive decline and mortality in AD.

          Methods

          In this post hoc analysis of a randomized controlled trial (Nilvad), we measured the beat-to-beat response of BP upon active standing in mild-to-moderate AD. This included the initial drop (nadir within 40 seconds) and recovery after 1 minute, both expressed relative to resting values. We examined the relationship between a small or large initial drop (median split) and unimpaired (≥100%) or impaired recovery (<100%) with 1.5-year change in Alzheimer’s Disease Assessment—cognitive subscale (ADAS-cog) scores and all-cause mortality.

          Results

          We included 55 participants (age 73.1 ± 6.2 years). Impaired BP recovery was associated with higher increases in ADAS-cog scores (systolic: β [95% confidence interval] = 5.6 [0.4–10.8], p = .035; diastolic: 7.6 [2.3–13.0], p = .006). During a median follow-up time of 49 months, 20 participants died. Impaired BP recovery was associated with increased mortality (systolic: HR [95% confidence interval] = 2.9 [1.1–7.8], p = .039; diastolic: HR [95% confidence interval] = 5.5 [1.9–16.1], p = .002). The initial BP drop was not associated with any outcome. Results were adjusted for age, sex, and intervention group.

          Conclusions

          Failure to fully recover BP after 1 minute of standing is associated with cognitive decline and mortality in AD. As such, BP recovery can be regarded as an easily obtained marker of progression rate of AD.

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          Most cited references52

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          NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease

          In 2011, the National Institute on Aging and Alzheimer’s Association created separate diagnostic recommendations for the preclinical, mild cognitive impairment, and dementia stages of Alzheimer’s disease. Scientific progress in the interim led to an initiative by the National Institute on Aging and Alzheimer’s Association to update and unify the 2011 guidelines. This unifying update is labeled a “research framework” because its intended use is for observational and interventional research, not routine clinical care. In the National Institute on Aging and Alzheimer’s Association Research Framework, Alzheimer’s disease (AD) is defined by its underlying pathologic processes that can be documented by postmortem examination or in vivo by biomarkers. The diagnosis is not based on the clinical consequences of the disease (i.e., symptoms/signs) in this research framework, which shifts the definition of AD in living people from a syndromal to a biological construct. The research framework focuses on the diagnosis of AD with biomarkers in living persons. Biomarkers are grouped into those of β amyloid deposition, pathologic tau, and neurodegeneration [AT(N)]. This ATN classification system groups different biomarkers (imaging and biofluids) by the pathologic process each measures. The AT(N) system is flexible in that new biomarkers can be added to the three existing AT(N) groups, and new biomarker groups beyond AT(N) can be added when they become available. We focus on AD as a continuum, and cognitive staging may be accomplished using continuous measures. However, we also outline two different categorical cognitive schemes for staging the severity of cognitive impairment: a scheme using three traditional syndromal categories and a six-stage numeric scheme. It is important to stress that this framework seeks to create a common language with which investigators can generate and test hypotheses about the interactions among different pathologic processes (denoted by biomarkers) and cognitive symptoms. We appreciate the concern that this biomarker-based research framework has the potential to be misused. Therefore, we emphasize, first, it is premature and inappropriate to use this research framework in general medical practice. Second, this research framework should not be used to restrict alternative approaches to hypothesis testing that do not use biomarkers. There will be situations where biomarkers are not available or requiring them would be counterproductive to the specific research goals (discussed in more detail later in the document). Thus, biomarker-based research should not be considered a template for all research into age-related cognitive impairment and dementia; rather, it should be applied when it is fit for the purpose of the specific research goals of a study. Importantly, this framework should be examined in diverse populations. Although it is possible that β-amyloid plaques and neurofibrillary tau deposits are not causal in AD pathogenesis, it is these abnormal protein deposits that define AD as a unique neurodegenerative disease among different disorders that can lead to dementia. We envision that defining AD as a biological construct will enable a more accurate characterization and understanding of the sequence of events that lead to cognitive impairment that is associated with AD, as well as the multifactorial etiology of dementia. This approach also will enable a more precise approach to interventional trials where specific pathways can be targeted in the disease process and in the appropriate people.
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            Clinical diagnosis of Alzheimer's disease: Report of the NINCDS-ADRDA Work Group* under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease

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                Author and article information

                Contributors
                Role: Decision Editor
                Journal
                J Gerontol A Biol Sci Med Sci
                J Gerontol A Biol Sci Med Sci
                gerona
                The Journals of Gerontology Series A: Biological Sciences and Medical Sciences
                Oxford University Press (US )
                1079-5006
                1758-535X
                November 2020
                25 May 2020
                25 May 2020
                : 75
                : 11
                : 2169-2176
                Affiliations
                [1 ] Department of Geriatric Medicine, Radboudumc Alzheimer Center, Radboud University Medical Center, Donders Institute for Brain Cognition and Behaviour , Nijmegen, The Netherlands
                [2 ] Mercer’s Institute for Research on Ageing, St. James’s Hospital , Dublin, Ireland
                [3 ] Department of Medical Gerontology, Trinity College Institute of Neuroscience , Dublin, Ireland
                Author notes
                Address correspondence to: Jurgen Claassen, MD, PhD, Department of Geriatric Medicine, Radboud University Medical Center, P.O. Box 9101 (925), 6500 HB Nijmegen, The Netherlands. E-mail: jurgen.claassen@ 123456radboudumc.nl
                Article
                glaa129
                10.1093/gerona/glaa129
                7566323
                32449919
                ecf8eea5-4023-4c5f-b01a-991def18baf9
                © The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 21 September 2019
                : 18 May 2020
                : 12 June 2020
                Page count
                Pages: 8
                Funding
                Funded by: Dutch Alzheimer Society;
                Award ID: WE.09-2015-03
                Funded by: Alzheimer’s Drug Discovery Foundation;
                Award ID: 20121210
                Funded by: European Commission Framework 7 Programme Health Theme;
                Award ID: 279093
                Categories
                THE JOURNAL OF GERONTOLOGY: Medical Sciences
                Alzheimers and Dementia
                AcademicSubjects/MED00280
                AcademicSubjects/SCI00960

                Geriatric medicine
                alzheimer’s disease,dementia,resilience,blood pressure,continuous monitoring
                Geriatric medicine
                alzheimer’s disease, dementia, resilience, blood pressure, continuous monitoring

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