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      The Effects of Tau, Amyloid, and White Matter Lesions on Mobility, Dual Tasking, and Balance in Older People

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          Abstract

          Background

          This study aimed to investigate whether white matter lesions (WML), β-amyloid-, and tau pathologies are independently associated with mobility, dual tasking, and dynamic balance performance in older nondemented individuals.

          Methods

          We included 299 older people (mean, SD, age: 71.8, 5.6 years) from the Swedish BioFINDER study, whereof 175 were cognitively unimpaired and 124 had mild cognitive impairment (MCI). In multivariable regression analyses, dependent variables included mobility (Timed Up & Go [TUG]), dual tasking (TUG with a simultaneous subtraction task, that is, TUG-Cog, as well as dual task cost), and balance (Figure-of-eight). The analyses were controlled for age, sex, education, diagnosis (ie, MCI), and comorbidity (stroke, diabetes, and ischemic heart disease). Independent variables included WML volume, and measures of β-amyloid (abnormal cerebrospinal fluid [CSF] Aβ42/40 ratio) and tau pathology (CSF phosphorylated tau [p-tau]).

          Results

          Multivariable regression analyses showed that an increased WML volume was independently associated with decreased mobility, that is, TUG (standardized β = 0.247; p < .001). Tau pathology was independently associated with dual tasking both when using the raw data of TUG-Cog ( β = 0.224; p = .003) and the dual-task cost ( β= −0.246; p = .001). Amyloid pathology was associated with decreased balance, that is, Figure-of-eight ( β = 0.172; p = .028). The independent effects of WML and tau pathology were mainly observed in those with MCI, which was not the case for the effects of amyloid pathology on balance.

          Conclusions

          Common brain pathologies have different effects where WML are independently associated with mobility, tau pathology has the strongest effect on dual tasking, and amyloid pathology seems to be independently associated with balance. Although these novel findings need to be confirmed in longitudinal studies, they suggest that different brain pathologies have different effects on mobility, balance, and dual-tasking in older nondemented individuals.

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          Most cited references56

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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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            Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration

            Summary Cerebral small vessel disease (SVD) is a common accompaniment of ageing. Features seen on neuroimaging include recent small subcortical infarcts, lacunes, white matter hyperintensities, perivascular spaces, microbleeds, and brain atrophy. SVD can present as a stroke or cognitive decline, or can have few or no symptoms. SVD frequently coexists with neurodegenerative disease, and can exacerbate cognitive deficits, physical disabilities, and other symptoms of neurodegeneration. Terminology and definitions for imaging the features of SVD vary widely, which is also true for protocols for image acquisition and image analysis. This lack of consistency hampers progress in identifying the contribution of SVD to the pathophysiology and clinical features of common neurodegenerative diseases. We are an international working group from the Centres of Excellence in Neurodegeneration. We completed a structured process to develop definitions and imaging standards for markers and consequences of SVD. We aimed to achieve the following: first, to provide a common advisory about terms and definitions for features visible on MRI; second, to suggest minimum standards for image acquisition and analysis; third, to agree on standards for scientific reporting of changes related to SVD on neuroimaging; and fourth, to review emerging imaging methods for detection and quantification of preclinical manifestations of SVD. Our findings and recommendations apply to research studies, and can be used in the clinical setting to standardise image interpretation, acquisition, and reporting. This Position Paper summarises the main outcomes of this international effort to provide the STandards for ReportIng Vascular changes on nEuroimaging (STRIVE).
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              The Timed “Up & Go”: A Test of Basic Functional Mobility for Frail Elderly Persons

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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
                April 2021
                07 June 2020
                07 June 2020
                : 76
                : 4
                : 683-691
                Affiliations
                [1 ] Department of Health Sciences, Faculty of Medicine, Lund University , Sweden
                [2 ] Clinical Memory Research Unit, Faculty of Medicine, Lund University , Sweden
                [3 ] Memory Clinic, Skåne University Hospital , Malmö, Sweden
                [4 ] Norwegian National Advisory Unit on Ageing and Health, Vestfold Hospital Trust , Tonsberg, Norway
                [5 ] Department of Geriatric Medicine, Oslo University Hospital , Norway
                [6 ] Diagnostic Radiology, Department of Clinical Sciences, Lund University , Sweden
                [7 ] Image and Function, Skane University Hospital , Lund, Sweden
                [8 ] Wallenberg Center for Molecular Medicine, Lund University , Sweden
                Author notes
                Address correspondence to: Maria H. Nilsson, PhD, Department of Health Sciences, Faculty of Medicine, Lund University, Lund, Sweden. E-mail: maria_h.nilsson@ 123456med.lu.se
                Author information
                http://orcid.org/0000-0002-6580-6721
                http://orcid.org/0000-0001-8649-9874
                Article
                glaa143
                10.1093/gerona/glaa143
                8011701
                32506119
                5bed3fd2-d185-4aab-846b-d34785b1197e
                © 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 License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 12 October 2019
                : 31 May 2020
                : 07 July 2020
                Page count
                Pages: 9
                Funding
                Funded by: Swedish Research Council, DOI 10.13039/501100004359;
                Award ID: 2016-00906
                Funded by: Crafoord foundation;
                Funded by: Knut and Alice Wallenberg foundation;
                Award ID: 2017-0383
                Funded by: Marianne and Marcus Wallenberg foundation;
                Award ID: 2015.0125
                Funded by: Lund University, DOI 10.13039/501100003252;
                Funded by: Swedish Alzheimer Foundation;
                Award ID: AF-745911
                Funded by: Swedish Brain Foundation;
                Award ID: FO2019-0326
                Award ID: FO2019-0029
                Funded by: Parkinson foundation of Sweden;
                Award ID: 1127718
                Funded by: Skåne University Hospital Foundation;
                Award ID: 2019-o000032
                Funded by: Swedish federal government under the ALF agreement;
                Award ID: 2018-Projekt0279
                Categories
                THE JOURNAL OF GERONTOLOGY: Medical Sciences
                Gait, Balance and Weakness
                AcademicSubjects/MED00280
                AcademicSubjects/SCI00960

                Geriatric medicine
                biomarkers,dementia,magnetic resonance imaging,postural balance,difficulty walking

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