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      Neuroimaging modalities in the detection of Alzheimer's disease-associated biomarkers

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          Abstract

          Alzheimer's disease (AD) is the most common cause of dementia. Neuropathological changes in AD patients occur up to 10–20 years before the emergence of clinical symptoms. Specific diagnosis and appropriate intervention strategies are crucial during the phase of mild cognitive impairment (MCI) and AD. The detection of biomarkers has emerged as a promising tool for tracking the efficacy of potential therapies, making an early disease diagnosis, and prejudging treatment prognosis. Specifically, multiple neuroimaging modalities, including magnetic resonance imaging (MRI), positron emission tomography, optical imaging, and single photon emission-computed tomography, have provided a few potential biomarkers for clinical application. The MRI modalities described in this review include structural MRI, functional MRI, diffusion tensor imaging, magnetic resonance spectroscopy, and arterial spin labelling. These techniques allow the detection of presymptomatic diagnostic biomarkers in the brains of cognitively normal elderly people and might also be used to monitor AD disease progression after the onset of clinical symptoms. This review highlights potential biomarkers, merits, and demerits of different neuroimaging modalities and their clinical value in MCI and AD patients. Further studies are necessary to explore more biomarkers and overcome the limitations of multiple neuroimaging modalities for inclusion in diagnostic criteria for AD.

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          The diagnosis of dementia due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease

          The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of revising the 1984 criteria for Alzheimer's disease (AD) dementia. The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available. We present criteria for all-cause dementia and for AD dementia. We retained the general framework of probable AD dementia from the 1984 criteria. On the basis of the past 27 years of experience, we made several changes in the clinical criteria for the diagnosis. We also retained the term possible AD dementia, but redefined it in a manner more focused than before. Biomarker evidence was also integrated into the diagnostic formulations for probable and possible AD dementia for use in research settings. The core clinical criteria for AD dementia will continue to be the cornerstone of the diagnosis in clinical practice, but biomarker evidence is expected to enhance the pathophysiological specificity of the diagnosis of AD dementia. Much work lies ahead for validating the biomarker diagnosis of AD dementia. Copyright © 2011. Published by Elsevier Inc.
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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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              Neuropathological stageing of Alzheimer-related changes

              Eighty-three brains obtained at autopsy from nondemented and demented individuals were examined for extracellular amyloid deposits and intraneuronal neurofibrillary changes. The distribution pattern and packing density of amyloid deposits turned out to be of limited significance for differentiation of neuropathological stages. Neurofibrillary changes occurred in the form of neuritic plaques, neurofibrillary tangles and neuropil threads. The distribution of neuritic plaques varied widely not only within architectonic units but also from one individual to another. Neurofibrillary tangles and neuropil threads, in contrast, exhibited a characteristic distribution pattern permitting the differentiation of six stages. The first two stages were characterized by an either mild or severe alteration of the transentorhinal layer Pre-alpha (transentorhinal stages I-II). The two forms of limbic stages (stages III-IV) were marked by a conspicuous affection of layer Pre-alpha in both transentorhinal region and proper entorhinal cortex. In addition, there was mild involvement of the first Ammon's horn sector. The hallmark of the two isocortical stages (stages V-VI) was the destruction of virtually all isocortical association areas. The investigation showed that recognition of the six stages required qualitative evaluation of only a few key preparations.
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                Author and article information

                Contributors
                Journal
                Psychoradiology
                Psychoradiology
                psyrad
                Psychoradiology
                Oxford University Press
                2634-4416
                2023
                22 June 2023
                22 June 2023
                : 3
                : kkad009
                Affiliations
                Department of Periodical Press, West China Hospital, Sichuan University , Chengdu 610000, China
                Department of Neurology, Chifeng University of Affiliated Hospital , Chifeng 024000, China
                Department of Neurology, the Second Affiliated Hospital of Harbin Medical University , Harbin 150081, China
                Department of General Surgery, Chengdu Integrated Traditional Chinese Medicine and Western Medicine Hospital , Chengdu 610000, China
                Author notes
                Correspondence: Yaoheng Lu, luyaoheng93@ 123456gmail.com
                Correspondence: Qian Li, drliqianhmu@ 123456sina.com
                Author information
                https://orcid.org/0000-0001-5023-6095
                Article
                kkad009
                10.1093/psyrad/kkad009
                11003434
                38666112
                afb3ad9e-7083-4abe-a1ae-32c6a5a53ddd
                © The Author(s) 2023. Published by Oxford University Press on behalf of West China School of Medicine/West China Hospital (WCSM/WCH) of Sichuan University.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( https://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@ 123456oup.com

                History
                : 07 May 2023
                : 04 June 2023
                : 20 June 2023
                : 11 July 2023
                Page count
                Pages: 17
                Funding
                Funded by: National Natural Science Foundation of China, DOI 10.13039/501100001809;
                Award ID: 82001240
                Funded by: Natural Science Foundation of Heilongjiang Province, DOI 10.13039/501100005046;
                Award ID: YQ2021H011
                Funded by: China Postdoctoral Science Foundation, DOI 10.13039/501100002858;
                Award ID: 2020M670925
                Award ID: 2022T150172
                Funded by: Postdoctoral Foundation of Hei Long Jiang Province, DOI 10.13039/501100004027;
                Award ID: LBH‐Z19027
                Award ID: LBH‐TZ2019
                Funded by: Sichuan Provincial Administration of Traditional Chinese Medicine, DOI 10.13039/501100016350;
                Award ID: 2021MS286
                Funded by: Natural Science Foundation of Inner Mongolia, DOI 10.13039/501100004763;
                Award ID: 2019MS08185
                Categories
                Review
                AcademicSubjects/MED00385
                AcademicSubjects/MED00800
                AcademicSubjects/MED00870
                AcademicSubjects/SCI01870
                AcademicSubjects/SCI02100

                alzheimer's disease,biomarker,neuroimaging modality,diagnosis

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