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      Magnetic resonance imaging brain atrophy assessment in primary age-related tauopathy (PART)

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          Abstract

          Alzheimer disease (AD) is a neurodegenerative disorder characterized pathologically by the accumulation of amyloid-beta (Aβ) plaques and tau neurofibrillary tangles (NFTs). Recently, primary age-related tauopathy (PART) has been described as a new anatomopathological disorder where NFTs are the main feature in the absence of neuritic plaques. However, since PART has mainly been studied in post-mortem patient brains, not much is known about the clinical or neuroimaging characteristics of PART. Here, we studied the clinical brain imaging characteristics of PART focusing on neuroanatomical vulnerability by applying a previously validated multiregion visual atrophy scale. We analysed 26 cases with confirmed PART with paired clinical magnetic resonance imaging (MRI) acquisitions. In this selected cohort we found that upon correcting for the effect of age, there is increased atrophy in the medial temporal region with increasing Braak staging ( r = 0.3937, p = 0.0466). Upon controlling for Braak staging effect, predominantly two regions, anterior temporal ( r = 0.3638, p = 0.0677) and medial temporal ( r = 0.3836, p = 0.053), show a trend for increased atrophy with increasing age. Moreover, anterior temporal lobe atrophy was associated with decreased semantic memory/language ( r = − 0.5823, p = 0.0056; and r = − 0.6371, p = 0.0019, respectively), as was medial temporal lobe atrophy ( r = − 0.4445, p = 0.0435). Overall, these findings support that PART is associated with medial temporal lobe atrophy and predominantly affects semantic memory/language. These findings highlight that other factors associated with aging and beyond NFTs could be involved in PART pathophysiology.

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          Primary age-related tauopathy (PART): a common pathology associated with human aging.

          We recommend a new term, "primary age-related tauopathy" (PART), to describe a pathology that is commonly observed in the brains of aged individuals. Many autopsy studies have reported brains with neurofibrillary tangles (NFTs) that are indistinguishable from those of Alzheimer's disease (AD), in the absence of amyloid (Aβ) plaques. For these "NFT+/Aβ-" brains, for which formal criteria for AD neuropathologic changes are not met, the NFTs are mostly restricted to structures in the medial temporal lobe, basal forebrain, brainstem, and olfactory areas (bulb and cortex). Symptoms in persons with PART usually range from normal to amnestic cognitive changes, with only a minority exhibiting profound impairment. Because cognitive impairment is often mild, existing clinicopathologic designations, such as "tangle-only dementia" and "tangle-predominant senile dementia", are imprecise and not appropriate for most subjects. PART is almost universally detectable at autopsy among elderly individuals, yet this pathological process cannot be specifically identified pre-mortem at the present time. Improved biomarkers and tau imaging may enable diagnosis of PART in clinical settings in the future. Indeed, recent studies have identified a common biomarker profile consisting of temporal lobe atrophy and tauopathy without evidence of Aβ accumulation. For both researchers and clinicians, a revised nomenclature will raise awareness of this extremely common pathologic change while providing a conceptual foundation for future studies. Prior reports that have elucidated features of the pathologic entity we refer to as PART are discussed, and working neuropathological diagnostic criteria are proposed.
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            The National Alzheimer's Coordinating Center (NACC) Database: an Alzheimer disease database.

            The National Alzheimer's Coordinating Center (NACC) is responsible for developing and maintaining a database of patient information collected from the 29 Alzheimer disease centers (ADCs) funded by the National Institute on Aging. Each of the centers collects center-determined data elements on patients enrolled into its center and transmits a minimum dataset to NACC. Data are managed differently at each center depending on that center's research needs. The centers' data systems vary from a single personal computer running spreadsheet software to a network of servers running an advanced data management system such as Oracle. The challenge for NACC is to expand and adjust previously collected data elements into an integrated database that could be used for administrative as well as research purposes. In addition, NACC sought to allow the centers to have the flexibility they needed for data submission. To accomplish this task, NACC designed a database that contained separate specific datasets each with individual data elements. NACC also designed a data management system to easily collect and manage these data. The NACC web site (www.alz.washington.edu) was created to allow access to the data.
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              The Revised National Alzheimer’s Coordinating Center’s Neuropathology Form—Available Data and New Analyses

              Neuropathologic evaluation remains the gold standard for determining the presence and severity of aging-related neurodegenerative diseases. Researchers at U.S. Alzheimer’s Disease Centers (ADCs) have worked for >30 years studying human brains, with the goals of achieving new research breakthroughs. Harmonization and sharing among the 39 current and past ADCs is promoted by the National Alzheimer’s Coordinating Center (NACC), which collects, audits, and disburses ADC-derived data to investigators on request. The past decades have witnessed revised disease definitions paired with dramatic expansion in the granularity and multimodality of the collected data. The NACC database now includes cognitive test scores, comorbidities, drug history, neuroimaging, and links to genomics. Relatively, recent advances in the neuropathologic diagnoses of Alzheimer’s disease, frontotemporal lobar degeneration (FTLD), and vascular contributions to cognitive impairment and dementia catalyzed a 2014 update to the NACC Neuropathology Form completed by all ADCs. New focal points include cerebrovascular disease (including arteriolosclerosis, microbleeds, and microinfarcts), hippocampal sclerosis, TDP-43, and FTLD. Here, we provide summary data and analyses to illustrate the potential for both hypothesis-testing and also generating new hypotheses using the NACC Neuropathology data set, which represents one of the largest multi-center databases of carefully curated neuropathologic information that is freely available to researchers worldwide.
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                Author and article information

                Contributors
                tiago@med.uminho.pt
                Journal
                Acta Neuropathol Commun
                Acta Neuropathol Commun
                Acta Neuropathologica Communications
                BioMed Central (London )
                2051-5960
                9 December 2019
                9 December 2019
                2019
                : 7
                : 204
                Affiliations
                [1 ]ISNI 0000 0004 4655 1975, GRID grid.436922.8, Division of Neuroradiology, , Hospital de Braga, ; Braga, Portugal
                [2 ]ISNI 0000000122986657, GRID grid.34477.33, Department of Epidemiology, National Alzheimer’s Coordinating Center, , University of Washington, ; Seattle, Washington USA
                [3 ]ISNI 0000 0004 0635 0263, GRID grid.255951.f, School of Urban and Regional Planning, Institute for Human Health and Disease Intervention, , Florida Atlantic University, ; Boca Raton, Florida USA
                [4 ]ISNI 0000 0001 0670 2351, GRID grid.59734.3c, Department of Pathology, Nash Family Department of Neuroscience, Friedman Brain Institute, Ronald M. Loeb Center for Alzheimer’s Disease, , Icahn School of Medicine at Mount Sinai, ; New York, NY USA
                [5 ]ISNI 0000 0001 2159 175X, GRID grid.10328.38, Life and Health Sciences Research Institute (ICVS), School of Medicine, , University of Minho, ; Campus Gualtar, 4710-057 Braga, Portugal
                [6 ]ICVS/3B’s—PT Government Associate Laboratory, Braga/Guimarães, Portugal
                Author information
                http://orcid.org/0000-0003-0509-0562
                Article
                842
                10.1186/s40478-019-0842-z
                6902469
                31818331
                cf599340-c87a-4ab9-b97a-d495730ee13e
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 24 September 2019
                : 7 November 2019
                Funding
                Funded by: NIA/NIH
                Award ID: U01 AG016976
                Categories
                Research
                Custom metadata
                © The Author(s) 2019

                primary age-related tauopathy,alzheimer disease,mri,brain imaging

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