{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T02:35:01Z","timestamp":1792636501190,"version":"4.5.0"},"reference-count":175,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T00:00:00Z","timestamp":1663804800000},"content-version":"vor","delay-in-days":264,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["A&amp;D Transl Res &amp; Clin Interv"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Coronavirus disease 2019 (COVID\u201019) has caused &gt;3.5 million deaths worldwide and affected &gt;160 million people. At least twice as many have been infected but remained asymptomatic or minimally symptomatic. COVID\u201019 includes central nervous system manifestations mediated by inflammation and cerebrovascular, anoxic, and\/or viral neurotoxicity mechanisms. More than one third of patients with COVID\u201019 develop neurologic problems during the acute phase of the illness, including loss of sense of smell or taste, seizures, and stroke. Damage or functional changes to the brain may result in chronic sequelae. The risk of incident cognitive and neuropsychiatric complications appears independent from the severity of the original pulmonary illness. It behooves the scientific and medical community to attempt to understand the molecular and\/or systemic factors linking COVID\u201019 to neurologic illness, both short and long term.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This article describes what is known so far in terms of links among COVID\u201019, the brain, neurological symptoms, and Alzheimer's disease (AD) and related dementias. We focus on risk factors and possible molecular, inflammatory, and viral mechanisms underlying neurological injury. We also provide a comprehensive description of the Alzheimer's Association Consortium on Chronic Neuropsychiatric Sequelae of SARS\u2010CoV\u20102 infection (CNS SC2) harmonized methodology to address these questions using a worldwide network of researchers and institutions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Successful harmonization of designs and methods was achieved through a consensus process initially fragmented by specific interest groups (epidemiology, clinical assessments, cognitive evaluation, biomarkers, and neuroimaging). Conclusions from subcommittees were presented to the whole group and discussed extensively. Presently data collection is ongoing at 19 sites in 12 countries representing Asia, Africa, the Americas, and Europe.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>The Alzheimer's Association Global Consortium harmonized methodology is proposed as a model to study long\u2010term neurocognitive sequelae of SARS\u2010CoV\u20102 infection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>The following review describes what is known so far in terms of molecular and epidemiological links among COVID\u201019, the brain, neurological symptoms, and AD and related dementias (ADRD)<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The primary objective of this large\u2010scale collaboration is to clarify the pathogenesis of ADRD and to advance our understanding of the impact of a neurotropic virus on the long\u2010term risk of cognitive decline and other CNS sequelae. No available evidence supports the notion that cognitive impairment after SARS\u2010CoV\u20102 infection is a form of dementia (ADRD or otherwise). The longitudinal methodologies espoused by the consortium are intended to provide data to answer this question as clearly as possible controlling for possible confounders. Our specific hypothesis is that SARS\u2010CoV\u20102 triggers ADRD\u2010like pathology following the extended olfactory cortical network (EOCN) in older individuals with specific genetic susceptibility.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The proposed harmonization strategies and flexible study designs offer the possibility to include large samples of under\u2010represented racial and ethnic groups, creating a rich set of harmonized cohorts for future studies of the pathophysiology, determinants, long\u2010term consequences, and trends in cognitive aging, ADRD, and vascular disease.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>We provide a framework for current and future studies to be carried out within the Consortium. and offers a \u201cgreen paper\u201d to the research community with a very broad, global base of support, on tools suitable for low\u2010 and middle\u2010income countries aimed to compare and combine future longitudinal data on the topic.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The Consortium proposes a combination of design and statistical methods as a means of approaching causal inference of the COVID\u201019 neuropsychiatric sequelae. We expect that deep phenotyping of neuropsychiatric sequelae may provide a series of candidate syndromes with phenomenological and biological characterization that can be further explored. By generating high\u2010quality harmonized data across sites we aim to capture both descriptive and, where possible, causal associations.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/trc2.12348","type":"journal-article","created":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T07:01:44Z","timestamp":1663830104000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Chronic neuropsychiatric sequelae of SARS\u2010CoV\u20102: Protocol and methods from the Alzheimer's Association Global Consortium"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6423-4461","authenticated-orcid":false,"given":"Gabriel A.","family":"de Erausquin","sequence":"first","affiliation":[{"name":"The Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases Joe and Teresa Long School of Medicine University of Texas Health San Antonio  San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"Snyder","sequence":"additional","affiliation":[{"name":"Alzheimer's Association  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Traolach S.","family":"Brugha","sequence":"additional","affiliation":[{"name":"University of Leicester  Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudha","family":"Seshadri","sequence":"additional","affiliation":[{"name":"The Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases Joe and Teresa Long School of Medicine University of Texas Health San Antonio  San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Carrillo","sequence":"additional","affiliation":[{"name":"Alzheimer's Association  Chicago Illinois 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