{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T15:47:26Z","timestamp":1790264846449,"version":"4.1.0"},"reference-count":13,"publisher":"SAGE Publications","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2021,4,20]]},"abstract":"<jats:p>As an established treatment for movement disorders, deep brain stimulation (DBS) has been adapted for the treatment of Alzheimer\u2019s disease (AD) by modulating fornix activity. Although it is generally regarded as a safe intervention in patients over 65 years of age, the complex neurophysiology and interconnection within circuits connected to the fornix warrants a careful ongoing evaluation of the true benefit and risk potential of DBS on slowing cognitive decline in AD patients. Here we report on a patient who died long after being implanted with a DBS device who donated her brain for neuropathologic study. The autopsy confirmed multiple proteinopathies including AD-related change, diffuse neocortical Lewy body disease, TDP-43 proteinopathy, and a nonspecific tauopathy. We discuss the possible mechanisms of these overlapping neurodegenerative disorders and caution that future studies of DBS for AD will need to take these findings into consideration.<\/jats:p>","DOI":"10.3233\/jad-201415","type":"journal-article","created":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T12:40:50Z","timestamp":1614948050000},"page":"1383-1387","source":"Crossref","is-referenced-by-count":2,"title":["Multiple Neurodegenerative Pathologies in an Alzheimer\u2019s Disease Patient Treated with Fornical Deep Brain Stimulation"],"prefix":"10.1177","volume":"80","author":[{"given":"Bartholomew","family":"White","sequence":"first","affiliation":[{"name":"Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA"},{"name":"Current affiliation: Department of Pathology, Emory School of Medicine, Atlanta, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantine G.","family":"Lyketsos","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul B.","family":"Rosenberg","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther S.","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA"},{"name":"Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liam","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA"},{"name":"Current affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","reference":[{"key":"10.3233\/JAD-201415_ref1","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1002\/ana.22089","article-title":"A phase I trial of deep brain stimulation of memory circuits in Alzheimer\u2019s disease","volume":"68","author":"Laxton","year":"2010","journal-title":"Ann Neurol"},{"key":"10.3233\/JAD-201415_ref2","doi-asserted-by":"crossref","first-page":"777","DOI":"10.3233\/JAD-160017","article-title":"A phase II study of fornix deep brain stimulation in mild Alzheimer\u2019s disease","volume":"54","author":"Lozano","year":"2016","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-201415_ref3","doi-asserted-by":"crossref","first-page":"597","DOI":"10.3233\/JAD-180121","article-title":"Deep brain stimulation targeting the fornix for mild Alzheimer dementia (the ADvance Trial): A 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management of dementia with Lewy bodies: Third report of the DLB Consortium","volume":"65","author":"McKeith","year":"2005","journal-title":"Neurology"},{"key":"10.3233\/JAD-201415_ref7","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s00401-011-0845-8","article-title":"A harmonized classification system for FTLD-TDP pathology","volume":"122","author":"Mackenzie","year":"2011","journal-title":"Acta Neuropathol"},{"key":"10.3233\/JAD-201415_ref8","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1093\/brain\/awz099","article-title":"Limbic-predominant age-related TDP-43 encephalopathy (LATE): Consensus working group report","volume":"142","author":"Nelson","year":"2019","journal-title":"Brain"},{"key":"10.3233\/JAD-201415_ref9","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s00401-007-0261-2","article-title":"Co-morbidity of TDP-43 proteinopathy in Lewy body related diseases","volume":"114","author":"Nakashima-Yasuda","year":"2007","journal-title":"Acta Neuropathol"},{"key":"10.3233\/JAD-201415_ref10","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1002\/ana.25246","article-title":"Combined neuropathological pathways account for age-related risk of dementia","volume":"84","author":"Power","year":"2018","journal-title":"Ann Neurol"},{"key":"10.3233\/JAD-201415_ref11","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/s00441-017-2672-2","article-title":"Postmortem studies of deep brain stimulation for Parkinson\u2019s disease: A systematic review of the literature","volume":"373","author":"Reddy","year":"2018","journal-title":"Cell Tissue Res"},{"key":"10.3233\/JAD-201415_ref12","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.brs.2017.11.012","article-title":"Chronic deep brain stimulation in an Alzheimer\u2019s disease mouse model enhances memory and reduces pathological hallmarks","volume":"11","author":"Mann","year":"2018","journal-title":"Brain Stimul"},{"key":"10.3233\/JAD-201415_ref13","doi-asserted-by":"crossref","first-page":"2493","DOI":"10.1038\/npp.2017.100","article-title":"Entorhinal cortical deep brain stimulation rescues memory deficits in both young and old mice genetically engineered to model Alzheimer\u2019s disease","volume":"42","author":"Xia","year":"2017","journal-title":"Neuropsychopharmacology"}],"container-title":["Journal of Alzheimer's 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