{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:29:10Z","timestamp":1791919750946,"version":"4.3.4"},"reference-count":106,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T00:00:00Z","timestamp":1750809600000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>INTRODUCTION<\/jats:title><jats:p>Deep brain stimulation of the fornix (fx\u2010DBS) is being investigated for treatment of Alzheimer's disease (AD). The therapy aims at alleviating memory and cognitive circuit dysfunction. In preclinical models of AD, electrical stimulation of the memory circuit has demonstrated a possible disease\u2010modifying potential. Here we examined changes resulting from fx\u2010DBS in hippocampal atrophy and amyloid accumulation in AD patients with fx\u2010DBS.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Repeated magnetic resonance imaging and positron emission tomography (PET) images acquired over the course of 12 months were used to assess changes in hippocampal volume in 36 ADvance trial patients compared to 40 matched untreated AD patients from the Alzheimer's Disease Neuroimaging Initiative, and in 10 separate patients with repeated flutemetamol PET and cerebrospinal fluid (CSF) markers.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>We observed a reduction of hippocampal atrophy and amyloid beta (A\u03b2) PET binding, and an increase in the CSF A\u03b2\/total\u2010tau ratio in DBS patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>These findings highlight the potential of fornix deep brain stimulation to modify AD biomarkers and possibly progression in some patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Fornix deep brain stimulation (fx\u2010DBS) is being investigated to treat Alzheimer's disease (AD).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Results show that fx\u2010DBS modifies imaging and cerebrospinal fluid (CSF) markers.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>It reduces hippocampal atrophy and increases the amyloid beta\/total\u2010tau CSF ratio.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These findings highlight the potential of fx\u2010DBS to modify AD.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.70394","type":"journal-article","created":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T02:30:37Z","timestamp":1750905037000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Biomarker changes associated with fornix deep brain stimulation in Alzheimer's disease"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0995-8226","authenticated-orcid":false,"given":"J\u00fcrgen","family":"Germann","sequence":"first","affiliation":[{"name":"Division of Neurosurgery, Department of Surgery University Health Network University of Toronto  Toronto Ontario Canada"},{"name":"Krembil Research Institute University Health Network  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert S. 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