{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T16:31:16Z","timestamp":1786379476926,"version":"build-2736575974"},"reference-count":102,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Alzheimer's disease (AD) lacks effective disease-modifying therapies and scalable, ecologically valid biomarkers to monitor treatment response. Transcranial pulse stimulation (TPS) is an emerging non-invasive neuromodulation technique with potential to attenuate cognitive decline. Sensitive digital endpoints are needed to quantify intervention-related changes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To develop and validate connected-speech\u2013derived digital biomarkers as a longitudinal framework for monitoring TPS treatment response in AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this open-label, single-arm pilot study, 32 patients with AD were compared to cognitively healthy controls. A three-stage framework was implemented: (1) machine-learning classification using linguistic features to derive a parsimonious biomarker panel; (2) construction of a Speech Composite Index (SCI) calibrated against the CERAD total score (CTS); and (3) longitudinal SCI tracking in a sub-cohort receiving TPS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The classifier discriminated AD from controls with an AUROC of 0.879 and an F1-score of 0.825. The SCI showed strong convergent validity with global cognition (CTS: r\u2009=\u20090.76, p\u2009&lt;\u20090.001; MMSE: r\u2009=\u20090.76, p\u2009&lt;\u20090.001) and executive function (Stroop interference: r\u2009=\u2009\u22120.51, p\u2009=\u20090.015). Longitudinal modeling demonstrated a significant positive deviation from a CERAD-based progression reference (\u03b2_time\u2009=\u20090.057 z-units\/month, p\u2009=\u20090.013), indicating relative stabilization of speech performance. Individual trajectories were heterogeneous (range \u22120.053 to +0.336) without significant demographic associations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Connected-speech\u2013derived digital biomarkers can serve as scalable longitudinal endpoints for neuromodulatory interventions in AD. The SCI captures treatment-related dynamics and may support response stratification. Further validation in larger, sham-controlled multicenter studies is needed to establish clinical utility and specificity to TPS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877261456294","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T08:24:43Z","timestamp":1780475083000},"page":"1249-1267","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Connected-speech digital biomarkers for monitoring transcranial pulse stimulation in Alzheimer's disease: A pilot study"],"prefix":"10.1177","volume":"112","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9536-408X","authenticated-orcid":false,"given":"Daniel","family":"Wiechmann","sequence":"first","affiliation":[{"name":"Institute for Logic, Language and Computation, University of Amsterdam, Amsterdam, the Netherlands"},{"name":"Exaia Technologies, Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"G\u00fcnes","sequence":"additional","affiliation":[{"name":"Alexius\/Josef Krankenhaus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elma","family":"Kerz","sequence":"additional","affiliation":[{"name":"Exaia Technologies, Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Qiao","sequence":"additional","affiliation":[{"name":"Exaia Technologies, Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"K\u00f6hne","sequence":"additional","affiliation":[{"name":"Alexius\/Josef Krankenhaus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Sprick","sequence":"additional","affiliation":[{"name":"Alexius\/Josef Krankenhaus"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"e_1_3_3_2_2","unstructured":"World Health Organization. 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