{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T16:31:21Z","timestamp":1786379481059,"version":"build-2736575974"},"reference-count":59,"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"}],"funder":[{"name":"Hilary and Galen Weston Foundation"},{"name":"Temerty-Tanz-TDRA"},{"name":"TDRA-MITO2i"}],"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>Mild cognitive impairment (MCI), a prodromal stage of Alzheimer's disease and related dementias (ADRD), represents a critical window for intervention. Although mitochondrial dysfunction is increasingly implicated in neurodegeneration, most therapies target downstream protein aggregation. Transcranial photobiomodulation (tPBM) delivers near-infrared light to enhance mitochondrial respiration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We hypothesized that tPBM in MCI would be safe, feasible, and associated with improvements in cognition, mitochondrial function, and default mode network (DMN) functional connectivity (FC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a single-blind, randomized, sham-controlled pilot trial (NCT05563298) in adults \u226550 years with MCI. Twenty participants were randomized 1:1 to active or sham devices. Active devices delivered pulsed 810-nm light for 20\u2005min per session; shams emitted light for 2\u2005seconds. Stimulation targeted DMN hubs and the olfactory bulb. Participants self-administered treatment at home six days per week for six weeks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Adherence was high (active 96.9%; sham 94.2%). Adverse events (AEs) were reported by 10 of 20 participants (4 active, 6 sham). No serious AEs occurred. Compared with sham, active tPBM produced greater improvement in global cognition (Mini-Mental State Examination; p\u2009=\u20090.03, d = 1.05) and episodic memory (California Verbal Learning Test-II long-delay recognition; p\u2009=\u20090.02, d = 1.09). Serum pyruvate and lactate increased with a reduced lactate-to-pyruvate (L\/P) ratio (p\u2009=\u20090.007, d = -1.37). DMN FC increased (p\u2009=\u20090.014, d = 1.25), and plasma IL-6 declined (p\u2009=\u20090.02, r = -0.52).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Home-based tPBM was safe, well tolerated, and feasible, with high adherence and mild AEs. Cognitive, metabolic, and network-level findings are consistent with enhanced mitochondrial efficiency and anti-inflammatory effects. These results support larger, double-blind, multicenter trials to evaluate tPBM as a mitochondria-targeted therapy in early ADRD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877261453911","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T08:30:27Z","timestamp":1780475427000},"page":"1445-1458","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["A multimodal evaluation of transcranial photobiomodulation in mild cognitive impairment: Cognitive, metabolic, and neuroimaging outcomes of a pilot randomized controlled trial"],"prefix":"10.1177","volume":"112","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2125-1090","authenticated-orcid":false,"given":"Neda","family":"Rashidi-Ranjbar","sequence":"first","affiliation":[{"name":"Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, ON, 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