{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T03:14:40Z","timestamp":1788146080472,"version":"build-2803163510"},"reference-count":54,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":58,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["A&amp;amp;D Transl Res &amp;amp; Clin Interv"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Alzheimer's disease (AD) pathological processes begin decades before symptom onset. Early intervention in high\u2010risk populations may be crucial for prevention. We investigated the effect of an intervention utilizing virtual reality (VR) cognitive\u2010motor training on cerebral blood flow (CBF) and cognitive functioning in middle\u2010aged adults at high AD risk due to parental history.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      In this randomized controlled trial, participants (\n                      <jats:italic>n<\/jats:italic>\n                      = 79) were randomly assigned to: VR cognitive\u2013motor training while walking on a treadmill (VR+T,\n                      <jats:italic>n<\/jats:italic>\n                      = 24, treatment); VR cognitive training without treadmill (VR\u2010T,\n                      <jats:italic>n<\/jats:italic>\n                      = 21, active control); treadmill walking while watching documentaries (TV+T,\n                      <jats:italic>n<\/jats:italic>\n                      = 20, active control); or no intervention (\n                      <jats:italic>n<\/jats:italic>\n                      = 14, passive control). Training consisted of 45\u2010min sessions, twice weekly, for 12 weeks. CBF was measured at resting state using arterial spin labeling (ASL) at baseline, 3\u2010month, and 6\u2010month follow\u2010up. Cognition was assessed using a comprehensive neuropsychological battery. We applied the intent\u2010to\u2010treat approach.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      All groups improved in executive functions and memory over time (all\n                      <jats:italic>p<\/jats:italic>\n                      \u2010values &lt; 0.05), with no consistent between\u2010group differences at follow\u2010up. CBF of the VR+T group significantly increased at 3 months in the superior (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.013, middle (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.014), and inferior (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.003) frontal gyri compared to the passive control group, which showed a decline in CBF over the same period. No significant differences in frontal CBF change were observed between VR+T and the TV+T active control group. This increase was sustained for 6 months in the superior (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.035) and middle (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.028) frontal gyri. In contrast, in the middle temporal gyrus, the VR+T group had lower CBF at 3 months, compared to the VR\u2010T (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.033) and to the passive control groups (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.004).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Cognitive\u2010motor VR training increased CBF in frontal regions susceptible to early AD\u2010related changes in middle\u2010aged adults at high AD risk. This intervention shows promise as a preventive approach and may be suitable for implementation as a home\u2010based program for individuals at high risk.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/trc2.70265","type":"journal-article","created":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T06:06:55Z","timestamp":1780121215000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Virtual reality\u2010based cognitive\u2010motor training in middle\u2010aged adults at high Alzheimer's disease risk improves frontal cortex cerebral blood flow: A randomized controlled trial"],"prefix":"10.1002","volume":"12","author":[{"given":"Maayan","family":"Harel","sequence":"first","affiliation":[{"name":"Social Cognitive &amp; Affective Neuroscience (SCAN) Center Department of Psychology Bar\u2010Ilan University  Ramat Gan Israel"},{"name":"Clinical Brain Imaging R&amp;D (C.BIRD) Center Division of Diagnostic 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