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However, the neuroanatomical changes underpinning ALF remain undetermined. Eighteen presymptomatic autosomal dominant AD mutation carriers and 12 non-carriers underwent ALF assessment with a list, a story, and visual figure, testing 30-min and 7-day recall of each, separately. T1 and diffusion-weighted MRI were acquired. Cortical thickness was estimated for 13 pre-defined grey matter regions, with streamline tractography assessing associated structural connectivity. In mutation carriers, lower verbal ALF performance (list and story) was strongly associated with thinner prefrontal cortex (PFC) across four contiguous regions bilaterally. This association was absent in non-carriers. No associations were found between ALF and the thickness\/volume of medial temporal lobe (MTL) structures. The association between ALF and PFC connectivity was weaker than for cortical thickness. Our results suggest that early subtle pathological change in PFC underpins ALF development, highlighting the central role of PFC dysfunction in very early AD-related cognitive decline. ALF may represent a qualitatively different (non-MTL driven) form of forgetting compared with the short interval forgetting that develops at later disease stages.<\/jats:p>","DOI":"10.1093\/braincomms\/fcaf478","type":"journal-article","created":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T12:53:41Z","timestamp":1765025621000},"source":"Crossref","is-referenced-by-count":2,"title":["Accelerated forgetting in presymptomatic Alzheimer\u2019s: mediation by prefrontal cortical degeneration"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1616-2886","authenticated-orcid":false,"given":"Christopher S","family":"Parker","sequence":"first","affiliation":[{"name":"Dementia Research Centre, UCL Queen Square Institute of Neurology , London, WC1N 3AR ,","place":["UK"]},{"name":"UCL Hawkes Institute, Department of Computer Science , London, WC1V 6LJ 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,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian J","family":"Crutch","sequence":"additional","affiliation":[{"name":"Dementia Research Centre, UCL Queen Square Institute of Neurology , London, WC1N 3AR ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick C","family":"Fox","sequence":"additional","affiliation":[{"name":"Dementia Research Centre, UCL Queen Square Institute of Neurology , London, WC1N 3AR ,","place":["UK"]},{"name":"UK Dementia Research Institute at UCL , London, NW1 3BT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip S J","family":"Weston","sequence":"additional","affiliation":[{"name":"Dementia Research Centre, UCL Queen Square Institute of Neurology , London, WC1N 3AR ,","place":["UK"]},{"name":"UK Dementia Research Institute at UCL , London, NW1 3BT 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