{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:08:13Z","timestamp":1777396093066,"version":"3.51.4"},"reference-count":50,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2023,5,2]],"date-time":"2023-05-02T00:00:00Z","timestamp":1682985600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2023,5,2]]},"abstract":"<jats:p>Background: Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays an important role in regulating synaptic activity and plasticity. Objective: Given that type-2 diabetes (T2DM) increases the risk of cognitive decline, and studies have suggested lower BDNF levels may be a risk factor of diabetic neurovascular complications, we sought to investigate total white matter hyperintensities (WMH) as a moderator of the effect of BDNF on hippocampal volume and cognition. Methods: Older adults without dementia from the Alzheimer\u2019s Disease Neuroimaging Initiative (N\u200a=\u200a454 including 49 with T2DM and 405 without diabetes) underwent neuropsychological evaluation, magnetic resonance imaging to quantify hippocampal and WMH volumes, and blood draw to assess BDNF. Results: Adjusting for age, sex, and APOE \u025b4 carrier status, there was a significant interaction between total WMH and BDNF on bilateral hippocampal volume in the non-T2DM group (t\u200a=\u200a2.63, p\u200a=\u200a0.009). Examination of main effect models with a dichotomous high\/low BNDF group revealed a significant main effect for low BDNF (t\u200a=\u200a\u20134.98, p\u200a&lt;\u200a0.001), such that as WMH increased, bilateral hippocampal volume decreased. There was also a significant interaction between total WMH and BDNF on processing speed in the non-T2DM group (t\u200a=\u200a2.91, p\u200a=\u200a0.004). There was a significant main effect for low BDNF (t\u200a=\u200a\u20133.55, p\u200a&lt;\u200a0.001) such that as WMH increased, processing speed decreased. The interactions were not significant in the T2DM group. Conclusion: These results further elucidate the protective role that BDNF plays on cognition, as well as the cognitive effects of WMH.<\/jats:p>","DOI":"10.3233\/jad-221178","type":"journal-article","created":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T12:24:56Z","timestamp":1679401496000},"page":"141-149","source":"Crossref","is-referenced-by-count":6,"title":["Brain Derived Neurotrophic Factor Interacts with White Matter Hyperintensities to Influence Processing Speed and Hippocampal Volume in Older Adults"],"prefix":"10.1177","volume":"93","author":[{"given":"Einat K.","family":"Brenner","sequence":"first","affiliation":[{"name":"Department of Psychiatry, University of California San Diego, La Jolla, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"for the Alzheimer\u2019s Disease Neuroimaging Initiative","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra J.","family":"Weigand","sequence":"additional","affiliation":[{"name":"San Diego State University\/UC San Diego Joint Doctoral Program in Clinical Psychology, San Diego, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauren","family":"Edwards","sequence":"additional","affiliation":[{"name":"San Diego State University\/UC San Diego Joint Doctoral Program in Clinical Psychology, San Diego, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelsey R.","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of California San Diego, La Jolla, CA, USA"},{"name":"Research Service, VA San Diego Healthcare System, San Diego, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily C.","family":"Edmonds","sequence":"additional","affiliation":[{"name":"Banner Alzheimer\u2019s Institute, Tucson, AZ, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark 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