{"doi":"10.3233/jad-221178","title":"Brain Derived Neurotrophic Factor Interacts with White Matter Hyperintensities to Influence Processing Speed and Hippocampal Volume in Older Adults","abstract":"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's Disease Neuroimaging Initiative (N = 454 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 ɛ4 carrier status, there was a significant interaction between total WMH and BDNF on bilateral hippocampal volume in the non-T2DM group (t = 2.63, p = 0.009). Examination of main effect models with a dichotomous high/low BNDF group revealed a significant main effect for low BDNF (t = -4.98, p < 0.001), 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 = 2.91, p = 0.004). There was a significant main effect for low BDNF (t = -3.55, p < 0.001) 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.","journal":"Journal of Alzheimer s Disease","year":2023,"id":365327,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9657,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":243718,"name":"for the Alzheimer’s Disease Neuroimaging Initiative","orcid":null,"position":1,"is_corresponding":false},{"id":316752,"name":"Alexandra J. Weigand","orcid":"0000-0002-7931-1383","position":2,"is_corresponding":false},{"id":300910,"name":"Lauren Edwards","orcid":"0000-0002-8434-9669","position":3,"is_corresponding":false},{"id":316753,"name":"Kelsey R. Thomas","orcid":"0000-0003-4277-8876","position":4,"is_corresponding":false},{"id":336798,"name":"Emily C. Edmonds","orcid":"0000-0002-5130-0500","position":5,"is_corresponding":false},{"id":316758,"name":"Mark W. Bondi","orcid":"0000-0002-1742-3451","position":6,"is_corresponding":false},{"id":316754,"name":"Katherine J. Bangen","orcid":"0000-0002-1363-3179","position":7,"is_corresponding":false},{"id":905843,"name":"Einat K. Brenner","orcid":"0000-0002-0172-8277","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-19T01:14:46.760245Z","pmid":"36970903","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}