{"doi":"10.3233/jad-220708","title":"Hypothalamic Functional Connectivity and Apathy in People with Alzheimer’s Disease and Cognitively Normal Healthy Controls","abstract":"BACKGROUND: Earlier studies have described the neural markers of apathy in Alzheimer's disease (AD) and mild cognitive impairment (MCI), but few focused on the motivation circuits. Here, we targeted hypothalamus, a hub of the motivation circuit. OBJECTIVE: To examine hypothalamic resting state functional connectivity (rsFC) in relation to apathy. METHODS: We performed whole-brain regression of hypothalamic rsFC against Apathy Evaluation Scale (AES) total score and behavioral, cognitive, and emotional subscores in 29 patients with AD/MCI and 28 healthy controls (HC), controlling for age, sex, education, cognitive status, and depression. We evaluated the results at a corrected threshold and employed path analyses to assess possible interaction between hypothalamic rsFCs, apathy and depression/memory. Finally, we re-examined the findings in a subsample of amyloid-β-verified AD. RESULTS: AES total score correlated negatively with hypothalamic precuneus (PCu)/posterior cingulate cortex (PCC) and positively with left middle temporal gyrus (MTG) and supramarginal gyrus rsFCs. Behavioral subscore correlated negatively with hypothalamic PCu/PCC and positively with middle frontal gyrus rsFC. Cognitive subscore correlated positively with hypothalamic MTG rsFC. Emotional subscore correlated negatively with hypothalamic calcarine cortex rsFC. In path analyses, hypothalamic-PCu/PCC rsFC negatively modulated apathy and, in turn, depression. The model where hypothalamic MTG rsFC and memory independently modulated apathy also showed a good fit. The findings of diminished hypothalamic-PCu/PCC rsFC in relation to apathy and, in turn, depression were confirmed in amyloid-verified AD. CONCLUSION: The findings together support a role of altered hypothalamic connectivity in relation to apathy and depression, and modulation of apathy by memory dysfunction.","journal":"Journal of Alzheimer s Disease","year":2022,"id":258023,"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":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8893,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":320092,"name":"Simon Zhornitsky","orcid":"0000-0003-2024-7062","position":1,"is_corresponding":false},{"id":523572,"name":"Herta H. Chao","orcid":"0000-0002-4827-6757","position":2,"is_corresponding":false},{"id":235262,"name":"Christopher H. van Dyck","orcid":"0000-0003-1779-097X","position":3,"is_corresponding":false},{"id":320093,"name":"Chiang‐Shan R. Li","orcid":"0000-0002-9393-1212","position":4,"is_corresponding":false},{"id":712607,"name":"Shefali Chaudhary","orcid":"0000-0003-4505-0506","position":0,"is_corresponding":true}],"reference_count":106,"raw_metadata":null,"created_at":"2026-07-19T00:25:38.634785Z","pmid":"36314209","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":[]}