{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T18:04:54Z","timestamp":1766599494330,"version":"build-2065373602"},"reference-count":66,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T00:00:00Z","timestamp":1626393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Comorbid occurrence of tinnitus and emotional symptoms of anxiety and depression is highly prevalent. The Ginkgo biloba extract EGb 761\u00ae has been shown to be effective in reducing neuropsychiatric symptoms in patients with dementia and tinnitus. Methods: We performed a mediation analysis to evaluate direct effects of EGb 761\u00ae on tinnitus severity, as well as indirect effects mediated by symptoms of depression and anxiety and by changed cognition. We pooled data from subsets of patients suffering from tinnitus that were enrolled in three double-blind, randomized, placebo-controlled clinical trials, which investigated the efficacy of EGb 761\u00ae (240 mg\/day for 22\u201324 weeks) in dementia with concomitant neuropsychiatric symptoms. Results: In total, 594 patients suffered from tinnitus (EGb 761\u00ae, 289; placebo, 305). Direct effects of EGb 761\u00ae on tinnitus severity (p &lt; 0.001) in patients with mild to moderate dementia were found to represent about 60% of the total effect, whereas the indirect effects (p &lt; 0.001) mediated by improvement of anxiety, depression and cognition represented about 40% of the total effect. Conclusions: EGb 761\u00ae could be considered as a supporting treatment for tinnitus in elderly patients suffering from dementia, with added benefit in those with symptoms of depression or anxiety.<\/jats:p>","DOI":"10.3390\/jcm10143151","type":"journal-article","created":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T10:52:58Z","timestamp":1626432778000},"page":"3151","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The Influence of Depression, Anxiety and Cognition on the Treatment Effects of Ginkgo biloba Extract EGb 761\u00ae in Patients with Tinnitus and Dementia: A Mediation Analysis"],"prefix":"10.3390","volume":"10","author":[{"given":"Petra","family":"Br\u00fcggemann","sequence":"first","affiliation":[{"name":"Tinnitus Center, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00edlia","family":"S\u00f3ria","sequence":"additional","affiliation":[{"name":"Medical Scientific Services, Dr. Willmar Schwabe GmbH & Co. KG, 76227 Karlsruhe, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8182-2572","authenticated-orcid":false,"given":"Juliette","family":"Brandes-Schramm","sequence":"additional","affiliation":[{"name":"Medical Scientific Services, Dr. Willmar Schwabe GmbH & Co. KG, 76227 Karlsruhe, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9587-6632","authenticated-orcid":false,"given":"Birgit","family":"Mazurek","sequence":"additional","affiliation":[{"name":"Tinnitus Center, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1007\/s00106-019-0633-7","article-title":"A multidisciplinary European guideline for tinnitus: Diagnostics, assessment, and treatment","volume":"67","author":"Cima","year":"2019","journal-title":"HNO"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.jalz.2014.04.514","article-title":"At the interface of sensory and motor dysfunctions and Alzheimer\u2019s disease","volume":"11","author":"Albers","year":"2015","journal-title":"Alzheimer Dement."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Jafari, Z., Kolb, B.E., and Mohajerani, M.H. (2019). Age-related hearing loss and tinnitus, dementia risk, and auditory amplification outcomes. Ageing Res. Rev., 56.","DOI":"10.1016\/j.arr.2019.100963"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Neff, P., Sim\u00f5es, J., Psatha, S., Nyamaa, A., Boecking, B., Rausch, L., Dettling-Papargyris, J., Funk, C., Brueggemann, P., and Mazurek, B. (2021). The impact of tinnitus distress on cognition. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-81728-0"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.2147\/CIA.S157877","article-title":"Ginkgo biloba extract EGb 761\u00ae alleviates neurosensory symptoms in patients with dementia: A meta-analysis of treatment effects on tinnitus and dizziness in randomized, placebo-controlled trials","volume":"13","author":"Spiegel","year":"2018","journal-title":"Clin. Interv. Aging"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"68","DOI":"10.5935\/0946-5448.20170013","article-title":"Tinnitus Patients Suffering from Anxiety and Depression: A Review","volume":"21","author":"Ziai","year":"2017","journal-title":"Int. Tinnitus J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1007\/s11136-012-0338-9","article-title":"Analysis of mental disorders in tinnitus patients performed with Composite International Diagnostic Interview","volume":"22","author":"Zirke","year":"2013","journal-title":"Qual. Life Res."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Salviati, M., Bersani, F.S., Valeriani, G., Minichino, A., Panico, R., Romano, G.F., Mazzei, F., Testugini, V., Altissimi, G., and Cianfrone, G. (2014). A Brain Centred View of Psychiatric Comorbidity in Tinnitus: From Otology to Hodology. Neural Plast., 2014.","DOI":"10.1155\/2014\/817852"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"29","DOI":"10.5935\/0946-5448.20130005","article-title":"The relationship of perceived severity of tinnitus with depression, anxiety, hearing status, age and gender in individuals with tinnitus","volume":"18","author":"Udupi","year":"2013","journal-title":"Int. Tinnitus J."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Br\u00fcggemann, P., Szczepek, A.J., Rose, M., McKenna, L., Olze, H., and Mazurek, B. (2016). Impact of Multiple Factors on the Degree of Tinnitus Distress. Front. Hum. Neurosci., 10.","DOI":"10.3389\/fnhum.2016.00341"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"76","DOI":"10.5935\/0946-5448.20160015","article-title":"Relationship between Subjective Tinnitus Perception and Psychiatric Discomfort","volume":"20","author":"Fetoni","year":"2016","journal-title":"Int. Tinnitus J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.heares.2015.08.005","article-title":"Auditory\u2013limbic interactions in chronic tinnitus: Challenges for neuroimaging research","volume":"334","author":"Leaver","year":"2016","journal-title":"Hear. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"413","DOI":"10.2147\/NDT.S77786","article-title":"Coexistence of anxiety sensitivity and psychiatric comorbidities in patients with chronic tinnitus","volume":"11","author":"Gul","year":"2015","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"34","DOI":"10.4306\/pi.2018.15.1.34","article-title":"Effects of Anxiety Sensitivity and Hearing Loss on Tinnitus Symptom Severity","volume":"15","author":"Moon","year":"2018","journal-title":"Psychiatry Investig."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Folmer, R.L. (2002). Long-term reductions in tinnitus severity. BMC Ear Nose Throat Disord., 2.","DOI":"10.1186\/1472-6815-2-3"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/bs.pbr.2021.01.028","article-title":"On the relationship between tinnitus distress, cognitive performance and aging","volume":"262","author":"Brueggemann","year":"2021","journal-title":"Prog. Brain Res."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Ruan, Q., Yu, Z., Zhang, W., Ruan, J., Liu, C., and Zhang, R. (2018). Cholinergic Hypofunction in Presbycusis-Related Tinnitus with Cognitive Function Impairment: Emerging Hypotheses. Front. Aging Neurosci., 10.","DOI":"10.3389\/fnagi.2018.00098"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"15220","DOI":"10.1038\/s41598-017-15574-4","article-title":"Identification of a Neurocognitive Mechanism Underpinning Awareness of Chronic Tinnitus","volume":"7","author":"Trevis","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.clinph.2016.12.028","article-title":"Selective attentional impairment in chronic tinnitus: Evidence from an event-related potentials study","volume":"128","author":"Mannarelli","year":"2017","journal-title":"Clin. Neurophysiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.cpr.2017.12.006","article-title":"A systematic review and meta-analysis of psychological functioning in chronic tinnitus","volume":"60","author":"Trevis","year":"2018","journal-title":"Clin. Psychol. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1146\/annurev-pharmtox-010818-021556","article-title":"Therapeutic Approaches to the Treatment of Tinnitus","volume":"59","author":"Langguth","year":"2019","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Baldo, P., Dor\u00e9e, C., Molin, P., McFerran, D., and Cecco, S. (2012). Antidepressants for patients with tinnitus. Cochrane Database Syst. Rev., 2012.","DOI":"10.1002\/14651858.CD003853.pub3"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"S14","DOI":"10.1017\/S0022215115000808","article-title":"The use of benzodiazepines for tinnitus: Systematic review","volume":"129","author":"Jufas","year":"2015","journal-title":"J. Laryngol. Otol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Wegner, I., Hall, D.A., Smit, A.L., McFerran, D., and Stegeman, I. (2018). Betahistine for tinnitus. Cochrane Database Syst. Rev., 2018.","DOI":"10.1002\/14651858.CD013093.pub2"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Wagner, H., and Ulrich-Merzenich, G. (2013). Ginkgo biloba Extract EGb 761\u00ae: From an Ancient Asian Plant to a Modern European Herbal Medicinal Product. Evidence and Rational Based Research on Chinese Drugs, Springer Vienna.","DOI":"10.1007\/978-3-7091-0442-2"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.biopha.2016.11.013","article-title":"Long-term pre-treatment of antioxidant Ginkgo biloba extract EGb-761 attenuates cerebral-ischemia-induced neuronal damage in aged mice","volume":"85","author":"Zhou","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/BF00504988","article-title":"Effect of an extract of Ginkgo biloba on rat brain energy metabolism in hypoxia","volume":"327","author":"Karcher","year":"1984","journal-title":"Naunyn-Schmiedeberg Arch. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.phrs.2007.09.011","article-title":"Stabilization of mitochondrial function by Ginkgo biloba extract (EGb 761)","volume":"56","author":"Hauptmann","year":"2007","journal-title":"Pharmacol. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"25","DOI":"10.2174\/1389450003349380","article-title":"Ginkgo Biloba Extract (EGb 761) and CNS Functions Basic Studies and Clinical Applications","volume":"1","author":"DeFeudis","year":"2000","journal-title":"Curr. Drug Targets"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"S21","DOI":"10.1017\/S1041610212000592","article-title":"Effects of the standardized Ginkgo biloba extract EGb 761\u00ae on neuroplasticity","volume":"24","author":"Heiser","year":"2012","journal-title":"Int. Psychogeriatr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.phrs.2009.02.012","article-title":"Ginkgo biloba extract (EGb761\u00ae) influences monoaminergic neurotransmission via inhibition of NE uptake, but not MAO activity after chronic treatment","volume":"60","author":"Fehske","year":"2009","journal-title":"Pharmacol. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1111\/j.1476-5381.2009.00580.x","article-title":"The Ginkgo biloba extract EGb 761\u00ae and its main constituent flavonoids and ginkgolides increase extracellular dopamine levels in the rat prefrontal cortex","volume":"159","author":"Yoshitake","year":"2010","journal-title":"Br. J. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1016\/j.neuint.2011.05.007","article-title":"Antidepressant-like effect of a Ginkgo biloba extract (EGb761) in the mouse forced swimming test: Role of oxidative stress","volume":"59","author":"Rojas","year":"2011","journal-title":"Neurochem. Int."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"S25","DOI":"10.1017\/S1041610212000567","article-title":"Ginkgo biloba leaf extract (EGb 761\u00ae) and its specific acylated flavonol constituents increase dopamine and acetylcholine levels in the rat medial prefrontal cortex: Possible implications for the cognitive enhancing properties of EGb 761\u00ae","volume":"24","author":"Kehr","year":"2012","journal-title":"Int. Psychogeriatr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.neulet.2009.07.089","article-title":"Improvement of auditory discrimination learning by Ginkgo biloba extract EGb 761\u00ae","volume":"463","author":"Moeller","year":"2009","journal-title":"Neurosci. Lett."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1016\/0091-3057(90)90107-S","article-title":"Effects of an extract of Ginkgo Biloba (EGB 761) on \u201clearned helplessness\u201d and other models of stress in rodents","volume":"36","author":"Porsolt","year":"1990","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_37","first-page":"441","article-title":"Ginkgo biloba extract in the treatment of tinnitus: A systematic review","volume":"7","year":"2011","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/j.jpsychires.2006.05.004","article-title":"Ginkgo biloba special extract EGb 761\u00ae in generalized anxiety disorder and adjustment disorder with anxious mood: A randomized, double-blind, placebo-controlled trial","volume":"41","author":"Woelk","year":"2007","journal-title":"J. Psychiatr. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1017\/S1041610217001892","article-title":"Treatment effects of Ginkgo biloba extract EGb 761\u00ae on the spectrum of behavioral and psychological symptoms of dementia: Meta-analysis of randomized controlled trials","volume":"30","author":"Savaskan","year":"2017","journal-title":"Int. Psychogeriatr."},{"key":"ref_40","first-page":"45","article-title":"Prim\u00e4r therapieresistente depressive Verstimmung \u00e4lterer Patienten mit Hirnleistungsst\u00f6rungen: Wirksamkeit der Kombination von Ginkgo-biloba-Extrakt EGb-761 mit Antidepressiva [Primary therapy-resistant depressive instability in elderly patients with cerebral disorders: Efficacy of a combination of Ginkgo biloba extract EGb 761 with antidepressants]","volume":"3","author":"Schubert","year":"1993","journal-title":"Geriatr Forsch"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1176\/appi.psy.47.4.282","article-title":"Relationship between Tinnitus Severity and Psychiatric Disorders","volume":"47","author":"Svedlund","year":"2006","journal-title":"J. Psychosom. Res."},{"key":"ref_42","first-page":"4","article-title":"Ginkgo biloba special extract in dementia with neuropsychiatric features. A randomised, placebo-controlled, double-blind clinical trial","volume":"57","author":"Napryeyenko","year":"2007","journal-title":"Arzneimittelforschung"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1002\/gps.2662","article-title":"Efficacy and safety of a once-daily formulation of Ginkgo biloba extract EGb 761 in dementia with neuropsychiatric features: A randomized controlled trial","volume":"26","author":"Ihl","year":"2010","journal-title":"Int. J. Geriatr. Psychiatry"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1016\/j.jpsychires.2012.03.003","article-title":"Ginkgo biloba extract EGb 761\u00ae in dementia with neuropsychiatric features: A randomised, placebo-controlled trial to confirm the efficacy and safety of a daily dose of 240 mg","volume":"46","author":"Herrschaft","year":"2012","journal-title":"J. Psychiatr. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"S240","DOI":"10.1002\/acr.20543","article-title":"Measures of adult pain: Visual Analog Scale for Pain (VAS Pain), Numeric Rating Scale for Pain (NRS Pain), McGill Pain Questionnaire (MPQ), Short-Form McGill Pain Questionnaire (SF-MPQ), Chronic Pain Grade Scale (CPGS), Short Form-36 Bodily Pain Scale (SF-36 BPS), and Measure of Intermittent and Constant Osteoarthritis Pain (ICOAP)","volume":"63","author":"Hawker","year":"2011","journal-title":"Arthritis Care Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1044\/1059-0889(2012\/12-0010)","article-title":"Psychometric Evaluation of Visual Analog Scale for the Assessment of Chronic Tinnitus","volume":"21","author":"Adamchic","year":"2012","journal-title":"Am. J. Audiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"10S","DOI":"10.1212\/WNL.48.5_Suppl_6.10S","article-title":"The Neuropsychiatric Inventory: Assessing psychopathology in dementia patients","volume":"48","author":"Cummings","year":"1997","journal-title":"Neurology"},{"key":"ref_48","unstructured":"Erzigkeit, H. (1992). SKT Manual. A Short Cognitive Performance Test for Assessing Memory and Attention, Geromed GmbH. Concise Version."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1024\/1662-9647\/a000104","article-title":"SKT Short Cognitive Performance Test and Activities of Daily Living in Dementia: The Journal of Gerontopsychology and Geriatric Psychiatry","volume":"27","author":"Lehfeld","year":"2014","journal-title":"GeroPsych"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"S44","DOI":"10.1055\/s-2003-40458","article-title":"Magnitude of Effect and Special Approach to Ginkgo biloba Extract EGb 761\u00ae in Cognitive Disorders","volume":"36","year":"2003","journal-title":"Pharmacopsychiatry"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.2147\/CIA.S72728","article-title":"Efficacy and tolerability of Ginkgo biloba extract EGb 761\u00ae in dementia: A systematic review and meta-analysis of randomized placebo-controlled trials","volume":"9","author":"Gauthier","year":"2014","journal-title":"Clin. Interv. Aging"},{"key":"ref_52","unstructured":"MacKinnon, D.P. (2008). Multivariate applications series. Introduction to Statistical Mediation Analysis, Taylor & Francis Group\/Lawrence Erlbaum Associates."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"290","DOI":"10.2307\/270723","article-title":"Asymptotic Confidence Intervals for Indirect Effects in Structural Equation Models","volume":"13","author":"Sobel","year":"1982","journal-title":"Sociol. Methodol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1080\/00273171.2010.498290","article-title":"Quantifying and Testing Indirect Effects in Simple Mediation Models When the Constituent Paths Are Nonlinear","volume":"45","author":"Hayes","year":"2010","journal-title":"Multivar. Behav. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1007\/s11096-018-0654-4","article-title":"Ginkgo biloba extract EGb 761\u00ae versus pentoxifylline in chronic tinnitus: A randomized, double-blind clinical trial","volume":"40","author":"Sejna","year":"2018","journal-title":"Int. J. Clin. Pharm."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1001\/archneurol.2010.362","article-title":"Hearing Loss and Incident Dementia","volume":"68","author":"Lin","year":"2011","journal-title":"Arch. Neurol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1111\/coa.12607","article-title":"The relationship between hearing impairment and cognitive function: A meta-analysis in adults","volume":"41","author":"Taljaard","year":"2016","journal-title":"Clin. Otolaryngol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.brainres.2016.03.016","article-title":"The neural correlates of cognitive dysfunction in phantom sounds","volume":"1642","author":"Vanneste","year":"2016","journal-title":"Brain Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1177\/0891988706292758","article-title":"Assessment of Anxiety in Dementia: An Investigation into the Association of Different Methods of Measurement","volume":"19","author":"Gibbons","year":"2006","journal-title":"J. Geriatr. Psychiatry Neurol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1590\/S1807-59322011000800008","article-title":"Attenuation of neuropsychiatric symptoms and caregiver burden in Alzheimer\u2019s disease by motor intervention: A controlled trial","volume":"66","author":"Stella","year":"2011","journal-title":"Clinics"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2400","DOI":"10.1096\/fj.06-7649com","article-title":"EGb 761 enhances adult hippocampal neurogenesis and phosphorylation of CREB in transgenic mouse model of Alzheimer\u2019s disease","volume":"21","author":"Tchantchou","year":"2007","journal-title":"FASEB J."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1146\/annurev.psych.58.110405.085542","article-title":"Mediation Analysis","volume":"58","author":"MacKinnon","year":"2007","journal-title":"Annu. Rev. Psychol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Van den Berge, M.J.C.V.D., Free, R.H., Arnold, R., De Kleine, E., Hofman, R., van Dijk, J.M.C., and Van Dijk, P. (2017). Cluster Analysis to Identify Possible Subgroups in Tinnitus Patients. Front. Neurol., 8.","DOI":"10.3389\/fneur.2017.00115"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Simoes, J., Neff, P., Schoisswohl, S., Bulla, J., Schecklmann, M., Harrison, S., Vesala, M., Langguth, B., and Schlee, W. (2019). Toward Personalized Tinnitus Treatment: An Exploratory Study Based on Internet Crowdsensing. Front. Public Health, 7.","DOI":"10.3389\/fpubh.2019.00157"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40780-015-0014-7","article-title":"Meta-analysis of the efficacy and safety of Ginkgo biloba extract for the treatment of dementia","volume":"1","author":"Hashiguchi","year":"2015","journal-title":"J. Pharm. Health Care Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e876","DOI":"10.1097\/MAO.0000000000002403","article-title":"Cognitive Performance in Chronic Tinnitus Patients: A Cross-Sectional Study Using the RBANS-H","volume":"40","author":"Cardon","year":"2019","journal-title":"Otol. Neurotol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/14\/3151\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:30:57Z","timestamp":1760164257000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/14\/3151"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,16]]},"references-count":66,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["jcm10143151"],"URL":"https:\/\/doi.org\/10.3390\/jcm10143151","relation":{},"ISSN":["2077-0383"],"issn-type":[{"type":"electronic","value":"2077-0383"}],"subject":[],"published":{"date-parts":[[2021,7,16]]}}}