{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T05:59:15Z","timestamp":1793771955574,"version":"4.6.1"},"reference-count":225,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T00:00:00Z","timestamp":1732147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Parkinson\u2019s disease (PD) is a progressive neurodegenerative disorder that affects over 1% of population over age 60. It is defined by motor and nonmotor symptoms including a spectrum of cognitive impairments known as Parkinson\u2019s disease dementia (PDD). Currently, the only US Food and Drug Administration-approved treatment for PDD is rivastigmine, which inhibits acetylcholinesterase and butyrylcholinesterase increasing the level of acetylcholine in the brain. Due to its limited efficacy and side effect profile, rivastigmine is often not prescribed, leaving patients with no treatment options. PD has several derangements in neurotransmitter pathways (dopaminergic neurons in the nigrostriatal pathway, kynurenine pathway (KP), acetylcholine, \u03b17 nicotinic receptor, and N-methyl-D-aspartate (NMDA) receptors) and rivastigmine is only partially effective as it only targets one pathway. Kynurenic acid (KYNA), a metabolite of tryptophan metabolism, affects the pathophysiology of PDD in multiple ways. Both galantamine (\u03b17 nicotinic receptor) and memantine (antagonist of the NMDA subtype of the glutamate receptor) are KYNA modulators. When used in combination, they target multiple pathways. While randomized controlled trials (RCTs) with each drug alone for PD have failed, the combination of galantamine and memantine has demonstrated a synergistic effect on cognitive enhancement in animal models. It has therapeutic potential that has not been adequately assessed, warranting future randomized controlled trials. In this review, we summarize the KYNA-centric model for PD pathophysiology and discuss how this treatment combination is promising in improving cognitive function in patients with PDD through its action on KYNA.<\/jats:p>","DOI":"10.3390\/brainsci14121163","type":"journal-article","created":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T12:25:42Z","timestamp":1732191942000},"page":"1163","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Galantamine-Memantine Combination in the Treatment of Parkinson\u2019s Disease Dementia"],"prefix":"10.3390","volume":"14","author":[{"given":"Emma D.","family":"Frost","sequence":"first","affiliation":[{"name":"Cooper Neurological Institute, Cooper University Health Care, Camden, NJ 08103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swanny X.","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Neurology, Montefiore 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0540-4816","authenticated-orcid":false,"given":"Nicholas","family":"Vigilante","sequence":"additional","affiliation":[{"name":"Cooper Medical School, Rowan University, Camden, NJ 08103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5974-8986","authenticated-orcid":false,"given":"Briana P.","family":"Murray","sequence":"additional","affiliation":[{"name":"Chase Brexton Health Care, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian M.","family":"Walker","sequence":"additional","affiliation":[{"name":"Cooper Neurological Institute, Cooper University Health Care, Camden, NJ 08103, USA"},{"name":"Cooper Medical School, Rowan University, Camden, NJ 08103, 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Echeverria","sequence":"additional","affiliation":[{"name":"Research and Development Department, Bay Pines VAHCS, Bay Pines, FL 33744, USA"},{"name":"Medicine Department, Universidad San Sebasti\u00e1n, Concepci\u00f3n 4081339, B\u00edo B\u00edo, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6261-9816","authenticated-orcid":false,"given":"Ludmil","family":"Mitrev","sequence":"additional","affiliation":[{"name":"Cooper Medical School, Rowan University, Camden, NJ 08103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2232-1409","authenticated-orcid":false,"given":"Mitchel A.","family":"Kling","sequence":"additional","affiliation":[{"name":"Department of Geriatrics and Gerontology, New Jersey Institute for Successful Aging, Rowan-Virtua School of Osteopathic Medicine, Stratford, NJ 08084, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balaji","family":"Krishnaiah","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David B.","family":"Lovejoy","sequence":"additional","affiliation":[{"name":"Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW 2113, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6289-5386","authenticated-orcid":false,"given":"Shafiqur","family":"Rahman","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings, SD 57007, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5532-0031","authenticated-orcid":false,"given":"Trevor 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