Original ContributionsEffects of Memantine on Clinical Ratings, Fluorodeoxyglucose Positron Emission Tomography Measurements, and Cerebrospinal Fluid Assays in Patients With Moderate to Severe Alzheimer Dementia: A 24-Week, Randomized, Clinical TrialWang, Tao MD, PhD*; Huang, Qiu PhD†; Reiman, Eric M. MD‡; Chen, Kewei PhD†‡; Li, Xia MD, PhD*; Li, Guanjun MD*; Lin, Zhiguang MD*; Li, Chunbo MD, PhD*; Xiao, Shifu MD, PhD*Author Information From the *Department of Geriatric Psychiatry, Shanghai Mental Health Center, and Alzheimer’s Disease and Related Disorders Center, and †Med-X Research Institution, Shanghai Jiao Tong University, Shanghai, China; and ‡Banner Alzheimer’s Institute, Translational Genomics Research Institute, University of Arizona, and Arizona Alzheimer’s Consortium, Phoenix, AZ. Received June 13, 2012; accepted after revision January 2, 2013. Reprints: Shifu Xiao, MD, PhD, Department of Geriatric Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China; 600 South Wan Ping Rd, XuHui District, Shanghai, China (e-mail: [email protected]). This study was supported by the Shanghai Science and Technology Committee (grants 08411951100, 10ZR1425800, and 11ZR1416700), the China Ministry of Science and Technology (grants 2009BAI77B03 and 2012ZX09303), and the National Natural Science Foundation of China (project 81201030). Lundbeck A/S provided an unrestricted research grant (IIT_12484A). Part of the abstract of this article has been orally presented at the Alzheimer’s Association International Conference on Alzheimer’s Disease 2011 (AAICAD 2011) in Paris, France, July 15 to July 22, 2011. ClinicalTrials.gov registry no. NCT00800709 (www.clinicaltrials.gov) Journal of Clinical Psychopharmacology: October 2013 - Volume 33 - Issue 5 - p 636-642 doi: 10.1097/JCP.0b013e31829a876a Buy Metrics Abstract Most experts consider that memantine has a symptomatic treatment, but clinical trials have not yet provided compelling evidence to support a disease-modifying effect. We investigate the effects of memantine on clinical ratings; fluorodeoxyglucose positron emission tomography (FDG-PET) measurements, which can monitor disease-modifying effect; and cerebrospinal fluid (CSF) assays in patients with moderate to severe probable Alzheimer disease (AD) dementia. Twenty-two patients completed a 24-week, double-blind, placebo-controlled, randomized clinical trial of memantine, titrated up to 10 mg twice per day using the Severe Impairment Battery, AD Assessment Scale-Cognitive subscale, Mini-Mental State Examination, FDG-PET measurements of the regional cerebral metabolic rate for glucose (CMRgl), and CSF amyloid β (Aβ) and tau assays. An automated brain mapping algorithm and predefined regions of interest were each used to analyze treatment-related regional CMRgl effects. In comparison with the placebo group, the memantine treatment group had significantly less cognitive decline on the Severe Impairment Battery and significantly less CMRgl declines in regions preferentially affected by AD. There were no significant treatment effects on CSF Aβ1-42, CSF Aβ1-40, total tau, or phosphor-tau levels or ratios. This relatively small and brief randomized clinical trial suggests an association between memantine’s clinical benefit and its effects on FDG-PET measurements in AD-affected brain regions. Larger and longer studies are needed to confirm these findings, extend them to earlier clinical and preclinical stages of AD, and help determine the extent to which FDG-PET should be qualified for use as a reasonably likely surrogate end point in the evaluation of putative AD-modifying treatments. © 2013 by Lippincott Williams & Wilkins.