Overview
Name: Tacrine
Synonyms: Cognex™
Chemical Name: 1,2,3,4-tetrahydro-9-acridinamine monohydrochloride monohydrate
Therapy Type: Small Molecule (timeline)
Target Type: Cholinergic System (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Approved)
Company: Pfizer, Shionogi Pharma
Background
Tacrine is a reversible acetylcholinesterase inhibitor. Originally developed by Warner-Lambert Co., tacrine was the first such drug to be introduced for the treatment of Alzheimer's disease in a range of countries in South America, Asia, Europe, Australia, and the United States in 1995 and 1996. Because of its liver toxicity and attendant requirement for monitoring liver function, tacrine prescriptions dropped after other acetylcholinesterase inhibitors were introduced, and its use has been largely discontinued.
Last Updated: 08 May 2014
Further Reading
No Available Further Reading
Overview
Name: Edonerpic
Synonyms: T-817 MA, T 817
Chemical Name: 1-{3-[2-(1-benzothiophen-5-yl)ethoxy] propyl}-3-azetidinol maleate
Therapy Type: Small Molecule (timeline)
Target Type: Other (timeline), Unknown
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Discontinued)
Company: Toyama Chemical Co., Ltd.
Background
T-817MA is an orally available neurotrophic agent being developed for the treatment of Alzheimer's disease by Toyama Chemical, a company of the Fujifilm Group. T-817MA reportedly activates sigma receptors. The compound has been reported in various cell-based and preclinical models to protect neurons against Aβ-induced neurotoxicity and memory deficits (e.g. Hirata et al., 2005; Nguyen et al., 2007; Kimura et al., 2009). T-817MA appears to act by promoting neurite outgrowth and preserving synaptic plasticity in the cortex and hippocampus (Takamura et al., 2013).
A treatment benefit has also been reported in sensorimotor gating, which is a biomarker for cognitive deficits in schizophrenia, as well as in models of hearing loss; however, no clinical development is ongoing in these indications (Seo et al., 2008; Uehara et al., 2012; Yamashita et al., 2008).
Edonerpic was reported to enhance cortical synaptic plasticity and motor function recovery after stroke, both in mice (Abe et al., 2018; Pines et al., 2019). In Abe et al., edonerpic’s target was proposed to be collapsin response mediator protein 2 (CRMP2), a cytosolic phosphoprotein involved in neurite outgrowth, ion channel trafficking, and synaptic plasticity. However, other investigators dispute that edonerpic binds to CRMP2 (Moutal et al., 2019, reviewed in Takahashi 2019; Khanna et al., 2020). The compound was subsequently reported to act via CRMP2 and the Arc protein to improve long-term neurological recovery in a mouse model of traumatic brain injury (Chen et al., 2022).
Findings
Phase 1 development for T-817MA began in 2005. From 2008 to 2011, a multicenter Phase 2a trial in North America compared a once-daily dose of 224 mg of T-817MA to placebo in 373 patients with mild to moderate Alzheimer's disease who are stable on donepezil. The primary outcome was cognitive function as measured by the ADAS-cog; secondary outcomes were safety and overall impression using the ADCS Global Clinical Impression of Change (CGIC) and ADCS Activities of Daily Living (ADL). In this trial, only 72.1 percent of patients on placebo, versus 61.6 percent on T-817MA, completed the trial, limiting conclusions that can be drawn from its results. Within these limitations, T-817MA appeared to show potential to slow cognitive and functional decline. Numerical differences on cognitive, clinical, and functional readouts favored treatment but fell short of statistical significance. Results of a neuropsychiatric measure favored placebo, also without statistical significance. A small imaging sub-study indicated trends favoring T-817MA, again not statistically significantly. Side effects included diarrhea, nausea, dizziness, and headache; two serious adverse events were considered possibly related to the study drug (Schneider et al., 2013).
In March 2014, the North American consortium Alzheimer's Disease Cooperative Study (ADCS) started another one-year, Phase 2 study of T-817MA called Noble. It compared 224 mg to 448 mg of T-817MA once daily and to placebo. It enrolled 484 patients with mild to moderate Alzheimer's disease who were already taking donepezil or rivastigmine, with or without memantine. This study used the ADAS-cog and ADCS-CGIC as primary outcomes, and safety as well as ADCS-ADL, FAQ, NPI, and MMSE as secondary outcomes. Unlike most ADCS trials, this study received no federal funding but was fully sponsored by Toyama. This trial was completed in May 2017.
On July 19, 2017, Fujifilm Corporation announced that the Noble trial had failed to reach its primary endpoint, and that there were no differences between the groups on secondary endpoints. According to the press release, exploratory analyses spotted biomarker signals in CSF p-tau levels and hippocampal volume, and post-hoc analyses hinted at a possible subgroup effect on cognition. Fujifilm announced its intention to continue developing T-817MA (see company press release). In November 2017, results presented at CTAD confirmed that Edonerpic had failed to outperform placebo on the primary or any of the secondary outcomes. Some biomarkers showed changes, but the changes did not all trend in the same direction. Diarrhea, vomiting, and weight loss were more common in the treatment groups than placebo, and more people in the treatment arms discontinued the trial. Dropouts in the placebo, low and high dose were 11.4, 29.5, and 24.1 percent, respectively (see Dec 2017 conference news).
The complete trial data has been published (Jul 2019 news; Schneider et al., 2019). Among biomarkers, CSF phospho-tau181 and total tau decreased in the high-dose group compared with placebo, while Aβ40 and Aβ42 did not change. Treatment caused no change in hippocampal volume, but ventricular volume increased in the high-dose group.
In February 2016, another Phase 1 trial started. It compared pharmacokinetic parameters of a single dose of T-817MA between otherwise healthy volunteers with mildly, moderately, or severely impaired liver function and people with normal liver function. This trial enrolled 36 people in Florida, and was completed in August 2016.
In April 2019, the company began a Phase 2 trial, enrolling 45 people in Japan to evaluate whether edonerpic improves rehabilitation of partial arm paralysis due to stroke.
A Phase 2 trial began in December 2019 to assess edonerpic’s effect on disease-related biomarkers in 200 people with mild cognitive impairment due to AD, or mild AD, whose clinical diagnosis was confirmed by CSF Aβ and tau abnormality. Participants took 224 mg edonerpic daily for one month, then 448 mg or placebo for an additional 17 months. The primary outcome was change in CSF pTau181 from baseline. Secondary outcomes included CSF total tau, pTau217, Aβ, NfL, neurogranin, and YKL; plasma NfL and Aβ, clinical dementia rating, brain volume, EEG measures, safety, and pharmacokinetics. The trial enrolled 221 participants at 31 sites in Europe. It failed to meet its primary endpoint, according to results presented at the October 2023 CTAD conference. Edonerpic did not change CSF ptau181 compared to placebo. Treatment did not affect most of the secondary endpoints, including the CDR-SB and the Cognitive-Functional Composite, and EEG measures. Just more than 80 percent of the treated group completed the trial. Treatment was deemed safe, although those on edonerpic ended with lower total brain volume and higher ventricular volume, with no change in hippocampal volume.
For details on T-817MA trials, see clinicaltrials.gov.
Last Updated: 06 Nov 2023
Further Reading
No Available Further Reading
Overview
Name: Suritozole
Synonyms: MD 26479
Therapy Type: Small Molecule (timeline)
Target Type: Other Neurotransmitters (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Discontinued)
Company: Aventis Pharmaceuticals, Inc. (was Hoechst)
Background
Suritozole is an inverse agonist at the GABA(A) receptor (Miller et al., 1992). GABA(A) receptor activity affects cholinergic function in the hippocampus and cerebral cortex (Richter et al., 1982; Wenk, 1984). This drug was found to improve memory performance in rats with scopolamine-induced memory acquisition deficits (Moran et al., 1992).
Last Updated: 09 Jan 2014
Further Reading
No Available Further Reading
Overview
Name: ST101
Synonyms: ZSET1446
Chemical Name: spiro[imidazo[1,2-a]pyridine-3,2-indan]-2(3H)-one
Therapy Type: Small Molecule (timeline)
Target Type: Unknown
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Inactive)
Company: Sonexa Therapeutics, Inc.
Background
ST101 is an orally active azaindolizinone derivative that has been reported to be a cognitive enhancer. The compound may have pleiotropic effects. It has been reported to induce APP, cleave APP at a novel site that precludes subsequent Aβ generation, and reduce brain Aβ levels and improve memory function in transgenic mice and non-human primates (Green et al., 2011). ST101 also has been reported to stimulate the cholingergic system, activate a number of intracellular signaling pathways such as ERK1/2 following stimulation with dopamine D1 and NMDA receptors, and target voltage-gated calcium channels (Shioda et al., 2011; Ito et al., 2007; Moriguchi et al., 2012). One preclinical study in the senescence-accelerated prone mouse strain 8 (SAMP8) reported a treatment effect on behavioral assays and brain amyloid deposition (Yamaguchi et al., 2012).
Findings
Two Phase 2 trials in Alzheimer's disease, conducted at multiple sites in the United States and Canada, have been completed. One compared three doses of ST101 to placebo in 168 people with mild to moderate Alzheimer's disease on the ADAS-cog, ADCS-ADL, and ADCS-GCI. This trial ended in September 2010. The other trial compared three lower doses of ST101 to placebo in 210 people with mild to moderate AD who also were on donepezil treatment against the same outcome measures. Results have not been reported in the literature.
In 2011, Sonexa also ran a small proof-of-concept study comparing ST101 tablets to placebo in 25 people with essential tremor. For all trials of ST101 see clinicaltrials.gov.
Last Updated: 25 Oct 2023
Further Reading
No Available Further Reading
Overview
Name: Simvastatin
Synonyms: Zocor®, Lipex®, Lipovas®, Denan®
Therapy Type: Small Molecule (timeline)
Target Type: Cholesterol
Condition(s): Alzheimer's Disease, Mild Cognitive Impairment
U.S. FDA Status: Alzheimer's Disease (Inactive), Mild Cognitive Impairment (Phase 4)
Company: Merck
Approved for: Hypercholesterolemia and diabetic cardiomyopathy.
Background
Simvastatin is an oral HMG-CoA reductase inhibitor prescribed extensively throughout the world for the treatment of hypercholesterolemia and diabetic cardiomyopathy. Simvastatin was developed by Merck, Sharp & Dohme. Since its FDA approval in 1991, it has come to be marketed by a variety of companies under different brand names in different countries. The drug's indication calls for it to be used along with dietary changes to reduce elevated levels of total or LDL cholesterol and triglycerides.
Elevated LDL cholesterol and low HDL cholesterol both are risk factors for heart disease. Simvastatin is a methylated form of lovastatin. In vivo, it is hydrolyzed to generate a metabolite that competes with the substrate HMG-CoA for the liver enzyme HMG-CoA reductase; this interference with the enzyme's activity reduces the level of the cholesterol precursor mevalonic acid.
Simvastatin reduces mortality and the risk of nonfatal heart attacks in people with hypercholesterolemia. Its side effects include a risk for muscle injury, and its label and dosing regimen has been updated accordingly. In the United Kingdom, simvastatin is available over the counter; in some countries generic forms are sold. Simvastatin is widely used in a secondary prevention mode in routine medical care, where screening for elevated risk of cardiovascular disease with a cholesterol blood test in midlife can trigger prescription of statin therapy. Along with other statins, the clinical success and development path of simvastatin has served as a conceptual model for developing anti-amyloid drugs as a secondary prevention tool to treat preclinical Alzheimer's disease (see eFAD essay).
Simvastatin, which crosses the blood-brain barrier, has been tested for the treatment of symptomatic and preclinical Alzheimer's disease. The rationale grew out of epidemiological research that suggested significant overlap between cardiovascular and Alzheimer's diseases. For example, long-term statin treatment to lower cholesterol was shown to confer some protection against incident Alzheimer's and AD neuropathology at death. A large body of literature on cell biology and animal studies suggests that statin treatment affects APP processing, lowers levels of the Aβ peptide, and might have neuroprotective effects. Small clinical trials generated signals of a possible benefit that did not hold up in larger treatment trials; trials targeting earlier stages of the disease are still ongoing (see below).
Findings
Widespread clinical interest in statins for the treatment of Alzheimer's began around 2002, when a clinical trial in Germany reported a signal that simvastatin treatment was able to lower both cholesterol and Aβ levels in the CSF of Alzheimer's disease patients. This six-month study was negative on the overall outcome of CSF Aβ40 or 42 levels, but it did report a correlated reduction of CSF 24S-hydroxycholesterol and Aβ40 as seen in post-hoc analysis of the more mildly affected subgroup. The same year, an open-label study of six months of simvastatin treatment in 18 AD patients at a memory clinic in Germany reported reductions detected in the blood of brain-derived 24S-hydroxycholesterol as being an indicator that simvastatin affected cholesterol production in the brain of AD patients. (See Simons et al., 2002; Locatelli et al., 2002; news story.)
In 2003, an open-label biochemical study of 19 people with Alzheimer's disease conducted in Sweden reported changes in CSF metabolites of APP processing and a signal for cognitive improvement in response to three months of simvastatin treatment. However, subsequent results based on 12 months of treatment in the same patients showed that while brain cholesterol metabolism indeed changed, there was no clear change in CSF or plasma levels of Aβ42. Analysis of APP isoforms suggested that simvastatin treatment may favor the nonamyloidogenic pathway of APP processing, but the clinical relevance of this finding was unclear. (See Sjogren et al., 2003; Hoglund et al., 2005.)
These early signals did not translate into a clinical benefit in the multicenter CLASP trial of 406 patients with mild to moderate AD conducted in North America by the Alzheimer's Diseases Cooperative Study between 2003 and 2007. CLASP evaluated the safety and efficacy of an 18-month course of simvastatin to slow the progression of AD as measured by the ADAS-Cog and global clinical change as measured by the ADCS-CGIC. In this trial, simvastatin safely lowered lipid levels but did not stem progressive decline in cognition or function (see Sano et al., 2011; news story). CLASP came to be seen as definitive evidence that simvastatin does not benefit symptomatic Alzheimer's disease.
Other studies continue to investigate simvastatin for its effects at earlier stages of the disease, i.e., amnestic mild cognitive impairment/prodromal Alzheimer's disease, and in cognitively normal people at elevated risk of developing AD.
An open-label study of three months of simvastatin treatment in 12 patients with AD or amnestic mild cognitive impairment and hypercholesterolemia reduced cholesterol synthesis in the brain but had no effect on CSF biomarkers of AD (Serrano-Pozo et al., 2010).
Between 2002 and 2005, a 14-week Phase 4 trial in 35 cognitively normal people with elevated blood cholesterol compared simvastatin and pravastatin—a different statin that does not enter the brain—for their ability to alter CSF levels of AD and inflammatory markers. This study reported that simvastatin, but not pravastatin, reduced CSF levels of phospho-tau-181 but had no effect on total tau, Aβ42, Aβ40, soluble Aβ precursorprotein (sAβPP), or F2-isoprostanes (Riekse et al., 2006). This study was conducted at the University of Washington in Seattle, which is currently recruiting for a follow-up study that started in 2010 and is set to run until 2015. This second trial is evaluating how one year of simvastatin treatment in 120 cognitively normal, middle-aged adults affects CSF levels of Aβ42, t-tau, p-tau181, inflammatory markers, and neuroprotection as measured via CSF levels of the growth factor BDNF.
The University of Wisconsin, Madison, is evaluating simvastatin in cognitively normal people who are at elevated risk because they have a parent with AD. Between 2005 and 2009, the ESPRIT study compared simvastatin to placebo for changes in CSF levels of Aβ, as well as markers of cholesterol metabolism and inflammation. This study included an MRI substudy to assess cerebral perfusion, as well as cognitive testing. These investigators found no specific effect of simvastatin on CSF Aβ or tau levels, but did report a benefit on aspects of cognitive function (Carlsson et al., 2008). In 2009, this site began SHARP, a follow-up study attempting to evaluate a longer course of simvastatin on similar outcome measures, but this trial, NCT00939822, appears to have been halted.
A larger study began in 2009 and is set to run through 2019. At 17 centers throughout Germany, the SIMaMCI study will randomize 445 people with both self-reported and measurable memory impairment but preserved function to a two-year course of either 60 mg of simvastatin or placebo once daily . This study measures the time until participants "convert" to dementia, with conversion being defined as an increase of the Clinical Dementia Rating (CDR) score past 0.5. The trial also measures change in the ADAS-Cog battery and in the Free and Cued Selective Reminding Test (FCSRT), a memory test frequently used at the prodromal stage of AD.
For all clinical trials of simvastatin in AD, see clinicaltrials.gov.
Last Updated: 25 Oct 2023
Further Reading
No Available Further Reading
Overview
Name: SGS-742
Synonyms: CGP-36742, DVD-742
Chemical Name: (3-Aminopropyl)butylphosphinic acid
Therapy Type: Small Molecule (timeline)
Target Type: Other Neurotransmitters (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Discontinued)
Company: Novartis Pharmaceuticals Corporation, Saegis Pharmaceuticals, Inc.
Background
SGS742 is a GABA(B) receptor antagonist.
Last Updated: 16 Oct 2013
Further Reading
No Available Further Reading
Overview
Name: SB 202026
Synonyms: Memric
Chemical Name: Sabcomeline
Therapy Type: Small Molecule (timeline)
Target Type: Other Neurotransmitters (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Discontinued)
Background
SB 202026 is a selective muscarinic M1 receptor partial agonist.
Last Updated: 16 Dec 2013
Further Reading
No Available Further Reading
Overview
Name: Sabeluzole
Synonyms: R58735
Therapy Type: Small Molecule (timeline)
Target Type: Unknown
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Inactive)
Last Updated: 09 Jan 2014
Further Reading
No Available Further Reading
Overview
Name: Rosiglitazone
Synonyms: Rosiglitazone maleate, Avandia
Chemical Name: 5-[[4-[2-(methyl-pyridin-2-yl-amino)ethoxy]phenyl]methyl]thiazolidine-2,4-dione, AVANDIA®
Therapy Type: Small Molecule (timeline)
Target Type: Other (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Discontinued)
Company: GlaxoSmithKline (GSK)
Background
Rosiglitazone is an antidiabetic medication that lowers blood glucose by sensitizing pancreatic target cells to insulin. Rosiglitazone belongs to the thiazolidinedione class of peroxisome-proliferator activated receptor γ agonists; PPARγ is a nuclear receptor predominantly expressed in adipose tissue, whose activation influences expression of genes involved in glucose and lipid metabolism. The FDA approved rosiglitazone for treatment of Type 2 diabetes in 1999, but side effects soon started being reported (Sep 2003 news) and their use was restricted in 2010 after having been linked to heart attacks and strokes (see New York Times article).
PPARγ has come to be a target of interest for Alzheimer's drug development because of an overlap of metabolic disease and Alzheimer's disease risk factors. Cell-based and animal studies have implicated PPARγ, in particular, as playing a role in neuroinflammatory processes in neurodegenerative conditions. For example, PPARγ activation has been shown to modulate the microglial response to amyloid deposition in such a way that it increases Aβ phagocytosis and decreases cytokine release (see Dec 2012 news story; Mandrekar-Colucci et al., 2012).
Rosiglitazone has been variously reported to improve behavioral outcomes, normalize brain glucocorticoid receptor levels, activate wnt signaling, and decrease insoluble Aβ42 levels in mutant human APP/PS transgenic mice (Pedersen et al, 2006; Escribano et al., 2009; Toledo and Inestrosa, 2010; O'Reilly and Lynch, 2011). It was also reported to stimulate generation of mitochondria in mouse brain, and to protect synapses in hippocampal slice cultures against Aβ oligomer toxicity by way of increasing the number of mitochondria in neuronal spines and dendrites (Strum et al., 2007; Xu et al., 2013). Anti-inflammatory and anti-tau hyperphosphorylation effects have also been proposed (Xu et al. 2014; Yu et al., 2014).
Findings
A dozen clinical studies have evaluated rosiglitazone in AD.
Starting in 1999, a pilot study at the Veterans Affairs/University of Washington tested a six-month course of 4 mg per day of rosiglitazone or placebo in 30 people with amnestic MCI or mild AD. It reported a treatment benefit on recall and attention, as well as stable plasma Aβ in the treatment group versus declining plasma Aβ in the placebo group, claiming a slowing of disease progression (Nov 2002 news; Watson et al., 2005).
Subsequently, GSK ran four Phase 1 trials in a total of 142 patients to assess drug interactions, an extended-release formulation, and pharmacokinetics. From May 2004 to July 2008, GSK conducted a multicenter Phase 2 study in North America and the United Kingdom. It evaluated the effect of a one-year course of 8 mg per day of rosiglitazone on global and regional functional brain activity and cognition in 80 people with mild to moderate Alzheimer's disease. This trial reported an early increase in glucose metabolism, but no evidence for a slowing of progression at one year (Tzimopoulou et al., 2010).
From January 2004 to May 2005, GSK ran a large Phase 2 trial at 67 centers in Europe and New Zealand, comparing 2 and 8 mg of rosiglitazone per day to placebo in 511 patients with mild to moderate AD for their ability to change baseline ADAS-cog or Clinician's Interview-Based Impression of Change plus caregiver input (CIBIC+) levels. The trial missed its primary endpoint, but a subgroup analysis found a treatment benefit on the higher dose in ApoE4 non-carriers, prompting a pharmacogenomic Phase 3 program (Sep 2006 news; Risner et al., 2006).
In July 2006, GSK started two 54-week Phase 3 studies of add-on therapy in people with mild to moderate Alzheimer's disease. One compared 2 and 8 mg per day of rosiglitazone plus donepezil to donepezil alone in 1,496 participants, the other compared the same doses of rosiglitazone added to any of the three cholinesterase inhibitors approved for AD in 1,485 participants. Both these multinational trials stratified participants into ApoE4 carriers and non-carriers. ADAS-cog and CDR-SB served as co-primary outcome measures. Both trials were negative. Rosiglitazone showed no effect on cognition or function with either dose, or in any ApoE genotype (Harrington et al., 2011).
Between February 2007 and September 2008, a third Phase 3 trial compared a six-month course of either 2 mg/day or 8 mg/day rosiglitazone monotherapy to donepezil treatment in 693 people with mild to moderate AD. The ADAS-cog and CIBIC+ input were co-primary endpoints. This trial, too, was negative, with no significant difference between the groups on either outcome (Gold et al., 2011). In all Phase 3 trials, peripheral edema was the most significant adverse effect.
GSK subsequently terminated two open-label extension trials, and discontinued evaluating rosiglitazone for an indication in Alzheimer's disease.
Last Updated: 11 Mar 2016
Further Reading
No Available Further Reading
Overview
Name: Rofecoxib
Synonyms: Vioxx™
Therapy Type: Small Molecule (timeline)
Target Type: Inflammation (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Discontinued)
Company: Merck
Approved for: Withdrawn from market
Background
The NSAID rofecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor. Its anti-inflammatory and analgesic effects appear to result from the inhibition of prostaglandin synthesis. In 2004, Merck voluntarily withdrew rofecoxib amid controversy over cardiovascular side effects (Sep 2004 news story).
In Alzheimer's research, interest in NSAIDs arose when epidemiological studies started reporting lower rates of Alzheimer's disease or protection of cognition among people who had been taking these drugs for chronic treatment of inflammatory conditions (e.g., Mar 1997 news story; in't Veld et al., 1998; Nov 2001 news story; Vlad et al., 2008; Obermann et al., 2013). Experimental studies supported the argument that inflammation plays a role in Alzheimer's pathogenesis, prompting a wave of clinical trials of various NSAIDs, such as ibuprofen, naproxen celecoxib, and R-flurbiprofen.
Findings
Three clinical trials of rofecoxib in Alzheimer's disease have been conducted. In 2000 and 2001, the Alzheimer's Disease Study Group conducted a 40-center trial that compared one year of treatment with 25 mg once daily of rofexocib or 220 mg twice daily of naproxen to placebo in 351 people with mild to moderate Alzheimer's disease. The trial assessed whether these drugs would slow cognitive decline, but found that neither showed any consistent benefit over placebo (Jul 2002 conference story; Aisen et al., 2003).
In 2004, Merck scientists published results of a larger, company-sponsored trial of of the same once-daily dose of 25 mg rofecoxib or placebo, given for one year, in 692 people with mild to moderate Alzheimer's disease. In this study, too, rofecoxib showed no effect on either cognitive or clinical/functional outcomes (Reines et al., 2004).
Similarly, a trial evaluating whether rofecoxib could delay a diagnosis of Alzheimer's disease in 725 people with mild cognitive impairment was negative, as well (see Thal et al., 2005; Aisen, 2005; and Aisen et al., 2008).
Last Updated: 25 Oct 2023
Further Reading
No Available Further Reading
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