Anti-Inflammatory Treatment for Age-Associated Memory Impairment: A Double-Blind Placebo-Controlled Trial
Condition: Memory Disorders
MeSH terms: Memory Disorders
Study type: Interventional
Phase: Phase 3

Summary: 
      This project is designed to study whether anti-inflammatory drugs, such as celecoxib, may
      delay age-related mental decline. We are also looking at genetic risk and brain structure as
      potential predictors of mental decline. We believe people with age-associated memory
      impairment who take celecoxib will show less evidence of mental decline than those receiving
      placebo (an inactive pill) after 18 months. We expect that brain structure at the start of
      the study, memory performance as indicated by tests, and age will be additional predictors of
      mental decline. We also predict that cognitive decline (i.e., decline in thinking and memory)
      and treatment response will vary according to genetic factors that may correlate with the age
      at which dementia begins. We believe other variables such as prior educational achievement,
      memory capability at the outset of the study, and gender may influence mental decline and
      treatment response. We will study people with age-associated memory impairment (mild memory
      complaints, decreased performance in selected memory tests), between 40 and 90 years of age.
      The subjects will be randomly (i.e., by a process similar to flipping a coin) assigned to
      treatment groups. The subjects will receive either an inactive substance (placebo) or
      celecoxib (400 mg/day). The subjects will receive a magnetic resonance imaging (MRI) scan,
      FDG PET scan, routine laboratory blood tests, electrocardiogram and cognitive tests. They
      will be followed for approximately 18 months and asked to return at specific intervals for
      follow-up testing. Measures of brain structure will be derived from baseline MRI scans and
      metabolic activity from PET scans, and blood will be drawn and tested to determine which
      forms (genotypes) of certain genetically determined cellular components the patient has.
    

Detailed description: 
      Several observational epidemiological studies indicate that anti-inflammatory treatments
      attenuate or prevent the symptoms of one of the most common mental disorders of late life,
      Alzheimer's disease (AD). Neuropathological studies also support inflammatory or immune
      mechanisms in AD, including findings of reactive microglia within or near AD lesions. Such
      evidence, however, is circumstantial, and controlled, randomized drug trials are needed to
      determine efficacy.

      This project is designed to determine if the commonly used nonsteroidal anti-inflammatory
      drug (NSAID), celecoxib, is efficacious in delaying progression of cognitive symptoms in
      people with age-related cognitive losses who are at risk for developing AD. A total of 135
      subjects with age-associated memory impairment (AAMI) who are at risk for further cognitive
      decline (age 40 to 90 years) will be randomized (double-blind design) to one of two treatment
      groups: celecoxib (400 mg/d) or placebo, and followed for 18 months. All randomized subjects
      will receive magnetic resonance imaging (MRI) scans, FDG PET scans, and selective genotyping
      (apolipoprotein E [APOE] and genetic risk for AD onset (e.g., APOE-4). Subjects receiving
      celecoxib are expected to show less evidence of cognitive decline than those receiving
      placebo. The proposed project builds upon our group's prior work on early detection of AD
      using brain imaging, genetic risk, and neuropsychological assessments. This project also is a
      logical follow-up to recent observational studies of a promising early intervention and will
      represent one of the first controlled, anti-inflammatory treatment trials for persons at high
      risk for age-related cognitive decline and the eventual development of AD.

      Subjects will be followed closely to ensure that medication is safely used, without side
      effects (e.g., gastrointestinal, renal, etc.).
    

Intervention name(s): Celecoxib
Intervention type(s): Drug
Intervention MeSH terms: Celecoxib
Allocation: Randomized
Masking: Double
Primary purpose: Treatment
Keywords: Age associated memory impairment; Mild cognitive impairment