18-Month Study of Memory Effects of Curcumin
Condition: Age-associated Cognitive Impairment; Mild Cognitive Impairment (MCI)
MeSH terms: Cognitive Dysfunction
Intervention: Curcumin; Placebo
Intervention description: Six Theracurmin capsules (containing 30 mg of curcumin each) per day for 18 months.; Six capsules per day for 18 months.
Intervention MeSH terms: Curcumin
Phase: Phase 2
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 46.0
Sex: All
Minimum age: 50 Years
Maximum age: 90 Years
Healthy volunteers: No
Keywords: Curcumin; Turmeric; Memory; Cognitive Impairment; Brain Imaging; Supplement

Summary:

      This project is designed to study the effects of the dietary supplement curcumin on
      age-related cognitive impairment. In particular, the study seeks to determine the effects of
      curcumin on cognitive decline and the amount of abnormal amyloid protein in the brain.
      Genetic risk will also be studied as a potential predictor of cognitive decline.

      Subjects will be randomly assigned to one of two treatment groups: either a placebo twice
      daily or the curcumin supplement (Theracurmin®, containing 90 mg of curcumin). The
      investigators expect that the volunteers receiving the curcumin supplement will show less
      evidence of decline after 18 months than those receiving the placebo. The investigators
      predict that cognitive decline and treatment response will vary according to genetic risk for
      Alzheimer's.

      The investigators will study subjects with memory complaints aged 50-90 years. Initially,
      subjects will undergo a clinical assessment, an MRI and a blood draw to determine genetic
      risk and to rule out other neurodegenerative disorders linked to memory complaints.
      Subsequently, subjects will undergo an
      -(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile (FDDNP) PET
      scan and a baseline neuropsychological assessment to confirm a diagnosis of MCI or normal
      aging. Once enrolled, subjects will begin taking the supplement (either curcumin or a
      placebo). Some of the initial subjects will be asked to return every three months for regular
      MRIs. Every 6 months, subjects will also receive neuropsychological assessments. At the
      conclusion of the study, subjects will be asked to complete a final neuropsychological
      assessment, MRI scan, PET scan and blood draw. Additional blood will be drawn at baseline and
      at 18 months and frozen to assess inflammatory markers if cognitive outcomes are positive.

      FDDNP-PET scans will be used to measure the amount of abnormal amyloid plaque- and tau
      tangle-proteins in the brain; the MRIs will be used to monitor supplement side effects and
      measure brain structure; the neuropsychological assessments will monitor rates of cognitive
      decline; the blood draws will be used to determine genetic risk and to test levels of
      inflammatory markers.
    

Eligibility criteria:

        Inclusion Criteria

          1. Agreement to participate in the 18-month double-blind, placebo-controlled clinical
             trial of curcumin.

          2. Diagnostic criteria for mild cognitive impairment (MCI) or any age related memory
             decline according to standard criteria (Petersen et al, 2001; Crook et al, 1986).

          3. Age 50 to 90 years.

          4. No significant cerebrovascular disease: modified Ischemic Score of < 4 (Rosen et al,
             1980).

          5. Adequate visual and auditory acuity to allow neuropsychological testing.

          6. Screening laboratory tests and EKG without significant abnormalities that might
             interfere with the study.

        Exclusion Criteria

          1. Diagnosis of probable Alzheimer's disease (AD) or any other dementia (e.g., vascular,
             Lewy body, frontotemporal) (McKhann et al, 1984).

          2. Evidence of other neurological or physical illness that can produce cognitive
             deterioration. Volunteers with a history of stroke, TIA, carotid bruits, or lacunes on
             MRI scans will be excluded.

          3. Inability to undergo MRI.

          4. Evidence of Parkinson's disease as determined by the motor examination (items 18-31)
             of the Unified Parkinson's Disease Rating Scale (Fahn et al, 1987).

          5. History of myocardial infarction within the previous year, or unstable cardiac
             disease.

          6. Uncontrolled hypertension (systolic BP > 170 or diastolic BP > 100).

          7. History of significant liver disease, clinically-significant pulmonary disease,
             diabetes, or cancer.

          8. Current diagnosis of any major psychiatric disorder according to the DSM-IV TR
             criteria (APA, 2000).

          9. Current diagnosis or history of alcoholism or substance addiction.

         10. Regular use of any medication that may affect cognitive functioning including:
             centrally active beta-blockers, narcotics, Clonidine, anti-Parkinsonian medications,
             antipsychotics, benzodiazepines, systemic corticosteroids, medications with
             significant cholinergic or anticholinergic effects, anti-convulsants, or Warfarin.
             Occasional chloral hydrate use will be allowed, but discouraged, for insomnia.

         11. Use of more than one multivitamin per day. Vitamins other than the standard
             multivitamin supplement will not be allowed.

         12. Use of medications known to affect FDDNP-PET binding (e.g., ibuprofen, naproxen).

         13. Use of more than one daily baby aspirin (81mg) and/or use of any medication containing
             curcumin.

         14. Use of cognitive enhancing supplements (e.g. Ginkgo biloba).

         15. Use of any investigational drugs within the previous month or longer, depending on
             drug half-life.

         16. Pregnancy.

         17. HIV infection.

         18. Evidence of vasogenic edema; specifically, evidence of more than 4 cerebral
             microhemorrhages (regardless of their anatomical location or diagnostic
             characterization as "possible" or "definite") or a single area of superficial
             siderosis), or evidence of a prior macrohemorrhage at screening or baseline.