Brain Imaging and Mental Disorders of Aging Intervention

NCT00267163 | Completed Phase 4

• 2 other identifiers: IA00909R01AG018487-06
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this project is to determine if a cholinesterase inhibitor is more effective than placebo in delaying cognitive and brain functional decline in people at risk for Alzheimer's disease.

Conditions

Cognition Disorders

Keywords

Alzheimer's disease; Mild Cognitive Impairment

Outcome Measures

Primary Outcomes (1)

• Changes in cognition and brain metabolism measured by PET and MRI scans, and neuropsychological testing

  at 18 months

Study Arms (2)

1.

EXPERIMENTAL

Drug: donepezil

2.

PLACEBO COMPARATOR

Drug: Placebo

Interventions

donepezil DRUG

1.

Placebo DRUG

2.

Eligibility Criteria

• Age: 40 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Agreement to participate in a 18 month clinical trial
• NIMH diagnostic criteria for age-associated memory impairment (AAMI)
• Age 40 to 90 years
• MMSE score between 24 and 30 (unless \< 8 years of educational achievement)
• No significant cerebrovascular disease - modified Ischemic Score of \< 4
• The following medications are allowed if stable for \> 1 month: antidepressants (without anticholinergic effects) if not currently depressed and no history of major depression for 2 years; estrogen replacement therapy; thyroid replacement therapy as long as patient is euthyroid
• On entering the study, there must be a family member or potential caregiver available in case the patient develops cognitive impairment that interferes with independent study participation.
• Memory and verbal fluency cut-off scores increasing the probability of incipient dementia (Buschke-Fuld - 34; verbal fluency - 46 for letters, 7 for categories; Benton Visual Retention - 5)
• Adequate visual and auditory acuity to allow neuropsychological testing
• Screening laboratory tests and ECG without significant abnormalities that might interfere with the study

You may not qualify if:

• Diagnosis of possible or probable AD or any other dementia (e.g., vascular, Lewy body, frontotemporal)
• Evidence of neurologic or other physical illness that could produce cognitive deterioration, including Parkinson's disease; volunteers with a history of TIAs, carotid bruits, or lacunes on MRI scan will be excluded
• History of myocardial infarction within the previous year or unstable cardiac disease
• Uncontrolled hypertension, history of significant liver disease, clinically significant pulmonary disease, diabetes, or cancer
• Such current major psychiatric disorders as mania, according to DSMIV criteria, within the previous two years
• Current diagnosis or history of alcoholism or drug dependence
• Evidence of untreated depression
• Use of any of the following drugs: centrally active beta-blockers, narcotics, clonidine, anti-Parkinsonian medications, antipsychotics, benzodiazepines, systemic corticosteroids, medications with significant cholinergic or anticholinergic effects, anti-convulsants, or warfarin; vitamins other than the standard multivitamin supplement, ginkgo biloba, and any nutraceuticals will not be allowed; once enrolled in the study, occasional chloral hydrate use will be allowed, but discouraged, for insomnia
• Use of any investigational drugs within the previous month or longer, depending on drug half-life
• Contraindication for MRI scan (e.g., metal in body, claustrophobia)

Sponsors & Collaborators

• National Institute on Aging (NIA): lead

Study Sites (1)

UCLA, The Semel Institute for Neuroscience and Human Behavior

Los Angeles, California, 90024, United States

Location

Related Publications (5)

• Small SA, Stern Y, Tang M, Mayeux R. Selective decline in memory function among healthy elderly. Neurology. 1999 Apr 22;52(7):1392-6. doi: 10.1212/wnl.52.7.1392.

  PMID: 10227623 BACKGROUND

• Small GW, Chen ST, Komo S, Ercoli L, Bookheimer S, Miller K, Lavretsky H, Saxena S, Kaplan A, Dorsey D, Scott WK, Saunders AM, Haines JL, Roses AD, Pericak-Vance MA. Memory self-appraisal in middle-aged and older adults with the apolipoprotein E-4 allele. Am J Psychiatry. 1999 Jul;156(7):1035-8. doi: 10.1176/ajp.156.7.1035.

  PMID: 10401448 BACKGROUND

• Ercoli LM, Siddarth P, Dunkin JJ, Bramen J, Small GW. MMSE items predict cognitive decline in persons with genetic risk for Alzheimer's disease. J Geriatr Psychiatry Neurol. 2003 Jun;16(2):67-73. doi: 10.1177/0891988703016002001.

  PMID: 12801154 BACKGROUND

• Silverman DH, Small GW, Chang CY, Lu CS, Kung De Aburto MA, Chen W, Czernin J, Rapoport SI, Pietrini P, Alexander GE, Schapiro MB, Jagust WJ, Hoffman JM, Welsh-Bohmer KA, Alavi A, Clark CM, Salmon E, de Leon MJ, Mielke R, Cummings JL, Kowell AP, Gambhir SS, Hoh CK, Phelps ME. Positron emission tomography in evaluation of dementia: Regional brain metabolism and long-term outcome. JAMA. 2001 Nov 7;286(17):2120-7. doi: 10.1001/jama.286.17.2120.

  PMID: 11694153 BACKGROUND

• Small GW, Ercoli LM, Silverman DH, Huang SC, Komo S, Bookheimer SY, Lavretsky H, Miller K, Siddarth P, Rasgon NL, Mazziotta JC, Saxena S, Wu HM, Mega MS, Cummings JL, Saunders AM, Pericak-Vance MA, Roses AD, Barrio JR, Phelps ME. Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer's disease. Proc Natl Acad Sci U S A. 2000 May 23;97(11):6037-42. doi: 10.1073/pnas.090106797.

  PMID: 10811879 BACKGROUND

MeSH Terms

Conditions

Cognition Disorders; Alzheimer Disease; Cognitive Dysfunction

Interventions

Donepezil

Condition Hierarchy (Ancestors)

Neurocognitive Disorders; Mental Disorders; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Indans; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds

Study Officials

• Gary W. Small, MD

  University of California, Los Angeles, Neuropsychiatric Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH

Study Record Dates

• First Submitted: December 16, 2005
• First Posted: December 20, 2005
• Study Start: September 1, 2000
• Primary Completion: July 1, 2007
• Study Completion: July 1, 2007
• Last Updated: August 29, 2008

Record last verified: 2008-08

Locations

US (1)