Donepezil and Brain Activity Patterns in Those at Risk For Alzheimer's Disease

Alzheimer's Disease Clinical Trial

Official title:

Efficacy of Donepezil in Normalizing Brain Activation Patterns in People Genetically at Risk for Alzheimer's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00408525
• Other study ID #: 040686
• Status: Completed
• Phase: Phase 1
• First received: December 5, 2006
• Last updated: February 1, 2018
• Start date: December 2006
• Est. completion date: August 24, 2012

Study information

• Verified date: February 2018
• Source: Vanderbilt University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to examine patterns of brain activity in people who are at risk for memory problems (e.g., Alzheimer's disease or dementia)before and after the medication donepezil. Although genetic testing will be done, the results will not be shared with study participants.

Once the genetic testing is completed subjects may continue to the second phase of the study. During this time they will be asked to take the medication donepezil (which is approved by the FDA for the treatment of Alzheimer's disease).

Donepezil is not FDA approved for healthy volunteers and is therefore considered investigational in this study.

Description:

HYPOTHESIS

1. Cognitively intact individuals with normal brain morphology at genetic risk for developing Alzheimer's' Disease (AD) show alterations in brain activation patterns during tasks that require memory compared to similar individuals with lower risk for developing AD.

2. Donepezil, a cholinesterase inhibitor, can normalize such brain activation patterns in subjects at risk for AD.

SPECIFIC AIMS

1. To replicate a recent study1, and compare brain activation in subjects genetically at risk for AD (carriers of the є4 allele of the apolipoprotein E gene (APOE)) with subjects at lower risk for AD (lacking the є4 allele) during tasks that require memory, via functional magnetic resonance imaging (fMRI).

2. To determine if administration of a drug currently indicated in the treatment of AD, donepezil, can reverse fMRI brain activation patterns of at risk subjects to patterns similar to those of subjects at lower genetic risk for AD.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: August 24, 2012
• Est. primary completion date: August 24, 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 40 Years to 85 Years

Eligibility

Inclusion Criteria:

• Subjects may report experiencing subjective memory dysfunction, however they must be found by clinical evaluation to have no memory dysfunction

• Neuropsychological test battery in the normal range

• Ages 40-85

Exclusion Criteria:

• Dementia (Mini-Mental State Exam less than 25/30)

• Left-handedness

• Current medication that could influence cognition

• Medical, psychiatric, and neurologic conditions, including cerebrovascular disease or uncontrolled hypertension

• Claustrophobia

• Surgical clips or implants

• Pacemakers or other implanted electronic devices

• History of sheet metal work

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Drug:
• donepezil
donepezil 5 mg tablets, total dose per day 10 mg for 6 week duration of study. Taken once per day.

Locations

Country	Name	City	State
United States	Vanderbilt University Medical Center	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Vanderbilt University

Country where clinical trial is conducted

United States, 

References & Publications (9)

Bookheimer SY, Strojwas MH, Cohen MS, Saunders AM, Pericak-Vance MA, Mazziotta JC, Small GW. Patterns of brain activation in people at risk for Alzheimer's disease. N Engl J Med. 2000 Aug 17;343(7):450-6. — View Citation

Borroni B, Colciaghi F, Pastorino L, Pettenati C, Cottini E, Rozzini L, Monastero R, Lenzi GL, Cattabeni F, Di Luca M, Padovani A. Amyloid precursor protein in platelets of patients with Alzheimer disease: effect of acetylcholinesterase inhibitor treatment. Arch Neurol. 2001 Mar;58(3):442-6. — View Citation

Burggren AC, Small GW, Sabb FW, Bookheimer SY. Specificity of brain activation patterns in people at genetic risk for Alzheimer disease. Am J Geriatr Psychiatry. 2002 Jan-Feb;10(1):44-51. — View Citation

Morris JC. Is Alzheimer's disease inevitable with age?: Lessons from clinicopathologic studies of healthy aging and very mild alzheimer's disease. J Clin Invest. 1999 Nov;104(9):1171-3. Review. — View Citation

Padovani A, Pastorino L, Borroni B, Colciaghi F, Rozzini L, Monastero R, Perez J, Pettenati C, Mussi M, Parrinello G, Cottini E, Lenzi GL, Trabucchi M, Cattabeni F, Di Luca M. Amyloid precursor protein in platelets: a peripheral marker for the diagnosis of sporadic AD. Neurology. 2001 Dec 26;57(12):2243-8. — View Citation

Reiman EM, Caselli RJ, Yun LS, Chen K, Bandy D, Minoshima S, Thibodeau SN, Osborne D. Preclinical evidence of Alzheimer's disease in persons homozygous for the epsilon 4 allele for apolipoprotein E. N Engl J Med. 1996 Mar 21;334(12):752-8. — View Citation

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. — View Citation

Small GW, Mazziotta JC, Collins MT, Baxter LR, Phelps ME, Mandelkern MA, Kaplan A, La Rue A, Adamson CF, Chang L, et al. Apolipoprotein E type 4 allele and cerebral glucose metabolism in relatives at risk for familial Alzheimer disease. JAMA. 1995 Mar 22-29;273(12):942-7. — View Citation

Smith CD, Andersen AH, Kryscio RJ, Schmitt FA, Kindy MS, Blonder LX, Avison MJ. Women at risk for AD show increased parietal activation during a fluency task. Neurology. 2002 Apr 23;58(8):1197-202. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in brain activation patterns as measured in an fMRI.		8 weeks