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Implications of Amyloid Pathology

This study is currently recruiting participants.
Verified December 2009 by National Institute on Aging (NIA)
Sponsor:
Information provided by:
National Institute on Aging (NIA)
ClinicalTrials.gov Identifier:
NCT00900770
First received: May 11, 2009
Last updated: December 23, 2009
Last verified: December 2009
History of Changes
  Purpose

The purpose of this study is to determine whether asymptomatic older individuals with high amyloid burden will subsequently manifest cognitive impairment and eventually progress to clinical Alzheimer's Disease (AD).


Condition
Alzheimer's Disease

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Implications of Amyloid Deposition in Clinically Normal Older Individuals

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by National Institute on Aging (NIA):

Primary Outcome Measures:
  • Pittsburgh Compound B (PiB) and F-18 fluorodeoxyglucose (FDG) PET Scan [ Time Frame: at 1 month ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Cognitive and functional assessments [ Time Frame: Baseline and annually for 5 years ] [ Designated as safety issue: No ]
  • Lumbar Puncture (optional) [ Time Frame: Baseline ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: November 2008
Estimated Study Completion Date: March 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
PIB+ NC
PIB positive, cognitively normal individuals with foci of elevated PIB retention in cortical regions typically affected in AD
PIB- NC
PIB negative, cognitively normal individuals without amyloid deposition

Detailed Description:

There is compelling evidence supporting amyloid as one of the key pathologic agents in AD. Autopsy studies suggest the amount and location of fibrillar amyloid deposition does not relate strongly to the degree and type of clinical impairment, compared to tau pathology and neuronal loss. A substantial percentage of individuals known to be cognitively intact prior to death demonstrate significant amyloid pathology at autopsy. PIB-PET studies of older normal individuals have also demonstrated significant amyloid deposition in substantial percentages.

This study will test the hypothesis that amyloid is associated with synaptic dysfunction and neuronal damage. While some individuals are able to compensate for amyloid-related toxicity for an extended time period, sensitive imaging and neuropsychological markers will reveal that normal subjects with evidence of high amyloid burden do demonstrate evidence of abnormality consistent with prodromal AD.

The study will use a combination of functional, structural, and cognitive measures to detect early effects of amyloid deposition, and will utilize PIB retention in order to characterize the relationship of amyloid to neuropsychological and imaging markers of prodromal AD. The relationship of PIB retention to genetic, plasma and cerebrospinal fluid (CSF) biomarkers will be explored. These preliminary data will be used to determine whether asymptomatic older individuals with high amyloid burden will subsequently manifest cognitive impairment and eventually progress to clinical AD. When completed, this project will either provide evidence that the presence of amyloid deposition is a useful biomarker for incipient AD or raise the possibility that amyloid deposition examined in isolation is insufficient to predict early symptoms and progression of AD.

  Eligibility

Ages Eligible for Study:   60 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Longitudinal cohort of the Massachusetts Alzheimer's Disease Research Center and community volunteers

Criteria

Inclusion Criteria:

  • Age range from 60 to 90 years
  • Clinical Dementia Rating (CDR) Score of 0
  • Mini Mental State Exam of 27-30
  • A study partner who can answer questions pertaining to daily functioning
  • Perform within 1.5 standard deviation of age and education matched norms on screening tests of attention and executive function, language, visuospatial perception and episodic memory
  • Stable medications for at least 30 days
  • Fluent in English
  • Modified Hachinski Score of <4
  • Geriatric Depression Scale Score <10

Exclusion Criteria:

  • Diagnosis of MCI or dementia
  • Individuals with contraindications to MRI (i.e., implanted metal including pacemakers, cerebral spinal fluid shunts, aneurysm clips, artificial heart valves, ear implants or metal/foreign objects in the eyes and those with a history of claustrophobia)
  • Unstable medications or on medications with CNS effects including cholinesterase inhibitors, memantine, and antidepressants
  • Major psychiatric disorders such as schizophrenia, schizoaffective disorder, major affective disorder, or treatment with ECT (mild depression that is well treated with stable dose of SSRI antidepressants will be allowed)
  • Multiple sclerosis or other autoimmune disorders
  • Huntington's disease
  • Head injury, post-traumatic dementia or seizures
  • Metabolic encephalopathy, CNS infection, hydrocephalus
  • Cardiovascular disease, stroke, congestive heart failure
  • Substance abuse within the past 2 years
  • Active cancer
  • Active hematological, renal, pulmonary, endocrine or hepatic disorders
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00900770

Locations
United States, Massachusetts
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Kelly O'Keefe     617-726-6212     kokeefe1@partners.org    
Contact: Meghan Frey     617-732-8085     mfrey1@partners.org    
Principal Investigator: Reisa A. Sperling, MD            
Sub-Investigator: Keith A. Johnson, MD            
Sponsors and Collaborators
National Institute on Aging (NIA)
Investigators
Principal Investigator: Reisa Sperling, MD Director of Clinical Research, Memory Disorders Unit, Brigham and Women's Hospital
  More Information

Publications:

Responsible Party: Reisa Sperling, MD, Director of Clinical Research, Memory Disorders Unit, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT00900770     History of Changes
Other Study ID Numbers: IA0158, 2P50AG005134-268381
Study First Received: May 11, 2009
Last Updated: December 23, 2009
Health Authority: United States: Federal Government

Keywords provided by National Institute on Aging (NIA):
dementia
mild cognitive impairment
beta amyloid

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
 Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders

ClinicalTrials.gov processed this record on May 21, 2013