Implications of Amyloid Pathology

NCT ID: NCT00900770

Last Updated: 2009-12-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

100 participants

Study Classification

OBSERVATIONAL

Study Start Date

2008-11-30

Study Completion Date

2014-03-31

Brief Summary

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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).

Detailed Description

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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.

Conditions

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Alzheimer's Disease

Keywords

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dementia mild cognitive impairment beta amyloid

Study Design

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Observational Model Type

COHORT

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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PIB+ NC

PIB positive, cognitively normal individuals with foci of elevated PIB retention in cortical regions typically affected in AD

No interventions assigned to this group

PIB- NC

PIB negative, cognitively normal individuals without amyloid deposition

No interventions assigned to this group

Eligibility Criteria

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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
Minimum Eligible Age

60 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute on Aging (NIA)

NIH

Sponsor Role lead

Responsible Party

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Brigham and Women's Hospital

Principal Investigators

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Reisa Sperling, MD

Role: PRINCIPAL_INVESTIGATOR

Director of Clinical Research, Memory Disorders Unit, Brigham and Women's Hospital

Locations

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Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Countries

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United States

Facility Contacts

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Kelly O'Keefe

Role: primary

Meghan Frey

Role: backup

References

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Dickerson BC, Bakkour A, Salat DH, Feczko E, Pacheco J, Greve DN, Grodstein F, Wright CI, Blacker D, Rosas HD, Sperling RA, Atri A, Growdon JH, Hyman BT, Morris JC, Fischl B, Buckner RL. The cortical signature of Alzheimer's disease: regionally specific cortical thinning relates to symptom severity in very mild to mild AD dementia and is detectable in asymptomatic amyloid-positive individuals. Cereb Cortex. 2009 Mar;19(3):497-510. doi: 10.1093/cercor/bhn113. Epub 2008 Jul 16.

Reference Type BACKGROUND
PMID: 18632739 (View on PubMed)

Aizenstein HJ, Nebes RD, Saxton JA, Price JC, Mathis CA, Tsopelas ND, Ziolko SK, James JA, Snitz BE, Houck PR, Bi W, Cohen AD, Lopresti BJ, DeKosky ST, Halligan EM, Klunk WE. Frequent amyloid deposition without significant cognitive impairment among the elderly. Arch Neurol. 2008 Nov;65(11):1509-17. doi: 10.1001/archneur.65.11.1509.

Reference Type BACKGROUND
PMID: 19001171 (View on PubMed)

Jack CR Jr, Lowe VJ, Senjem ML, Weigand SD, Kemp BJ, Shiung MM, Knopman DS, Boeve BF, Klunk WE, Mathis CA, Petersen RC. 11C PiB and structural MRI provide complementary information in imaging of Alzheimer's disease and amnestic mild cognitive impairment. Brain. 2008 Mar;131(Pt 3):665-80. doi: 10.1093/brain/awm336. Epub 2008 Feb 7.

Reference Type BACKGROUND
PMID: 18263627 (View on PubMed)

Mintun MA, Larossa GN, Sheline YI, Dence CS, Lee SY, Mach RH, Klunk WE, Mathis CA, DeKosky ST, Morris JC. [11C]PIB in a nondemented population: potential antecedent marker of Alzheimer disease. Neurology. 2006 Aug 8;67(3):446-52. doi: 10.1212/01.wnl.0000228230.26044.a4.

Reference Type BACKGROUND
PMID: 16894106 (View on PubMed)

Other Identifiers

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2P50AG005134-268381

Identifier Type: -

Identifier Source: secondary_id

2P50AG005134

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IA0158

Identifier Type: -

Identifier Source: org_study_id