The purpose of this study is to determine whether asymptomatic older individuals with high amyloid burden will subsequently develop cognitive impairment and eventually progress to clinical Alzheimer's disease.
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There is compelling evidence supporting amyloid, a protein, as one of the key pathologic agents in Alzheimer's disease. 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.
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 preclinical Alzheimer's.
The study will use a combination of functional, structural, and cognitive measures to detect early effects of amyloid deposition and will utilize PIB retention (as seen on a type of neuroimaging) to characterize the relationship of amyloid to neuropsychological and imaging markers of preclinical Alzheimer's. The relationship of PIB retention to genetic, plasma, and cerebrospinal fluid biomarkers will be explored. These preliminary data will be used to determine whether asymptomatic older individuals with high amyloid burden will subsequently develop cognitive impairment and eventually progress to clinical Alzheimer's disease. When completed, this project will either provide evidence that 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 Alzheimer's.
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Geolocation is 42.339904, -71.0898892
Brigham and Women's Hospital
National Institute on Aging (NIA)
Reisa Sperling, MD
Director of Clinical Research, Memory Disorders Unit, Brigham and Women's Hospital