Implications of Amyloid Pathology
Implications of Amyloid Pathology
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.
|Min Age||Max Age||Gender||Healthy Volunteers|
- Age 60-90
- Clinical Dementia Rating (CDR) score of 0; Mini Mental State Exam score of 27-30
- A study partner who can answer questions pertaining to daily functioning
- Able to perform within 1.5 standard deviation of age- and education-matched norms on screening tests of attention, 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 of <10
- Diagnosis of mild cognitive impairment (MCI) or dementia
- Contraindications to MRI (i.e., implanted metal such as pacemakers, cerebralspinal fluid shunts, aneurysm clips, artificial heart valves, ear implants) or a history of claustrophobia)
- Major psychiatric disorders (mild depression 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, central nervous system 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
- Prohibited medications: Unstable medications or medications with central nervous system effects, including cholinesterase inhibitors, memantine, and antidepressants
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.
|Map Marker||City||State||Zip Code||Status||Primary Contact|
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