Gary W. Small

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The apolipoprotein E type 4 allele (APOE-epsilon 4) is genetically associated with the common late onset familial and sporadic forms of Alzheimer's disease (AD). Risk for AD increased from 20% to 90% and mean age at onset decreased from 84 to 68 years with increasing number of APOE-epsilon 4 alleles in 42 families with late onset AD. Thus APOE-epsilon 4(More)
BACKGROUND The epsilon4 allele of the apolipoprotein E gene (APOE) is the chief known genetic risk factor for Alzheimer's disease, the most common cause of dementia late in life. To determine the relation between brain responses to tasks requiring memory and the genetic risk of Alzheimer's disease, we performed APOE genotyping and functional magnetic(More)
The authors used 2-(1-(6-[(2-[18F]fluoroethyl)(methyl)amino]-2-naphthyl)ethylidene)malononitrile ([18F]FDDNP), a hydrophobic radiofluorinated derivative of 2-(1-[6-(dimethylamino)-2-naphthyl]ethylidene)malononitrile (DDNP), in conjunction with positron emission tomography to determine the localization and load of neurofibrillary tangles (NFTs) and(More)
BACKGROUND Amyloid senile plaques and tau neurofibrillary tangles are neuropathological hallmarks of Alzheimer's disease that accumulate in the cortical regions of the brain in persons with mild cognitive impairment who are at risk for Alzheimer's disease. Noninvasive methods to detect these abnormal proteins are potentially useful in developing surrogate(More)
CONTEXT Deficits in cerebral glucose utilization have been identified in patients with cognitive dysfunction attributed to various disease processes, but their prognostic and diagnostic value remains to be defined. OBJECTIVE To assess the sensitivity and specificity with which cerebral metabolic patterns at a single point in time forecast subsequent(More)
The onset of Alzheimer's disease (AD) is accompanied by a complex and distributed pattern of neuroanatomic change, difficult to distinguish clinically from dynamic alterations in normal aging. Extreme variations in the sulcal patterns of the human cortex have made it difficult to identify diffuse and focal variations in cortical structure in(More)
Cholinesterase inhibitors are the 'first-line' agents in the treatment of Alzheimer's disease. This article presents the latest information on their pharmacokinetic properties and pharmacodynamic activity. Tacrine was the first cholinesterase inhibitor approved by regulatory agencies, followed by donepezil, rivastigmine and recently galantamine. With the(More)
The association between [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) counts obtained 8 h before death and neurofibrillary tangle (NFT) staining density in a patient with Alzheimer's disease (AD) was evaluated. In our patient FDG-PET counts were globally decreased with a greater focal deficit in the left medial temporal region independent(More)
Senile plaques (SPs) and neurofibrillary tangles (NFTs) are hallmark pathologies accompanying the neurodegeneration involved in Alzheimer's disease (AD), for which beta-amyloid (Abeta) peptide is a major constituent of SPs. Our laboratories previously developed the hydrophobic, fluorescent molecular-imaging probe(More)
The major known genetic risk for Alzheimer's disease (AD), apolipoprotein E-4 (APOE-4), is associated with lowered parietal, temporal, and posterior cingulate cerebral glucose metabolism in patients with a clinical diagnosis of AD. To determine cognitive and metabolic decline patterns according to genetic risk, we investigated cerebral metabolic rates by(More)