Familial Alzheimer disease: Decreases in CSF A 42 levels precede cognitive decline

Department of Medicine, University of Toronto, Toronto, Ontario, Canada
Neurology (Impact Factor: 8.3). 08/2005; 65(2):323-5. DOI: 10.1212/01.wnl.0000171397.32851.bc
Source: PubMed

ABSTRACT CSF amyloid beta-peptide 42 (A beta(42)) levels in presymptomatic subjects with pathogenic mutations in the PS1 gene are significantly lower than in an age-matched control group. Consequently, in these subjects, there is a window of opportunity estimated as at least 4 to 12 years to evaluate the ability of any putative prophylactic therapy to decrease, arrest, or reverse abnormalities in A beta(42) metabolism many years before clinical symptoms of Alzheimer disease are otherwise likely to occur.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Neuropsychological assessment has featured prominently over the past 30 years in the characterization of dementia associated with Alzheimer disease (AD). Clinical neuropsychological methods have identified the earliest, most definitive cognitive and behavioral symptoms of illness, contributing to the identification, staging, and tracking of disease. With increasing public awareness of dementia, disease detection has moved to earlier stages of illness, at a time when deficits are both behaviorally and pathologically selective. For reasons that are not well understood, early AD pathology frequently targets large-scale neuroanatomical networks for episodic memory before other networks that subserve language, attention, executive functions, and visuospatial abilities. This chapter reviews the pathognomonic neuropsychological features of AD dementia and how these differ from "normal," age-related cognitive decline and from other neurodegenerative diseases that cause dementia, including cortical Lewy body disease, frontotemporal lobar degeneration, and cerebrovascular disease.
    Cold Spring Harbor Perspectives in Medicine 04/2012; 2(4):a006171. DOI:10.1101/cshperspect.a006171 · 7.56 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: IntroductionThe diagnosis of Alzheimer's disease (AD) currently relies on clinical criteria that are primarily based on the presence of an amnestic syndrome of the mesial temporal lobe type. In recent years, new diagnostic tools have been developed, such as the possibility of measuring a set of proteins directly involved in the pathophysiological process of AD. A profile suggestive of AD has been defined, characterized by decreased beta-amyloid peptide, combined with increased Tau protein and phopho-Tau.
    Revue Neurologique 06/2011; 167(6):474-484. DOI:10.1016/j.neurol.2010.10.007 · 0.60 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cognitive neuroscience involves the simultaneous analysis of behavioral and neurological data. Common practice in cognitive neuroscience, however, is to limit analyses to the inspection of descriptive measures of association (e.g., correlation coefficients). This practice, often combined with little more than an implicit theoretical stance, fails to address the relationship between neurological and behavioral measures explicitly. This article argues that the reduction problem, in essence, is a measurement problem. As such, it should be solved by using psychometric techniques and models. We show that two influential philosophical theories on this relationship, identity theory and supervenience theory, can be easily translated into psychometric models. Upon such translation, they make explicit hypotheses based on sound theoretical and statistical foundations, which renders them empirically testable. We examine these models, show how they can elucidate our conceptual framework, and examine how they may be used to study foundational questions in cognitive neuroscience. We illustrate these principles by applying them to the relation between personality test scores, intelligence tests, and neurological measures.
    Psychological Inquiry 04/2011; 22(2):67-87. DOI:10.1080/1047840X.2011.550181 · 6.65 Impact Factor