Sharpen that needle.

Archives of neurology (Impact Factor: 7.01). 08/2010; 67(8):918-20. DOI: 10.1001/archneurol.2010.151
Source: PubMed
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    ABSTRACT: ABSTRACT OBJECTIVE: To determine whether amyloid burden, as indexed by Pittsburgh compound B (PiB) retention, identifies patients with Parkinson disease with mild cognitive impairment (PD-MCI) compared to those with normal cognition (PD-nl). A related aim is to determine whether amyloid burden predicts cognitive decline in a cohort of subjects with PD without dementia. METHODS: In this prospective cohort study, we examined 46 subjects with PD without dementia, of whom 35 had normal cognition and 11 met criteria for PD-MCI at study baseline. All subjects underwent standardized neurologic and neuropsychological examinations and PiB PET at baseline, and clinical examinations were conducted annually for up to 5 years. RESULTS: At baseline, precuneus PiB retention did not distinguish PD-MCI from PD-nl. Subjects with PD-MCI declined more rapidly than PD-nl subjects on cognitive tests of memory, executive function, and activation retrieval. Of the 35 PD-nl subjects, 8 progressed to PD-MCI and 1 to dementia; of the 11 PD-MCI subjects, 5 converted to dementia. Both higher PiB retention and a diagnosis of PD-MCI predicted a greater hazard of conversion to a more severe diagnosis. Baseline PiB retention predicted worsening in executive function over time. The APOE ε4 allele also related to worsening in executive function, as well as visuospatial function, activation retrieval, and performance on the Mini-Mental State Examination. In contrast to its relation to cognitive decline, PiB retention did not affect progression of motor impairment. CONCLUSIONS: At baseline measurements, amyloid burden does not distinguish between cognitively impaired and unimpaired subjects with PD without dementia, but our data suggest that amyloid contributes to cognitive, but not motor, decline over time.
    Neurology 12/2012; 80(1). DOI:10.1212/WNL.0b013e31827b1a07 · 8.30 Impact Factor
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    ABSTRACT: The assumption of a rapidly spreading ‘epidemic’ of Alzheimer's disease (AD), the result of aging populations worldwide, coupled with no effective medication for this condition, has incited a move to bring about the prevention of AD before the appearance of clinical symptoms. The following discussion details the establishment of a research conglomerate designed to prevent AD by means of the systematic detection of biomarker changes in healthy middle-aged or younger people. Among the biomarkers currently being standardized are changes in amyloid-β in cerebrospinal fluid (CSF), and deposition of amyloid-β plaques in the living brain detectable by means of brain scans. Possession of one specific allele of the APOE gene is an additional biomarker. However, these molecular features are merely indicators of increased risk, and pre-symptomatic dementia cannot be definitively diagnosed on the basis of the presence of one or more of them. The composition, distribution, and function of the key molecule being tracked, amyloid-β, remains poorly understood and, highly significant, a large number of individuals with a heavy amyloid load in their brains live to old age with no behavioral signs of dementia. The concluding section considers preparations for a randomized controlled trial designed to detect and eliminate amyloid-β deposition very early in its formation.A number of proofing corrections were not included in the version of this article originally published 22 April 2013. These corrections have been made in this final version.
    BioSocieties 06/2013; 8(2). DOI:10.1057/biosoc.2013.5 · 1.26 Impact Factor
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    ABSTRACT: Reliable biomarkers for Alzheimer's disease (AD) are highly needed in the clinic. As a fluid surrounding the brain and reflecting the major neuropathological features characteristic to the AD brain, the cerebrospinal fluid (CSF) provides the natural source for AD biomarkers. The expected use of an ideal AD biomarker is for the following purposes: (1) diagnosis, (2) prediction, (3) monitoring of disease progression, and (4) drug discovery. Review of the literature revealed that CSF analysis, specifically amyloid-beta (Aβ42, total (T)-tau, and phosphorylated (P)-tau, are reliable markers for AD diagnosis, even at very early stages, particularly vs. healthy controls, while more limited evidence for distinguishing from other dementias. As for prediction, abnormal CSF markers are predictors of cognitive decline in healthy subjects, converting from MCI to development of AD, and of the rate of cognitive decline in mild AD. Regarding monitoring disease progression, the use of CSF biomarkers does not seem very promising since a comparison of the marker levels between baseline and following years of follow-up revealed a remarkable stability of biomarker levels in CSF. As for the use in drug discovery, it is estimated that using CSF markers for the selection of subjects for clinical trials may reduce robustly sample size and trial costs. Yet, since no effective drug is currently available, the contribution of CSF AD biomarkers in drug discovery cannot be currently fully assessed. Nevertheless, testing CSF for evidence of CNS inflammation may help safety monitoring in AD clinical trials. Factors affecting CSF biomarker levels that should be taken into account are assay variability as well as effects of age, gender, apoE and other genetic variations, education, and time of day. Much effort has been and is still being dedicated into developing and validating CSF AD biomarkers by many centers in the world. Identifying additional CSF components, reflecting not only the lesions characteristic to AD (plaques and tangles) but also more functional and structural brain parameters, may provide a wider profile of the changes taking place in AD brains, and be further used as reliable CSF biomarkers for AD monitoring.
    Journal of Molecular Neuroscience 11/2011; 47(1):1-14. DOI:10.1007/s12031-011-9665-5 · 2.76 Impact Factor