Alzheimer's disease: progress in prediction

Alzheimer's Disease Research Center, Mayo Clinic College of Medicine, Rochester, MN, USA.
The Lancet Neurology (Impact Factor: 21.9). 01/2010; 9(1):4-5. DOI: 10.1016/S1474-4422(09)70330-8
Source: PubMed
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    • "Among scientists, health professionals, and policymakers, interest in the disease has grown in recent years due to the growing demands for care by patients and a number of important research findings, including the identification of additional genetic risk factors and the release of new diagnostic guidelines [6] [7]. This complements other recent scientific developments in potential drug therapies, diagnostic procedures [8], and other research on potential risk factors, such as dietary choices, chronic disease, and medication usage [9] [10]. Single-country surveys have looked at public attitudes and beliefs about Alzheimer's disease [11] [12]. "
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    ABSTRACT: The objective of this paper is to understand how the public's beliefs in five countries may change as more families have direct experience with Alzheimer's disease. The data are derived from a questionnaire survey conducted by telephone (landline and cell) with 2678 randomly selected adults in France, Germany, Poland, Spain, and the United States. The paper analyzes the beliefs and anticipated behavior of those in each country who report having had a family member with Alzheimer's disease versus those who do not. In one or more countries, differences were found between the two groups in their concern about getting Alzheimer's disease, knowledge that the disease is fatal, awareness of certain symptoms, and support for increased public spending. The results suggest that as more people have experience with a family member who has Alzheimer's disease, the public will generally become more concerned about Alzheimer's disease and more likely to recognize that Alzheimer's disease is a fatal disease. The findings suggest that other beliefs may only be affected if there are future major educational campaigns about the disease. The publics in individual countries, with differing cultures and health systems, are likely to respond in different ways as more families have experience with Alzheimer's disease.
    International Journal of Alzheimer's Disease 09/2012; 2012:903645. DOI:10.1155/2012/903645
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    • "It should be noted that despite these general group patterns, the rate of amyloid-b deposition was highly variable from one subject to another, for instance there was no amyloid-b accumulation in a PiB + healthy control with a global neocortical PiB SUVR pons of + 0.90 while it was ongoing in a patient with Alzheimer's disease with a global neocortical PiB SUVR pons of + 1.2 (Fig. 4). As a whole, the dynamics of amyloid-b deposition are unlikely to be constant and are probably more consistent with a sigmoid curve, but with a different timing as previously proposed (Perrin et al., 2009; Aisen et al., 2010; Frisoni et al., 2010; Jack et al., 2010a; Petersen, 2010; Weiner et al., 2010; Ewers et al., 2011; Sperling et al., 2011a) (Figs 4 and 6). Indeed, PiB accumulation was found to be significantly higher in PiB + compared with PiB À individuals. "
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    ABSTRACT: Amyloid-β deposition in Alzheimer's disease is thought to start while individuals are still cognitively unimpaired and it is hypothesized that after an early phase of fast accumulation, a plateau is reached by the time of cognitive decline. However, few longitudinal Pittsburgh compound B-positron emission tomography studies have tested this hypothesis, and with conflicting results. The purpose of this work is to further our understanding of the dynamics of amyloid-β deposition in a large longitudinal cohort. A total of 32 patients with Alzheimer's disease, 49 subjects with mild cognitive impairment and 103 healthy controls underwent two Pittsburgh compound B-positron emission tomography scans 18 months apart. For each participant, a parametric map of Pittsburgh compound B-positron emission tomography rate of change was created [(follow-up scan - baseline scan)/follow-up duration] and entered in a voxelwise three-way analysis of covariance, with clinical status (healthy controls, mild cognitive impairment or Alzheimer's disease), disease progression (clinical conversion from healthy controls to mild cognitive impairment or Alzheimer's disease, or from mild cognitive impairment to Alzheimer's disease) and Pittsburgh compound B status (positive versus negative) as independent factors. Only a significant effect of the Pittsburgh compound B status was found: both Pittsburgh compound B-positive and -negative subjects showed a significant increase in amyloid-β deposition, with this increase being significantly higher in Pittsburgh compound B-positive individuals. This finding suggests either that Pittsburgh compound B-negative individuals have slower rates of amyloid-β accumulation than positive, or that the proportion of individuals showing significant increase in amyloid-β deposition, termed 'Pittsburgh compound B accumulators', is higher within the Pittsburgh compound B-positive group than within the Pittsburgh compound B-negative group. The bimodal distribution of the individual rates of neocortical amyloid-β accumulation observed support the existence of 'Pittsburgh compound B non-accumulators' and 'Pittsburgh compound B accumulators' and different clustering analyses led to a consistent threshold to separate these two subgroups (0.014-0.022 standardized uptake value ratio(pons)/year). The voxelwise three-way analysis of covariance was thus recomputed with the 'Pittsburgh compound B accumulators' only and the results were almost unchanged, with the Pittsburgh compound B-positive group showing higher accumulation than the Pittsburgh compound B-negative group. Finally, a significant negative correlation was found between Pittsburgh compound B rate of change and Pittsburgh compound B baseline burden, but only in the Pittsburgh compound B-positive group (r= -0.24; P=0.025). Higher rates of amyloid-β deposition are associated with higher amyloid-β burden suggesting that amyloid-β deposition does not reach a plateau when cognitive impairments manifest but is instead an ongoing process present even at the Alzheimer's disease stage. amyloid-β accumulation also seems to slow down at the latest stages of the process, i.e. in participants with the highest amyloid burden. Furthermore, this study identified the existence of Pittsburgh compound 'accumulators' and 'non-accumulators', notably within the Pittsburgh compound B-negative group, which may be a relevant concept for future studies.
    Brain 05/2012; 135(Pt 7):2126-39. DOI:10.1093/brain/aws125 · 9.20 Impact Factor
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    • "Evidence suggests that these AD biomarkers do not reach abnormal levels or peak simultaneously but do so in an ordered manner, consequent with disease progression. Petersen [4] and Jack et al. [5] have stated that disease progression is essentially biphasic, with biomarkers of A␤ deposition first to become abnormal (e.g., cerebrospinal fluid (CSF) A␤), followed by neurodegeneration "
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    ABSTRACT: Biomarkers, both biological and imaging, are indicators of specific changes that characterize Alzheimer's disease (AD) progression in vivo. Knowing the precise relationship between biomarkers and disease severity would allow for accurate disease staging and possible forecasting of decline. Jack et al. suggested as an initial hypothesis that this relationship be sigmoidal; the objective of this article is to determine, using large-scale population data from ADNI, the precise shape of this association. We considered six different models (linear; quadratic; robust quadratic; local quadratic regression; penalized B-spline; and sigmoid) and used the Akaike Information Criterion to gauge how well these models compare in conforming to the data. We included 576 subjects (229 controls, 193 AD, and 154 mild cognitive impairment subjects who converted to AD) from the ADNI study, for whom baseline data on cerebrospinal fluid amyloid-β (Aβ)42, phosphorylated tau (p-tau), and total-tau (t-tau), hippocampal volumes, and FDG-PET were available. Analysis of this cross-sectional dataset showed that a local quadratic regression model was 42% more likely than a sigmoid to be the best model for Aβ42. This ratio augments to 22% and 73% for Penalized B-Spline in the case of p-tau and t-tau, respectively; to 3500% for the linear model for FDG-PET; and to 6700% for the Penalized B-Spline for hippocampal volumes. Preliminary, cross-sectional evidence therefore indicates that the shape of the association with disease severity is non-linear and differs between biomarkers.
    Journal of Alzheimer's disease: JAD 03/2012; 30(1):91-100. DOI:10.3233/JAD-2012-111367 · 4.15 Impact Factor
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