Article

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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Available from: ncbi.nlm.nih.gov
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    • "In this regard, a better and more comprehensive characterization of mild cognitive impairment (MCI) is essential for appropriate identification of incipient AD, since subjects with MCI are at a higher risk of developing AD (Mufson et al 2012). MCI is defined as the symptomatic predementia stage of AD in which subjects exhibit a memory impairment beyond what would be expected for their age, but do not fully accomplish the criteria for a diagnosis of dementia (Petersen 2010). As a consequence, MCI is considered a prodromal stage of dementia (Mufson et al 2012). "
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    ABSTRACT: Objective: Current diagnostic guidelines encourage further research for the development of novel Alzheimer's disease (AD) biomarkers, especially in its prodromal form (i.e. mild cognitive impairment, MCI). Magnetoencephalography (MEG) can provide essential information about AD brain dynamics; however, only a few studies have addressed the characterization of MEG in incipient AD. Approach: We analyzed MEG rhythms from 36 AD patients, 18 MCI subjects and 27 controls, introducing a new wavelet-based parameter to quantify their dynamical properties: the wavelet turbulence. Main results: Our results suggest that AD progression elicits statistically significant regional-dependent patterns of abnormalities in the neural activity (p < 0.05), including a progressive loss of irregularity, variability, symmetry and Gaussianity. Furthermore, the highest accuracies to discriminate AD and MCI subjects from controls were 79.4% and 68.9%, whereas, in the three-class setting, the accuracy reached 67.9%. Significance: Our findings provide an original description of several dynamical properties of neural activity in early AD and offer preliminary evidence that the proposed methodology is a promising tool for assessing brain changes at different stages of dementia.
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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.
    Full-text · Article · Sep 2012 · International Journal of Alzheimer's Disease
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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.
    Full-text · Article · May 2012 · Brain
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