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- Frisoni, Giovanni B, et al.
(författare)
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The pilot European Alzheimer's Disease Neuroimaging Initiative of the European Alzheimer's Disease Consortium.
- 2008
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Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 4:4, s. 255-64
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In North America, the Alzheimer's Disease Neuroimaging Initiative (ADNI) has established a platform to track the brain changes of Alzheimer's disease. A pilot study has been carried out in Europe to test the feasibility of the adoption of the ADNI platform (pilot E-ADNI). METHODS: Seven academic sites of the European Alzheimer's Disease Consortium (EADC) enrolled 19 patients with mild cognitive impairment (MCI), 22 with AD, and 18 older healthy persons by using the ADNI clinical and neuropsychological battery. ADNI compliant magnetic resonance imaging (MRI) scans, cerebrospinal fluid, and blood samples were shipped to central repositories. Medial temporal atrophy (MTA) and white matter hyperintensities (WMH) were assessed by a single rater by using visual rating scales. RESULTS: Recruitment rate was 3.5 subjects per month per site. The cognitive, behavioral, and neuropsychological features of the European subjects were very similar to their U.S. counterparts. Three-dimensional T1-weighted MRI sequences were successfully performed on all subjects, and cerebrospinal fluid samples were obtained from 77%, 68%, and 83% of AD patients, MCI patients, and controls, respectively. Mean MTA score showed a significant increase from controls (left, right: 0.4, 0.3) to MCI patients (0.9, 0.8) to AD patients (2.3, 2.0), whereas mean WMH score did not differ among the three diagnostic groups (between 0.7 and 0.9). The distribution of both MRI markers was comparable to matched US-ADNI subjects. CONCLUSIONS: Academic EADC centers can adopt the ADNI platform to enroll MCI and AD patients and older controls with global cognitive and structural imaging features remarkably similar to those of the US-ADNI.
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- Hampel, Harald, et al.
(författare)
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Core candidate neurochemical and imaging biomarkers of Alzheimer's disease.
- 2008
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Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 4:1, s. 38-48
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: In the earliest clinical stages of Alzheimer's disease (AD) when symptoms are mild, clinical diagnosis can be difficult. AD pathology most likely precedes symptoms. Biomarkers can serve as early diagnostic indicators or as markers of preclinical pathologic change. Candidate biomarkers derived from structural and functional neuroimaging and those measured in cerebrospinal fluid (CSF) and plasma show the greatest promise. Unbiased exploratory approaches, eg, proteomics or cortical thickness analysis, could yield novel biomarkers. The objective of this article was to review recent progress in selected imaging and neurochemical biomarkers for early diagnosis, classification, progression, and prediction of AD. METHODS: We performed a survey of recent research, focusing on core biomarker candidates in AD. RESULTS: A number of in vivo neurochemistry and neuroimaging techniques, which can reliably assess aspects of physiology, pathology, chemistry, and neuroanatomy, hold promise as biomarkers. These neurobiologic measures appear to relate closely to pathophysiologic, neuropathologic, and clinical data, such as hyperphosphorylation of tau, amyloid beta (Abeta) metabolism, lipid peroxidation, pattern and rate of atrophy, loss of neuronal integrity, functional and cognitive decline, as well as risk of future decline. Current advances in the neuroimaging of mediotemporal, neocortical, and subcortical areas of the brain of mild cognitive impairment (MCI) and AD subjects are presented. CSF levels of Abeta42, tau, and hyperphosphorylated tau protein (p-tau) can distinguish subjects with MCI who are likely to progress to AD. They also show preclinical alterations that predict later development of early AD symptoms. Studies on plasma Abeta are not entirely consistent, but recent findings suggest that decreased plasma Abeta42 relative to Abeta40 might increase the risk of AD. Increased production of Abeta in aging is suggested by elevation of BACE1 protein and enzyme activity in the brain and CSF of subjects with MCI. CSF tau and p-tau are increased in MCI as well and show predictive value. Other biomarkers might indicate components of a cascade initiated by Abeta, such as oxidative stress or inflammation. These merit further study in MCI and earlier. CONCLUSIONS: A number of neuroimaging candidate markers are promising, such as hippocampus and entorhinal cortex volumes, basal forebrain nuclei, cortical thickness, deformation-based and voxel-based morphometry, structural and effective connectivity by using diffusion tensor imaging, tractography, and functional magnetic resonance imaging. CSF Abeta42, BACE1, total tau, and p-tau are substantially altered in MCI and clinical AD. Other interesting novel marker candidates derived from blood are being currently proposed (phase I). Biomarker discovery through proteomic approaches requires further research. Large-scale international controlled multicenter trials (such as the U.S., European, Australian, and Japanese Alzheimer's Disease Neuroimaging Initiative and the German Dementia Network) are engaged in phase III development of the core feasible imaging and CSF biomarker candidates in AD. Biomarkers are in the process of implementation as primary outcome variables into regulatory guideline documents regarding study design and approval for compounds claiming disease modification.
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- Håkansson, Krister
(författare)
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O2-07-01: Unmarried Life: Paving the way for dementia?
- 2008
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 4:4, Supplement, s. T146-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Although social networks and activities have recently been suggested to protect against dementia, few long-term follow-up studies exist. The main purpose of our study was to evaluate whether midlife marital status is related to late-life cognitive function. Methods: Participants of the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study were derived from random, population-based samples previously studied. After an average follow-up of 21 years, 1449 individuals (73%) aged 65 to 79 years were re-examined in 1998. At re-examination 139 persons were diagnosed with some form of cognitive impairment: 82 of those with mild cognitive impairment (MCI) and 48 with Alzheimer's disease (AD)). The relation between midlife marital status and cognitive impairment was analyzed with adjustments for a number of other midlife factors, including education, BMI, cholesterol, blood pressure, occupation, physical activity, smoking habits and depression. Adjustments were also made for ApoE status, age at follow-up and gender. Results: Persons living with a partner in midlife were significantly less likely to show cognitive impairment compared to all other categories (single, separated or widowed). The highest risk increase was found for those widowed at midlife and still so at the follow-up (N=105). For Alzheimers disease specifically, the risk increase was almost eight-fold for this group compared to those married both at midlife and still so at late-life. Progressive adjustments for possible confounders did not weaken the associations. Conclusions: Living in a partner relation may imply cognitive and social challenges with a protective effect against cognitive impairment. Involvement of other factors is however suggested by the specific risk increase for widowed in relation to singles. Possible selection bias behind the strongly increased cognitive impairment risk for those widowed at midlife, in relation to the married group, seems unlikely. The long-term prospective design should also preclude any reverse causation effects behind the results.
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- Olsson, Veronica, et al.
(författare)
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Analysis of apoptotic processes in live cells
- 2006
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 2:3, Supplement, s. S439-S440
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Neuronal and synaptic loss can be observed in several neurologic disorders, like Alzheimer’s disease (AD). The mechanism behind cell death in AD has been intensively studied and apoptosis has been proposed to play a central role in death processes, primary affecting cholinergic neurons in the cerebral cortex and the limbic lobe. There are numerous potential death stimuli that may be relevant in AD, including inflammatory responses, growth factor deprivation, oxidative stress and direct effects of the β- amyloid peptide. Objective: In order to get further insights in the initiation of apoptotic processes, we have developed a set of caspase sensors. Methods: We have used fluorescence resonance energy transfer (FRET) technology to, in real time and at single cell level, monitor the crucial event of the activation cysteine aspartate proteases, central in apoptosis. The two chromophores ECFP and EYFP, separated by a caspase cleavage site, have been used to visualize the caspase cleavage event at a chosen subcellular location in different cellular models, including differentiated neuronal cells. Since several apoptotic signalling pathways may be involved, we have designed sensors that can be cleaved by caspase-3, -8 or -9, representing two possible pathways, the death receptor pathway and the mitochondrial pathway. The in vitromodel used initially to characterize the caspase sensors has been HeLa cells, stimulated with staurosporin. The condition of the cells and the different stages of apoptosis were identified by nuclear staining with Hoechst 33258. Results: Our preliminary data indicate that caspase cleavage is an early event in the apoptotic cascade initiated by staurosporin, and that it most likely begins central in the cell body as FRET signals can be detected at later stages only in the cell periphery. Over-expression of the sensors did not result in any detectable toxicity since cells were able to divide successfully and no morphological changes could be revealed. Conclusion: Using this approach, a better temporal and spatial understanding of the apoptotic processes will be achieved. This is necessary in order to identify therapeutic targets to prevent the massive loss of neurons in AD and related disorders.
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- Rosenberg, Lena, et al.
(författare)
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P2-251 : Assistive technology in the hands of people with dementia and their significant others
- 2008
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Ingår i: Alzheimer's & Dementia. - : John Wiley & Sons. - 1552-5260 .- 1552-5279. ; 4:4S Part 13, s. T445-T445
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThis is an in-depth, qualitative study of the process that takes place when a person with mild stage dementia is to become a user of assistive technology. The aim is to explore the interaction between the person with dementia, the home context, the assistive technology and significant others.MethodsData was collected through observations and in-depth interviews on repeated occasions in the homes of persons with dementia. Informants were persons with dementia and, depending on each case, other significant persons (e.g. family, neighbours, occupational therapists, home helpers). Each person with dementia together with the significant others that were related to him/her was considered as one case. Theoretical sampling guided the data collection and the analysis followed the principles of Grounded Theory. The three included cases encompassed a total of eleven informants and eight assistive technologies.ResultsPreliminary results indicate that the significant others in each case perceived the assistive technology in different ways and had different views about how it should be used and for what purposes, which also led them to take different steps of action. For example, significant others tried to help the person with dementia to interact with the assistive technology in a way that interfered with the person's own strategies. Moreover, the persons with dementia used assistive technology such as electronic calendar to keep up with forthcoming events but also, even more important to them, to recall what had happened and how they had felt in certain situations. This was in contrast to the significant others who expected the assistive technology to support the prospective memory rather than the episodic memory. Furthermore, the results showed that minor adjustments could profoundly change the meaning and usability of the technology, for example, the placement of it, or combining the assistive technology with another source of information.ConclusionsBased on these preliminary results, assistive technology should not be viewed or introduced as ready-to-use objects without adjustments to fit the user's needs and situation. The process of implementation needs time and attention, including consideration of the expectations and perceptions of the significant others of the person with dementia.
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