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Early AD (early + ad)
Selected AbstractsProteomic identification of nitrated brain proteins in early Alzheimer's disease inferior parietal lobuleJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 8b 2009Tanea T. Reed Abstract Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive decline in multiple cognitive domains. Its pathological hallmarks include senile plaques and neurofibrillary tangles. Mild cognitive impairment (MCI) is the earliest detectable stage of AD with limited symptomology and no dementia. The yearly conversion rate of patients from MCI to AD is 10,15%, although conversion back to normal is possible in a small percentage. Early diagnosis of AD is important in an attempt to intervene or slow the advancement of the disease. Early AD (EAD) is a stage following MCI and characterized by full-blown dementia; however, information involving EAD is limited. Oxidative stress is well-established in MCI and AD, including protein oxidation. Protein nitration also is an important oxidative modification observed in MCI and AD, and proteomic analysis from our laboratory identified nitrated proteins in both MCI and AD. Therefore, in the current study, a proteomics approach was used to identify nitrated brain proteins in the inferior parietal lobule from four subjects with EAD. Eight proteins were found to be significantly nitrated in EAD: peroxiredoxin 2, triose phosphate isomerase, glutamate dehydrogenase, neuropolypeptide h3, phosphoglycerate mutase1, H+, transporting ATPase, ,-enolase and fructose-1,6-bisphosphate aldolase. Many of these proteins are also nitrated in MCI and late-stage AD, making this study the first to our knowledge to link nitrated proteins in all stages of AD. These results are discussed in terms of potential involvement in the progression of this dementing disorder. [source] Working memory in early Alzheimer's disease: a neuropsychological reviewINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 2 2010J. D. Huntley Abstract Background Reports of the extent of working memory (WM) impairment in early Alzheimer's disease (AD) have been inconsistent. Using the model of WM proposed by Baddeley, neuropsychological evidence for the impairment of WM in early AD is evaluated. Method Literature searches were performed using Medline, PsycINFO and Embase databases. Individual papers were then examined for additional references not revealed by computerised searches. Results Phonological loop function is intact at the preclinical and early stages of AD, becoming more impaired as the disease progresses. In mild AD, there is impairment on tasks assessing visuospatial sketchpad (VSS) function; however, these tasks also require executive processing by the central executive system (CES). There is evidence that the CES is impaired in mild AD and may be affected in the earlier preclinical stage of the disease. Episodic buffer function may be impaired but further research is required. Conclusions Future research into central executive functioning at the earliest stages of the disease, combined with further longitudinal studies, needs to be carried out. Tasks to assess the proposed functions of the episodic buffer and specific tests of the VSS suitable for AD subjects need to be developed and validated. Learning more about these processes and how they are affected in AD is important in understanding and managing the cognitive deficits seen in the early stages of AD. Copyright © 2009 John Wiley & Sons, Ltd. [source] Neural correlates of verbal episodic memory in patients with MCI and Alzheimer's disease,,a VBM studyINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 11 2008Dirk T. Leube Abstract Objective The hippocampus is a key area for episodic memory processes. Hippocampal atrophy is a hallmark feature of Alzheimer's disease (AD). We used a new and automatized morphometric technique to better characterize brain atrophy in subjects with different levels of cognitive deficit. Methods In this study 21 participants with Mild Cognitive Impairment (MCI), 12 patients with early AD and 29 elderly control subjects were subjected to high resolution MRI and a neuropsychological test battery. Brain volume across participants, measured by voxel-based morphometry (VBM), was correlated with verbal memory capacity, measured with a verbal memory test (VLMT). Results Atrophy in the anterior hippocampus, the ento- and perirhinal cortex as well as the parahippocampal gyrus, middle temporal gyrus and anterior cingulate cortex correlated closely with episodic memory performance. Conclusions These brain areas are known to subserve episodic encoding of verbal material. The data contribute to a better understanding of atrophic brain processes in subjects at risk for AD. A combination of neuropsychological testing and voxel-based morphometry may serve as a diagnostic tool in the future. Copyright © 2008 John Wiley & Sons, Ltd. [source] Patient versus informant reported quality of life in the earliest phases of Alzheimer's diseaseINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 12 2006Asmus Vogel Abstract Objectives The study investigated if patient and informant reported Quality of Life (QoL) differed in early Alzheimer's disease (AD). In addition, we examined whether anosognosia had an impact on the agreement between patient and informant ratings of QoL and whether anosognosia, dementia severity, depression and behavioural symptoms were significantly correlated to QoL in early AD. Methods From a prospective research program including newly referred patients (age >60 years and MMSE,,,20), 48 patients with very early AD were included. QoL was assessed using the QoL-AD and EQ-5D scales. Anosognosia was rated on a categorical scale by an examiner. MMSE, Geriatric Depression Scale, Danish Adult Reading Test and Frontal Behavioural Inventory were also administered. Results On most QoL measures patients rated their QoL higher than their informants. Anosognosia was not associated with QoL but significantly with an inverse impact on the agreement between patient and informant ratings of QoL. Self-reported QoL was significantly correlated to depression but not to age, dementia severity, behavioural symptoms or memory impairment. Informant ratings of QoL were significantly correlated to behavioural symptoms and informant ratings on the EQ-5D Visual Analogue Scale were significantly correlated to patient reported depression. Conclusion Patients with early AD generally reported higher QoL than their informants. This disagreement was associated with the presence of anosognosia. Self-reported QoL did not correlate with the MMSE score. Behavioural changes and depressive symptoms may be associated with low QoL. Copyright © 2006 John Wiley & Sons, Ltd. [source] Conceptualization of mild cognitive impairment: a reviewINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 4 2004Heather S. Davis Abstract Background Several factors have prompted renewed interest in the concept of declines in cognitive function that occur in association with aging, in particular the area between normal cognition and dementia. We review the changing conceptualization of what has come to be known as mild cognitive impairment (MCI) in an effort to identify recent developments and highlight areas of controversy. Methods Standard MEDLINE search for relevant English-language publications on mild cognitive impairment and its associated terms, supplemented by hand searches of pertinent reference lists. Results Many conditions cause cognitive impairment which does not meet current criteria for dementia. Within this heterogenous group, termed ,Cognitive Impairment, No Dementia' (CIND), there are disorders associated with an increased risk of progression to dementia. Still, the conceptualization of these latter disorders remains in flux, with variability around assumptions about aging, the relationship between impairment and disease, and how concomitant functional impairment is classified. Amongst patients with MCI, especially its amnestic form, many will progress to Alzheimer's disease (AD). In contrast with clinic-based studies, where progression is more uniform, population-based studies suggest that the MCI classification is unstable in that context. In addition to Amnestic Mild Cognitive Impairment (AMCI), other syndromes exist and can progress to dementia. For example, an identifiable group with vascular cognitive impairment without dementia shows a higher risk of progression to vascular dementia, Alzheimer's disease and mixed dementia. Conclusions Recent attempts to profile patients at an increased risk of dementia suggest that this can be done in skilled hands, especially in people whose symptoms prompt them to seek medical attention. Whether these people actually have early AD remains to be determined. The more narrowly defined MCI profiles need to be understood in a population context of CIND. Copyright © 2004 John Wiley & Sons, Ltd. [source] The role of neuroimaging in mild cognitive impairmentNEUROPATHOLOGY, Issue 6 2007Hiroshi Matsuda The main purposes of neuroimaging in Alzheimer's disease (AD) have been moved from diagnosis of advanced AD to diagnosis of very early AD at a prodromal stage of mild cognitive impairment, prediction of conversion from mild cognitive impairment (MCI) to AD, and differential diagnosis from other diseases causing dementia. Structural MRI studies and functional studies using F-18 fluorodeoxyglucose-positron emission tomography (FDG-PET) and brain perfusion single-photon emission computed tomography (SPECT) are widely used in diagnosis of AD. Outstanding progress in diagnostic accuracy of these neuroimaging modalities has been obtained using statistical analysis on a voxel-by-voxel basis after spatial normalization of individual scans to a standardized brain-volume template instead of visual inspection or a conventional region of interest technique. In a very early stage of AD, this statistical approach revealed gray matter loss in the entorhinal and hippocampal areas and hypometabolism or hypoperfusion in the posterior cingulate cortex and precuneus. These two findings might be related in view of anatomical knowledge that the regions are linked through the circuit of Papez. This statistical approach also offers prediction of conversion from MCI to AD. Presence of hypometabolism or hypoperfusion in parietal association areas and entorhinal atrophy at the MCI stage has been reported to predict rapid conversion to AD. [source] Amyloid imaging in mild cognitive impairment subtypes,ANNALS OF NEUROLOGY, Issue 5 2009David A. Wolk MD Objective We utilized the amyloid imaging ligand Pittsburgh Compound B (PiB) to determine the presence of Alzheimer's disease (AD) pathology in different mild cognitive impairment (MCI) subtypes and to relate increased PiB binding to other markers of early AD and longitudinal outcome. Methods Twenty-six patients with MCI (13 single-domain amnestic-MCI [a-MCI], 6 multidomain a-MCI, and 7 nonamnestic MCI) underwent PiB imaging. Twenty-three had clinical follow-up (21.2 ± 16.0 [standard deviation] months) subsequent to their PiB scan. Results Using cutoffs established from a control cohort, we found that 14 (54%) patients had increased levels of PiB retention and were considered "amyloid-positive." All subtypes were associated with a significant proportion of amyloid-positive patients (6/13 single-domain a-MCI, 5/6 multidomain a-MCI, 3/7 nonamnestic MCI). There were no obvious differences in the distribution of PiB retention in the nonamnestic MCI group. Predictors of conversion to clinical AD in a-MCI, including poorer episodic memory, and medial temporal atrophy, were found in the amyloid-positive relative to amyloid-negative a-MCI patients. Longitudinal follow-up demonstrated 5 of 13 amyloid-positive patients, but 0 of 10 amyloid-negative patients, converted to clinical AD. Further, 3 of 10 amyloid-negative patients "reverted to normal." Interpretation These data support the notion that amyloid-positive patients are likely to have early AD, and that the use of amyloid imaging may have an important role in determining which patients are likely to benefit from disease-specific therapies. In addition, our data are consistent with longitudinal studies that suggest a significant percentage of all MCI subtypes will develop AD. Ann Neurol 2009;65:557,568 [source] Visual object recognition in early Alzheimer's disease: deficits in semantic processingACTA NEUROLOGICA SCANDINAVICA, Issue 2 2003S. Laatu Objectives , The purpose of the present study was to divide visual object recognition into different stages and to reveal which of these stages are impaired in early Alzheimer's disease (AD). Methods , Performance in object detection, familiarity detection, semantic name and word categorization, and identification with naming were studied by using two-choice reaction-time tasks. Ten patients with newly diagnosed AD and 14 healthy subjects were studied. Results , Patients with early AD had impairments in several stages of the object recognition process. After controlling for the basic visuomotor slowness, they were as fast and as accurate as the controls in object detection, but had difficulties in all stages that required semantic processing. Conclusions , Semantic memory impairments contribute to the deficits in visual object recognition in early AD. Thus, the semantic memory deficit may be manifested in several ways in the difficulties that AD patients experience in everyday life. [source] | ||||||||||