http://www.sage-hindawi.comThe latest articles from SAGE-Hindawi Access to Research© 2010, SAGE-Hindawi Access to Research. All rights reserved.http://www.sage-hindawi.com/journals/ijad/2009/278615.htmlObjective. To assess the ability of Alzheimer's disease (AD) patients to perceive emotional information and to assign subjective emotional rating scores to audiovisual presentations. Materials and Methods. 24 subjects (14 with AD, matched to controls for age and educational levels) were studied. After neuropsychological assessment, they watched a Neutral story and then a story with Emotional content. Results. Recall scores for both stories were significantly lower in AD (Neutral and Emotional: P=.001). CG assigned different emotional scores for each version of the test, P=.001, while ratings of AD did not differ, P=.32. Linear regression analyses determined the best predictors of emotional rating and recognition memory for each group among neuropsychological tests battery. Conclusions. AD patients show changes in emotional processing on declarative memory and a preserved ability to express emotions in face of arousal content. The present findings suggest that these impairments are due to general cognitive decline.Corina Satler, Carlos Uribe, Carlos Conde, Sergio Leme Da-Silva, and Carlos Tomaz© 2010, SAGE-Hindawi Access to Research. All rights reserved.http://www.sage-hindawi.com/journals/ijad/2009/481031.htmlDetecting aggregated amyloid peptides (Aβ plaques) presents targets for developing biomarkers of Alzheimer's disease (AD). Polymeric n-butyl-2-cyanoacrylate (PBCA) nanoparticles (NPs) were encapsulated with radiolabelled amyloid affinity I125-clioquinol (CQ, 5-chloro-7-iodo-8-hydroxyquinoline) as in vivo probes. I125-CQ-PBCA NPs crossed the BBB (2.3±0.9 ID/g) (P<.05) in the WT mouse (N = 210), compared to I125-CQ (1.0±0.4 ID/g). I125-CQ-PBCA NP brain uptake increased in AD transgenic mice (APP/PS1) versus WT (N = 38; 2.54×105±5.31×104 DLU/mm2; versus 1.98×105±2.22×104 DLU/mm2) and in APP/PS1/Tau. Brain increases were in mice intracranially injected with aggregated Aβ42 peptide (N = 17; 7.19×105±1.25×105 DLU/mm2), versus WT (6.07×105±7.47×104 DLU/mm2). Storage phosphor imaging and histopathological staining of the plaques, Fe2+ and Cu2+, validated results. I125-CQ-PBCA NPs have specificity for Aβ in vitro and in vivo and are promising as in vivo SPECT (I123), or PET (I124) amyloid imaging agents.Celeste A. Roney, Veera Arora, Padmakar V. Kulkarni, Peter P. Antich, and Frederick J. Bonte© 2010, SAGE-Hindawi Access to Research. All rights reserved.http://www.sage-hindawi.com/journals/ijad/2009/949271.htmlThe International Society for CNS Clinical Trials and Methodology (ISCTM) held its 4th Annual Autumn Conference in Toronto, Ontario, October 6-7, 2008. The purpose of the present report is to provide an overview of one of the sessions at the conference which focused on the designs and methodologies to be applied in clinical trials of new treatments for Alzheimer's disease (AD) with purported “disease-modifying” effects. The session began with a discussion of how neuroimaging has been applied in multiple sclerosis clinical trials (another condition for which disease modification claims have been achieved). The next two lectures provided a pharmaceutical industry perspective on some of the specific challenges and possible solutions for designing trials to measure disease progression and/or modification. The final lecture provided an academic viewpoint and the closing discussion included additional academic and regulatory perspectives on trial designs, methodologies, and statistical issues relevant to the disease modification concept.Aaron S. Kemp, George T. Grossberg, Steven J. Romano, Douglas L. Arnold, J. Michael Ryan, Roger Bullock, and David L. Streiner© 2010, SAGE-Hindawi Access to Research. All rights reserved.http://www.sage-hindawi.com/journals/ijad/2009/780720.htmlThis study compared the association of differing methods of dementia ascertainment, derived from multiple sources, with nursing home (NH) estimates of prevalence of dementia, length of stay, and costs an understudied issue. Subjects were 2050 new admissions to 59 Maryland NHs, from 1992 to 1995 followed longitudinally for 2 years. Dementia was ascertained at admission from charts, Medicare claims, and expert panel. Overall 59.5% of the sample had some indicator of dementia. The expert panel found a higher prevalence of dementia (48.0%) than chart review (36.9%) or Medicare claims (38.6%). Dementia cases had lower relative average per patient monthly costs, but longer NH length of stay compared to nondementia cases across all methods. The prevalence of dementia varied widely by method of ascertainment, and there was only moderate agreement across methods. However, lower costs for dementia among NH admissions are a robust finding across these methods.Ann L. Gruber-Baldini, Bruce Stuart, Ilene H. Zuckerman, Van Doren Hsu, Kenneth S. Boockvar, Sheryl Zimmerman, Steven Kittner, Charlene C. Quinn, J. Richard Hebel, Conrad May, and Jay Magaziner© 2010, SAGE-Hindawi Access to Research. All rights reserved.http://www.sage-hindawi.com/journals/ijad/2009/972178.htmlOxidative stress appears to be an early event involved in the pathogenesis of Alzheimer's disease. The present study was designed to investigate the neuroprotective effects of Centella asiatica against colchicine-induced memory impairment and oxidative damage in rats. Colchicine (15 μg/5 μL) was administered intracerebroventricularly in the lateral ventricle of male wistar rats. Morris water maze and plus-maze performance tests were used to assess memory performance tasks. Various biochemical parameters such as lipid peroxidation, nitrite, reduced glutathione, glutathione-S-transferase, superoxide dismutase, acetylcholinesterase were also assessed. ICV colchicine resulted marked memory impairment and oxidative damage. Chronic treatment with Centella asiatica extract (150 and 300 mg/kg, p.o.) for a period of 25 days, beginning 4 days prior to colchicine administration, significantly attenuated colchicine-induced memory impairment and oxidative damage. Besides, Centella asiatica significantly reversed colchicines administered increase in acetylcholinesterase activity. Thus, present study indicates protective effect of Centella asiatica against colchicine-induced cognitive impairment and associated oxidative damage.Anil Kumar, Samrita Dogra, and Atish Prakash© 2010, SAGE-Hindawi Access to Research. All rights reserved.http://www.sage-hindawi.com/journals/ijad/2009/632489.htmlThe relationship between total homocysteine (tHcy) and dementia risk remains controversial, as the association varies among populations and dementia subtypes. We studied a Venezuelan population that has high prevalence of both elevated tHcy and dementia. We tested the hypotheses that (1) elevated tHcy is associated with increased dementia risk, (2) the risk is greater for vascular dementia (VaD) than for Alzheimer's disease (AD), and (3) a history of stroke may partly explain this association. 2100 participants (≥55 years old) of the Maracaibo Aging Study underwent standardized neurological, neuropsychiatric, and cardiovascular assessments. Elevated tHcy was significantly associated with dementia, primarily VaD. When history of stroke and other confounding factors were taken into account, elevated tHcy remained a significant risk factor in older (>66 years), but not in younger (55–66 years) subjects. Ongoing studies of this population may provide insight into the mechanism by which tHcy increases risk for dementia.Inara J. Chacón, Aldrín E. Molero, Gloria Pino-Ramírez, José A. Luchsinger, Joseph H. Lee, and Gladys E. Maestre© 2010, SAGE-Hindawi Access to Research. All rights reserved.http://www.sage-hindawi.com/journals/ijad/2009/638145.htmlAlzheimer's disease (AD) can be diagnosed according to new research criteria proposed recently (Dubois et al., 2007). Diagnosis is made on grounds of episodic memory deficits and one pathological biomarker: cerebrospinal fluid (CSF) or structural/functional imaging. Goal was to investigate the dependence of episodic memory function on material (verbal, visuospatial), gender and premorbid intellectual ability (IQ). The new research criteria of AD were applied retrospectively using data of 68 patients (Mini-Mental-Status Examination, MMSE ≥ 22) from a university memory clinic. Women with lower IQ performed worse on visuospatial episodic memory than women with higher IQ and men with the same IQ. Thus, women with lower IQ appear to be particularly vulnerable to visuospatial episodic memory deficits despite similar CSF tau values indicating a similar activity of the neurodegenerative process. Gender, premorbid IQ, and visuospatial material need to be considered in the assessment of episodic memory breakdown applying the newly proposed research criteria for the diagnosis of AD.U. Beinhoff, H. Tumani, and M. W. Riepe© 2010, SAGE-Hindawi Access to Research. All rights reserved.http://www.sage-hindawi.com/journals/ijad/2009/257403.htmlBeta-secretase (BACE1) is the major enzyme participating in generation of toxic amyloid-beta (Aβ) peptides, identified in amyloid plaques of Alzheimer's disease (AD) brains. Its downregulation results in decreasing secretion of Aβ. Thus, BACE1 silencing by RNAi represents possible strategy for antiamyloid therapy in the treatment of AD. In this study, a series of newly designed sequences of synthetic and vector-encoded siRNAs (pSilencer, pcPURhU6, and lentivirus) were tested against overexpressed and endogenous BACE1 in several cell lines and in adult neural progenitor cells, derived from rat hippocampus. SiRNAs active in human, mouse, and rat cell models were shown to diminish the level of BACE1. In HCN A94 cells, two BACE1-specific siRNAs did not alter the expression of genes of BACE2 and several selected genes involved in neurogenesis (Synapsin I, βIII-Tubulin, Calbidin, NeuroD1, GluR2, CREB, MeCP2, PKR), however, remarkable lowering of SCG10 mRNA, coding protein of stathmin family, important in the development of nervous system, was observed.Malgorzata Sierant, Katarzyna Kubiak, Julia Kazmierczak-Baranska, Masaki Warashina, Tomoko Kuwabara, and Barbara Nawrot© 2010, SAGE-Hindawi Access to Research. All rights reserved.http://www.sage-hindawi.com/journals/ijad/2009/689285.htmlAmyloid β (Aβ) annular protofibrils (APFs) have been described where the structure is related to that of β barrel pore-forming bacterial toxins and exhibits cellular toxicity. To investigate the relationship of Aβ APFs to disease and their ultrastructural localization in brain tissue, we conducted a pre-embedding immunoelectron microscopic study using anti-annular protofibril antiserum. We examined brain tissues of young- and old-aged amyloid precursor protein transgenic mice (APP23), neprilysin knockout APP23 mice, and nontransgenic littermates. αAPF-immunoreactions tended to be found (1) on plasma membranes and vesicles inside of cell processes, but not on amyloid fibrils, (2) with higher density due to aging, APP transgene, and neprilysin deficiency, and (3) with higher positive rate at synaptic compartments in aged APP23, especially in neprilysin knockout APP23 mice. These findings imply that APFs are distinct from amyloid fibrils, interact with biological membranes, and might be related to synaptic dysfunction in Alzheimer model mouse brains.Hideko Kokubo, Rakez Kayed, Charles G. Glabe, Matthias Staufenbiel, Takaomi C. Saido, Nobuhisa Iwata, and Haruyasu Yamaguchi© 2010, SAGE-Hindawi Access to Research. All rights reserved.http://www.sage-hindawi.com/journals/ijad/2009/951548.htmlTo date, the beta amyloid (Aβ) cascade hypothesis remains the main pathogenetic model of Alzheimer's disease (AD), but its role in the majority of sporadic AD cases is unclear. The “mitochondrial cascade hypothesis” could explain many of the biochemical, genetic, and pathological features of sporadic AD. Somatic mutations in mitochondrial DNA (mtDNA) could cause energy failure, increased oxidative stress, and accumulation of Aβ, which in a vicious cycle reinforce the mtDNA damage and the oxidative stress. Despite the evidence of mitochondrial dysfunction in AD, no causative mutations in the mtDNA have been detected so far. Indeed, results of studies on the role of mtDNA haplogroups in AD are controversial. In this review we discuss the role of the mitochondria, and especially of the mtDNA, in the cascade of events leading to neurodegeneration, dementia, and AD.M. Mancuso, V. Calsolaro, D. Orsucci, C. Carlesi, A. Choub, S. Piazza, and G. Siciliano© 2010, SAGE-Hindawi Access to Research. All rights reserved.