Journal of Alzheimer's Disease - Volume 19, issue 2

Authors: Della Sala, Sergio | Cocchini, Gianna | Logie, Robert H. | Allerhand, Michael | MacPherson, Sarah E.

Article Type: Research Article

Abstract: Previous dual task studies have demonstrated minimal costs when healthy individuals simultaneously perform two tasks at their own individual ability levels. Conversely, Alzheimer's disease (AD) patients show dual task decrements, but it is unclear whether the problem arises at the encoding, maintenance, and/or retrieval phases of memory. Two experiments combined digit recall and visuo-motor tracking to investigate dual task effects during encoding, maintenance, and/or retrieval for AD patients compared with healthy adults. The demands of each single task were titrated for the ability of each participant. In Experiment 1, the dual task requirement was present throughout both encoding and retrieval …of digit recall and the differential dual task effects on a secondary tracking task were examined post-hoc. In Experiment 2, the impact of dual task during encoding only, during maintenance only, and during retrieval only was examined systematically. The findings suggest that the specific AD deficit reflects impairment of a cognitive function that supports the simultaneous performance of two tasks in the healthy brain, particularly during the encoding and retrieval phases of the memory task. Show more

Keywords: Alzheimer's disease, dual task, encoding, maintenance, retrieval, working memory

DOI: 10.3233/JAD-2010-1244

Citation: Journal of Alzheimer's Disease, vol. 19, no. 2, pp. 503-515, 2010

Authors: Vidoni, Eric D. | Honea, Robyn A. | Burns, Jeffrey M.

Article Type: Research Article

Abstract: Cognitive and physical decline are important predictors of functional independence in Alzheimer's disease (AD). However, little is known about AD-related neural change leading to decreased independence. We hypothesized that regional gray matter atrophy, including the medial frontal cortex, would be related to cognition, physical function, and functional independence. Individuals without dementia (n = 56) and subjects with early-stage AD (n = 58) underwent MRI and a comprehensive cognitive and physical function evaluation. The relationship of cognitive and physical function measures and independence performing complex daily activities was explored using correlation and mediation analysis. These results suggest that cognition had both …a strong direct effect and mediated the influence of physical function on independence for those with AD. We followed this with a voxel-based morphometric global conjunction analysis of imaging data within each group to identify neural substrates common to our function measures. Imaging evidence supported our mediation analysis results. Imaging evidence revealed that in AD, regional gray matter atrophy measures in medial frontal and temporo-parietal areas were related to decreased cognition, physical function, and independence. Loss of independence in early AD is closely related to impaired cognition associated with performing complex behaviors. People with early AD may have decreased gray matter volume in the medial frontal and temporal-parietal cortices that is associated with loss of independence in activities of daily living. These results are the first to identify regionally specific brain volume changes that may be related to functional dependence seen in early AD. Show more

Keywords: Activities of daily living, cognition, physical function, voxel-based morphometry

DOI: 10.3233/JAD-2010-1245

Citation: Journal of Alzheimer's Disease, vol. 19, no. 2, pp. 517-527, 2010

Authors: Cui, Jia | Chen, Qiuyue | Yue, Xiaojing | Jiang, Xuejun | Gao, George F. | Yu, Long-Chuan | Zhang, Yan

Article Type: Research Article

Abstract: Galanin and galanin receptors are upregulated in the brain regions associated with Alzheimer's disease (AD). However, the consequence of this overexpression is still unknown, particularly in human neurons. Here, we investigate the possible protective effects of galanin against intracellular amyloid-β (Aβ)1–42 toxicity, as well as other insults including staurosporine, etoposide, hydrogen peroxide, and serum depletion in cultured human primary neurons. The results show that galanin is protective against intracellular Aβ cytotoxicity and all of the above insults at sub-nanomolar physiological concentrations. The galanin protection may be mediated by galanin receptor 2 and down-regulation of Bax level. The data from …the present study provide a potential drug target for therapy or prevention of neurodegenerative diseases, including AD. Show more

Keywords: Alzheimer's disease, galanin, human primary neurons, neuronal loss

DOI: 10.3233/JAD-2010-1246

Citation: Journal of Alzheimer's Disease, vol. 19, no. 2, pp. 529-544, 2010

Authors: Coppus, Antonia M.W. | Evenhuis, Heleen M. | Verberne, Gert-Jan | Visser, Frank E. | Eikelenboom, Piet | van Gool, Willem A. | Janssens, A. Cecile J.W. | van Duijn, Cornelia M.

Article Type: Research Article

Abstract: In a prospective longitudinal cohort study of dementia and mortality in persons with Down syndrome aged 45 years and older, 85 postmenopausal women were followed for a mean follow-up time of 4.3 years (range 0.0 to 7.4 years). The effect of age at menopause on age at diagnosis of dementia and survival was estimated using correlation analysis and Cox Proportional Hazard Model. We found a significant correlation between age at menopause and age at diagnosis of dementia (ρ = 0.52; p < 0.001), and between age at menopause and age at death (ρ = 0.49; p = 0.01). Early age …at menopause is associated with a 1.8 fold increased risk of dementia: Hazard Ratio (HR): 1.82 (95%Confidence Interval (CI): 1.31–2.52) and with risk of death: HR: 2.05 (95%CI: 1.33–3.16). Our study suggests that age at menopause in women with Down syndrome is a determinant of age at onset of dementia and mortality. Show more

Keywords: Alzheimer's disease, APOE genotype, Down syndrome, menopause, mortality

DOI: 10.3233/JAD-2010-1247

Citation: Journal of Alzheimer's Disease, vol. 19, no. 2, pp. 545-550, 2010

Authors: Listì, Florinda | Caruso, Calogero | Lio, Domenico | Colonna-Romano, Giuseppina | Chiappelli, Martina | Licastro, Federico | Candore, Giuseppina

Article Type: Research Article

Abstract: Alzheimer's disease (AD) is a neurodegenerative disorder clinically characterized by cognitive deficit with progressive worsening of memory. Recent data indicate that neurons, as well as other brain cells, can express enzymes such as cyclooxygenases (COXs) and 5-lipoxygenase (5-LO) which are considered important in inflammatory cells. Moreover, it has been demonstrated that COX-2 and 5-LO enzymes play a considerable role in the pathophysiology of AD. In order to assess the possible role of COX-2 and 5-LO single nucleotide polymorphisms (SNPs) in AD, we examined their distribution in 341 AD patients and 190 controls from Northern Italy. A significant difference was observed …in the distribution of the −765G COX-2 and −1708A 5-LO alleles between AD cases and controls (p = 0.03 for −765G/C COX-2 SNP; and p = 0.007 for −1708G/A 5-LO SNP). Hence, COX-2 −765G and 5-LO −1708A alleles were overrepresented in AD patients and underrepresented in controls. Our data suggest that these alleles of COX-2 and 5-LO could be risk factors for AD. These results seem of some importance for a pharmacogenomic approach. Show more

Keywords: Alzheimer's disease, COX-2, 5-LO, pharmacogenomics

DOI: 10.3233/JAD-2010-1260

Citation: Journal of Alzheimer's Disease, vol. 19, no. 2, pp. 551-557, 2010

Authors: Ciaramella, Antonio | Bizzoni, Federica | Salani, Francesca | Vanni, Diego | Spalletta, Gianfranco | Sanarico, Nunzia | Vendetti, Silvia | Caltagirone, Carlo | Bossù, Paola

Article Type: Research Article

Abstract: Alzheimer's disease (AD) is characterized by abnormal accumulation of amyloid-β peptide (Aβ) into extracellular fibrillar deposits, paralleled by chronic neuroinflammatory processes. Although Aβ seems to be causative in AD brain damage, the role of the immune system and its mechanisms still remain to be clarified. We have recently shown that normal monocyte-derived dendritic cells (MDDCs), when differentiated in the presence of Aβ1–42 , acquire an inflammatory phenotype and a reduced antigen presenting ability. Here we studied MDDCs derived from AD patients in comparison with MDDCs obtained from healthy control subjects (HC). MDDCs from AD patients, at variance with HC-derived cells, …were characterized by an augmented cell recovery, a consistent increase in the expression of the pro-inflammatory ICAM-1 molecule, a decrease in the expression of the co-stimulatory CD40 molecule, and an impaired ability to induce T cell proliferation. Furthermore, MDDCs from AD produced higher amounts of IL-6 than HC-derived cells, confirming the more pronounced pro-inflammatory features of these cells in AD patients. Consistent results have been also obtained with monocytes, the MDDC precursors. In fact, while unstimulated monocytes do not appear to be different in AD and HC, after stimulation with lipopolysaccharide, AD monocytes overexpressed ICAM-1 with respect to controls, suggesting that common pathways of monocyte activation and MDDC differentiation are altered in AD. Overall, these findings show that AD-linked dysregulated immune mechanisms exist, which lead to dendritic cell-mediated over-activation of inflammation and impaired antigen presentation, thus supporting the view that immune cell activation could play an important role in AD pathogenesis. Show more

Keywords: Alzheimer's disease, innate immune cells, inflammation, monocyte-derived dendritic cells, monocytes

DOI: 10.3233/JAD-2010-1257

Citation: Journal of Alzheimer's Disease, vol. 19, no. 2, pp. 559-572, 2010

Authors: Rojo, Leonel E. | Alzate-Morales, Jans | Saavedra, Iván N. | Davies, Peter | Maccioni, Ricardo B.

Article Type: Research Article

Abstract: We describe the interactions of two benzimidazole derivatives, astemizole (AST) and lansoprazole (LNS), with anomalous aggregates of tau protein (neurofibrillary tangles). Interestingly, these compounds, with important medical applications in the treatment of allergies and gastrointestinal disorders respectively, specifically bind to aggregated variants of tau protein and to paired helical filaments isolated from brains of Alzheimer's disease (AD) patients. These ligands appear to be a powerful tool to tag brain-isolated tau-aggregates and heparin-induced polymers of recombinant tau. The interactions of AST and LNS with tau aggregates were assessed by classical radioligand assays, surface plasmon resonance, and bioinformatic approaches. The affinity of …AST and LNS for tau aggregates was comparatively higher than that for amyloid-β polymers according to our data. This is relevant since senile plaques are also abundant but are not pathognomonic in AD patients. Immunochemical studies on paired helical filaments from brains of AD patients and surface plasmon resonance studies confirm these findings. The capacity of these drugs to penetrate the blood-brain barrier was evaluated: i) in vitro by parallel artificial membrane permeability assay followed by experimental Log P determinations; and ii) in vivo by pharmacokinetic studies comparing distribution profiles in blood and brain of mice using HPLC/UV. Importantly, our studies indicate that the brain/blood concentration ratios for these compounds were suitable for their use as PET radiotracers. Since neurofibrillary tangles are positively correlated with cognitive impairment, we concluded that LNS and AST have a great potential in PET neuroimaing for in vivo early detection of AD and in reducing the formation of neurofibrillary tangles. Show more

Keywords: Alzheimer's disease, benzimidazoles, neurofibrillary tangles, neuroimaging, radiotracers, surface plasmon resonance, tangles, tau aggregates

DOI: 10.3233/JAD-2010-1262

Citation: Journal of Alzheimer's Disease, vol. 19, no. 2, pp. 573-589, 2010

Authors: Stellos, Konstantinos | Panagiota, Victoria | Sachsenmaier, Saskia | Trunk, Theresia | Straten, Guido | Leyhe, Thomas | Seizer, Peter | Geisler, Tobias | Gawaz, Meinrad | Laske, Christoph

Article Type: Research Article

Abstract: Cerebrovascular dysfunction is a common finding in patients with Alzheimer's disease (AD) and may contribute to cognitive decline. Abundant evidence suggests that vascular and neuronal repair mechanisms are mediated by circulating progenitor cells in vivo. Whether CD34+ and, specifically, CD34+ /CD133+ progenitor cells are involved in the pathophysiology of AD is poorly understood so far. In the present study, peripheral blood concentrations of circulating CD34+ /CD133+ and CD34+ progenitor cells were measured in 45 AD patients and in 30 healthy elderly controls by flow cytometry. The severity of dementia was assessed by Mini-Mental Status Examination and …Clinical Dementia Rating scale. AD patients were stratified into two groups showing mild (n = 17) and moderate to severe (n = 28) dementia. In the present study, AD patients with moderate to severe dementia, but not those with mild dementia, showed significantly increased circulating CD34+ /CD133+ and CD34+ progenitor cells compared to healthy elderly controls independent of cardiovascular risk factors and medication. In addition, the number of circulating CD34+ /CD133+ progenitor cells in AD patients was significantly inversely correlated with cognitive function, age, and plasma levels of SDF-1, the most potent chemokine for progenitor cells. Our findings suggest a stage-dependent upregulation of circulating CD34+ /CD133+ and CD34+ progenitor cells in AD patients, which could take part in tissue healing processes of the brain in AD. Show more

Keywords: Alzheimer's disease, CD133, CD34, dementia, SDF-1

DOI: 10.3233/JAD-2010-1261

Citation: Journal of Alzheimer's Disease, vol. 19, no. 2, pp. 591-600, 2010

Authors: Coduras, Alicia | Rabasa, Isabel | Frank, Ana | Bermejo-Pareja, Felix | López-Pousa, Secundino | López-Arrieta, Jesús-María | Del Llano, Juan | León, Teresa | Rejas, Javier

Article Type: Research Article

Abstract: In this study, we analyzed the economic impact of one-year healthcare and non-healthcare resources utilization by patients with dementia of Alzheimer's disease (AD) under usual medical practice in Spain. A one-year, prospective, naturalistic, multicenter cohort study was designed to recruit patients with mild, moderate to severe, and severe AD according to Clinical Dementia Rating scale: the ECO study. Healthcare resources (medical visits, drugs and concomitant treatments, complementary and diagnostic tests, institutionalization and use of home-nursing facilities) and non-healthcare resources (inventory materials, consumables, professional and non-professional caregivers' time for care and supervision) were recorded and valued at 2006 prices. A total …of 560 patients with possible/probable AD by DSM-IV-NINCDS-ADRDA criteria were included in the study: 68% women, 77 ± 6 years old, 29% treatment naïve. Monthly average cost per patient was EURO1,425.73, and increased 10.08% at the end of the study (baseline monthly cost; EURO1,316.22). Non-healthcare costs EURO1059.00, 74.30% of total cost) decreased EURO4.30/month (0.40%) at the end of the year, while healthcare costs, which presented a total average of EURO366.66, grew by EURO136.94 in the period (54.06%), mainly due to cost of drugs, nursing home utilization, and institutionalization. The 87.26% of the overall cost (EURO1,244.22) was not financed by National Health Service (NHS), and the majority of this cost corresponded to caregiver-associated cost. The caregiver's total burden represented 70.86% of the overall cost-of-illness. In conclusion, monthly overall mean cost of dementia of AD type was high in Spain (EURO1,412.73). Almost 88% of the cost-of-illness is funded by the patient's own family, adding a financial burden to the suffering of these families. Show more

Keywords: Costs, dementia of Alzheimer type, healthcare resources utilization, non-healthcare resources, prospective, Spain

DOI: 10.3233/JAD-2010-1258

Citation: Journal of Alzheimer's Disease, vol. 19, no. 2, pp. 601-615, 2010

Authors: Wimo, Anders

Article Type: Article Commentary

DOI: 10.3233/JAD-2010-1268

Citation: Journal of Alzheimer's Disease, vol. 19, no. 2, pp. 617-619, 2010