Your search for: 'author:("Sabbagh, Marwan N.")' has returned 30 results. (0.029s) Save search

Authors: Decourt, Boris | Sabbagh, Marwan N.

Article Type: Review Article

Abstract: The diagnosis of Alzheimer's disease (AD) relies principally on clinical criteria for probable and possible AD as defined by the NINCDS-ADRDRA. The field is desperately lacking of biological markers to assist with AD diagnosis and verification of treatment efficacy. According to the Consensus Report of the Working Group on Molecular and Biochemical Markers of Alzheimer's Disease, in order to qualify as a biomarker the sample in question must adhere to certain basic requirements, including the ability to: reflect AD pathology and differentiate it from other dementia with an 80% sensitivity; be reliable and reproducible; be easy to perform and analyze; …remain relatively inexpensive. Beta secretases are crucial enzymes in the pathogenesis of AD. Given its primary role in brain amyloidogenesis and its ubiquitous expression, one may consider measuring peripheral BACE1 levels and activity as biomarkers of AD, like performed in the brain and cerebrospinal fluid. However, very little is known about the periphery and whether peripheral BACE1 is involved in AD pathogenesis or mirrors AD progression. Moreover, no investigation has focused on the possibility of monitoring peripheral BACE1 to assess the efficiency of BACE1 inhibitors during the course of clinical trials. Part of the problem may be attributed to the lack of sensitive molecular tools which are absolutely necessary to use BACE1 as a biomarker. In this review we evaluate the progress and feasibility of developing BACE1 as a biomarker for AD in different tissues. Show more

Keywords: Alzheimer's disease, BACE1, β-secretase, biomarker, blood, brain, cerebrospinal fluid

DOI: 10.3233/JAD-2011-110017

Citation: Journal of Alzheimer's Disease, vol. 24, no. s2, pp. 53-59, 2011

Authors: Arab, Lana | Sabbagh, Marwan N.

Article Type: Review Article

Abstract: As the number of patients with Alzheimer's disease (AD) is expected to grow, finding ways to prevent and lower the risk of AD becomes a crucial matter. Risk factors for developing AD have been identified including health conditions, dietary habits, genetics and heredity, gender, education, age, and lifestyle. Interventions targeted at some of these risk factors may offer opportunities for development of an optimal preventive strategy. Lifestyle habits which include dietary habits and physical activities appear to have positive effect on modifying many risk factors. Studies have shown controversial results when it comes to the relation between the adherence to …a Mediterranean diet and /or physical activity and the incidence of AD. Many population-based studies reported the positive association between antioxidants intake (like vitamin E and C), and polyunsaturated fatty acids whether it is from the diet or supplements on the cognitive performance. Future investigations should aim to determine objectively whether lifestyle modification through diet, exercise, or vitamins/supplements truly exert risk reduction or outright prevention. In this review, lifestyle habits are reviewed as they pertain to influence on risk of developing AD as well as on cognitive decline. Epidemiological studies and animal studies are reviewed. Show more

Keywords: Alzheimer's disease, lifestyle, Mediterranean diet, physical activity, prevention, risk

DOI: 10.3233/JAD-2010-091573

Citation: Journal of Alzheimer's Disease, vol. 20, no. 3, pp. 785-794, 2010

Authors: Baxter, Leslie C. | Sabbagh, Marwan N.

Article Type: Article Commentary

DOI: 10.3233/JAD-2006-10415

Citation: Journal of Alzheimer's Disease, vol. 10, no. 4, pp. 449-449, 2006

Authors: Connor, Donald J. | Sabbagh, Marwan N.

Article Type: Short Communication

Abstract: The Alzheimer's Disease Assessment Scale – Cognitive (ADAS-Cog) is the most commonly used primary outcome instrument in clinical trials for treatments of dementia. Variations in forms, administration procedures and scoring rules, along with rater turnover and intra-rater drift may decrease the reliability of the instrument. A survey of possible variations in the ADAS-Cog was administered to 26 volunteer raters at a clinical trials meeting. Results indicate notable protocol variations in the forms used, administration procedures, and scoring rules. Since change over time is used to determine treatment effect in clinical trials, standardizing the instrument's ambiguities and addressing common problems will …greatly increase the instrument's reliability and thereby enhance its sensitivity to treatment effects. Show more

Keywords: ADAS-Cog, administration, Alzheimer's disease, clinical trials, dementia

DOI: 10.3233/JAD-2008-15312

Citation: Journal of Alzheimer's Disease, vol. 15, no. 3, pp. 461-464, 2008

Authors: Reid, Richard T. | Sabbagh, Marwan N.

Article Type: Research Article

Abstract: Research on acetylcholinesterase inhibitors (ChEIs) indicates that long term exposure increases the level of nicotinic acetylcholine receptors (nAChRs) but the effects of donepezil on nAChRs are not well studied. Therefore, we investigated the effects of sub-chronic donepezil administration on nAChRs in rats and rat pheochromocytoma PC-12 cells. Male Sprague Dawley rats were administered donepezil (0.7 and 2.4 μmoles/kg), nicotine (2.5 μmoles/kg) or saline subcutaneously twice daily for 14 days, PC-12 cells were incubated with 10-6 to 10-4 M donepezil for 72 hours and nAChR levels were determined by receptor binding assay using the nAChR ligands [-3 H]-epibatidine (EPI) for non-α7 …nAChRs and [3 H]-methyllyconitine (MLA) for α7 nAChRs. Chronic donepezil administration at 1.4 μmoles/kg/day and 4.8 μmoles/ kg/day significantly increased [3 H]-epibatidine binding in the cortex to 126 ± 1.3% and 127 ± 3.2% of the saline control animals, respectively. [3 H]-MLA binding in the cortex increased to 114 ± 4.4% and 124 ± 2.8% of the control group for the high and low dose groups, respectively. Hippocampal [3 H]-EPI binding in the low dose and high dose groups significantly increased to 135 ± 3.6% and 125 ± 4.6% of the controls, respectively while there were no changes in the level of [3 H]-MLA binding. In striatal homogenates, neither [3 H]-EPI nor [3 H]-MLA binding were significantly effected at either dose of donepezil. In PC-12 cells, [3 H]-EPI binding was increased at the non-physiological 10-4 M concentration only. There was no effect of donepezil on [3 H]-MLA binding at any concentration examined. These results indicate that donepezil increases cortical α7 and non-α7 nAChRs, hippocampal non-α7 nAChRs but does not influence striatal nAChR levels. Furthermore, the lack of an effect on the α7-nAChRs in PC-12 cells suggests that the increase in cortical α7 nAChRs may be an indirect effect of increased acetylcholine levels in vivo. Show more

Keywords: donepezil, nicotinic receptor, Alzheimer's disease, PC-12 cells

DOI: 10.3233/JAD-2003-5602

Citation: Journal of Alzheimer's Disease, vol. 5, no. 6, pp. 429-436, 2003

Authors: Stipho, Faissal | Jackson, Robert | Sabbagh, Marwan N.

Article Type: Short Communication

Abstract: Background: Homozygous APOE ɛ 4 status is a well-known risk factor in the development of Alzheimer’s disease (AD). However, other genotypes of APOE have not yet been found to have equal clinical significance. There is a paucity of reports regarding clinically or pathologically described AD in APOE ɛ 2 homozygotes compared to the other alleles. Objective: To notify clinicians that patients with homozygous APOE ɛ 2 are also at risk of developing AD based on results from the largest prospectively gathered registry of brain samples to date. Methods: We queried the National Alzheimer’s Coordinating Center (NACC) database for autopsy-confirmed AD …cases. Of the Uniform Data Set (UDS) participants who are deceased, 5,779 were diagnosed with dementia at their last UDS visit prior to death, and autopsy data is available for 3,518. Results: Of the brains in the NACC database with pathologically confirmed dementia, seven were found to be homozygous for APOE ɛ 2 , which represents only 0.2% of the autopsy-confirmed sample. Furthermore, pathology-confirmed AD represents 29% (2/7) of the APOE ɛ 2/ ɛ 2 patients diagnosed with dementia. Conclusions: Although rare, autopsy-confirmed AD can be present in APOE ɛ 2/ ɛ 2 carriers. Show more

Keywords: Alzheimer’s disease, apolipoprotein, brain-derived neurotrophic factor, corticobasal degeneration, dementia, frontotemporal dementia

DOI: 10.3233/JAD-171060

Citation: Journal of Alzheimer's Disease, vol. 62, no. 4, pp. 1527-1530, 2018

Authors: Sleem, Tamara | Decourt, Boris | Sabbagh, Marwan N.

Article Type: Review Article

Abstract:  Huge investments continue to be made in treatment for Alzheimer’s disease (AD), with more than one hundred drugs currently in development. Pharmacological approaches and drug development, particularly those targeting amyloid-β, have dominated the therapeutic landscape. At the same time, there is also a growing interest in devices for treating AD. This review aimed to identify and describe devices under development for AD treatment. In this review, we queried the devices that are in development for the treatment of AD. PubMed was searched through the end of 2021 using the terms “device,” “therapeutics,” and “Alzheimer’s” for articles that report on devices …to treat AD. Ten devices with 31 references were identified as actively being developed for the treatment of AD. Many of these devices are far along in development. Device-based therapies are often overlooked when evaluating treatment approaches to AD. However, many devices for treating AD are in development and some show promising results. Show more

Keywords: Alzheimer’s disease, clinical trials, devices, treatment

DOI: 10.3233/ADR-230115

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 241-255, 2024

Authors: Sabbagh, Marwan N. | Messis, Chris | Friedland, Robert P. | Geula, Changiz

Article Type: Meeting Report

Abstract: Alzheimer's disease is growing in prevalence worldwide. Though many Western countries have developed programs of surveillance and care around Alzheimer's disease and dementia, certain regions of the world are beginning to recognize the magnitude of the disease burden in the general population. In the Middle East, there is growing awareness of the burden of Alzheimer's disease and how it impacts health economics, care delivery, and research. Here we summarize the proceedings of the 5th International Conference on Alzheimer's Disease in the Middle East. We had speakers from 20 countries updating the audience on progress toward improving healthcare and research related …to AD in this region of the world. Show more

Keywords: Alzheimer's disease, apolipoprotein E-4, Arab, Israeli, Middle East, pathogenesis

DOI: 10.3233/JAD-2012-120116

Citation: Journal of Alzheimer's Disease, vol. 30, no. 3, pp. 711-727, 2012

Authors: Sabbagh, Marwan N. | Galasko, Douglas | Koo, Edward | Thal, Leon J.

Article Type: Research Article

Abstract: Proposed treatments of Alzheimer's disease (AD) are most likely to succeed if they are based on an understanding of the complex biology of AD and its effects on cognition. Treatments may target a single or multiple components of the complex pathology of AD with the hope that by affecting an individual component of AD pathology, the disease course can be affected. One such component is amyloid-ß (Aß), a feature of the senile plaque. Aß may be critical for inducing the pathology seen in AD. Accumulation of Aß may result in a cascade of biochemical events leading to neuronal dysfunction, which …may present opportunities for intervention at multiple different points to slow disease progression. Treatment may be directed towards decreasing Aß production, increasing Aß removal, and decreasing Aß aggregation. Alternatively, treatment may be directed at more distal pathways by: modulating downstream events possibly due to Aß such as free radical toxicity, decreasing inflammation, preventing cell membrane damage, restoring calcium homeostasis, preventing excitotoxicity, and blocking the cellular response to injury by inhibiting neuronal apoptosis. This review underscores the complex biology of Aß specifically looking at the potential targets of therapeutics based on emerging knowledge of this biology. Show more

DOI: 10.3233/JAD-2000-23-405

Citation: Journal of Alzheimer's Disease, vol. 2, no. 3-4, pp. 231-259, 2000

Authors: Davidson, Skylar | Allenback, Gayle | Decourt, Boris | Sabbagh, Marwan N.

Article Type: Research Article

Abstract: Background: Although insulin dysregulation and resistance likely participate in Alzheimer’s disease (AD) etiologies, little is known about the correlation between type 2 diabetes mellitus (T2DM) and the progression of cognitive decline in patients with AD. Objective: To determine whether AD patients with T2DM experience more rapid cognitive decline than those without T2DM. Methods: All cognitive performance data and the presence or absence of T2DM comorbidity in patients with AD were derived from the US National Alzheimer’s Coordinating Center’s (NACC) Uniform Data Set (UDS). A search of the UDS identified 3,055 participants with AD who had more than one epoch completed. …The data set culled clinically diagnosed AD dementia patients who were assessed for diabetes type identified during at least 1 visit. These patients were divided into 2 groups based on whether they had a diagnosis of T2DM. The data from these groups were then analyzed for differences in cognitive decline based on neuropsychological test battery scores and a Clinician Dementia Rating using a general linear model. Results: Comparisons of the mean scores for 16 selected tests from the neuropsychological test battery showed no significant differences in baseline scores and scores at subsequent visits between the T2DM and nondiabetic groups. Conclusions: The results revealed no differences in cognitive decline metrics over the course of 5 visits in either study group. These data indicate that the presence of T2DM does not increase the rate of cognitive decline in AD. This finding contradicts expected disease burden and will need to be explored further. Show more

Keywords: Alzheimer’s disease, cognitive progression, National Alzheimer’s Coordinating Center, neuropsychological test battery, type 2 diabetes mellitus, Uniform Data Set

DOI: 10.3233/JAD-230489

Citation: Journal of Alzheimer's Disease, vol. 95, no. 4, pp. 1573-1584, 2023