Статті в журналах: "Alzhiemer's disease"

1

Nevins, A., and S. Cohn. "More Audiovisuals on Alzhiemer's Disease." Gerontologist 25, no. 5 (October 1, 1985): 551–52. http://dx.doi.org/10.1093/geront/25.5.551a.

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Nevins, A., and H. Rzetelny. "More Audiovisuals on Alzhiemer's Disease." Gerontologist 25, no. 5 (October 1, 1985): 552. http://dx.doi.org/10.1093/geront/25.5.552.

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3

Fontana, Andrea, and Ronald W. Smith. "Alzheimer's Disease Victims: The “Unbecoming” of Self and the Normalization of Competence." Sociological Perspectives 32, no. 1 (March 1989): 35–46. http://dx.doi.org/10.2307/1389006.

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This study examines the importance of routinized practices for the self Alzheimer's disease victims are observed in their daily lives. The deterioration of self is discussed, followed by a discussion of routinized actions and normalization practices by caregivers that allow the patients to be seen as competent selves. Finally, the last remnants of the self in Alzhiemer's patients are discussed. The authors conclude that when the individual self undergoes an “unbecoming” process, due to the mental deterioration caused by the disease, it is largely social practices that allow the self to continue to exist in the eyes of others.

4

Liu-Seifert, Hong, Eric Siemers, Karen Price, Baoguang Han, Katherine Selzler, David Henley, Karen Sundell, et al. "P2-390: COGNITION IMPAIRMENT PRECEDES AND PREDICTS FUNCTIONAL IMPAIRMENT IN MILD ALZHIEMER's DISEASE." Alzheimer's & Dementia 10 (July 2014): P621. http://dx.doi.org/10.1016/j.jalz.2014.05.1070.

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Rozemuller, J. M., P. Eikelenboom, W. Kamphorst, and F. C. Stam. "Lack of evidence for dysfunction of the blood-brain barrier in Alzhiemer's disease: An immunohistochemical study." Neurobiology of Aging 9 (January 1988): 383–91. http://dx.doi.org/10.1016/s0197-4580(88)80085-x.

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6

Kumari, Rima, Suman Khushwaha, and Rohit Gupta. "P1-086: Alzhiemer's disease: Differentiation from other dementias based on quantitative diffusion tensor imaging on 3 Tesla MRI." Alzheimer's & Dementia 5, no. 4S_Part_7 (July 2009): P198. http://dx.doi.org/10.1016/j.jalz.2009.04.090.

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Apostol, Marcin I., Ashley Wright, Matthew Graf, Jon Scherrer, Ken Kosik, and James Treanor. "P4-156: DISCOVERY OF NOVEL SMALL MOLECULE THERAPEUTICS FOR ALZHIEMER'S DISEASE BY TARGETING STERIC ZIPPERS INVOLVED IN TAU AGGREGATION." Alzheimer's & Dementia 15 (July 2019): P1334. http://dx.doi.org/10.1016/j.jalz.2019.06.3818.

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SR, SHARUNYA, VIJAYALAKSHMI DESAI, MEENAKSHI SINGH, and KUSUMA M. "Survey on Early Detection of Alzhiemer’s Disease Using Capsule Neural Network." International Journal of Artificial Intelligence 7, no. 1 (April 23, 2020): 7–12. http://dx.doi.org/10.36079/lamintang.ijai-0701.65.

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Alzheimer's disease (AD) is an disorder which is irreversible of the brain related to memory loss, mostly found in the old and aged population. Alzheimer's dementia results from the degeneration or loss of brain cells. The brain-imaging technologies most often used to diagnose AD is Magnetic resonance imaging (MRI). MRI or structural magnetic resonance is a very popular and actual technique used to diagnose AD. An MRI uses magnets and powerful radio waves to create a complete view of your brain. To actually detect the presence of Alzheimer’s, the MRI should me studied carefullyImplementation of CBIR Content Based Image Retrival which is a revolutionary computer aided diagnosis technique will create new abilities in MRI Magnetic resonance imaging in related image retrieval and training for recognition of development of AD in early stages

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Bezprozvanny, I. "Presenilins function as ER calcium leak channels: Implications for Alzhiemer’s disease." Biochemistry (Moscow) Supplement Series A: Membrane and Cell Biology 3, no. 3 (September 2009): 301. http://dx.doi.org/10.1134/s199074780903012x.

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Wojtunik-Kulesza, Karolina A., and Monika Waksmundzka- Hajnos. "Natural terpenes as substances with multidirectional biological activities." Postępy Polskiej Medycyny i Farmacji 6 (May 8, 2019): 43–50. http://dx.doi.org/10.5604/01.3001.0013.2320.

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Terpenes, secondary metabolites, are considered by scientists around the World. Multidirectional biological activities of these substances encourage researchers to their detail analysis towards numerous diseases such as neurodegenerative or metabolic. In the presented paper, authors have focused on Alzheimer’s disease and diabetes as potential direction of terpenes’ activity. According to available literature, terpenes exhibit satisfactory antioxidant activity and ability to inhibition AChE, BuChE (Alzhiemer’s disease) and α-amylase, α-glucosidase (diabetes). Basis of the presented research are both essential oils obtained from plants such as salvia, rosemary, basil and lemon balm being one of the main source of natural terpenes, and single compounds. Special attention is paid to monoterpenes as the main components of numerous essential oils. Among terpenes presented in the paper, activity of ocimene, carvone, pulegone, α-phellandrene exhibiting activity towards both free radical scavenging as well as AChE and BuChE inhibition, and α-pinene, citral, limonene that revealing inhibitory activity towards α-amylase and α-glucosidase should be emphasized.

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Oakley, Paul A. "Low-Dose Ionizing Radiation Therapy: A Novel Treatment for Post-Concussion Syndrome?" Dose-Response 19, no. 4 (October 2021): 155932582110443. http://dx.doi.org/10.1177/15593258211044341.

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A subset of victims who experience concussion suffer from persistent symptoms spanning months to years post-injury, termed post-concussion syndrome (PCS). Problematically, there is lack of consensus for the treatment of PCS. Concussion injury involves a neurometabolic cascade leading to oxidative stress and neuroinflammation which parallels the oxidative stress loading occuring from age-related neurodegenerative conditions. Historical and recent evidence has emerged showing the efficacy of low-dose radiation therapy for many human diseases including neurodegenerative diseases such as Alzhiemer’s disease (AD). Due to the pathognomonic similarities of oxidative stress and neuroinflammation involved in PCS and neurodegenerative disease, treatments that prove successful for neurodegenerative disease may prove successful for PCS. Recently, low-dose ionizing radiation therapy (LDIR) has been documented to show a reversal of many symptoms in AD, including improved cognition. LDIR is thought to induce a switching from proinflammatory M1 phenotype to an anti-inflammatory M2 phenotype. In other words, a continual upregulation of the adaptive protection systems via LDIR induces health enhancement. It is hypothesized LDIR treatment for PCS would mimic that seen from early evidence of LDIR treatment of AD patients who suffer from similar oxidative stress loading. We propose the application of LDIR is a promising, untapped treatment for PCS.

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Broulikova, H., V. Sládek, P. Čermáková, and M. Arltová. "PMH28 - ECONOMIC IMPACT OF EARLY TREATMENT ON LIFETIME COSTS OF ALZHIEMER’S DISEASE IN CZECHIA." Value in Health 21 (October 2018): S279—S280. http://dx.doi.org/10.1016/j.jval.2018.09.1664.

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13

V. Maju, Sonam, and Gnana Prakasi Oliver Sirya Pushpam. "A novel two-tier feature selection model for Alzheimer’s disease prediction." Indonesian Journal of Electrical Engineering and Computer Science 33, no. 1 (January 1, 2024): 227. http://dx.doi.org/10.11591/ijeecs.v33.i1.pp227-235.

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<span>The interdisciplinary research studies of <a name="_Hlk149917550"></a>artificial intelligence in health sector is bringing drastic life saving changes in the healthcare domain. One such aspect is the early disease prediction using machine learning and regression algorithms. The purpose of this research is to improve the prediction accuracy of Alzheimer ’s disease by analysing the correlation of unexplored Alzheimer causing diseases. The work proposes Chi square-lasso ridge linear (Chi-LRL) model, a new two-tier feature ranking model which recognizes the significance of including diabetes, blood pressure and body mass index as potential Alzhiemer predictive parameters. The newly added predictive parameters of Alzheimer’s disease were statistically verified along with the conventional prediction parameters using chi-square method (Chi) as Tier 1 and an embedded model of lasso, ridge and linear (LRL) Regression for feature ranking as Tier 2. The performance of the proposed Chi-LRL model with selected features were then analysed using machine learning algorithms for performance analysis. The result shows a noticeable performance by selecting eleven significant features and a 4.5% increase in the prediction accuracy of Alzheirmer disease.</span>

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Hoque, Mohibul, J. Ramanjaneyulu, D. Veeresh Babu, Monirul Islam, and V. B. Narayana Swamy. "Studies on Memory Enhancing Property of Sumenta - A Polymherbal Formulation in Experimentally Induced Alzhiemers Disease in Experimental Animals." Research Journal of Pharmacology and Pharmacodynamics 7, no. 2 (2015): 61. http://dx.doi.org/10.5958/2321-5836.2015.00013.0.

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15

Chi, Ying-Chen, Wei-Min Chu, Hsin-Yun Chang, and Tsung-Hsueh Lu. "International Variations in Dementia and Alzheimer Disease Diagnosis and Certification Habits and Their Associations With Dementia and Alzheimer Disease Mortality." Alzheimer Disease & Associated Disorders 37, no. 3 (July 2023): 215–21. http://dx.doi.org/10.1097/wad.0000000000000573.

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Objective: To examine international variations in national diagnosis and certification habits prefer recording dementia (D) versus Alzhiemer disease (AD) as the underlying cause of death (UCOD) and their associations with mortality rates of dementia and AD. Methods: We calculated proportions of D/D+AD and AD/D+AD deaths as proxies of national diagnosis and certification habits. Pearson correlation coefficients (r) were estimated to assess the associations of proportions with the mortality rates of dementia or AD among adults aged 75 to 84 years across 38 countries. Results: The countries with a high preference for recording dementia as the UCOD were Taiwan and Latvia with proportion of D/D+AD deaths of 92% and 88%, respectively, and those with a high preference for recording AD as the UCOD were Slovenia, Turkey, and Poland with proportion of AD/D+AD deaths of 100%, 99%, and 89%, respectively. The r values for the proportions and mortality rate for dementia and AD were 0.67 (95% CI: 0.44-0.81) and 0.46 (95% CI: 0.16-0.68), respectively. Conclusion: We identified a small number of countries with obvious natonal diagnosis and certification habits preferring dementia or AD and had moderate effects on international variations in the mortality rates of dementia and AD.

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Yıldırım, Meltem Pınar, and Burcu Ateş Özcan. "Alzheimer hastalığı ve beslenme ile ilişkisi." Sağlık ve Yaşam Bilimleri Dergisi 2, no. 2 (December 20, 2020): 66–73. http://dx.doi.org/10.33308/2687248x.202022165.

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Alzhiemer disease, which accounts for 70% of dementia caused by damage to the central nervous system, is a disease formed by combining genetic and environmental factors. In the pathogenesis of Alzheimer's disease, amyloid beta accumulation, Tau proteins, neurofibrillary tangles are involved. Inflammation, oxidative damage, insulin resistance, cholesterol, trace elements, metal exposure, carrying the Apolipoprotein E4 (ApoE) gene are risk factors. It is known that Alzheimer's disease does not occur with aging alone, environmental factors are needed. Although there is no definitive nutritional treatment for Alzheimer's disease, the Mediterranean diet is known to be protective and preventive against risk factors of Alzheimer's disease. The Mediterranean diet, which attracts attention with its rich consumption of fruits and vegetables, moderate consumption of white meat, limited in saturated fatty acids and rich in unsaturated fatty acids, is still popular today. Some changes in gout microbiota can affect Alzheimer's disease. Following a nutritional program that reduces inflammation, protects from free radicals and eliminates factors that increase nutritional amyloid beta accumulation can be protective. In addition to this nutrition program, vitamin and mineral supplements and probiotic supplements are recommended as a preventive for Alzheimer's.

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Sheffler, Julia, Greg Hajcak, Cynthia Vied, Melissa Meynadasy, and Russell Mach. "P300 Amplitude in Relation to Age, Neuropsychological Performance, and Genetic Risk for Alzheimer’s Disease." Innovation in Aging 4, Supplement_1 (December 1, 2020): 490. http://dx.doi.org/10.1093/geroni/igaa057.1585.

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Abstract The P300 event-related potential (ERP) is associated with aging and risk for Alzhiemer’s disease (AD) and mild cognitive impairment (MCI). Our study sought to replicate previous findings regarding P300 amplitude, age, and neuropsychological outcomes. We also sought to fill gaps in the literature by assessing associations in a primarily healthy sample of older adults (aged 60-75) and through use of comprehensive assessment procedures for ERPs, neuropsychological outcomes, and a genetic risk score (i.e., BDNF, APOE, and PSEN1 mutations). Approximately 25% of our total sample (N=72) met criteria for possible or probable mild cognitive impairment. We assessed whether the P300 elicited by auditory (oddball) and visual (go/nogo) paradigms were associated with performance across neuropsychological tests commonly used in clinical settings, which include cognitive domains of semantic, episodic, and visual memory, executive functioning, language (confrontation naming), abstract reasoning (visual and verbal), and attention. Further, we examined associations between P300 and multiple genetic risks for AD. Our findings demonstrated differences in outcomes between audio and visual tasks of P300, with visual tasks tending to show stronger relationships with neuropsychological and genetic factors. Neuropsychological measures of memory and executive functioning were most closely related to visual P300 amplitude. P300 amplitude was also significantly associated with a genetic risk score for AD, despite the sample generally performing in the normal range on most neuropsychological tasks. Overall, our study has implications for use of the P300 for early detection of risk for AD and for improving our understanding of the P300 as a cognitive biomarker.

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SUTTISANSANEE, Uthaiwan, and Kalyarat KRUAWAN. "Cholinesterase-inhibiting Potential and Anti-BACE1 Activities of Edible Leaves of Selected Thai Local Plants." Walailak Journal of Science and Technology (WJST) 16, no. 3 (December 1, 2019): 155–63. http://dx.doi.org/10.48048/wjst.2019.6220.

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Alzhiemer’s disease (AD) is common amongst the elderly and is associated with decline in brain functions in terms of memory and cognitive loss. The causes of the disease may occur through loss of presynaptic markers of cholinergic system and deposition of amyloid fibrils in the brain. Cholinesterases (ChEs) including acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are the key enzymes controlling degradation of neurotransmitters, acetylcholines (AChs), in cholinergic hypothesis. Whereas overproduction of b-secretase (BACE1) can generate insoluble b-amyloid peptides. Thus, retardation on enzyme reactions can lead to potential AD prevention. The aim of this research was to investigate in vitro anti-AD activity through key enzymes inhibitions from Thai local plants with edible sour leaves, including Garcinia cowa Roxb., Spondias pinnata (Linn.f.) Kurz, Syzygium gratum (Wight) S.N. Mitra., Tamarind indica L. and Cratoxylum formosum (Jack) Dyer. Leaves were extracted in organic solvents with different polarity index values (ethanol and hexane). As results, all plants possessed different degrees of anti-ChEs activity, in which ethanolic extracts of Spondias pinnata and Tamarind indica exhibited significantly higher ChEs inhibitory activities than Syzygium gratum, Garcinia cowa and Cratoxylum formosum, respectively. Interestingly, most hexane extracts exhibited higher anti-AChE activities than ethanol extracts, while the contrary results were observed in anti-BChE activity. Besides, only Cratoxylum formosum, Garcinia cowa and Tamarind indica extracts possessed anti-BACE1 activity. The information received from this study would be great support of future drug development or nutraceutical agents against AD occurrence regarding its cholinergic and b-amyloid formation hypotheses.

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Nadendla, Rama Rao, and Nagam Santhi Priya. "Development and Preclinical Testing of Nasal Aerosol for the Delivery of Novel Spray Dried Polyherbal Formulation to Treat Alzheimer’s Disease." Journal of Drug Delivery and Therapeutics 10, no. 3 (May 15, 2020): 185–94. http://dx.doi.org/10.22270/jddt.v10i3.4112.

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Alzheimer’s disease (AD) is an irreversible, progressive brain disorder that slowly destroys memory and thinking skills and eventually the ability to carry out the simplest tasks. The present investigation was undertaken to evaluate anti-alzheimer’s activity of novel herbal aerosol spray formulation containing pure extracts of Curcuma longa, Commiphora wightii and Withania somnifera.Pressurized aerosol packs containing polyherbal spray dried dispersions in the concentration range of 0.5, 1 and 2% w/v dispersed in 10/90, 20/80, 30/70/ 40/60, 50/50) propellant blends of HFA-134a were developed in 3 in 1 aerosol filling machine and evaluated. Behavioural studies were performed in male wistar rats and histopathological studies were performed. The preparations were also assessed for AChE inhibitory activity. Results with P values < 0.05 were considered statistically significant. Chitosan exhibited compatibility with the polyherbal extracts in FT-IR studies. DSC thermogram revealed an endothermic peak of 65ᵒC with chitosan. Spray dried poly herbal extracts exhibited a spherical morphology particle size distribution of 5-50µm with a practical yield of 20-30%. Aerosol formulations exhibited a particle size range below 10µm. average weight per actuation of canister was 7-8mg with a total 210 deliveries per pack. Zeta potential of the formulations was ±0.997. HPTLC fingerprinting showed band ranges at 256 and 366nm. The optimized aerosol spray in behavioral tests exhibited 10mg/kg and 20mg/kg intranasally reversed the scopolamine induced amnesia. Histopathological findings showed decreased Ach activity in male albino wistar rats. Percentage inhibition of formulation and standaed on AChE activity shoed an IC50 of 62% for 10mg/kg aerosol spray and 72% with 20mg/kg aerosol spray dosing. Keywords: alzhiemer’s disease; herbal; spray dried chitosan; aerosol; nasal spray;

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Kumari, Rima, Suman Khushwaha, Rohit Gupta, and D. C. Jain. "P3-086: Diffusion tensor tractography of white matter tracts within the temporal stem in Alzhiemer disease on 3 tesla MRI." Alzheimer's & Dementia 5, no. 4S_Part_12 (July 2009): P367. http://dx.doi.org/10.1016/j.jalz.2009.04.1162.

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Md Salahuddin, Abu Jafor, Md Rezaul Karim Khan, Md Muniruzzaman Bhuiyan, Nuruddin Md Eusuf, Rased Imam Zahid, Khairul Kabir Patwary, Muhammad Salahuddin, et al. "Association of Dementia in Ischemic Stroke: A Case Control Study." Bangladesh Journal of Neuroscience 30, no. 1 (January 31, 2014): 35–44. http://dx.doi.org/10.3329/bjn.v30i1.57363.

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Objectives: To evaluate the association of dementia in ischemic stroke. Methodology: This case control study was carried out in the department of Neurology at BSMMU, Dhaka from 1st January 2010 to 31st December 2011 for duration of two years to evaluate the association of dementia in ischemic stroke. The target population for this study include all patients presented with ischemic stroke at the range of 3 to 6 months after stroke with the age group of 40 to 70 years are included in this study and patients of dementia other than ischemic stroke like Alzhiemer’s disease, vit-B12 deficiency, thyroid dysfunction were excluded from this study. A total number of 120 respondents were included in this study. Age & sex matched 60 patients of ischemic stroke were selected as cases and rest 60 people were taken as control group. Informed written consent was taken from each patient or his/ her attendant. All information regarding history and physical findings; and other risk factors for dementia were collected to fill up the preformed questionnaire. Relevant physical examinations like nervous system examination, selected general and systemic examination were recorded. Result & Observation: Dementia was present in case and control group 18(30.0%) and 2(3.3%) respectively. The difference was statistically significant (p=0.001). Present smoking habit was more in case (45.0%) than in control group (16.7%) which was statistically significant (p=0.001) with a OR of 4.07 with a 95% CI of 1.89-8.75. Past smoking habit was more in case (16.7%) than control group (11.7%). Non-smoker was more in control (71.7%) than case group (38.3%). Diabetes mellitus was more common in case group (38.3%) than control group 5(8.3%) which was statistically significant (p=0.001) with a 6.84 OR and 95% CI of 2.39-19.6. Conclusion: The study permit to conclude that dementia is directly associated with ischemic stroke. We found a correlation between age, family history of dementia, hypertension, diabetes mellitus and dyslipidemia with dementia. Bangladesh Journal of Neuroscience 2014; Vol. 30 (1): 35-44

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"Heparin-binding growth factors exhibit differential affinities for B/A4 amyloid-containing structures in Alzhiemer's disease." Neurobiology of Aging 13 (January 1992): S45—S46. http://dx.doi.org/10.1016/0197-4580(92)90306-i.

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Fabbo, Andrea, Petra Bevilacqua, Glenda Garzetta, Elenza Zavatta, and Lucia Bergamini. "The “COGS CLUB” : A psychosocial intervention for people with Alzhiemer’s disease." Alzheimer's & Dementia 19, S5 (June 2023). http://dx.doi.org/10.1002/alz.065326.

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Zeng, Hei Yu, and Michael McAloon. "The “Asian flush syndrome”: ALDH2 Deficiency and Long-term Health Consequences." Journal of Student Research 12, no. 1 (February 28, 2023). http://dx.doi.org/10.47611/jsrhs.v12i1.4048.

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Harmful use of alcohol leads to roughly 3 million deaths worldwide every year, and is linked to the development of roughly 230 different types of disease (World Health Organization, 2016). As alcohol has the ability to diffuse through cell membranes, its toxicity can heavily impact almost all organs within the human body. A large proportion of the East Asian population experiences the “Asian flush syndrome” post-drinking, which induces characteristic facial-flushing symptoms caused by an aldehyde dehydrogenase (ALDH2) enzyme deficiency due to an ALDH2 gene mutation. In the past, investigations on links between ALDH2 deficiencies and long-term health consequences have been conducted with conclusive evidence that confirm that “Asian flushers'' have a predisposed risk for various diseases, including cancer and cardiovascular disease. This literature review systematically compiles research that explains the mechanisms behind ALDH2 deficient communities and increased health risks to esophageal cancer, cardiovascular disease, and Alzhiemer’s disease. Furthermore, it shows that risk levels for disease are compounded when alcohol intake is increased. The preventative measures and social factors are also considered, including recommendations for further interventions to increase awareness and decrease alcohol intake in affected individuals.

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Raju, Manu, Varun P. Gopi, V. S. Anitha, and Abishek Sherawat. "Early diagnosis of Alzhiemer’s disease using wavelet-pooling based deep convolutional neural network." Sādhanā 48, no. 3 (August 19, 2023). http://dx.doi.org/10.1007/s12046-023-02219-8.

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Stephenson, Henry G., Akshay Kohli, Steven R. Kecskemeti, Anna Rubinski, Michael Ewers, Andrew L. Alexander, Yuetiva Deming, et al. "Longitudinal trajectories of myelin loss in the context of Alzhiemer’s disease biomarkers, glial activation, and APOE4." Alzheimer's & Dementia 19, S17 (December 2023). http://dx.doi.org/10.1002/alz.080495.

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AbstractBackgroundLower measures of myelin have been associated with abnormal levels of AD biomarkers and APOE4 carriage. However, most human studies have been cross‐sectional, leaving the relationship between AD and myelin changes unclear. The purpose of this study was to determine the association between AD pathology, APOE4, glial activation, and longitudinal changes in quantitative R1 (qR1), a marker sensitive to myelination obtained via MPnRAGE MRI.MethodParticipants from the Wisconsin Registry for Alzheimer’s Prevention (WRAP) and Wisconsin Alzheimer’s Disease Research Center (ADRC) were selected based on available longitudinal MPnRAGE, clinical diagnosis, and APOE genotyping (N = 446). A subset (N = 141) included those with available baseline CSF (AB42/40, pTau181), and gliosis markers (sTREM2, GFAP, YKL40) measured using a robust prototype assay as part of the Roche NeuroToolKit research platform (Roche International). Longitudinal mean qR1 was estimated from white matter regions from the ICBM‐DTI‐81 atlas. In the overall sample, linear mixed effects models predicting regional qR1 (FDR‐corrected) with random intercepts and slopes were estimated controlling for sex, age centered within‐subjects (agec), age averaged within‐subjects (agegm), cognitive impairment, and APOE4 carriage as covariates. Two‐way interactions between impairment and APOE4 with agec were tested in the overall sample as were moderating effects of CSF amyloid‐positivity, pTau181, and gliosis markers on agec in the CSF sample.ResultIn the overall sample, older agec, agegm, and female sex were associated with lower qR1 in a majority of tracts indicating substantial longitudinal declines in qR1 over time and lower qR1 with advanced age and female sex. Sex, impairment, and APOE4 did not show significant agec interactions. Likewise, none of the CSF biomarkers moderated the effect of agec in the CSF subsample.ConclusionWhile aging is robustly associated with longitudinal demyelination as potentially indexed by qR1, these rates do not appear to be moderated by AD pathology, cognitive impairment, APOE4, or glial activation in early disease. Given the capacity for re‐myelination in the context of injury, longitudinal studies are critical for parsing myelin and AD relationships. Established associations between myelin and AD risk may reflect later disease processes, particularly in samples more enriched for tau pathology.

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Stephenson, Henry G., Akshay Kohli, Steven R. Kecskemeti, Anna Rubinski, Michael Ewers, Andrew L. Alexander, Yuetiva Deming, et al. "Longitudinal trajectories of myelin loss in the context of Alzhiemer’s disease biomarkers, glial activation, and APOE4." Alzheimer's & Dementia 19, S10 (December 2023). http://dx.doi.org/10.1002/alz.082011.

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AbstractBackgroundLower measures of myelin have been associated with abnormal levels of AD biomarkers and APOE4 carriage. However, most human studies have been cross‐sectional, leaving the relationship between AD and myelin changes unclear. The purpose of this study was to determine the association between AD pathology, APOE4, glial activation, and longitudinal changes in quantitative R1 (qR1), a marker sensitive to myelination obtained via MPnRAGE MRI.MethodParticipants from the Wisconsin Registry for Alzheimer’s Prevention (WRAP) and Wisconsin Alzheimer’s Disease Research Center (ADRC) were selected based on available longitudinal MPnRAGE, clinical diagnosis, and APOE genotyping (N = 446). A subset (N = 141) included those with available baseline CSF (AB42/40, pTau181), and gliosis markers (sTREM2, GFAP, YKL40) measured using a robust prototype assay as part of the Roche NeuroToolKit research platform (Roche International). Longitudinal mean qR1 was estimated from white matter regions from the ICBM‐DTI‐81 atlas. In the overall sample, linear mixed effects models predicting regional qR1 (FDR‐corrected) with random intercepts and slopes were estimated controlling for sex, age centered within‐subjects (agec), age averaged within‐subjects (agegm), cognitive impairment, and APOE4 carriage as covariates. Two‐way interactions between impairment and APOE4 with agec were tested in the overall sample as were moderating effects of CSF amyloid‐positivity, pTau181, and gliosis markers on agec in the CSF sample.ResultIn the overall sample, older agec, agegm, and female sex were associated with lower qR1 in a majority of tracts indicating substantial longitudinal declines in qR1 over time and lower qR1 with advanced age and female sex. Sex, impairment, and APOE4 did not show significant agec interactions. Likewise, none of the CSF biomarkers moderated the effect of agec in the CSF subsample.ConclusionWhile aging is robustly associated with longitudinal demyelination as potentially indexed by qR1, these rates do not appear to be moderated by AD pathology, cognitive impairment, APOE4, or glial activation in early disease. Given the capacity for re‐myelination in the context of injury, longitudinal studies are critical for parsing myelin and AD relationships. Established associations between myelin and AD risk may reflect later disease processes, particularly in samples more enriched for tau pathology.

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Douglas, David, Maged Goubran, Eugene Wilson, Guofan Xu, Pragya Tripathi, Dawn Holley, Steven Chao, et al. "Correlation between arterial spin labeling MRI and dynamic FDG on PET-MR in Alzheimer’s disease and non-Alzhiemer’s disease patients." EJNMMI Physics 2, S1 (May 18, 2015). http://dx.doi.org/10.1186/2197-7364-2-s1-a83.

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Gupta, Mohan, Swati Pant, Preeti Rana, Avinash Kumar, Chakrawarti Prasun, Maya S. Nair, Sarvesh Paliwal, and Sumitra Nain. "Investigation, scaffold hopping of novel donepezil-based compounds as anti-Alzhiemer’s agents: synthesis, in-silico and pharmacological evaluations." Scientific Reports 14, no. 1 (January 19, 2024). http://dx.doi.org/10.1038/s41598-024-51713-4.

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AbstractAlzheimer’s disease (AD) is a multifaceted neurodegenerative condition. The pathogenesis of AD is highly intricate and the disease is apparent in the aged population ~ 50–70 years old. Even after > 100 years of research, the root origin of AD and its pathogenesis is unclear, complex and multifaceted. Herein, we have designed and synthesized 9 novel molecules with three different heterocyclic scaffolds namely pyrrolidone-2-one, quinoline & indoline-2-one to imitate and explore the novel chemical space around donepezil. The synthesized molecules were evaluated for their potential as anti-Alzheimer’s agents through in-vitro and in-vivo studies in appropriate animal models. To further understand their interaction with acetylcholinesterase enzyme (AChE), extra-precision docking, and molecular dynamics simulation studies were carried out. As the number of compounds was limited to thoroughly explore the structure–activity relationship, atom-based 3D-quantitative structure–activity relationships (QSAR) studies were carried out to get more insights. All the designed compounds were found to inhibit AChE with IC50 in the micromolar range. From pyrrolidone-2-one series, 6-chloro-N-(1-(1-(3,4-dimethoxybenzyl)-2-oxopyrrolidin-3-yl)piperidin-4-yl)pyridine-3-sulfonamide (9), 2-(1-benzylpiperidin-4-yl)-6,7-dimethoxy-4-(4-methoxyphenyl)quinoline (18) from quinoline series and N-(1-benzylpiperidin-4-yl)-2-(2-oxoindolin-3-yl)acetamide (23) from indolin-2-one series inhibited AChE with an IC50 value of 0.01 µM. Based on other biochemical studies like lipid peroxidation, reduced glutathione, superoxide dismutase, catalase, nitrite, and behavioural studies (Morris water maze), compound 9 was found to be a potent AChE inhibitor which can be further explored as a lead molecule to design more potent and effective anti-Alzheimer’s agents.

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Alasmari, Fawaz, Farraj M. Alotaibi, Wedad Saeed Al-Qahtani, Abdullah F. AlAsmari, and Faleh Alqahtani. "Therapeutic effects of thymoquinone onAlzheimer’s disease through modulating amyloid beta neurotoxicity and neuro-inflammatory cytokine levels." CNS & Neurological Disorders - Drug Targets 21 (April 18, 2022). http://dx.doi.org/10.2174/1871527321666220418125057.

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Abstract: Alzheimer’s disease (AD) is a neurodegenerative disease that involves several impaired neuronal pathways. Modulating the amyloid-beta (β-amyloid) system are being tested to treat AD. Amyloid beta neurotoxicity is associated with neuroinflammation and plaque formation, further progressing AD. Protecting neurons from β-amyloid neurotoxicity could be an efficient strategy for the treatment of the AD. Thymoquinone (TQ) is an active ingredient in Nigella sativa (NS) and showed effective therapeutic properties in AD models. TQ was able to attenuate the behavioral dysfunctions in AD models. Moreover, TQ could attenuate the neuroinflammation properties in animals who have developed AD. In addition, studies showed that TQ could modulate β-amyloid neurotoxicity, an effect associated with improved AD behavioral symptoms. In this review, we highlighted the therapeutic effects of TQ on the progression of AD through modulating β-amyloid neurotoxicity and neuro-inflammatory cytokine levels. Other phenolic compounds present also in NS improved behavioral and neuronal impairments in AD models supported TQ anti-Alzhiemer efficacy.

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Norris, Christopher M., Sangderk Lee, Jenna L. Gollihue, Danielle S. Goulding, Pradoldej Sompol, Donna M. Wilcock, and Josh M. Morganti. "Astrocyte signaling regulates microglial and oligodendrocyte subpopulation changes in a diet‐based model of small cerebral vessel disease." Alzheimer's & Dementia 19, S24 (December 2023). http://dx.doi.org/10.1002/alz.083142.

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AbstractBackgroundVascular contributions to cognitive impairment and dementia (VCID) is the second leading cause of dementia behind Alzhiemer’s disease. Hyperhomocysteinemia (HHcy)‐inducing diets in mice recapitulate aspects of VCID including small cerebrovessel pathology, vascular inflammation and cognitive decline. Recently, we found signs of astrocytic Ca2+‐dysregulation and hyperactivation of calcineurin/NFAT activity in mice treated with HHcy diet (Sompol et al., 2023 J Neurosci 43:1797). Inhibition of astrocytic NFATs normalized cerebrovascular, synaptic, and cognitive function in HHcy mice, suggesting that reactive astrocytes alter the brain milieu during development of HHcy and small cerebrovessel pathology. Here, we used scRNA‐seq to further characterize the impact of astrocytic calcineurin/NFATs on multiple brain cell types in the context of HHcy.MethodSeven‐to‐eight week‐old male C57BL/6J mice received intrahippocampal injections of AAV2/5‐Gfa2‐EGFP (control) or AAV expressing the NFAT inhibitor VIVIT (i.e. AAV2/5‐Gfa2‐VIVIT‐EGFP). Mice were then fed with control chow(CT) or HHcy‐inducing chow enriched in methionine and deficient in folate and vitamins B6 and B12. After15 weeks of diet, brains were extracted and hippocampi dissected away, pooled and dissociated for transcriptional analyses. scRNA‐seq was used to identify diet and AAV‐dependent cell specific gene expression changes according to our previous work (Lee et al, 2023, Cell Reports, 112196).Result31 cell clusters were identified and assigned to 1 of 12 unique cell types using established gene markers. Analysis of differentially‐expressed genes showed that microglia and oligodendrocytes were most sensitive to diet and/or AAV treatment. In HHcy mice treated with control AAV (HHcy–EGFP), predominant microglial subpopulations exhibited upregulation of several disease‐associated microglial genes (e.g. Apoe, Il1b, Ccl5, Cebpb, Cybb) and downregulation of common homeostatic genes (e.g. P2ry12, Gpr34, Fcrls, Sparc). Oligodendrocyte subpopulations in the same mice also exhibited upregulation of disease related genes (e.g. Serpina3n, H2‐D1, C4b, Klk6). However, these patterns were mitigated in HHcy mice treated with AAV‐Gfa2‐VIVIT, who exhibited expression patterns in line with CT diet mice. Analyses of DEGs in other cell types and association with immunometabolic pathways are in progress.ConclusionResults suggest that reactive astrocyte signaling strongly regulates molecular phenotypes of other local glial cells and provides a potential target for preventing/resolving pathologic glial activity in VCID and other ADRDs.

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