Journal of Alzheimer's Disease Reports - Volume 3, issue 1

Authors: Kar, Subrata | Majumder, D. Dutta

Article Type: Research Article

Abstract: This study examined early detection of Alzheimer’s disease (AD) by diffusion tensor visualization-based methodology and neuro-fuzzy tools. Initially, we proposed a model for the early detection of AD using the measurement of apparent diffusion coefficient, fractional anisotropy, and gray matter, which can determine neurological disorder patterns and abnormalities in brain white matter. These are used as input parameters into fuzzy tools, and using fuzzy rules, we evaluate the AD score as an output variable that provides a useful platform to physicians in determining the status of the disease. In the second stage, we present an investigative study on AD and …used the neuro-fuzzy classification system for pattern recognition of either AD or healthy control. The experimental results are from 20 samples (14 for training, 3 for validation, and 3 for testing) used in an artificial neural network classification system. The neural network is trained with a training algorithm and the performance of the training algorithm is obtained by executing a fuzzy expert system. Out of 20 patients, 9 are AD patients and 11 are healthy control patients. We present a neuro-fuzzy tool as a better classifier for early detection of AD and obtain a satisfactory performance with 100% accuracy. Show more

Keywords: Alzheimer’s disease, apparent diffusion coefficient, diffusion tensor imaging, fractional anisotropy, gray matter, neuro-fuzzy classification system

DOI: 10.3233/ADR-180082

Citation: Journal of Alzheimer's Disease Reports, vol. 3, no. 1, pp. 1-18, 2019

Authors: Gandbhir, Omkar | Sundaram, Pazhani

Article Type: Research Article

Abstract: Alzheimer’s disease (AD) is the most common cause of dementia among elderly patients afflicted by neurodegenerative diseases, caused by the accumulation of amyloid-β (Aβ). Therapeutic interventions in targeting and restricting Aβ production resulted in little or no success. However, recent studies have shown signs of success in validating Aβ as a target. Recombinant Technologies LLC (RTL) has developed and studied its proprietary Amytrap peptide to remove Aβ from circulation which in turn depletes brain Aβ in a clinically relevant mouse model of AD. In the current study, this Amytrap peptide (the active pharmacological ingredient, API) has been linked to sepharose …matrix by click chemistry. The derivative namely ‘Amytrapper’ was confirmed to remove Aβ from the surrounding media spiked with Aβ42 . Additional testing performed on Amytrapper with sera and plasma containing Aβ42 showed retention of Aβ42 upon increasing concentrations of biotinylated Aβ42 (bio-Aβ42 ). Specificity of this binding was confirmed via 1) pre-blocking Amytrapper with cold (unbiotinylated) Aβ42 followed by binding experiment with biotinylated Aβ42 , 2) 2-dimensional SDS-PAGE analyses on samples harvested before and after the binding experiment, and 3) reconciling the amounts bound to beads and left over in the flow through. The results provide a proof of concept for our proposed prototype design for an Amytrapper device. The results suggest that extracorporeal clearance of Aβ42 by Amytrapper could be a way to manage accumulation of amyloid in AD and thus could become an added mode of therapy for disease modification. Show more

Keywords: Alzheimer’s disease, amyloid, amyloid-β peptides, Amytrapper, extracorporeal, plasmapheresis, Alzheimer’s therapy

DOI: 10.3233/ADR-180093

Citation: Journal of Alzheimer's Disease Reports, vol. 3, no. 1, pp. 19-29, 2019

Authors: Prato, Frank S. | Pavlosky, William F. | Foster, Steven C. | Thiessen, Jonathan D. | Beaujot, Roderic P.

Article Type: Review Article

Abstract: Significant advances in positron emission tomography (PET) and magnetic resonance imaging (MRI) brain imaging in the early detection of dementia indicate that hybrid PET/MRI would be an effective tool to screen for dementia in the population living with lifestyle risk factors. Here we investigate the associated costs and benefits along with the needed imaging infrastructure. A demographic analysis determined the prevalence of dementia and its incidence. The expected value of the screening program was calculated assuming a sensitivity and specificity of 0.9, a prevalence of 0.1, a QALY factor of 0.348, a willingness to pay $114,000 CAD and the cost …per PET/MRI scan of $2,000 CAD. It was assumed that each head PET/MRI could screen 3,000 individuals per year. The prevalence of dementia is increasing by almost two-fold every 20 years due to the increased population at ages where dementia is more prevalent. It has been shown that a five-year delay in the incidence of dementia would decrease the prevalence by some 45%. In Canada, a five-year delay corresponds to a health care savings of $27,000 CAD per subject per year. The expected value for screening was estimated at $23,745 CAD. The number of subjects to be screened per year in Canada, USA, and China between 60 and 79 was 11,405,000. The corresponding number of head-only hybrid PET/MRI systems needed is 3,800. A brain PET/MRI screening program is financially justifiable with respect to health care costs and justifies the continuing development of MRI compatible brain PET technology. Show more

Keywords: Brain PET, dementia demographics, dementia screening, hybrid PET/MRI, lifestyle risks, magnetic resonance imaging, MRI-compatible PET, positron emission tomography

DOI: 10.3233/ADR-180098

Citation: Journal of Alzheimer's Disease Reports, vol. 3, no. 1, pp. 31-45, 2019

Authors: Gamir-Morralla, Andrea | Sacristán, Sandra | Medina, Miguel | Iglesias, Teresa

Article Type: Research Article

Abstract: The nematode Caenorhabditis elegans (C. elegans) is a powerful model organism to study lifespan and aging, protein aggregation, and neurodegeneration, as well as to carry out drug screenings. The C. elegans strain aex-3 /T337 expresses human pathogenic V337M mutant tau under a pan-neuronal promoter and presents uncoordinated locomotion, accumulation of phosphorylated insoluble tau, and shortened lifespan. Herein we have used this strain to assay two compounds that could affect tau aggregation and/or phosphorylation, and looked for phenotypic changes in their lifespan and motility. The first compound is Thioflavin T (ThT), a member of the tetracycline family with protein …antiaggregant properties, yet to be tested in a tauopathy model. The second is a novel small molecule, NP103, a highly selective inhibitor of glycogen synthase kinase-3 (GSK-3), the main kinase contributing to pathogenic tau hyperphosphorylation. Importantly, we find that ThT extends lifespan of aex-3 /T337 worms as it does with control N2 animals, showing both strains similar locomotion features under this treatment. By contrast, NP103 improves the paralysis phenotype of aex-3 /T337 mutants but not their lifespan. Our results show that both treatments present beneficial effects for this model of tauopathy and encourage pursuing further investigations on their therapeutic potential for AD and other tauopathies. Show more

Keywords: Aging, Alzheimer’s disease, C. elegans, GSK-3, tau, tauopathy, Thioflavin T

DOI: 10.3233/ADR-180087

Citation: Journal of Alzheimer's Disease Reports, vol. 3, no. 1, pp. 47-57, 2019

Authors: Das, Tushar Kanti | Chakrabarti, Swarup Kumar | Zulkipli, Ihsan Nazurah | Abdul Hamid, Mas R.W.

Article Type: Research Article

Abstract: To date, dysregulation of the insulin signaling pathway in the brain has not been demonstrated unequivocally in Alzheimer’s disease (AD). The purpose of the study was to examine the possible dysregulation of insulin signaling pathway in an AD rat model. Furthermore, the present study investigated the effect of Donepezil and Curcumin on insulin signaling, insulin, and glucose levels in AD rat brain. The rats were induced to develop AD by intraperitoneal administration of Scopolamine. We found that glucose levels in plasma and brain were decreased in AD rats, whereas the insulin levels was increased in plasma but decreased in brain …in AD rats. In addition, insulin signaling proteins IR-β, IGF-1, IRS-1, IRS-2 p-Akt (Ser473), and Akt were markedly reduced in the AD rats. Furthermore, GLUT3 and GLUT4 levels in the brain were markedly reduced in AD rats. All these data were compared to Saline-treated control rats. Curcumin significantly increased glucose levels in plasma and in brain. However, insulin levels was decreased in plasma and was increased in AD rats’ brain. Moreover, GLUT3 and GLUT4 levels were significantly increased in Curcumin-treated AD rats. All these data were compared to Scopolamine– induced AD rats. Thus amelioration of impaired insulin signaling and improved glucose regulation in AD rats by Curcumin may be beneficial in the management of AD. Show more

Keywords: Alzheimer’s disease, curcumin, donepezil, glucose receptors, insulin signaling

DOI: 10.3233/ADR-180091

Citation: Journal of Alzheimer's Disease Reports, vol. 3, no. 1, pp. 59-70, 2019

Authors: Smalheiser, Neil R.

Article Type: Short Communication

Abstract: Mining the case report literature identified an intriguing, yet neglected finding: Deoxyribonuclease I (DNase I) as a possible treatment for Alzheimer’s disease. This finding is speculative, both because it is based on one patient, and because the underlying mechanism(s) of action remain obscure. However, further literature review revealed that there are several plausible mechanisms by which DNase I might affect the course of Alzheimer’s disease. Given that DNase I is an FDA-approved drug, with extensive studies in both animals and man in the context of other diseases, I suggest that investigation of DNAse I in Alzheimer’s disease is worthwhile.

Keywords: Case reports, Deoxyribonuclease I, incidental findings, literature-based discovery, lucidity, lucid dreaming, drug repurposing

DOI: 10.3233/ADR-190100

Citation: Journal of Alzheimer's Disease Reports, vol. 3, no. 1, pp. 71-76, 2019

Authors: Gandbhir, Omkar | Sundaram, Pazhani

Article Type: Research Article

Abstract: Alzheimer’s disease (AD) is the most common cause of dementia. Amyloid-β (Aβ42 ) is implicated in AD pathogenesis. We have designed a non-immune based proprietary therapeutic, called Amytrap, a conjugate containing a retro-inverso peptide, polyethylene glycol, and human serum albumin. Amytrap not only binds Aβ42 but also prevents and dissociates aggregated Aβ42 . Amytrap binds to the region in Aβ42 known to trigger its self-aggregation, thus disrupting aggregation. We have obtained proof of concept on AmyTrap in a clinically relevant mouse model, namely, AD-APPSWE/Tg2576. We synthesized and characterized Amytrap and confirmed its authenticity. Efficacy evaluations were performed on …young (5 months) and old (9 months) model mice. Amytrap was injected biweekly for a period of five months. Pharmacokinetics and safety toxicology were assessed in normal mice and rats, respectively. Post treatment, younger mice showed significant improvements in cognition and Aβ42 levels in plasma, brain, and cerebrospinal fluid, while older mice showed less significant benefits. Immunohistochemistry of brain sections showed similar differences between young and old mice. They all had diminished size and number of plaques in the brain of Amytrap-treated mice. Further, treated mice did not develop antibodies to Amytrap, suggesting Amytrap is non-immunogenic. Safety toxicological studies in rats showed that Amytrap was well tolerated and therefore safe (even at 50 X the efficacy dose). Stability tests showed Amytrap is stable at 4°C for up to one year. Efficacy and safety features make Amytrap a promising candidate for treating or modulating AD. Show more

Keywords: Alzheimer’s disease, amyloid, amyloid-β binder, Amytrap, efficacy, peptide, retro inverso peptide, therapy, toxicology

DOI: 10.3233/ADR-190107

Citation: Journal of Alzheimer's Disease Reports, vol. 3, no. 1, pp. 77-94, 2019

Authors: Manzano Palomo, Maria Sagrario | Anaya Caravaca, Belen | Balsa Bretón, Maria Angeles | Castrillo, Sergio Muñiz | Vicente, Asuncion de la Morena | Castro Arce, Eduardo | Alves Prez, María Teresa

Article Type: Research Article

Abstract: Background: Previous studies have shown that Souvenaid (medical food) can have benefits on memory, cognition, and function in early Alzheimer’s disease (AD) and mild cognitive impairment (MCI). Objective: Demonstrate that Souvenaid could improve or maintain cognition and has an effect on neurodegeneration biomarkers. Methods: This cohort study was carried out from June 2015 through December 2016 in the Neurology Department, Infanta Cristina Hospital, Madrid, Spain. MCI-HR-AD were recruited using Petersen criteria, neuropsychology (NPS), and 18 F-FDG PET scans to confirm the high risk of progression to dementia with one year of follow-up. Age, sex, vascular risk …factors (VRF), and NPS values (Barcelona brief version) were analyzed. 18 F-FDG PET scans were analyzed as a visual procedure. The study was approved by the Research Committee of ICH. Statistical analysis was made with SPSS 22.0 version. Results: Subjects included 43 MCI patients (58.5% women; mean age 69.78±7.89): 17 receiving Souvenaid® treatment (ST), 24 receiving no treatment (WT) and 2 who withdrew. No differences were seen in VRF, only hypercholesterolemia, and were less prevalent in the ST group (p  = 0.002). The rate of progression to dementia was 48.8% (no differences between groups, p  = 0.654). A second round of 18 F-FDG PET scans showed a significance worsening of glucose metabolism in WT (p  = 0.001) versus ST, in which it was low (p  = 0.050). For NPS testing, there was a significant worsening in memory performance in the WT group (p  = 0.011) and a stabilization in ST (p  = 0.083), as well as in executive functions and attention (worsening in WT, p  = 0.014). For the Subjective Changing Scale (SCS), caregivers indicated a stabilization/improvement in ST (p  = 0.017). Conclusion: Souvenaid had a significant effect on several cognitive domains, and on SCS in patients with MCI-HR-AD. Its intervention had an impact on preservation on 18 F-FDG PET scans. Show more

Keywords: Alzheimer’s disease, 18F-FDG PET scans, mild cognitive impairment, neuropsychology, Souvenaid®

DOI: 10.3233/ADR-190109

Citation: Journal of Alzheimer's Disease Reports, vol. 3, no. 1, pp. 95-102, 2019

Authors: Pasquini, Lorenzo | Rahmani, Farzaneh | Maleki-Balajoo, Somayeh | La Joie, Renaud | Zarei, Mojtaba | Sorg, Christian | Drzezga, Alexander | Tahmasian, Masoud

Article Type: Review Article

Abstract:  The posteromedial cortex (PMC) and medial temporal lobes (MTL) are two brain regions particularly vulnerable in Alzheimer’s disease (AD). We have reviewed the spatiotemporal patterns of amyloid-β and tau accumulation, local MTL functional alterations and MTL-PMC network reconfiguration, and propose a model to relate these elements to each other. Functional and structural MTL-PMC disconnection happen concomitant with amyloid-β plaques and neurofibrillary tau accumulation within these same regions. Ongoing disconnection is accompanied by dysfunctional intrinsic local MTL circuit hyperexcitability, which exacerbates across distinct clinical stages of AD. Our overarching model proposes a sequence of events relating the spatiotemporal patterns of amyloid-β …and tau accumulation to MTL-PMC disconnection and local MTL hyperexcitability. We hypothesize that cortical PMC amyloid-β pathology induces long-range information processing deficits through functional and structural MTL-PMC dysconnectivity at early disease stages, which in turn drives local MTL circuit hyperexcitability. Intrinsic local MTL circuit hyperexcitability subsequently accelerates local age-related tau deposition, facilitating tau spread from the MTL to the PMC, eventually resulting in extensive structural degeneration of white and grey matter as the disease advances. We hope that the present model may inform future longitudinal studies needed to test the proposed sequence of events. Show more

Keywords: Alzheimer’s disease, amyloid-β , default mode network, disconnection, hyperexcitability, medial temporal lobe, mild cognitive impairment, posteromedial cortex, tau

DOI: 10.3233/ADR-190121

Citation: Journal of Alzheimer's Disease Reports, vol. 3, no. 1, pp. 103-112, 2019

Authors: Guix, Francesc X. | Sartório, Carmem L. | ILL-Raga, Gerard

Article Type: Review Article

Abstract:  Human life unfolds not only in time and space, but also in the recollection and interweaving of memories. Therefore, individual human identity depends fully on a proper access to the autobiographical memory. Such access is hindered under pathological conditions such as Alzheimer’s disease, which affects millions of people worldwide. Unfortunately, no effective cure exists to prevent this disorder, the impact of which will rise alarmingly within the next decades. While Alzheimer’s disease is largely considered to be the outcome of amyloid-β (Aβ) peptide accumulation in the brain, conceiving this complex disorder strictly as the result of Aβ-neurotoxicity is perhaps a …too straight-line simplification. Instead, complementary to this view, the tableau of molecular disarrangements in the Alzheimer’s disease brain may be reflecting, at least in part, a loss of function phenotype in memory processing. Here we take BACE1 translation and degradation as a gateway to study molecular mechanisms putatively involved in the transition between memory and neurodegeneration. BACE1 participates in the excision of Aβ-peptide from its precursor holoprotein, but plays a role in synaptic plasticity too. Its translation is governed by eIF2α phosphorylation: a hub integrating cellular responses to stress, but also a critical switch in memory consolidation. Paralleling these dualities, the eIF2α -kinase HRI has been shown to be a nitric oxide-dependent physiological activator of hippocampal BACE1 translation. Finally, beholding BACE1 as a representative protease active in the CNS, we venture a new perspective on the cellular basis of memory, which may incorporate neurodegeneration in itself as a drift in memory consolidating systems. Show more

Keywords: Alzheimer’s disease, β-secretase, eIF2α, exosomes, heme-regulated eIF-2α kinase, memory, nitric oxide, physiological stress response, proteolysis, translation initiation

DOI: 10.3233/ADR-180089

Citation: Journal of Alzheimer's Disease Reports, vol. 3, no. 1, pp. 113-148, 2019

Authors: Chandra, Sujyoti | Pahan, Kalipada

Article Type: Research Article

Abstract: Deposition of extracellular senile plaques containing amyloid-β is one of the major neuropathological characteristics of Alzheimer’s disease (AD). Therefore, targeting amyloid-β dyshomeostasis is an important therapeutic strategy for treatment of AD. In this study, we demonstrate that gemfibrozil, an FDA-approved drug for hyperlipidemia, can lower the amyloid plaque burden in the hippocampus and cortex of the 5XFAD model of AD. Additionally, gemfibrozil reduced microgliosis and astrogliosis associated with plaque in these mice. Administration of gemfibrozil also improved spatial learning and memory of the 5XFAD mice. Finally, we delineate that gemfibrozil requires the transcription factor peroxisome proliferator-activated receptor alpha (PPARα ) …to exhibit its amyloid lowering and memory enhancing effects in 5XFAD mice. These results highlight a new therapeutic property of gemfibrozil and suggest that this drug may be repurposed for treatment of AD. Show more

Keywords: Alzheimer’s disease, gemfibrozil, glial activation, memory, plaques, PPARα

DOI: 10.3233/ADR-190104

Citation: Journal of Alzheimer's Disease Reports, vol. 3, no. 1, pp. 149-168, 2019

Authors: Gorantla, Nalini V. | Das, Rashmi | Mulani, Fayaj A. | Thulasiram, Hirekodathakallu V. | Chinnathambi, Subashchandrabose

Article Type: Research Article

Abstract: Tau is a phosphoprotein with natively unfolded conformation that functions to stabilize microtubules in axons. Alzheimer’s disease pathology triggers several modifications in tau, which causes it to lose its affinity towards microtubule, thus, leading to microtubule disassembly and loss of axonal integrity. This elicit accumulation of tau as paired helical filaments is followed by stable neurofibrillary tangles formation. A large number of small molecules have been isolated from Azadirachta indica with varied medicinal applications. The intermediate and final limonoids, nimbin and salannin respectively, isolated from Azadirachta indica , were screened against tau aggregation. ThS and ANS fluorescence assay showed …the role of intermediate and final limonoids in preventing heparin induced cross-β sheet formation and also decreased hydrophobicity, which are characteristic nature of tau aggregation. Transmission electron microscopy studies revealed that limonoids restricted the aggregation of tau to fibrils; in turn, limonoids led to the formation of short and fragile aggregates. Both the limonoids were non-toxic to HEK293T cells thus, substantiating limonoids as a potential lead in overcoming Alzheimer’s disease. Show more

Keywords: Aggregation, Alzheimer’s disease, limonoids, natural products, tau

DOI: 10.3233/ADR-190118

Citation: Journal of Alzheimer's Disease Reports, vol. 3, no. 1, pp. 169-178, 2019

Authors: Duggal, Pallavi | Mehan, Sidharth

Article Type: Review Article

Abstract: Neuronal microtubule (MT) tau protein provides cytoskeleton to neuronal cells and plays a vital role including maintenance of cell shape, intracellular transport, and cell division. Tau hyperphosphorylation mediates MT destabilization resulting in axonopathy and neurotransmitter deficit, and ultimately causing Alzheimer’s disease (AD), a dementing disorder affecting vast geriatric populations worldwide, characterized by the existence of extracellular amyloid plaques and intracellular neurofibrillary tangles in a hyperphosphorylated state. Pre-clinically, streptozotocin stereotaxically mimics the behavioral and biochemical alterations similar to AD associated with tau pathology resulting in MT assembly defects, which proceed neuropathological cascades. Accessible interventions like cholinesterase inhibitors and NMDA antagonist clinically …provides only symptomatic relief. Involvement of microtubule stabilizers (MTS) prevents tauopathy particularly by targeting MT oriented cytoskeleton and promotes polymerization of tubulin protein. Multiple in vitro and in vivo research studies have shown that MTS can hold substantial potential for the treatment of AD-related tauopathy dementias through restoration of tau function and axonal transport. Moreover, anti-cancer taxane derivatives and epothiolones may have potential to ameliorate MT destabilization and prevent the neuronal structural and functional alterations associated with tauopathies. Therefore, this current review strictly focuses on exploration of various clinical and pre-clinical features available for AD to understand the neuropathological mechanisms as well as introduce pharmacological interventions associated with MT stabilization. MTS from diverse natural sources continue to be of value in the treatment of cancer, suggesting that these agents have potential to be of interest in the treatment of AD-related tauopathy dementia in the future. Show more

Keywords: Alzheimer’s disease, epothiolones, microtubule destabilization, microtubule stabilizers, tauopathy, taxanes

DOI: 10.3233/ADR-190125

Citation: Journal of Alzheimer's Disease Reports, vol. 3, no. 1, pp. 179-218, 2019

Authors: Friel, Howard

Article Type: Review Article

Abstract: A five-year close reading of the scientific literature on late-onset Alzheimer’s disease (AD) has prompted the invention of a novel therapeutic method that biomechanistically targets the targetable disease-process targets of AD with one or another mixture of non-toxic pleiotropic natural compounds. The featured mixture herein is comprised of curcumin, resveratrol, and EGCG. The mixture’s targets include central pathological elements of AD (including amyloid, tau, synaptic dysfunction, oxidative stress, mitochondrial dysfunction, and aberrant neuroinflammation), modifiable risk factors, comorbidities, and epigenetic elements. The featured mixture and other such mixtures are suitable …for long-term use, and may be applied to any stage of AD, including primary and secondary prevention. Such mixtures also would be amenable for use as pre-treatment, co-treatment, and post-treatment applications with certain biopharmaceutical agents. The targeting focus here is the major credible hypotheses of AD. The focus of future such articles will include other AD-related targets, modifiable risk factors and comorbidities, APOE4 , epigenetic factors, bioavailability, dose response, and implications for clinical testing. The “universal targeting” method described herein—that is, “targeting the targetable targets” of AD using certain mixtures of natural compounds—is reprogrammable and thus is applicable to other chronic neurological conditions, including Parkinson’s disease, vascular dementia, ischemic-stroke prevention and recovery, and sports-related head injuries and sequelae leading to chronic traumatic encephalopathy. Show more

Keywords: Alzheimer’s disease, amyloid hypothesis, curcumin, epigallocatechin gallate (EGCG) , mitochondrial dysfunction, neuroinflammation, oxidative stress, resveratrol, synaptic dysfunction , tau

DOI: 10.3233/ADR-190127

Citation: Journal of Alzheimer's Disease Reports, vol. 3, no. 1, pp. 219-232, 2019

Authors: Wada-Isoe, Kenji | Kikuchi, Takashi | Umeda-Kameyama, Yumi | Mori, Takahiro | Akishita, Masahiro | Nakamura, Yu | on behalf of the ABC Dementia Scale Research Group

Article Type: Research Article

Abstract: Many studies use the global clinical dementia rating (CDR) of 0.5 as a criterion for mild cognitive impairment, but past studies have not fully discussed its validity. The authors developed the ABC Dementia Scale (ABC-DS) to accurately monitor the changes in activities for daily living, behavioral and psychological symptoms of dementia, and cognitive function. When we carried out a cluster analysis of ABC-DS scores of 110 individuals for whom global CDR was 0.5, there were three groups with different levels of activities for daily living and cognitive function. O’Bryant et al. proposed a new guideline to stage dementia using the …CDR sum of boxes scores (CDR-SOB). We used their proposal and ABC-DS scores to evaluate the validity of CDR 0.5 as a definition of mild cognitive impairment (MCI). We concluded that the CDR-SOB scores and ABC-DS score are more accurate than global CDR of 0.5 for specifying individuals with MCI. Show more

Keywords: ABC dementia scale, clinical dementia rating, cluster analysis, mild cognitive impairment, three-dimensional distance

DOI: 10.3233/ADR-190126

Citation: Journal of Alzheimer's Disease Reports, vol. 3, no. 1, pp. 233-239, 2019

Authors: Villalba, Arvey Camilo | García, Jenny | Ramos, Claudia | Cuastumal, Amanda Rosario | Aguillón, David | Aguirre-Acevedo, Daniel Camilo | Madrigal, Lucia | Lopera, Francisco

Article Type: Research Article

Abstract: Background: There are forms of Alzheimer’s disease (AD) that have an autosomal dominant inheritance pattern; one of them is caused by the E280A mutation in the gene that codes for Presenilin-1 (PSEN1 ). Studying families of people with this mutation allows the evaluation of characteristics of the subjects before cognitive decline begins. Objective: To determine whether having the mutation E280A in PSEN1 increases the risk of presenting mental disorders in adults under 30 years old who are in the preclinical stage of AD and may be eligible for primary prevention studies of AD. Methods: A …psychiatric evaluation was made to 120 people belonging to families with a history of early onset AD. Of these, 62 carried the E280A mutation in PSEN1 . The occurrence of mental disorders between carriers and non-carriers of the mutation was compared. Results: No statistically significant differences were found in the frequency of any mental disorder between the group of carriers and non-carriers of the mutation (Hazard Ratio: 0.80, 95% CI 0.49 to 1.31); nor were differences observed when evaluating specific disorders. Conclusion: The E280A mutation does not increase the risk of mental disorders before the age of 30 in the relatives of people affected by familial AD. Studies with larger sample sizes are required to assess the risk of low incidence mental disorders. Show more

Keywords: Alzheimer’s disease, behavioral symptoms, mental disorders, Presenilin-1

DOI: 10.3233/ADR-190139

Citation: Journal of Alzheimer's Disease Reports, vol. 3, no. 1, pp. 241-250, 2019

Authors: Shea, Thomas B. | Remington, Ruth

Article Type: Short Communication

Abstract: A nutritional supplement has maintained or improved cognitive performance for healthy adults and individuals with mild cognitive impairment (MCI). Performance varied between 93 healthy adults aged 18–73 years versus 43 aged 75–85 years and among individuals with MCI. Healthy adult performance was stratified by age and for MCI as “intact” or “impaired” (Dementia Rating Scale guidelines). Some older individuals performed as well as younger individuals. All intact individuals with MCI maintained baseline performance; only impaired individuals receiving the supplement maintained baseline performance. Variation among elderly individuals can preclude observation of efficacy. Supplementation may maintain rather than improve performance for some …individuals. Show more

Keywords: Cognitive impairment, lifestyle modification, nutritional supplements, dementia

DOI: 10.3233/ADR-190124

Citation: Journal of Alzheimer's Disease Reports, vol. 3, no. 1, pp. 251-255, 2019

Authors: Das, Tushar Kanti | Jana, Piyali | Chakrabarti, Swarup Kumar | Abdul Hamid, Mas R.W.

Article Type: Research Article

Abstract: Alzheimer’s disease (AD) is the most common form of dementia. Extracellular amyloid-β (Aβ) aggregation and tau hyperphosphorylation are the key drivers of AD. Glycogen synthase kinase 3 (GSK3) and cyclin dependent kinase 5 (Cdk5) have been known as leading applicants arbitrating abnormal tau hyperphosphorylation. Thus, we evaluated the efficacy and underlying mechanism of action of curcumin in scopolamine-induced AD rats in our study. We found that curcumin-treated AD rats markedly reduced the levels of Aβ40 and Aβ42 in the brain and in the plasma in comparison to untreated AD rats. Moreover, the levels of phosphorylated tau at Ser396 …(PHF13), Ser202/Thr205 (AT8), and Aβ40/42 (MOAB2) were decreased significantly in AD rats treated with curcumin. Phospho-GSK3β (Tyr216), the active form of GSK3β, and total GSK3β were significantly decreased in AD rats treated with curcumin. Furthermore, Cdk5 and its activators p35 and p25 were significantly decreased in curcumin-treated AD rats. The reduced levels of Cdk5, p35, p25, and GSK3β in curcumin-treated AD rats may result decreased Aβ aggregation and tau hyperphosphorylation, thus ameliorating AD. Impaired spatial memory and locomotor activity in AD rats were partially reversed by curcumin. Therefore, curcumin, as a natural compound present in turmeric, may be a more effective therapeutic agent in the treatment of AD in humans. Show more

Keywords: Alzheimer’s disease, amyloid-β , cyclin dependent kinase 5, curcumin, donepezil, glycogen synthase kinase 3β , tau hyperphosphorylation

DOI: 10.3233/ADR-190135

Citation: Journal of Alzheimer's Disease Reports, vol. 3, no. 1, pp. 257-267, 2019

Authors: Sichler, Marius E. | Löw, Maximilian J. | Schleicher, Eva M. | Bayer, Thomas A. | Bouter, Yvonne

Article Type: Research Article

Abstract: Sensorimotor deficits have been described in several neuropsychiatric disorders including Alzheimer’s disease. The aim of the present study was to evaluate possible sensorimotor gating deficits in the Tg4-42 mouse model of Alzheimer’s disease using the prepulse inhibition task (PPI). Previous studies indicated that the hippocampus is essentially involved in the regulation of PPI. We analyzed 7-month-old homozygous Tg4-42 mice as mice at this age display severe neuron loss especially in the CA1 region of the hippocampus. Our results revealed a reduced startle response and PPI in Tg4-42 mice. The observed deficits in startle response and PPI are likely due to …altered sensory processing abilities rather than hearing deficits as Tg4-42 displayed intact hearing in the fear conditioning task. The present study demonstrates for the first time that sensorimotor gating is impaired in Tg4-42 mice. Analyzing startle response as well as the PPI may offer valuable measurements to assess the efficacy of therapeutic strategies in the future in this Alzheimer’s disease model. Show more

Keywords: Alzheimer’s disease, cognitive deficits, fear conditioning, hippocampus, N-terminally truncated Aβ, neuron loss, prepulse inhibition, sensorimotor gating

DOI: 10.3233/ADR-190132

Citation: Journal of Alzheimer's Disease Reports, vol. 3, no. 1, pp. 269-278, 2019

Authors: Sharma, Anuja | Kumar, Yatender

Article Type: Review Article

Abstract: Alzheimer’s disease (AD), the ‘Plague of Twenty-First Century,’ is a crippling neurodegenerative disease that affects a majority of the older population globally. By 2050, the incidence of AD is expected to rise to 135 million, while no treatment(s) that can reverse or control the progression of AD are currently available. The treatment(s) in use are limited in their ability to manage the symptoms or slow the progression of the disease and can lead to some severe side effects. The overall care is economically burdensome for the affected individuals as well as the caretakers or family members. Thus, there is a …pressing need to identify and develop much safer alternative therapies that can better manage AD. This review discusses a multitude of such treatments borrowed from Ayurveda, traditional Chinese practices, meditation, and exercising for AD treatment. These therapies are in practice since ancient times and reported to be beneficial as anti-AD therapies. Ayurvedic drugs like turmeric, Brahmi , Ashwagandha , etc., management of stress by meditation, regular exercising, and acupuncture have been reported to be efficient in their anti-AD usage. Besides, a combination of vitamins and natural dietary intakes is likely to play a significant role in combating AD. We conclude that the use of such alternative strategies will be a stepping-stone in preventing, treating, curing, or managing the disease. Show more

Keywords: Acupuncture, alternative treatments, Alzheimer’s disease, Ayurveda, exercise, meditation

DOI: 10.3233/ADR-190137

Citation: Journal of Alzheimer's Disease Reports, vol. 3, no. 1, pp. 279-297, 2019

Authors: Vasefi, Maryam | Hudson, Mackenzie | Ghaboolian-Zare, Ehsan

Article Type: Review Article

Abstract: Neurocognitive disorders, such as Alzheimer’s disease (AD), affect millions of people worldwide and are characterized by cognitive decline. Human and animal studies have shown that chronic immune response and inflammation are important factors in the pathogenesis of AD. Chronic inflammation can accelerate the aggregation of amyloid-β peptides and later hyperphosphorylation of tau proteins. The exact etiology of AD is not clear, but genetics and environmental factors, such as age, family history, and lifestyle are linked to neurodegenerative diseases. Lifestyle habits, such as poor diet, are associated with inflammation and could accelerate or slow down the progression of neurodegenerative diseases. Here …we provide a review of the potential conditions and factors that stimulate the inflammatory processes in AD. An understanding of inflammatory mechanisms influencing the development of AD may help to protect against dementia and AD. Show more

Keywords: Alzheimer’s disease, diet, gluten sensitivity, inflammation, microbiome, oxidative stress

DOI: 10.3233/ADR-190152

Citation: Journal of Alzheimer's Disease Reports, vol. 3, no. 1, pp. 299-309, 2019

Authors: Shea, Thomas B. | Remington, Ruth

Article Type: Correction

DOI: 10.3233/ADR-199001

Citation: Journal of Alzheimer's Disease Reports, vol. 3, no. 1, pp. 311-311, 2019

Authors: Chandra, Vijay | Mehta, Veer Singh

Article Type: Research Article

Abstract: This observational study reports on the cause of memory loss in 500 consecutive patients. It confirms the previously reported finding in a smaller sample of 100 patients. There have been several publications suggesting that the prevalence of dementia is lower in certain communities but the reason is not known. This study was conducted to see if it could explain the variation between communities. Also, the observation that dementia with Lewy bodies (24.4%) outnumbers cases of Alzheimer’s disease (5.8%) has not been reported by any other investigators and needs to be verified. This finding could open a new topic of research …and also help in the management of patients. Show more

Keywords: 500 patients, dementia, dementia with Lewy bodies, India, memory loss

DOI: 10.3233/ADR-190140

Citation: Journal of Alzheimer's Disease Reports, vol. 3, no. 1, pp. 313-317, 2019