Journal of Alzheimer's Disease - Volume 76, issue 1

Authors: Perry, George

Article Type: Editorial

DOI: 10.3233/JAD-209004

Citation: Journal of Alzheimer's Disease, vol. 76, no. 1, pp. 1-1, 2020

Authors: Fotuhi, Majid | Mian, Ali | Meysami, Somayeh | Raji, Cyrus A.

Article Type: Review Article

Abstract: Anosmia, stroke, paralysis, cranial nerve deficits, encephalopathy, delirium, meningitis, and seizures are some of the neurological complications in patients with coronavirus disease-19 (COVID-19) which is caused by acute respiratory syndrome coronavirus 2 (SARS-Cov2). There remains a challenge to determine the extent to which neurological abnormalities in COVID-19 are caused by SARS-Cov2 itself, the exaggerated cytokine response it triggers, and/or the resulting hypercoagulapathy and formation of blood clots in blood vessels throughout the body and the brain. In this article, we review the reports that address neurological manifestations in patients with COVID-19 who may present with acute neurological symptoms (e.g., stroke), …even without typical respiratory symptoms such as fever, cough, or shortness of breath. Next, we discuss the different neurobiological processes and mechanisms that may underlie the link between SARS-Cov2 and COVID-19 in the brain, cranial nerves, peripheral nerves, and muscles. Finally, we propose a basic “NeuroCovid” classification scheme that integrates these concepts and highlights some of the short-term challenges for the practice of neurology today and the long-term sequalae of COVID-19 such as depression, OCD, insomnia, cognitive decline, accelerated aging, Parkinson’s disease, or Alzheimer’s disease in the future. In doing so, we intend to provide a basis from which to build on future hypotheses and investigations regarding SARS-Cov2 and the nervous system. Show more

Keywords: Alzheimer’s disease, anosmia, cerebrovascular disease, COVID-19, cytokines, SARS-Cov2, seizure, vasculitis

DOI: 10.3233/JAD-200581

Citation: Journal of Alzheimer's Disease, vol. 76, no. 1, pp. 3-19, 2020

Authors: Naughton, Sean X. | Raval, Urdhva | Pasinetti, Giulio M.

Article Type: Article Commentary

Abstract: There are a number of potential implications for the field of Alzheimer’s disease (AD) stemming from the global spread of SARS-CoV-2. Neuroinflammation is known to be a prominent feature of neurodegeneration and plays a major role in AD pathology. Immune response and excessive inflammation in COVID-19 may also accelerate the progression of brain inflammatory neurodegeneration, and elderly individuals are more susceptible to severe outcomes after SARS-CoV-2 infection. Individuals with type 2 diabetes (T2D) are at an increased risk for AD as well as severe outcomes after SARS-CoV-2 infection. Genetic and socioeconomic factors influencing the rates of T2D, AD, and COVID-19 …severity may create an exceptionally high-risk profile for certain demographics such as African Americans and Hispanic Americans. Type I interferon response plays an important role in both host response to viral infection, as well as AD pathology and may be a sensible therapeutic target in both AD and COVID-19. Show more

Keywords: Alzheimer’s disease, amyloid, COVID-19, SARS-CoV-2

DOI: 10.3233/JAD-200537

Citation: Journal of Alzheimer's Disease, vol. 76, no. 1, pp. 21-25, 2020

Authors: Schindler, Suzanne E. | Jicha, Gregory A. | Nelson, Peter T. | Keene, C. Dirk | Blennow, Kaj | Molinuevo, José Luis | Masters, Colin L. | Hansson, Oskar | Teunissen, Charlotte E. | Galasko, Douglas | Shaw, Leslie M. | Levey, Allan I. | Silverberg, Nina

Article Type: Short Communication

Abstract: The coronavirus disease 2019 (COVID-19) pandemic led to an abrupt halt of many Alzheimer’s disease (AD) research studies at sites spanning the world. This is especially true for studies requiring in-person contact, such as studies collecting biofluids. Since COVID-19 is likely to remain a threat for an extended period, the resumption of fluid biomarker studies requires the development and implementation of procedures that minimize the risk of in-person visits to participants, staff, and individuals handling the biofluid samples. Some issues to consider include structuring the visit workflow to minimize contacts and promote social distancing; screening and/or testing participants and staff …for COVID-19; wearing masks and performing hand hygiene; and precautions for handling, storing, and analyzing biofluids. AD fluid biomarker research remains a vitally important public health priority and resuming studies requires appropriate safety procedures to protect research participants and staff. Show more

Keywords: Alzheimer’s disease, biofluids, biomarkers, COVID-19, safety

DOI: 10.3233/JAD-200684

Citation: Journal of Alzheimer's Disease, vol. 76, no. 1, pp. 27-31, 2020

Authors: Benaque, Alba | Gurruchaga, Miren Jone | Abdelnour, Carla | Hernández, Isabel | Cañabate, Pilar | Alegret, Montserrat | Rodríguez, Isabel | Rosende-Roca, Maitee | Tartari, Juan Pablo | Esteban, Ester | López, Rogelio | Gil, Silvia | Vargas, Liliana | Mauleón, Ana | Espinosa, Ana | Ortega, Gemma | Sanabria, Angela | Pérez, Alba | Alarcón, Emilio | González-Pérez, Antonio | Marquié, Marta | Valero, Sergi | Tárraga, Lluís | Ruiz, Agustín | Boada, Mercè | for the Research Center and Memory Clinic, Fundació ACE

Collaborators: Morera, Amèrica | Guitart, Marina | Gailhajanet, Anna | Tantinya, Natalia | Moreno, Mariola | Preckler, Silvia | Lafuente, Asunción | Aguilera, Nuria | Buendia, Mar | Pancho, Ana | Ibarria, Marta | Diego, Susana | Jofresa, Sara | Roberto, Natalia | de Rojas, Itziar | Moreno-Grau, Sonia | Montrreal, Laura | Martín, Elvira

Article Type: Research Article

Abstract: Background: Fundació ACE is a non-profit organization providing care based on a holistic model to persons with cognitive disorders and their families for 25 years in Barcelona, Spain. Delivering care to this vulnerable population amidst the COVID-19 pandemic has represented a major challenge to our institution. Objective: To share our experience in adapting our model of care to the new situation to ensure continuity of care. Methods: We detail the sequence of events and the actions taken within Fundació ACE to swiftly adapt our face-to-face model of care to one based on telemedicine consultations. We characterize …individuals under follow-up by the Memory Unit from 2017 to 2019 and compare the number of weekly visits in 2020 performed before and after the lockdown was imposed. Results: The total number of individuals being actively followed by Fundació ACE Memory Unit grew from 6,928 in 2017 to 8,147 in 2019. Among those newly diagnosed in 2019, most patients had mild cognitive impairment or mild dementia (42% and 25%, respectively). Weekly visits dropped by 60% following the suspension of face-to-face activity. However, by April 24 we were able to perform 78% of the visits we averaged in the weeks before confinement began. Discussion: We have shown that Fundació ACE model of care has been able to successfully adapt to a health and social critical situation as COVID-19 pandemic. Overall, we were able to guarantee the continuity of care while preserving the safety of patients, families, and professionals. We also seized the opportunity to improve our model of care. Show more

Keywords: Alzheimer’s disease, coronavirus, mild cognitive impairment, pandemics, telemedicine

DOI: 10.3233/JAD-200547

Citation: Journal of Alzheimer's Disease, vol. 76, no. 1, pp. 33-40, 2020

Authors: Boutoleau-Bretonnière, Claire | Pouclet-Courtemanche, Hélene | Gillet, Aurelie | Bernard, Amelie | Deruet, Anne Laure | Gouraud, Ines | Mazoue, Aurelien | Lamy, Estelle | Rocher, Laetitia | Kapogiannis, Dimitrios | El Haj, Mohamad

Article Type: Research Article

Abstract: Background: Neuropsychiatric symptoms, such as depression, anxiety, apathy, agitation, and hallucinations, are frequent in Alzheimer’s disease (AD) and their prevalence tends to increase with external stressors. Objective: We offer the first investigation of the effects of confinement during the COVID-19 crisis on neuropsychiatric symptoms in patients with AD. Methods: We contacted caregivers of 38 patients with AD who were confined to their homes for nearly two months and asked them to report whether patients experienced any change in neuropsychiatric symptoms during, compared to before, the confinement and rate its severity and impact on themselves using the …Neuropsychiatric Inventory-Questionnaire. Results: Among the 38 patients, only 10 demonstrated neuropsychiatric changes during the confinement. Cognitive function of these 10 patients, assessed with the Mini-Mental State Examination, was worse than that of patients who did not demonstrate neuropsychiatric changes. Interestingly, among the 10 patients with neuropsychiatric changes, the duration of confinement significantly correlated with the severity of symptoms as well as with their caregivers’ distress. Discussion: The confinement seems to impact neuropsychiatric symptomatology in AD patients with low baseline cognitive function. Show more

Keywords: Alzheimer’s disease, confinement, COVID-19, neuropsychiatric symptoms

DOI: 10.3233/JAD-200604

Citation: Journal of Alzheimer's Disease, vol. 76, no. 1, pp. 41-47, 2020

Authors: Pei, Yixuan (Amy) | Davies, Julie | Zhang, Melanie | Zhang, Han-Ting

Article Type: Review Article

Abstract: Deemed as incurable, Alzheimer’s disease (AD) research is becoming less convoluted as our understanding of its pathology increases. With current treatments focusing on merely mitigating the symptoms of AD, there have been many attempts to find a molecular culprit to serve as the single underlying cause and therapeutic target for clinical applications to approach the disease from its roots. Indeed, over the course of decades, the endless search for a singular target culprit in AD has uncovered a cascade of pathological defects, adding on to each other throughout the progression of the disease. The developmental patterns of amyloid-β (Aβ) oligomers …have been studied as a means to discover the complex molecular interplay between various immune responses, genetic mutations, pathway disturbances, and regulating factors that disturb synapse homeostasis before disease manifestation. This new understanding has shifted the underlying goal of the research community from merely removing Aβ oligomers to finding methods that can predict high risk individuals and resorting to cocktail-drug treatments in an attempt to regulate multiple pathways that cumulatively result in the debilitating symptoms of the disease. By utilizing various assays from immuno-targeting to molecular biomarkers, we then interfere in the molecular cascades in an endeavor to avoid synapse dysfunction before disease maturity. Here, we review the current literature supporting the importance of synapses in AD, our current understanding of the molecular interactions leading up to clinical diagnoses, and the techniques used in targeted therapies. Show more

Keywords: Alzheimer’s disease, amyloid-β oligomers, biomarker, long-term depression, long-term potentiation, synapse

DOI: 10.3233/JAD-191334

Citation: Journal of Alzheimer's Disease, vol. 76, no. 1, pp. 49-62, 2020

Authors: de la Torre, Jack C.

Article Type: Review Article

Abstract: This review attempts to examine two key elements in the evolution of cognitive impairment in the elderly who develop heart failure. First, major left side heart parts can structurally and functionally deteriorate from aging wear and tear to provoke hemodynamic instability where heart failure worsens or is initiated; second, heart failure is a major inducer of cognitive impairment and Alzheimer’s disease in the elderly. In heart failure, when the left ventricular myocardium of an elderly person does not properly contract, it cannot pump out adequate blood to the brain, raising the risk of cognitive impairment due to the intensification of …chronic brain hypoperfusion. Chronic brain hypoperfusion originates from chronically reduced cardiac output which progresses as heart failure worsens. Other left ventricular heart parts, including atrium, valves, myocardium, and aorta can contribute to the physiological shortfall of cardiac output. It follows that hemodynamic instability and perfusion changes occurring from the aging heart’s blood pumping deficiency will, in time, damage vulnerable brain cells linked to specific cognitive regulatory sites, diminishing neuronal energy metabolism to a level where progressive cognitive impairment is the outcome. Could cognitive impairment progress be reversed with a heart transplant? Evidence is presented detailing the errant hemodynamic pathways leading to cognitive impairment during aging as an offshoot of inefficient structural and functional heart parts and their contribution to heart failure. Show more

Keywords: Aortic valve, brain hypoperfusion, cardiac output, cognitive impairment, heart failure, hemodynamics, mitral valve

DOI: 10.3233/JAD-200296

Citation: Journal of Alzheimer's Disease, vol. 76, no. 1, pp. 63-84, 2020

Authors: Itzhaki, Ruth F.

Article Type: Editorial

Abstract: There has been much interest in the clinical trial of GV972 for treatment of Alzheimer’s disease in that the data have indicated that the compound is protective against cognitive decline. This effect has been attributed to a remodelling of the gut microbiota. I suggest that the effect might be caused by an antiviral action of GV971 against herpes simplex virus type 1 in brain, which many studies have strongly implicated as having a major role in Alzheimer’s disease. The antiviral action of GV971 is proposed on the basis that it is an acidic polysaccharide consisting of linear sodium oligomannurarate molecules …of a range of sizes, derived from brown algae. Marine-derived polysaccharides are well known for possessing various bioactivities, including antiviral and antibacterial properties. Show more

Keywords: Algae, antiviral, GV971, Herpes simplex virus type 1, marine polysaccharides, seaweed

DOI: 10.3233/JAD-200210

Citation: Journal of Alzheimer's Disease, vol. 76, no. 1, pp. 85-87, 2020

Authors: Jacus, Jean-Pierre | Mayelle, Amandine | Voltzenlogel, Virginie | Cuervo-Lombard, Christine-Vanessa | Antoine, Pascal

Article Type: Short Communication

Abstract: This study aimed to provide a model of awareness in Alzheimer’s disease using the stage of the disease as a risk factor. Awareness was assessed using three methods (patient-caregiver discrepancy, prediction-performance discrepancy, clinical rating). Twenty-five healthy control subjects and sixty-one patients participated, with measures of cognition, apathy, depression, and awareness. These measures were introduced into a manual backward regression. Confounding factors impacting at least 15% of the exposure factor estimate were maintained in the model. Except for the prediction performance discrepancy, also presenting cognitive associations, the other awareness assessments suggested a major role of depression and apathy as impacting factors.

Keywords: Alzheimer’s disease, apathy, awareness, depression

DOI: 10.3233/JAD-200017

Citation: Journal of Alzheimer's Disease, vol. 76, no. 1, pp. 89-95, 2020