Journal of Alzheimer's Disease - Volume 77, issue 2

Authors: Yamamoto, Vicky | Bolanos, Joe F. | Fiallos, John | Strand, Susanne E. | Morris, Kevin | Shahrokhinia, Sanam | Cushing, Tim R. | Hopp, Lawrence | Tiwari, Ambooj | Hariri, Robert | Sokolov, Rick | Wheeler, Christopher | Kaushik, Ajeet | Elsayegh, Ashraf | Eliashiv, Dawn | Hedrick, Rebecca | Jafari, Behrouz | Johnson, J. Patrick | Khorsandi, Mehran | Gonzalez, Nestor | Balakhani, Guita | Lahiri, Shouri | Ghavidel, Kazem | Amaya, Marco | Kloor, Harry | Hussain, Namath | Huang, Edmund | Cormier, Jason | Wesson Ashford, J. | Wang, Jeffrey C. | Yaghobian, Shadi | Khorrami, Payman | Shamloo, Bahman | Moon, Charles | Shadi, Payam | Kateb, Babak

Article Type: Review Article

Abstract: COVID-19 is a severe infectious disease that has claimed >150,000 lives and infected millions in the United States thus far, especially the elderly population. Emerging evidence has shown the virus to cause hemorrhagic and immunologic responses, which impact all organs, including lungs, kidneys, and the brain, as well as extremities. SARS-CoV-2 also affects patients’, families’, and society’s mental health at large. There is growing evidence of re-infection in some patients. The goal of this paper is to provide a comprehensive review of SARS-CoV-2-induced disease, its mechanism of infection, diagnostics, therapeutics, and treatment strategies, while also focusing on less attended aspects …by previous studies, including nutritional support, psychological, and rehabilitation of the pandemic and its management. We performed a systematic review of >1,000 articles and included 425 references from online databases, including, PubMed, Google Scholar, and California Baptist University’s library. COVID-19 patients go through acute respiratory distress syndrome, cytokine storm, acute hypercoagulable state, and autonomic dysfunction, which must be managed by a multidisciplinary team including nursing, nutrition, and rehabilitation. The elderly population and those who are suffering from Alzheimer’s disease and dementia related illnesses seem to be at the higher risk. There are 28 vaccines under development, and new treatment strategies/protocols are being investigated. The future management for COVID-19 should include B-cell and T-cell immunotherapy in combination with emerging prophylaxis. The mental health and illness aspect of COVID-19 are among the most important side effects of this pandemic which requires a national plan for prevention, diagnosis and treatment. Show more

Keywords: Alzheimer’s disease, coronavirus, COVID-19, COVID-19 diagnostics, COVID-19 test, mental health, SARS-CoV-2, SARS-CoV-2 treatment, Remdesivir, Hydroxychloroquine, Avigan, Actemra, COVID-19 Nutrition, COVID-19 Rehabilitation, COVID-19 Clinical manifestations, COVID-19 Risk factors and comorbidities, COVID-19 Vaccines, COVID-19 immunotherapy, COVID-19 Natural Killer Cells and stem cell therapy, COVID-19 Janus Kinase Inhibitor 1 and 2, COVID-19 air filtration, Nanomedicine for COVID-19, COVID-19 mental disorders, COVID-19 domestic abuse, COVID-19 Alzheimer’s Disease and dementia, COVID-19 complications, COVID-19 Screening, COVID-19 ophthalmology, COVID-19 Neurological implications, COVID-19 antiviral, COVID-19 Steroids, COVID-19 Convalescent plasma, COVID-19 anticoagulants, COVID-19 monoclonal antibodies

DOI: 10.3233/JAD-200831

Citation: Journal of Alzheimer's Disease, vol. 77, no. 2, pp. 459-504, 2020

Authors: Arroyo-Anlló, Eva M. | Sánchez, Jorge Chamorro | Gil, Roger

Article Type: Review Article

Abstract: Alzheimer’s disease (AD) provides a valuable field of research into impairment of self-consciousness (SC), because AD patients have a reduced capacity to understand their mental world, to experience and relive previous personal events, as well as to interpret thoughts, feelings, and beliefs about themselves. Several studies observed that AD patients had an altered SC, but not a complete abolition of it. Emotions are an integral part of the construction of personal identity, therefore of Self. In general, most studies on emotion in AD patients have observed that emotion is not completely abolished and it lets them better remember autobiographical events …with greater emotional charge. The positive effect of autobiographical memories rich in emotional content, evoked directly/automatically by sensorial stimuli such as familiar odors or music, could be used to reestablish/reinforce the permanence and coherence of the Self in AD. We studied the research of empirical evidence supporting the power of the sensorial cues associated with emotion, which could be capable of enhancing the SC in AD. We presented the studies about “Emotional stimulations” using odor, music, or taste cues in AD. All studies have shown to have a positive impact on SC in AD patients such as odor-evoked autobiographical memories, taste/odor-evoked autobiographical memories, emotional sensorial stimulation using musical cues, and multi-sensorial stimulations using healing gardens. We found research supporting the notion that emotional sensorial stimulations can even temporarily exalt memory, affective state, and personal identity, that is, the SC in AD. The emotional sensory stimulations could be used as a tool to activate the SC in AD and hence improve the quality of life of patients and caregivers. Show more

Keywords: Alzheimer’s disease, dementia, emotion, healing garden, music, neurodegenerative disease, non-pharmacological therapy, odor, self-consciousness, sensorial stimulation, smell, taste

DOI: 10.3233/JAD-200408

Citation: Journal of Alzheimer's Disease, vol. 77, no. 2, pp. 505-521, 2020

Authors: Lim, Sahnah | Mohaimin, Sadia | Min, Deborah | Roberts, Timothy | Sohn, Young-Jin | Wong, Jazmine | Sivanesathurai, Ragavan | Kwon, Simona C. | Trinh-Shevrin, Chau

Article Type: Review Article

Abstract: Background: The Asian American, Native Hawaiian, and Pacific Islander (AANHPI) aging population is rapidly growing and the burden of Alzheimer’s disease and its related dementias (ADRD) will likely mirror this demographic growth. AANHPIs face significant barriers in obtaining timely ADRD diagnosis and services; yet little is known about ADRD in this population. Objective: The study objective is to conduct a systematic review on the published literature on ADRD among AANHPIs to identify gaps and priorities to inform future research and action plans. Methods: The systematic review was conducted following the PRISMA Protocol for Systematic Reviews. Co-author …(TR), an experienced Medical Librarian, searched PubMed, EMBASE, PsycINFO, Cochrane Central of Clinical Trials, Ageline, and Web of Science for peer-reviewed articles describing ADRD among AANHPIs. The search was not limited by language or publication date. Each citation was reviewed by two trained independent reviewers. Conflicts were resolved through consensus. Results: The title/abstract and full texts of 1,447 unique articles were screened for inclusion, yielding 168 articles for analysis. Major research topics included prevalence, risk factors, comorbidities, interventions and outreach, knowledge and attitudes, caregiving, and detection tools. A limited number of studies reported on national data, on NHPI communities generally, and on efficacy of interventions targeting AANHPI communities. Conclusion: To our knowledge, this is the first systematic review on ADRD among AANHPI populations. Our review provides a first step in mapping the extant literature on ADRD among this underserved and under-researched population and will serve as a guide for future research, policy, and intervention. Show more

Keywords: Dementia, inequalities, race, review

DOI: 10.3233/JAD-200509

Citation: Journal of Alzheimer's Disease, vol. 77, no. 2, pp. 523-537, 2020

Authors: Tsugawa, Akito | Sakurai, Shu | Inagawa, Yuta | Hirose, Daisuke | Kaneko, Yoshitsugu | Ogawa, Yusuke | Serisawa, Shuntaro | Takenoshita, Naoto | Sakurai, Hirofumi | Kanetaka, Hidekazu | Hirao, Kentaro | Shimizu, Soichiro

Article Type: Article Commentary

Abstract: The ongoing coronavirus disease 2019 (COVID-19) pandemic has substantially affected patients with dementia and their caregivers. However, we found not all Alzheimer’s disease (AD) patients were afraid of COVID-19 infection. Therefore, we investigated the association between rate of awareness of COVID-19 and depressive tendency in AD. 126 consecutive outpatients with AD were enrolled in this study from May 25, on the day when the declaration of emergency was lifted in Japan, through June 30, 2020. In addition to routine psychological tests, the participants were asked the following two questions: “Do you know COVID-19?” and “Why are you wearing a face …mask?”. Moderate to severe AD patients were found to have a low COVID-19 recognition rate and did not fully understand why they were wearing face masks. In addition, because they did not understand the seriousness of the COVID-19 outbreak, their Geriatric Depression Scale scores were also substantially lower. These results may appear to simply indicate that people with severe dementia are unaware of current events. However, these results provide insights into how to care for patients with dementia and how to allocate the time and support of our limited staff during the COVID-19 outbreak. Show more

Keywords: Alzheimer’s disease, COVID-19, dementia, dementia care

DOI: 10.3233/JAD-200832

Citation: Journal of Alzheimer's Disease, vol. 77, no. 2, pp. 539-541, 2020

Authors: Denner, Joachim | Tanzi, Rudolph | Jacobson, Steve

Article Type: Article Commentary

Abstract: Animal models to study Alzheimer’s disease (AD) pathogenesis are under development. Since herpesviruses have been postulated to be capable of triggering the pathogenic process, AD animal models (mouse, pig, and non-human primates) should be controlled for the presence of these viruses. Only virus-free models allow studying the genetic factors and the effect of adding viruses. Roseoloviruses such as human herpesvirus 6 and the related viruses in the animals are the main topic of this commentary.

Keywords: Alzheimer’s disease, animal models, human herpesvirus 6, roseoloviruses

DOI: 10.3233/JAD-200591

Citation: Journal of Alzheimer's Disease, vol. 77, no. 2, pp. 543-545, 2020

Authors: Heller, Adam | Coffman, Sheryl S. | Jarvis, Karalee

Article Type: Short Communication

Abstract: Knowing that Alzheimer’s disease (AD) nucleates in the entorhinal cortex (EC), samples of 12 EC specimens were probed for crystals by a protocol detecting fewer than 1/5000th of those present. Of the 61 crystals found, 31 were expected and 30 were novel. Twenty-one crystals of iron oxides and 10 atherosclerosis-associated calcium pyrophosphate dihydrate crystals were expected and found. The 30 unexpected crystals were NLRP3-inflammasome activating calcium oxalate dihydrate (12) and titanium dioxide (18). Their unusual distribution raises the possibility that some were of AD origination sites.

Keywords: Alzheimer’s disease pathogenesis, calcium oxalate dihydrate, inflammasome activating crystals, titanium dioxide

DOI: 10.3233/JAD-200535

Citation: Journal of Alzheimer's Disease, vol. 77, no. 2, pp. 547-550, 2020

Authors: Vogels, Thomas | Vargová, Gréta | Brezováková, Veronika | Quint, Wim Hendricus | Hromádka, Tomáš

Article Type: Research Article

Abstract: Background: Neuronal accumulation of hyperphosphorylated and truncated tau aggregates is one of the major defining factors and key drivers of neurodegeneration in Alzheimer’s disease and other tauopathies. Objective: We developed an AAV-induced model of tauopathy mediated by human truncated tau protein without familial frontotemporal dementia-related mutations to study tau propagation and the functional consequences of tau pathology. Methods: We performed targeted transductions of the hippocampus or entorhinal cortex in adult mice followed by histological analysis to study the progression of hippocampal tau pathology and tau spreading. We performed behavioral analysis of mice with AAV-induced hippocampal tau …pathology. Results: AAV-induced hippocampal tau pathology was characterized by tau hyperphosphorylation (AT8 positivity), sarkosyl insolubility, and the presence of neurofibrillary tangles. AAV-induced tau pathology was associated with microgliosis and hypertrophic astrocytes in the absence of cognitive deficits. Additionally, the co-expression of mCherry fluorescent protein and human truncated tau enabled us to detect both local spreading of human tau and spreading from the entorhinal cortex to the synaptically connected dentate gyrus. Conclusion: Targeted delivery of AAV with truncated tau protein into subcortical and cortical structures of mammalian brains represents an efficient approach for creating temporally and spatially well-defined tau pathology suitable for in vivo studies of tau propagation and neuronal circuit deficits in Alzheimer’s disease. Show more

Keywords: Adeno-associated virus, Alzheimer’s disease, dementia, mice, tau protein, tauopathies

DOI: 10.3233/JAD-200047

Citation: Journal of Alzheimer's Disease, vol. 77, no. 2, pp. 551-568, 2020

Authors: Melgarejo, Jesus D. | Aguirre-Acevedo, Daniel C. | Gaona, Ciro | Chavez, Carlos A. | Calmón, Gustavo E. | Silva, Eglé R. | de Erausquin, Gabriel A. | Gil, Mario | Mena, Luis J. | Terwilliger, Joseph D. | Arboleda, Humberto | Scarmeas, Nikolaos | Lee, Joseph H. | Maestre, Gladys E.

Article Type: Research Article

Abstract: Background: Dementia of the Alzheimer’s type (DAT) impacts Hispanics disproportionately, with almost a twofold elevated risk of developing DAT, as well as earlier onset of the disease, than in non-Hispanic Whites. However, the role of main risk factors for DAT, such as APOE-ɛ 4 and blood pressure (BP) levels, remains uncertain among Hispanics. Objective: To investigate the association of APOE-ɛ 4 and BP levels, measures with 24-h ambulatory BP monitoring, with incidence of DAT in an elderly cohort of Hispanics. Methods: 1,320 participants from the Maracaibo Aging Study, free of dementia at the baseline, and with …ambulatory BP measurements and APOE genotype available were included. Adjusted Cox proportional models were performed to examine 1) the incidence of DAT and 2) the relationship between BP levels and DAT according to APOE genotypes. Models were adjusted by competing risk of death before the onset of DAT. Model performance was assessed by likelihood test. Results: The average follow-up time was 5.3 years. DAT incidence was 5.8 per 1000 person-year. APOE-ɛ 4 carriers had a higher risk of DAT. In unadjusted analyses, conventional, 24-h, and nighttime systolic BP levels were significantly higher in participants who developed DAT and of APOE-ɛ 4 carriers (p < 0.05). After adjustment for competing risks, only higher nighttime systolic BP was associated with DAT incidence, but only among subjects carrying APOE-ɛ 4. Conclusion: In this Hispanic population, both APOE-ɛ 4 genotype and assessment of nocturnal systolic BP (rather than diurnal or office BP) were necessary to estimate DAT risk. Show more

Keywords: Alzheimer’s disease, ambulatory blood pressure monitoring, Apolipoprotein E, dementia of Alzheimer’s type, Hispanics, night-time blood pressure

DOI: 10.3233/JAD-200430

Citation: Journal of Alzheimer's Disease, vol. 77, no. 2, pp. 569-579, 2020

Authors: Stypa, Vanessa | Haussermann, Peter | Fleiner, Tim | Neumann, Sandra

Article Type: Research Article

Abstract: Background: The Quality of Life–Alzheimer’s Disease (QoL-AD) scale is a widely used measure of quality of life (QoL) in dementia. Although the instrument has been validated in several languages, the psychometric properties of the German self-report version have not yet been analyzed. Objective: This study examines the internal consistency, test-retest reliability, and construct validity of the German QoL-AD self-report scale. Methods: The sample included 30 patients suffering from mild to moderate Alzheimer’s disease or vascular dementia (19 females; mean age 77.3 years; mean Mini-Mental State Examination (MMSE) score 19.7 points). To determine test-retest reliability, the QoL-AD …self-report scale was re-administered four to seven days apart. For construct validity analysis, the Dementia Quality of Life instrument (DQoL), Geriatric Depression Scale (GDS), MMSE, and an adapted short form of the Neuropsychiatric Inventory (NPI) were used. Results: The German QoL-AD self-report scale shows an internal consistency of α = 0.79 and a test-retest reliability of r  = 0.75 (p  < 0.01). Regarding construct validity, there was a significant positive correlation between the total scores of the QoL-AD and DQoL (r  = 0.47, p  < 0.05). The analysis revealed no significant correlations with the GDS or the adapted NPI. No association could be observed between the QoL-AD and the MMSE (r  = 0.01), confirming divergent validity. Conclusion: The results indicate that the German QoL-AD self-report scale is a suitable instrument for assessing QoL in patients suffering from mild to moderate dementia, thus supporting its use in clinical practice and research. Show more

Keywords: Alzheimer’s disease, dementia, Germany, quality of life, reliability and validity, self report

DOI: 10.3233/JAD-200400

Citation: Journal of Alzheimer's Disease, vol. 77, no. 2, pp. 581-590, 2020

Authors: Badji, Atef | de la Colina, Adrián Noriega | Boshkovski, Tommy | Sabra, Dalia | Karakuzu, Agah | Robitaille-Grou, Marie-Christine | Gros, Charley | Joubert, Sven | Bherer, Louis | Lamarre-cliche, Maxime | Stikov, Nikola | Gauthier, Claudine J. | Cohen-Adad, Julien | Girouard, Hélène

Article Type: Research Article

Abstract: Background: Vascular risk factors such as arterial stiffness play an important role in the etiology of Alzheimer’s disease (AD), presumably due to the emergence of white matter lesions. However, the impact of arterial stiffness to white matter structure involved in the etiology of AD, including the corpus callosum remains poorly understood. Objective: The aims of the study are to better understand the relationship between arterial stiffness, white matter microstructure, and perfusion of the corpus callosum in older adults. Methods: Arterial stiffness was estimated using the gold standard measure of carotid-femoral pulse wave velocity (cfPWV). Cognitive performance …was evaluated with the Trail Making Test part B-A. Neurite orientation dispersion and density imaging was used to obtain microstructural information such as neurite density and extracellular water diffusion. The cerebral blood flow was estimated using arterial spin labelling. Results: cfPWV better predicts the microstructural integrity of the corpus callosum when compared with other index of vascular aging (the augmentation index, the systolic blood pressure, and the pulse pressure). In particular, significant associations were found between the cfPWV, an alteration of the extracellular water diffusion, and a neuronal density increase in the body of the corpus callosum which was also correlated with the performance in cognitive flexibility. Conclusion: Our results suggest that arterial stiffness is associated with an alteration of brain integrity which impacts cognitive function in older adults. Show more

Keywords: Aging, Alzheimer’s disease, arterial spin labelling, arterial stiffness, corpus callosum, diffusion weighted imaging

DOI: 10.3233/JAD-200668

Citation: Journal of Alzheimer's Disease, vol. 77, no. 2, pp. 591-605, 2020