Journal of Alzheimer's Disease - Volume Pre-press, issue Pre-press

Authors: Baazaoui, Narjes | Iqbal, Khalid

Article Type: Review Article

Abstract: COVID-19 emerged as a global pandemic starting from Wuhan in China and spread at a lightning speed to the rest of the world. One of the potential long-term outcomes that we speculate is the development of neurodegenerative diseases as a long-term consequence of SARS-CoV-2 especially in people that have developed severe neurological symptoms. Severe inflammatory reactions and aging are two very strong common links between neurodegenerative diseases and COVID-19. Thus, patients that have very high viral load may be at high risk of developing long-term adverse neurological consequences such as dementia. We hypothesize that people with neurodegenerative diseases such as …Alzheimer’s disease, Parkinson’s disease, and aged people are at higher risk of getting the COVID-19 than normal adults. The basis of this hypothesis is the fact that SARS-CoV-2 uses as a receptor angiotensin-converting enzyme 2 to enter the host cell and that this interaction is calcium-dependent. This could then suggest a direct relationship between neurodegenerative diseases, ACE-2 expression, and the susceptibility to COVID-19. The analysis of the available literature showed that COVID-19 virus is neurotropic and was found in the brains of patients infected with this virus. Furthermore, that the risk of having the infection increases with dementia and that infected people with severe symptoms could develop dementia as a long-term consequence. Dementia could be developed following the acceleration of the spread of prion-like proteins. In the present review we discuss current reports concerning the prevalence of COVID-19 in dementia patients, the individuals that are at high risk of suffering from dementia and the potential acceleration of prion-like proteins spread following SARS-CoV-2 infection. Show more

Keywords: ACE receptors, Alzheimer’s disease, dementia, Parkinson’s disease, prion-like proteins, SARS-CoV-2

DOI: 10.3233/JAD-220105

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-18, 2022

Authors: Hao, Jing | Guo, Yanping | Guo, Keke | Yang, Qingcheng

Article Type: Review Article

Abstract: Alzheimer’s disease (AD) is a neurodegenerative disease of unknown pathological origin. The clinical diagnosis of AD is time-consuming and needs to a combination of clinical evaluation, psychological testing, and imaging assessments. Biomarkers may be good indicators for the clinical diagnosis of AD; hence, it is important to identify suitable biomarkers for the diagnosis and treatment of AD. Peripheral inflammatory biomarkers have been the focus of research in recent years. This review summarizes the role of inflammatory biomarkers in the disease course of AD.

Keywords: Alzheimer’s disease, biomarkers, inflammatory, neurodegeneration

DOI: 10.3233/JAD-215422

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-10, 2022

Authors: Høilund-Carlsen, Poul F. | Revheim, Mona-Elisabeth | Alavi, Abass

Article Type: Article Commentary

Abstract: Three decades with the amyloid hypothesis, nearly two with amyloid-PET imaging, and one with testing of anti-amyloid therapy have not yielded benefits to patients with Alzheimer’s disease (AD). It is time to focus on more promising options, e.g., infection, low dose radiation, and atherosclerosis. The relevance of the latter in managing AD has fluctuated from being significant to insignificant. Current methodologies for detecting cerebral atherosclerosis reflect advanced changes in only major arteries. In contrast, 18 F-sodium fluoride PET imaging assessing early-stage cerebral atherosclerosis regionally or in the entire vascular bed may provide new insight in this age-related process in dementia.

Keywords: Alzheimer’s disease, amyloid-β, dementia, 18F-sodium fluoride PET, NaF

DOI: 10.3233/JAD-220190

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-4, 2022

Authors: Tsiakiri, Anna | Vlotinou, Pinelopi | Terzoudi, Aikaterini | Heliopoulos, Ioannis | Vadikolias, Konstantinos

Article Type: Research Article

Abstract: Background: Prolonged periods of social deprivation, such as COVID-19-related lockdowns, are associated with deleterious effects on cognitive functions. Objective: The aim of this study was to gauge the effect of prolonged social isolation on the cognitive function of older adults with neurocognitive disorders. Methods: We recruited 125 older adults with minor or major neurocognitive disorders divided into two groups. The control group was tested at the first period of the study (October 2018–May 2019), whereas the experimental group was evaluated at the second chronological period of the study (October 2020–May 2021) during the second wave of …COVID-19. Neuropsychological tests were performed at baseline and six months after baseline. Results: In the control group, significant changes in the scores from the Montreal Cognitive Assessment (MoCA; p  = 0.049) and the Functional Rating Scale for Symptoms of Dementia (FRSSD; p  = 0.005) were found between baseline and follow-up assessments, whereas no changes were identified in Mini-Mental State Examination (MMSE; p  = 0.229) and Geriatric Depression Scale (GDS; p  = 0.619) scores. In the experimental group, the scores from all neuropsychological tests (MoCA, MMSE, GDS, and FRSSD; p  < 0.001 for all) were significantly different at follow-up when compared with those at baseline measurements. Moreover, significant deterioration of specific functions assessed in MMSE and FRSSD was detected, especially in the experimental group. Conclusion: This study highlights cognitive functions directly affected by social deprivation of individuals with neurocognitive disorders. The findings can be used in the rehabilitation from confinement and its negative consequences. Show more

Keywords: Cognitive functions, COVID-19, emotional status, neurocognitive disorders

DOI: 10.3233/JAD-220118

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-11, 2022

Authors: Nakanishi, Miharu | Yamasaki, Syudo | Ando, Shuntaro | Endo, Kaori | Richards, Marcus | Hiraiwa-Hasegawa, Mariko | Kasai, Kiyoto | Nishida, Atsushi

Article Type: Research Article

Abstract: Background: Middle-aged adults may be the ideal target group for dementia-related stigma reduction interventions to encourage the utilization of services among those who may become family caregivers. Neighborhood social cohesion may diminish dementia-related stigma, particularly in terms of perceived public attitudes. The COVID-19 pandemic can further negatively impact perceived public stigma. Objective: To investigate the association between neighborhood social cohesion and dementia-related stigma during the pre- and current COVID-19 period. Methods: We employed a cross-sectional design using data from a large population-based cohort, the Tokyo Teen Cohort, in Japan. Overall, 2,469 mothers of 16-year-old adolescents self-completed …a questionnaire comprising nine dementia-related stigma questions evaluating perceived public and personal attitudes. Neighborhood social cohesion was assessed using a five-item instrument. The participants were divided into two groups according to the time of assessment: prior to the pandemic’s onset (February 2019–March 2020) and during the pandemic (April 2020–July 2021). A multiple regression analysis of stigma was performed using neighborhood social cohesion as an independent variable, and caring experience, age, educational level, and working status as covariates. Results: Personal and perceived public stigma were significantly lower in participants who perceived greater neighborhood social cohesion. However, level of personal and perceived public stigma did not differ between pre- and during the pandemic period. Conclusion: Neighborhood social cohesion may be a modifiable factor for dementia-related stigma. A localized intervention to enhance social cohesion in the neighborhood community would promote the utilization of services among those who may become family caregivers. Show more

Keywords: Asia, dementia, middle aged, mothers, social stigma

DOI: 10.3233/JAD-220043

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-10, 2022

Authors: Karikari, Thomas K.

Article Type: Research Article

Abstract: The recent academic and commercial development, and regulatory approvals, of blood-based Alzheimer’s disease (AD) biomarkers are breakthrough developments of immense potential. However, clinical validation studies and therapeutic trial applications are limited almost exclusively to non-Hispanic White cohorts often including highly-educated, high-earning participants. This commentary argues that the true benefits of blood tests for AD will be realized by active inclusion of diverse groups including minoritized populations, people of socioeconomic status different from those included in existing cohorts, and residents of low- and middle-income countries. The article discusses key factors that are critical for a successful implementation of diversity programs.

Keywords: Alzheimer’s disease, amyloid-β, blood biomarker, dementia, diagnostics, low- and middle-income countries, minoritized populations, neurofilament light, phosphorylated tau

DOI: 10.3233/JAD-215730

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-8, 2022

Authors: Mozersky, Jessica | Roberts, J. Scott | Rumbaugh, Malia | Chhatwal, Jasmeer | Wijsman, Ellen | Galasko, Douglas | Blacker, Deborah | on behalf of AGREED

Article Type: Review Article

Abstract: In this article we address how the recent, and anticipated upcoming, FDA approvals of novel anti-amyloid medications to treat individuals with mild Alzheimer’s disease (AD) dementia could impact disclosure of biomarker results among asymptomatic research participants. Currently, research is typically the context where an asymptomatic individual may have the option to learn their amyloid biomarker status. Asymptomatic research participants who learn their amyloid status may have questions regarding the meaning of this result and the implications for accessing a potential intervention. After outlining our rationale, we provide examples of how current educational materials used in research convey messages regarding amyloid …positivity and the availability of treatments, or lack thereof. We suggest language to improve messaging, as well as strengths of current materials, in addressing these issues for research participants. Although novel medications are currently only approved for use among symptomatic individuals, their availability may have implications for disclosure among asymptomatic research participants with evidence of amyloid deposition, who may be especially interested in information on these interventions for potential prevention, or future treatment, of mild cognitive impairment or dementia due to AD. Show more

Keywords: Alzheimer’s disease, amyloid, asymptomatic disclosure, biomarkers, dementia, new medications, research ethics

DOI: 10.3233/JAD-220113

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-9, 2022

Authors: Largent, Emily A. | Bhardwaj, Twisha | Clapp, Justin T. | Sykes, Olivia Saúl | Harkins, Kristin | Grill, Joshua D.

Article Type: Research Article

Abstract: Background: Participants in Alzheimer’s disease (AD) prevention studies are generally required to enroll with a study partner; this requirement constitutes a barrier to enrollment for some otherwise interested individuals. Analysis of dyads enrolled in actual AD trials suggests that the study partner requirement shapes the population under study. Objective: To understand if individuals can identify someone to serve as their study partner and whether they would be willing to ask that individual. Methods: We conducted semi-structured interviews with cognitively unimpaired, English-speaking older adults who had previously expressed interest in AD research by signing up for a …research registry. We also interviewed their likely study partners. Audio-recorded interviews were transcribed and coded in an iterative, team-based process guided by a content analysis approach. Results: We interviewed 60 potential research participants and 17 likely study partners. Most potential participants identified one or two individuals they would be willing to ask to serve as their study partner. Interviewees saw value in the study partner role but also understood it to entail burdens that could make participation as a study partner more difficult. The role was seen as relatively more burdensome for individuals in the workforce or with family responsibilities. Calls from the researcher to discuss the importance of the role and the possibility of virtual visits were identified as potential strategies for increasing study partner availability. Conclusion: Efforts to increase recruitment, particularly representative recruitment, of participants for AD prevention studies should reduce barriers to participation by thoughtfully designing the study partner role. Show more

Keywords: Alzheimer’s disease, ethics, registries, research, research design

DOI: 10.3233/JAD-220061

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-13, 2022

Authors: Daly, Timothy | Mastroleo, Ignacio | Migliaccio, Raffaella

Article Type: Research Article

Abstract: Given the unknown therapeutic value of targeting Alzheimer’s disease pathology and the discovery of robust risk factors for dementia, non-pharmacological risk reduction (RR) is increasingly offered as an alternative to targeting Alzheimer’s disease pathology. While RR will surely be a useful tool to make public health gains, we propose solutions to three possible issues with over-reliance on multi-domain interventions to achieve RR: limited individual impact, an exclusive focus on later life, and overlooking social determinants of dementia. We argue in favor of a broader debate within the research community and greater society about how different therapeutic avenues should be explored.

Keywords: Alzheimer’s disease, dementia, health inequities, multidomain interventions, public health, risk reduction, social determinants of health

DOI: 10.3233/JAD-215647

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-4, 2022

Authors: Schindler, Suzanne E.

Article Type: Article Commentary

Abstract: Predicting not just if but when cognitively normal individuals will develop the onset of Alzheimer’s disease (AD) dementia seems increasingly feasible, as evidenced by converging findings from several approaches and cohorts. These estimates may improve the efficiency of clinical trials by better identifying cognitively normal individuals at high risk of developing AD symptoms. As models are refined, the implications of disclosing estimates of the age of AD symptom onset must be examined, since telling a cognitively normal individual the age they are expected to develop AD symptoms may have different implications than disclosing increased risk for AD dementia.

Keywords: A4 study, Alzheimer’s disease, amyloid chronicity, amyloid clock, amyloid duration, amyloid PET, amyloid time, disclosure, symptom onset

DOI: 10.3233/JAD-215722

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-5, 2022