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

Authors: Manivannan, Madhumitha | Heunis, Julia | Hooper, Sarah M. | Bernstein Sideman, Alissa | Lui, Kristi P. | Possin, Katherine L. | Chiong, Winston

Article Type: Research Article

Abstract: Background: Financial mismanagement and abuse in dementia have serious consequences for patients and their families. Vulnerability to these outcomes reflects both patient and contextual factors. Objective: Our study aimed to assess how multidisciplinary care coordination programs assist families in addressing psychosocial vulnerabilities and accessing needed resources. Methods: Our study was embedded in a clinical trial of the Care Ecosystem, a telephone- and internet-based supportive care intervention for patients with dementia and caregivers. This program is built around the role of the Care Team Navigator (CTN), an unlicensed dementia care guide who serves as the patient and …caregiver’s primary point of contact, screening for common problems and providing support. We conducted a qualitative analysis of case summaries from a subset of 19 patient/caregiver dyads identified as having increased risk for financial mismanagement and abuse, to examine how Care Ecosystem staff identified vulnerabilities and provided support to patients and families. Results: CTNs elicited patient and caregiver needs using templated conversations to address common financial and legal planning issues in dementia. Sources of financial vulnerability included changes in patients’ behavior, caregiver burden, intrafamily tension, and confusion about resources to facilitate end-of-life planning. The Care Ecosystem staff’s rapport with their dyads helped them address these issues by providing emotional support, information on how to access financial, medical, and legal resources, and improving intra-familial communication. Conclusion: The Care Ecosystem offers a scalable way to address vulnerabilities to financial mismanagement and abuse in patients and caregivers through coordinated care by unlicensed care guides supported by a multidisciplinary team. Show more

Keywords: Care navigation, caregivers, dementia, financial management

DOI: 10.3233/JAD-215284

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-11, 2021

Authors: Park, Mincheol | Baik, Kyoungwon | Lee, Young-gun | Kang, Sung Woo | Jung, Jin Ho | Jeong, Seong Ho | Lee, Phil Hyu | Sohn, Young H. | Ye, Byoung Seok

Article Type: Correction

DOI: 10.3233/JAD-219020

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

Authors: Nami, Mohammad | Thatcher, Robert | Kashou, Nasser | Lopes, Dahabada | Lobo, Maria | Bolanos, Joe F. | Morris, Kevin | Sadri, Melody | Bustos, Teshia | Sanchez, Gilberto E. | Mohd-Yusof, Alena | Fiallos, John | Dye, Justin | Guo, Xiaofan | Peatfield, Nicholas | Asiryan, Milena | Mayuku-Dore, Alero | Krakauskaite, Solventa | Soler, Ernesto Palmero | Cramer, Steven C. | Besio, Walter G. | Berenyi, Antal | Tripathi, Manjari | Hagedorn, David | Ingemanson, Morgan | Gombosev, Marinela | Liker, Mark | Salimpour, Yousef | Mortazavi, Martin | Braverman, Eric | Prichep, Leslie S. | Chopra, Deepak | Eliashiv, Dawn S. | Hariri, Robert | Tiwari, Ambooj | Green, Ken | Cormier, Jason | Hussain, Namath | Tarhan, Nevzat | Sipple, Daniel | Roy, Michael | Yu, John S. | Filler, Aaron | Chen, Mike | Wheeler, Chris | Ashford, J. Wesson | Blum, Kenneth | Zelinsky, Deborah | Yamamoto, Vicky | Kateb, Babak

Article Type: Review Article

Abstract: The COVID-19 pandemic has accelerated neurological, mental health disorders, and neurocognitive issues. However, there is a lack of inexpensive and efficient brain evaluation and screening systems. As a result, a considerable fraction of patients with neurocognitive or psychobehavioral predicaments either do not get timely diagnosed or fail to receive personalized treatment plans. This is especially true in the elderly populations, wherein only 16% of seniors say they receive regular cognitive evaluations. Therefore, there is a great need for development of an optimized clinical brain screening workflow methodology like what is already in existence for prostate and breast exams. Such a …methodology should be designed to facilitate objective early detection and cost-effective treatment of such disorders. In this paper we have reviewed the existing clinical protocols, recent technological advances and suggested reliable clinical workflows for brain screening. Such protocols range from questionnaires and smartphone apps to multi-modality brain mapping and advanced imaging where applicable. To that end, the Society for Brain Mapping and Therapeutics (SBMT) proposes the Brain, Spine and Mental Health Screening (NEUROSCREEN) as a multi-faceted approach. Beside other assessment tools, NEUROSCREEN employs smartphone guided cognitive assessments and quantitative electroencephalography (qEEG) as well as potential genetic testing for cognitive decline risk as inexpensive and effective screening tools to facilitate objective diagnosis, monitor disease progression, and guide personalized treatment interventions. Operationalizing NEUROSCREEN is expected to result in reduced healthcare costs and improving quality of life at national and later, global scales. Show more

Keywords: Brain mapping, brain screening, cMEG, mental health screening, neuro-screening, neurotechnologies, preventive medicine, qEEG

DOI: 10.3233/JAD-215240

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-21, 2021

Authors: Zhang, Li-Na | Li, Meng-Jie | Shang, Ying-Hui | Liu, Yun-Ru | Han-Chang, Huang | Lao, Feng-Xue

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD) characterized by neurofibrillary tangles caused by hyperphosphorylated tau is the most common cause of dementia. Zeaxanthin (Zea), derived from fruits and vegetables, may reduce the risk of AD. Endoplasmic reticulum stress (ERS) might cause memory impairment in AD. Objective: Here, we studied protective role of Zea on the relationship among ERS, activity of glycogen synthase kinase 3β (GSK-3β, tau phosphorylated kinase), and p-Tau (Ser 396 and Thr 231). Methods: The results were obtained in non-RA and RA group by using different treatment, such as 9-cis-retinoic acid (RA), TM (ERS inducer), Zea, 4-PBA …(ERS inhibitor), and SB216763 (GSK-3β inhibitor). The methods included flow cytometry and MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] for the detections of cell cycle and cell viability and western blot as a third measure of proteins in relation to ERS and tau phosphorylation. We have collected and analyzed all the data that suggested application of drugs for the treatment in non-RA and RA group. Results: Zea displays its protection on TM-induced cell injury, upregulation of GRP78 expression, and change of GSK-3β activity and tau phosphorylation when 4-PBA and SB216763 interfere with the process. Conclusion: These studies indicated that Zea is in vicious circle in ERS, GSK-3β, and tau phosphorylation, and further reflect its potential value in AD. Show more

Keywords: Alzheimer’s disease, glycogen synthase kinase 3β, SB216763, tau, Zeaxanthin

DOI: 10.3233/JAD-215408

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-14, 2021

Authors: Zhang, Qiaoyang | Zhang, Min | Chen, Yun | Cao, Yin | Dong, Guanzhong

Article Type: Research Article

Abstract: Background: Serum non-high-density lipoprotein-cholesterol (non-HDL-C) levels may be associated with cognitive function. Objective: The objective of this study was to evaluate the association between non-HDL-C and cognitive function among American elders. Methods: We used data from the 2011 to 2014 U.S. National Health and Nutrition Examination Survey (NHANES). A total of 3,001 participants aged over 60 years were enrolled in our analysis. The cognitive function was evaluated with the word learning subtest from the Consortium to Establish a Registry for Alzheimer’s disease (CERAD W-L), the Animal Fluency Test (AFT), and the digit symbol substitution test (DSST). …We also created a composite cognitive z-score to represent a global cognition. We applied multivariate linear regression analyses to estimate the associations between non-HDL-C levels and all domains of cognitive function. Further, the generalized additive model and the smooth curve were conducted to investigate the dose-response relationship between non-HDL-C and global cognition. Results: Serum non-HDL-C was positively associated with global cognition (β = 0.20, 95% CI: 0.11, 0.28), AFT score (β = 0.54, 95% CI: 0.33, 0.76), and DSST score (β = 1.13, 95% CI: 0.56, 1.69) after fully adjusted. While non-HDL-C was not related to CERAD W-L score. In addition, an inverted U-shape curve was observed in the dose-response relationship between non-HDL-C and global cognition (p for non-linearity <  0.001). Conclusion: Serum non-HDL-C is positively and nonlinearly associated with cognitive function among American older adults. Maintaining serum cholesterol levels at an appropriate range may be helpful to the cognitive health of the elderly. Show more

Keywords: Cholesterol, cognitive function, NHANES, non-HDL-C, older adults

DOI: 10.3233/JAD-215250

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-10, 2021

Authors: Bian, Zhihong | Liu, Xia | Feng, Tian | Yu, Haibo | Hu, Xiao | Hu, Xinran | Bian, Yuting | Sun, Hongming | Tadokoro, Koh | Takemoto, Mami | Yunoki, Taijun | Nakano, Yumiko | Fukui, Yusuke | Morihara, Ryuta | Abe, Koji | Yamashita, Toru

Article Type: Research Article

Abstract: Background: Recent studies have revealed that atrial fibrillation (AF) patients have a high risk of developing cognitive impairment, vascular dementia, and Alzheimer’s disease (AD). Some reports suggest that the application of oral anticoagulant with an appropriate dose may have a preventive effect on AD. However, which oral anticoagulant drug is more appropriate for preventing AD and the underlying mechanism(s) is still unknown. Objective: The aim of the present study was to assess the treatment effect of rivaroxaban administration as well as investigate the roles of PAR-1 and PAR-2 in the AD + CAA mice model. Methods: In the …present study, we compared a traditional oral anticoagulant, warfarin, and a direct oral anticoagulant (DOAC), rivaroxaban, via long-term administration to an AD with cerebral amyloid angiopathy (CAA) mice model. Results: Rivaroxaban treatment attenuated neuroinflammation, blood-brain barrier dysfunction, memory deficits, and amyloid-β deposition through PAR-1/PAR-2 inhibition in the AD + CAA mice model compared with warfarin and no-treatment groups. Conclusion: The present study demonstrates that rivaroxaban can attenuate AD progress and can be a potential choice to prevent AD. Show more

Keywords: Alzheimer’s disease, cerebral amyloid angiopathy chronic cerebral hypoperfusion, rivaroxaban, warfarin

DOI: 10.3233/JAD-215318

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-13, 2021

Authors: Johansen, Michelle C. | Wang, Wendy | Zhang, Michael J. | Alonso, Alvaro | Wong, Dean F. | Gottesman, Rebecca F. | Chen, Lin Y.

Article Type: Research Article

Abstract: The aim of this study is to determine if there is an association between atrial arrhythmias and brain amyloid-β (Aβ), measured on florbetapir (FBP) PET. 346 nondemented participants from the Atherosclerosis Risk in Communities study underwent FBP-PET, 185 also wore Zio® XT Patch. The associations between global cortical Aβ (>  1.2 standardized uptake value ratio) and history of atrial fibrillation, zio-defined atrial tachycardia and premature atrial contractions, each, were evaluated. Among nondemented community-dwelling older adults, we did not find an association between atrial arrhythmias and Aβ. Other brain pathology may underlie the association described between atrial arrhythmias and cognition.

Keywords: Arrhythmias, atrial fibrillation, cognitive impairment, imaging

DOI: 10.3233/JAD-215378

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-5, 2021

Authors: Daly, Timothy | Mastroleo, Ignacio | Henry, Vincent | Bourdenx, Mathieu

Article Type: Research Article

Abstract: Two potential disease-modifying approaches for dementia are being vigorously tested: the early targeting of the neuropathology of Alzheimer’s disease (AD) and multi-domain lifestyle interventions to promote resilience to neuropathology. We apply the “web of information” model of clinical translation to both approaches to argue firstly that tests of treatments aiming to achieve clinically meaningful outcomes should remain simple, and secondly, that building clinically-meaningful treatments should be kept separate from public health policy which means promoting wide-reaching action against risk factors now with available information.

Keywords: Alzheimer’s disease, clinical trials, dementia, innovation, public health, treatment

DOI: 10.3233/JAD-215492

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-4, 2021

Authors: Benca, Ruth | Herring, W. Joseph | Khandker, Rezaul | Qureshi, Zaina

Article Type: Research Article

Abstract: Background: Sleep disturbances are frequent in Alzheimer’s disease (AD). This review summarizes the impact of sleep disturbances on AD patients and their caregivers and the effects of currently available sleep therapies. Methods: Published studies (January 1985–March 2020) assessing the burden associated with insomnia/sleep disturbances in the AD population and insomnia treatment effects were identified by searching PubMed, Embase and Cochrane Library and screened against inclusion criteria. Findings: This review included 58 studies which assessed patient and caregiver burden, institutionalization, and insomnia treatments in AD patients with sleep disturbances. Sleep disturbances were associated with worse cognition, functional …ability, and behavioral and neuropsychological functioning, including increased depression and anxiety. Health status and quality of life of both patients and caregivers were reduced in the presence of sleep disturbances, with caregiver burden driven largely by disruptive nocturnal behaviors including nighttime awakenings and wanderings. Sleep disturbances were also associated with institutionalization. Although significant associations between sleep problems and clinical outcomes were apparent, there was generally no control for other influencing factors (e.g. cognitive status). With respect to insomnia treatments, bright light, and behavioral therapies as well as drugs such as trazodone, risperidone and suvorexant showed some promise in AD patients, but studies were primarily small and limited data were available, particularly in regard to insomnia treatment effects on associated clinical burden. Interpretation: Sleep disturbances are a significant problem for AD patients and caregivers. They are associated with behavioral and psychological problems and cognitive decline and impose a burden on caregivers, but remain poorly characterized and under-researched. As the global population is aging and AD is on the rise, data from larger, prospective trials are required to fully understand the clinical correlates of sleep disturbances and the impact of insomnia treatments on AD patients and their caregivers. Show more

Keywords: Insomnia, Alzheimer’s disease, sleep disturbances, literature review, caregiver burden, clinical burden, institutionalization, treatment guidelines

DOI: 10.3233/JAD-215324

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-27, 2021

Authors: Posis, Alexander Ivan B. | Tarraf, Wassim | Gonzalez, Kevin A. | Soria-Lopez, Jose A. | Léger, Gabriel C. | Stickel, Ariana M. | Daviglus, Martha L. | Lamar, Melissa | Zeng, Donglin | González, Hector M.

Article Type: Research Article

Abstract: Background: Studies of cumulative anticholinergic drug burden on cognitive function and impairment are emerging, yet few for Hispanics/Latinos. Objective: To examine associations between anticholinergic use and neurocognitive performance outcomes among diverse Hispanics/Latinos. Methods: This prospective cohort study included diverse Hispanic/Latino participants, enrolled in the Study of Latinos-Investigation of Neurocognitive, from New York, Chicago, Miami, and San Diego (n  = 6,249). Survey linear regression examined associations between anticholinergic use (measured during baseline [Visit 1] and average 7-year follow up [Visit 2]) with global cognition, episodic learning, memory, phonemic fluency, processing speed, executive functioning, and average 7-year change. …Results: Anticholinergic use was associated with lower cognitive global cognition (β= –0.21; 95% CI [–0.36; –0.05]), learning (β= –0.27; 95% CI [–0.47; –0.07]), memory (β= –0.22; 95% CI [–0.41; –0.03]), and executive functioning (β= –0.22; 95% CI [–0.40; –0.03]) scores, particularly among those who took anticholinergics at both visits. Anticholinergic use was associated with faster decline in global cognition, learning, and verbal fluency (β: –0.28 [95% CI: –0.55, –0.01]; β: –0.28 [95% CI: –0.55, –0.01]; β: –0.25, [95% CI –0.47, –0.04], respectively). Sex modified associations between anticholinergic use with global cognition, learning, and executive functioning (F 3  = 3.59, F 3  = 2.84, F 3  = 3.88, respectively). Conclusion: Anticholinergic use was associated with lower neurocognitive performance, especially among those who used anticholinergics at both visits, among a study population of diverse Hispanics/Latinos. Findings will support evidence-based decisions regarding anticholinergic prescriptions and efforts to minimize cognitive impact. Show more

Keywords: Aging, cognition, cognitive function, cohort study, neurocognitive tests, hispanics, latinos

DOI: 10.3233/JAD-215247

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-13, 2021