Journal of Alzheimer's Disease - Volume 86, issue 1

Authors: Talan, Jamie

Article Type: Obituary

DOI: 10.3233/JAD-229000

Citation: Journal of Alzheimer's Disease, vol. 86, no. 1, pp. 1-3, 2022

Authors: Stepler, Kaitlyn E. | Gillyard, Taneisha R. | Reed, Calla B. | Avery, Tyra M. | Davis, Jamaine S. | Robinson, Renã A.S.

Article Type: Review Article

Abstract: African American/Black adults are twice as likely to have Alzheimer’s disease (AD) compared to non-Hispanic White adults. Genetics partially contributes to this disparity in AD risk, among other factors, as there are several genetic variants associated with AD that are more prevalent in individuals of African or European ancestry. The phospholipid-transporting ATPase ABCA7 (ABCA7 ) gene has stronger associations with AD risk in individuals with African ancestry than in individuals with European ancestry. In fact, ABCA7 has been shown to have a stronger effect size than the apolipoprotein E (APOE ) ɛ 4 allele in African American/Black adults. ABCA7 …is a transmembrane protein involved in lipid homeostasis and phagocytosis. ABCA7 dysfunction is associated with increased amyloid-beta production, reduced amyloid-beta clearance, impaired microglial response to inflammation, and endoplasmic reticulum stress. This review explores the impact of ABCA7 mutations that increase AD risk in African American/Black adults on ABCA7 structure and function and their contributions to AD pathogenesis. The combination of biochemical/biophysical and ‘omics-based studies of these variants needed to elucidate their downstream impact and molecular contributions to AD pathogenesis is highlighted. Show more

Keywords: African Americans, Alzheimer’s disease, Blacks, health status disparities, human ABCA7 protein, proteomics, single nucleotide polymorphism, subfamily A of ATP binding cassette transporter

DOI: 10.3233/JAD-215306

Citation: Journal of Alzheimer's Disease, vol. 86, no. 1, pp. 5-19, 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. 86, no. 1, pp. 21-42, 2022

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

Article Type: Short Communication

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. 86, no. 1, pp. 43-48, 2022

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

Article Type: Article Commentary

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. 86, no. 1, pp. 49-52, 2022

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. 86, no. 1, pp. 53-65, 2022

Authors: Liu, Ruijie | Gao, Chenhao | Shang, Junkui | Sun, Ruihua | Wang, Wenjing | Li, Wei | Gao, Dandan | Huo, Xuejing | Shi, Yingying | Wang, Yanliang | Wang, Fengyu | Zhang, Jiewen

Article Type: Research Article

Abstract: Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) caused by NOTCH3 mutations is the most common monogenic hereditary pattern of cerebral small vessel disease. The aggregation of the mutant NOTCH3 may play a cytotoxic role in CADASIL. However, the main mechanism of this process remains unclear. Objective: We aimed to investigate the possible pathogenesis of the mutant NOTCH3 in CADASIL. Methods: The clinical information of two pedigrees were collected and analyzed. Furthermore, we constructed cell lines corresponding to this mutation in vitro . The degradation of the extracellular domain of NOTCH3 (NOTCH3ECD …) was analyzed by Cycloheximide Pulse-Chase Experiment. Flow cytometry and cell counting kit-8 assay were performed to observe the effects of the NOTCH3 mutation on mitochondrial function and apoptosis. Results: We confirmed a de novo heterozygous missense NOTCH3 mutation (c.1690G > A, p. A564T) in two pedigrees. In vitro , the NOTCH3ECD aggregation of A564T mutant may be related to their more difficult to degrade. The mitochondrial membrane potential was attenuated, and cell viability was significant decreased in NOTCH3ECD A564T group. Interestingly, BAX and cytochrome c were significantly increased, which are closely related to the mitochondrial-mediated pathway to apoptosis. Conclusion: In our study, the aggregation of NOTCH3ECD A564T mutation may be associated with more difficult degradation of the mutant, and the aggregation may produce toxic effects to induce apoptosis through the mitochondrial-mediated pathway. Therefore, we speculated that mitochondrial dysfunction may hopefully become a new breakthrough point to explain the pathogenesis of cysteine-sparing NOTCH3 mutations. Show more

Keywords: Apoptosis, CADASIL, cysteine-sparing NOTCH3 mutation, flow cytometry, mitochondrial dysfunction

DOI: 10.3233/JAD-215256

Citation: Journal of Alzheimer's Disease, vol. 86, no. 1, pp. 67-81, 2022

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

Article Type: Research Article

Abstract: Background: Sleep disturbances are frequent in Alzheimer’s disease (AD). Objective: To summarize 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. Results: 58 studies assessing patient and caregiver burden, institutionalization, and insomnia treatments in AD patients with sleep disturbances were identified. Sleep disturbances were associated with worse cognition, functional …ability, and behavioral and neuropsychological functioning. Health status and quality of life of both patients and caregivers were reduced in the presence of sleep disturbances. 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). Bright light and behavioral therapies as well as drugs showed some promise in AD patients, but studies were primarily small and limited data were available, particularly in regard to the effect on associated clinical burden. Conclusion: Sleep disturbances are a significant problem for AD patients and caregivers, associated with behavioral and psychological problems and cognitive decline. However, they remain poorly characterized and under-researched. As the global population is aging and AD is on thes rise, data from larger, prospective trials are required to fully understand the clinical correlates of sleep disturbances and the impact insomnia treatments can have. Show more

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

DOI: 10.3233/JAD-215324

Citation: Journal of Alzheimer's Disease, vol. 86, no. 1, pp. 83-109, 2022

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. 86, no. 1, pp. 111-123, 2022

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. 86, no. 1, pp. 125-134, 2022