Journal of Alzheimer's Disease - Volume 79, issue 1

Authors: Li, Clara | Neugroschl, Judith | Zhu, Carolyn W. | Aloysi, Amy | Schimming, Corbett A. | Cai, Dongming | Grossman, Hillel | Martin, Jane | Sewell, Margaret | Loizos, Maria | Zeng, Xiaoyi | Sano, Mary

Article Type: Review Article

Abstract: Mobile technologies are becoming ubiquitous in the world, changing the way we communicate and provide patient care and services. Some of the most compelling benefits of mobile technologies are in the areas of disease prevention, health management, and care delivery. For all the advances that are occurring in mobile health, its full potential for older adults is only starting to emerge. Yet, existing mobile health applications have design flaws that may limit usability by older adults. The aim of this paper is to review barriers and identify knowledge gaps where more research is needed to improve the accessibility of mobile …health use in aging populations. The same observations might apply to those who are not elderly, including individuals suffering from severe mental or medical illnesses. Show more

Keywords: Design considerations, mHealth, mobile health, mobile technology, older adults

DOI: 10.3233/JAD-200485

Citation: Journal of Alzheimer's Disease, vol. 79, no. 1, pp. 1-8, 2021

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

Article Type: Review Article

Abstract: Generalized lockdown caused by COVID-19, necessary yesterday, can no longer be that of tomorrow. It will no longer be possible to cram the humblest into cramped areas, but priority must be given to prevention (certainly with physical barriers, hydro-alcoholic gel, face masks), biological diagnosis, isolation, and also the care of any infected person. COVID-19 has hit the most vulnerable first in terms of biological inequality, such as Alzheimer’s disease (AD) patients. Those with AD can have sensorial deficits and perception troubles, including visual difficulties and the inability to recognize faces and emotions. Face masks and physical distancing can disrupt facial …familiarity and make it more difficult to recognize emotional facial expressions. It can provoke distress, which the visitor can perceive and feel obligated to take off the face mask. This gesture should not be considered as an act of indiscipline, but an act of empathy. Transparent face masks could improve the suffering of AD patients, distraught in the presence of their loved ones whose masks hide their faces. Wearing a mask should not be due to fear of punishment, but as an understanding of the responsibility of each individual in the control of the current pandemic. It may be necessary to convince more citizens of this civic duty, using clear and attractive messaging in order to standardize the wearing of face masks for the general public and to adapt them to the needs of patients. Show more

Keywords: Alzheimer’s disease, COVID-19, ethics, mask, physical distancing

DOI: 10.3233/JAD-201233

Citation: Journal of Alzheimer's Disease, vol. 79, no. 1, pp. 9-14, 2021

Authors: Bishop, Kelly C. | Husain-Krautter, Sehba | Ketcham, Jonathan D. | Kuminoff, Nicolai V. | Schimming, Corbett

Article Type: Other

Abstract: We hypothesize that analyzing individual-level secondary data with instrumental variable (IV) methods can advance knowledge of the long-term effects of air pollution on dementia. We discuss issues in measurement using secondary data and how IV estimation can overcome biases due to measurement error and unmeasured variables. We link air-quality data from the Environmental Protection Agency’s monitors with Medicare claims data to illustrate the use of secondary data to document associations. Additionally, we describe results from a previous study that uses an IV for pollution and finds that PM2.5 ’s effects on dementia are larger than non-causal associations.

Keywords: Air pollution, aged, dementia, instrumental variables, research design, selection bias

DOI: 10.3233/JAD-200497

Citation: Journal of Alzheimer's Disease, vol. 79, no. 1, pp. 15-23, 2021

Authors: Maderna, Emanuela | Visonà, Silvia | Bolcato, Vittorio | Redaelli, Veronica | Caroppo, Paola | Montalbetti, Lorenza | Giaccone, Giorgio | Osculati, Antonio

Article Type: Short Communication

Abstract: Nasu-Hakola disease is a rare autosomal recessive disorder associated to mutations in TREM2 and DAP12 genes, neuropathologically characterized by leukoencephalopathy with axonal spheroids. We report the neuropathologic findings of a 51-year-old female with a homozygous mutation (Q33X) of TREM2 gene. Beside severe cerebral atrophy and hallmarks of Nasu-Hakola disease, significant Alzheimer’s disease lesions were present. Neurofibrillary changes showed an atypical topographic distribution being severe at spots in the neocortex while sparing the mesial temporal structures. Our finding suggests that TREM2 genetic defects may favor Alzheimer’s disease pathology with neurofibrillary changes not following the hierarchical staging of …cortical involvement identified by Braak. Show more

Keywords: Alzheimer’s disease, braak staging, mutation, neurofibrillary pathology, TREM2 gene

DOI: 10.3233/JAD-201085

Citation: Journal of Alzheimer's Disease, vol. 79, no. 1, pp. 25-30, 2021

Authors: Radhakrishnan, Nila S. | Mufti, Mariam | Ortiz, Daniel | Maye, Suzanne T. | Melara, Jennifer | Lim, Duke | Rosenberg, Eric I. | Price, Catherine C.

Article Type: Short Communication

Abstract: Patients admitted with COVID-19 can develop delirium due to predisposing factors, isolation, and the illness itself. Standard delirium prevention methods focus on interaction and stimulation. It can be challenging to deliver these methods of care in COVID settings where it is necessary to increase patient isolation. This paper presents a typical clinical vignette of representative patients in a tertiary care hospital and how a medical team modified an evidence-based delirium prevention model to deliver high-quality care to COVID-19 patients. The implemented model focuses on four areas of delirium-prevention: Mobility, Sleep, Cognitive Stimulation, and Nutrition. Future studies will be needed to …track quantitative outcome measures. Show more

Keywords: Alzheimer’s disease, COVID-19, dementia, hospitalization, quality of health care, tertiary care centers

DOI: 10.3233/JAD-200696

Citation: Journal of Alzheimer's Disease, vol. 79, no. 1, pp. 31-36, 2021

Authors: Zingel, Rebecca | Bohlken, Jens | Riedel-Heller, Steffi | Barth, Sebastian | Kostev, Karel

Article Type: Research Article

Abstract: Background: No studies have been conducted to date on the association between low-density lipoprotein cholesterol (LDL-C), statin use classified into low, medium, and high statin dosages, and dementia in German general practices. Objective: The goal of this retrospective case-control study was to investigate the relationship between elevated LDL-C, statins, and dementia in elderly persons followed in general practices in Germany. Methods: This study included patients aged 65 or older with an initial dementia diagnosis between January 2015 and December 2019 and at least one documented LDL-C value within the year prior to the dementia diagnosis. These …patients were treated in one of 963 general practices which document LDL-C in Germany. Dementia cases were matched to non-dementia controls using propensity scores based on age, sex, and comorbidities. Logistic regression models were conducted to assess a possible association between accelerated LDL-C, statins, and dementia. Results: The study included 12,236 patients with dementia and 12,236 non-dementia controls. In total, 2,528 of the dementia patients were diagnosed with vascular dementia. The use of all dosages of statin use was negatively associated with all-cause dementia (OR: 0.80 for low dose, OR: 0.92 for medium dose, and OR: 0.85 for high dose) and with vascular dementia (OR: 0.61 for low dose, OR: 0.77 for medium dose, and OR: 0.74 for high dose). There was no clinically relevant association between elevated LDL-C and dementia. Conclusion: A negative association was found between all dosage use of statin therapy and all-cause dementia and vascular dementia in elderly patients in general practices in Germany. Show more

Keywords: Dementia, low-density lipoprotein cholesterol, statin, vascular dementia

DOI: 10.3233/JAD-201176

Citation: Journal of Alzheimer's Disease, vol. 79, no. 1, pp. 37-46, 2021

Authors: Yee, Evangeline | Ma, Da | Popuri, Karteek | Wang, Lei | Beg, Mirza Faisal | and for the Alzheimer’s Disease Neuroimaging Initiative | and the Australian Imaging Biomarkers and Lifestyle flagship study of ageing

Article Type: Research Article

Abstract: Background: In recent years, many convolutional neural networks (CNN) have been proposed for the classification of Alzheimer’s disease. Due to memory constraints, many of the proposed CNNs work at a 2D slice-level or 3D patch-level. Objective: Here, we propose a subject-level 3D CNN that can extract the neurodegenerative patterns of the whole brain MRI and converted into a probabilistic Dementia score. Methods: We propose an efficient and lightweight subject-level 3D CNN featuring dilated convolutions. We trained our network on the ADNI data on stable Dementia of the Alzheimer’s type (sDAT) from stable normal controls (sNC). To …comprehensively evaluate the generalizability of our proposed network, we performed four independent tests which includes testing on images from other ADNI individuals at various stages of the dementia, images acquired from other sites (AIBL), images acquired using different protocols (OASIS), and longitudinal images acquired over a short period of time (MIRIAD). Results: We achieved a 5-fold cross-validated balanced accuracy of 88%in differentiating sDAT from sNC, and an overall specificity of 79.5%and sensitivity 79.7%on the entire set of 7,902 independent test images. Conclusion: Independent testing is essential for estimating the generalization ability of the network to unseen data, but is often lacking in studies using CNN for DAT classification. This makes it difficult to compare the performances achieved using different architectures. Our comprehensive evaluation highlighting the competitive performance of our network and potential promise for generalization. Show more

Keywords: 3D CNN, dementia of Alzheimer’s type (DAT), magnetic resonance imaging

DOI: 10.3233/JAD-200830

Citation: Journal of Alzheimer's Disease, vol. 79, no. 1, pp. 47-58, 2021

Authors: Barker, Warren | Quinonez, Carlos | Greig, Maria T. | Behar, Raquel | Chirinos, Cesar | Rodriguez, Rosemarie A. | Rosselli, Monica | Rodriguez, Miriam J. | Cid, Rosie Curiel | Rundek, Tatjana | McFarland, Karen | Hanson, Kevin | Smith, Glenn | DeKosky, Steven | Vaillancourt, David | Adjouadi, Malek | Marsiske, Michael | Ertekin-Taner, Nilufer | Golde, Todd | Loewenstein, David A. | Duara, Ranjan

Article Type: Research Article

Abstract: Background: Plasma NfL (pNfL) levels are elevated in many neurological disorders. However, the utility of pNfL in a clinical setting has not been established. Objective: In a cohort of diverse older participants, we examined: 1) the association of pNfL to age, sex, Hispanic ethnicity, diagnosis, and structural and amyloid imaging biomarkers; and 2) its association to baseline and longitudinal cognitive and functional performance. Methods: 309 subjects were classified at baseline as cognitively normal (CN) or with cognitive impairment. Most subjects had structural MRI and amyloid PET scans. The most frequent etiological diagnosis was Alzheimer’s disease (AD), …but other neurological and neuropsychiatric disorders were also represented. We assessed the relationship of pNfL to cognitive and functional status, primary etiology, imaging biomarkers, and to cognitive and functional decline. Results: pNfL increased with age, degree of hippocampal atrophy, and amyloid load, and was higher in females among CN subjects, but was not associated with Hispanic ethnicity. Compared to CN subjects, pNfL was elevated among those with AD or FTLD, but not those with neuropsychiatric or other disorders. Hippocampal atrophy, amyloid positivity and higher pNfL levels each added unique variance in predicting greater functional impairment on the CDR-SB at baseline. Higher baseline pNfL levels also predicted greater cognitive and functional decline after accounting for hippocampal atrophy and memory scores at baseline. Conclusion: pNfL may have a complementary and supportive role to brain imaging and cognitive testing in a memory disorder evaluation, although its diagnostic sensitivity and specificity as a stand-alone measure is modest. In the absence of expensive neuroimaging tests, pNfL could be used for differentiating neurodegenerative disease from neuropsychiatric disorders. Show more

Keywords: Alzheimer’s disease, amyloid, diagnosis, hippocampal atrophy, magnetic resonance imaging, plasma neurofilament light, positron emission tomography

DOI: 10.3233/JAD-200901

Citation: Journal of Alzheimer's Disease, vol. 79, no. 1, pp. 59-70, 2021

Authors: Tran, Linh | Jung, Jeah | Carlin, Caroline | Lee, Sunmin | Zhao, Chen | Feldman, Roger

Article Type: Research Article

Abstract: Background: Many patients with Alzheimer’s disease and related dementia (ADRD) have chronic hepatitis C due to the high prevalence of both conditions among elderly populations. Direct-acting antivirals (DAAs) are effective in treating hepatitis C virus (HCV). However, the complexity of ADRD care may affect DAA use and outcomes among patients with HCV and ADRD. Little information exists on uptake of DAAs, factors associated with DAA use, and health benefits of DAAs among patients with HCV and ADRD. Objective: To examine use and survival benefits of DAAs in Medicare patients with HCV and ADRD. Methods: The study …included Medicare patients with HCV between 2014 and 2017. We estimated Cox proportional hazards regressions to examine the association between having ADRD and DAA use, and the relation between DAA use and survival among patients with HCV and ADRD. Results: The adjusted hazard of initiating a DAA was 50% lower in patients with ADRD than those without ADRD (adjusted HR = 0.50, 95% CI: 0.46–0.54). The hazard of DAA use among ADRD patients with behavioral disturbances was 68% lower than non-ADRD patients (adjusted HR = 0.32, 95% CI: 0.28–0.37). DAA treatment was associated with a significant reduction in mortality among ADRD patients (adjusted HR = 0.52, 95% CI: 0.44–0.61). Conclusion: The rate of DAA treatment in patients with HCV and ADRD was low, particularly among those with behavioral disturbance. The survival benefits of DAA treatment for patients with ADRD were substantial. Show more

Keywords: Alzheimer’s disease, comorbidity, dementia, direct-acting antivirals, hepatitis C

DOI: 10.3233/JAD-200949

Citation: Journal of Alzheimer's Disease, vol. 79, no. 1, pp. 71-83, 2021

Authors: Rodríguez-Salgado, Ana M. | Llibre-Guerra, Jorge J. | Tsoy, Elena | Peñalver-Guia, Ana Ibis | Bringas, Giosmany | Erlhoff, Sabrina J. | Kramer, Joel H. | Allen, Isabel Elaine | Valcour, Victor | Miller, Bruce L. | Llibre-Rodríguez, Juan J. | Possin, Katherine L.

Article Type: Research Article

Abstract: Background: Rapid technological advances offer a possibility to develop cost-effective digital cognitive assessment tools. However, it is unclear whether these measures are suitable for application in populations from Low and middle-income countries (LMIC). Objective: To examine the accuracy and validity of the Brain Health Assessment (BHA) in detecting cognitive impairment in a Cuban population. Methods: In this cross-sectional study, 146 participants (cognitively healthy = 53, mild cognitive impairment (MCI) = 46, dementia = 47) were recruited at primary care and tertiary clinics. The main outcomes included: accuracy of the BHA and the Montreal Cognitive Assessment (MoCA) in discriminating between controls and cognitively …impaired groups (MCI and dementia) and correlations between the BHA subtests of memory, executive functions, and visuospatial skills and criterion-standard paper-and-pencil tests in the same domains. Results: The BHA had an AUC of 0.95 (95% CI: 0.91–0.98) in discriminating between controls and cognitively impaired groups (MCI and dementia, combined) with 0.91 sensitivity at 0.85 specificity. In discriminating between control and MCI groups only, the BHA tests had an AUC of 0.94 (95% CI: 0.90–0.99) with 0.71 sensitivity at 0.85 specificity. Performance was superior to the MoCA across all diagnostic groups. Concurrent and discriminant validity analyses showed moderate to strong correlations between the BHA tests and standard paper-and-pencil measures in the same domain and weak correlations with standard measures in unrelated domains. Conclusion: The BHA has excellent performance characteristics in detecting cognitive impairment including dementia and MCI in a Hispanic population in Cuba and outperformed the MoCA. These results support potential application of digital cognitive assessment for older adults in LMIC. Show more

Keywords: Mild cognitive impairment, primary care, tablet-based cognitive screening

DOI: 10.3233/JAD-200985

Citation: Journal of Alzheimer's Disease, vol. 79, no. 1, pp. 85-94, 2021