Journal of Alzheimer's Disease - Volume 85, issue 1

Authors: Mandal, Pravat K. | Perry, George

Article Type: Editorial

DOI: 10.3233/JAD-215354

Citation: Journal of Alzheimer's Disease, vol. 85, no. 1, pp. 1-5, 2022

Authors: Fu, Xin | Liu, Qiantong | Sun, Xiaowei | Chang, Hui | Liu, Ying | Han, Jiatong

Article Type: Review Article

Abstract: Alzheimer’s disease (AD) is a common progressive neurodegenerative disease. In recent years, the research on the treatment of AD with Chinese medicine is increasing and the results are optimistic, which may provide some new options for the treatment of AD. Existing animal and clinical studies have found that Danggui Shaoyao San (DSS), which has been used in gynecological diseases, is effective in the treatment of AD. As the main component of DSS, macromolecular polysaccharide plays an indispensable role in the treatment of AD. In addition to anti-inflammatory, anti-neuronal injury, and immune regulation, polysaccharides extracted from Danggui Shaoyao San (p-DSS) also …have good activities in hypoglycemia, and participate in the physiological regulation of ubiquitination, iron metabolism, intestinal flora, estrogen, and autophagy. Given that there is little systematic analysis of p-DSS, this paper reviews the possible mechanism of p-DSS in the treatment of AD, so as to provide reference for further research. Show more

Keywords: Alzheimer’s disease, estrogens, hypoglycemic, intestinal flora, iron metabolism, polysaccharides of Danggui-Shaoyao-San

DOI: 10.3233/JAD-210656

Citation: Journal of Alzheimer's Disease, vol. 85, no. 1, pp. 7-19, 2022

Authors: Ruiz-Adame, Manuel

Article Type: Research Article

Abstract: Background: The World Health Organization has estimated that worldwide around 50 million people have dementia. The World Alzheimer Report estimated that between 2 and 10% of all cases of dementia begin before the age of 65. Early and young onset dementias (EYOD) provoke more working, social, family, and economic consequences than late onset dementias. All general studies about costs of dementias show that most of them are indirect or social costs. Despite that, very few studies have been performed in EYOD. Objective: To do a systematic review of literature about indirect or social costs in EYOD to know …the state of knowledge and to discover gaps that should be filled. Methods: A systematic review was performed in the main database: Scopus, PsychInfo, Web of Science (Web of Science Core Collection, Medline and SciELO), and CINAHL. Additionally, we looked for reviews in Cochrane and in the International Prospective Register Of Systematic Reviews (PROSPERO). Results: Most of the studies are about costs of dementias in general, but they do no differentiate costs for the case of EYOD. Many studies highlight the increased costs for EYOD but very little included evidence of that. 135 papers were selected. Finally, only two were studies providing data. EYOD reduce the odds to get or maintain a job. Most of the care is provided by informal caregivers. The costs in EYOD are 39.26% higher among EYOD than in late onset. Conclusion: There is a lack of studies about social and indirect costs in EYOD. More evidence is needed. Show more

Keywords: Early onset dementias, indirect cost, social costs, young onset dementias

DOI: 10.3233/JAD-215204

Citation: Journal of Alzheimer's Disease, vol. 85, no. 1, pp. 21-29, 2022

Authors: Pavlik, Valory N. | Burnham, Samantha C. | Kass, Joseph S. | Helmer, Catherine | Palmqvist, Sebastian | Vassilaki, Maria | Dartigues, Jean-François | Hansson, Oskar | Masters, Colin L. | Pérès, Karine | Petersen, Ronald C. | Stomrud, Erik | Butler, Lesley | Coloma, Preciosa M. | Teitsma, Xavier M. | Doody, Rachelle | Sano, Mary | for the CONCORD-AD investigators

Article Type: Review Article

Abstract: Longitudinal observational cohort studies are being conducted worldwide to understand cognition, biomarkers, and the health of the aging population better. Cross-cohort comparisons and networks of registries in Alzheimer’s disease (AD) foster scientific exchange, generate insights, and contribute to the evolving clinical science in AD. A scientific working group was convened with invited investigators from established cohort studies in AD, in order to form a research collaboration network as a resource to address important research questions. The Connecting Cohorts to Diminish Alzheimer’s Disease (CONCORD-AD) collaboration network was created to bring together global resources and expertise, to generate insights and improve understanding …of the natural history of AD, to inform design of clinical trials in all disease stages, and to plan for optimal patient access to disease-modifying therapies once they become available. The network brings together expertise and data insights from 7 cohorts across Australia, Europe, and North America. Notably, the network includes populations recruited through memory clinics as well as population-based cohorts, representing observations from individuals across the AD spectrum. This report aims to introduce the CONCORD-AD network, providing an overview of the cohorts involved, reporting the common assessments used, and describing the key characteristics of the cohort populations. Cohort study designs and baseline population characteristics are compared, and available cognitive, functional, and neuropsychiatric symptom data, as well as the frequency of biomarker assessments, are summarized. Finally, the challenges and opportunities of cross-cohort studies in AD are discussed. Show more

Keywords: Alzheimer’s disease, biomarkers, cognitive function, cohort, CONCORD-AD network, dementia, observational study, population characteristics

DOI: 10.3233/JAD-210525

Citation: Journal of Alzheimer's Disease, vol. 85, no. 1, pp. 31-45, 2022

Authors: Shad, Kaneez Fatima | Soubra, Wissam | Cordato, Dennis John

Article Type: Research Article

Abstract: Brain stem neural tracts and nuclei may be disturbed prior to observable neuronal atrophy in AD. In this perspective, we discuss the notion of functional deficits presenting prior to structural abnormalities in Alzheimer’s disease (AD). Imaging of inferior colliculi using magnetic resonance spectroscopy (MRS) shows significant decrease in the neuronal markers, N acetyl aspartate/creatine ratio and increase in the glial marker myo-Inositol, in subjects with Mini-Mental State Examination scores greater than 24 and with no signs of atrophy in their MRI of the medial temporal lobe. Abnormalities in components of the auditory event-related potentials (ERPs) are described in cognitive impairment …including AD. We observed a significant decrease in amplitude and increase in latency during the first 10 ms of auditory evoked potentials measured on electroencephalography (EEG) indicating slow auditory response of the brainstem. EEG spectral power recorded at the cortex is also associated with neural activity at the level of the inferior colliculi. We postulate that a functional examination of auditory afferent pathways, using non-invasive techniques, such as MRS, brain stem auditory evoked potentials (BAEPs) and ERPs may improve diagnostic accuracy of AD. Functional changes precede structural changes and it is important to further understand the relationship between biochemical and electrophysiological measures such as MRS, BAEPs and EEG. Show more

Keywords: Alzheimer’s disease, brain stem auditory potentials, electroencephalography, magnetic resonance spectroscopy

DOI: 10.3233/JAD-215206

Citation: Journal of Alzheimer's Disease, vol. 85, no. 1, pp. 47-53, 2022

Authors: Franklin, Gustavo L. | Meira, Alex T. | Barbosa, Maira Tonidandel | Teive, Hélio A.G. | Caramelli, Paulo

Article Type: Short Communication

Abstract: The significant increment in life expectancy, associated to the existence of high-performing older adults, and the appropriate diagnosis of early dementias, lead to an uncommon scenario, of healthy parents accompanying their children with Alzheimer’s disease or another dementia to medical consultations. Here, we reported three peculiar clinical vignettes of patients diagnosed with a dementia, who were accompanied by healthy parents. This is a modern situation that tends to become more frequent, and must be properly discussed, since multidisciplinary care and specific training are necessary.

Keywords: Alzheimer’s disease, dementia, diagnosis, early-onset dementia, management

DOI: 10.3233/JAD-215234

Citation: Journal of Alzheimer's Disease, vol. 85, no. 1, pp. 55-58, 2022

Authors: Schwarz, Christopher G. | Knopman, David S. | Ramanan, Vijay K. | Lowe, Val J. | Wiste, Heather J. | Cogswell, Petrice M. | Utianski, Rene L. | Senjem, Matthew L. | Gunter, Jeffrey R. | Vemuri, Prashanthi | Petersen, Ronald C. | Jack Jr., Clifford R.

Article Type: Short Communication

Abstract: We present the case of a cognitively unimpaired 77-year-old man with elevated, asymmetric, and longitudinally increasing Flortaucipir tau PET despite normal (visually negative) amyloid PET. His atypical tau PET signal persisted and globally increased in a follow-up scan five years later. Across eight years of observations, temporoparietal atrophy was observed consistent with tau PET patterns, but he retained the cognitively unimpaired classification. Altogether, his atypical tau PET signal is not explained by any known risk factors or alternative pathologies, and other imaging findings were not remarkable. He remains enrolled for further observation.

Keywords: Alzheimer’s disease, AV-1451, case reports, Flortaucipir, PET imaging, tau proteins

DOI: 10.3233/JAD-215052

Citation: Journal of Alzheimer's Disease, vol. 85, no. 1, pp. 59-64, 2022

Authors: Chen, Ke-Liang | Li, Pei-Xi | Sun, Yi-Min | Chen, Shu-Fen | Zuo, Chuan-Tao | Wang, Jian | Dong, Qiang | Cui, Mei | Yu, Jin-Tai

Article Type: Short Communication

Abstract: Mutations in Presenilin-1 (PSEN1 ) have been found to be associated with very early onset Alzheimer’s disease (VEOAD). Here, we reported two patients with VEOAD caused by de novo PSEN1 mutations. A 33-year-old man with a de novo p.F177S mutation in PSEN1 presented with progressive decline in memory and daily function. A 37-year-old woman with a de novo PSEN1 p.L381V mutation presented with onset memory impairment, developed cerebellar syndrome, rigidity, and spastic paraparesis. The Amyloid/Tau/Neurodegeneration (ATN) biomarker profiles of both patients were A + T + (N)+. Our finding increases the genetic knowledge of VEOAD and extends the ethnic …distribution of PSEN1 mutations. Show more

Keywords: Mutation, PSEN1, sporadic cases, very early onset Alzheimer’s disease

DOI: 10.3233/JAD-215167

Citation: Journal of Alzheimer's Disease, vol. 85, no. 1, pp. 65-71, 2022

Authors: Schmitter-Edgecombe, Maureen | Brown, Katelyn | Luna, Catherine | Chilton, Reanne | Sumida, Catherine A. | Holder, Lawrence | Cook, Diane

Article Type: Research Article

Abstract: Background: Compensatory aids can help mitigate the impact of progressive cognitive impairment on daily living. Objective: We evaluate whether the learning and sustained use of an Electronic Memory and Management Aid (EMMA) application can be augmented through a partnership with real-time, activity-aware transition-based prompting delivered by a smart home. Methods: Thirty-two adults who met criteria for amnestic mild cognitive impairment (aMCI) were randomized to learn to use the EMMA app on its own (N  = 17) or when partnered with smart home prompting (N  = 15). The four-week, five-session manualized EMMA training was conducted individually in participant homes …by trained clinicians. Monthly questionnaires were completed by phone with trained personnel blind to study hypotheses. EMMA data metrics were collected continuously for four months. For the partnered condition, activity-aware prompting was on during training and post-training months 1 and 3, and off during post-training month 2. Results: The analyzed aMCI sample included 15 EMMA-only and 14 partnered. Compared to the EMMA-only condition, by week four of training, participants in the partnered condition were engaging with EMMA more times daily and using more basic and advanced features. These advantages were maintained throughout the post-training phase with less loss of EMMA app use over time. There was little differential impact of the intervention on self-report primary (everyday functioning, quality of life) and secondary (coping, satisfaction with life) outcomes. Conclusion: Activity-aware prompting technology enhanced acquisition, habit formation and long-term use of a digital device by individuals with aMCI. (ClinicalTrials.gov NCT03453554). Show more

Keywords: Alzheimer’s disease, assistive technology, dementia, functional status, memory training, quality of life, real-time systems, reminder system, smart health aids, supervised machine learning

DOI: 10.3233/JAD-215022

Citation: Journal of Alzheimer's Disease, vol. 85, no. 1, pp. 73-90, 2022

Authors: Chum, Phoebe P. | Hakim, Md A. | Behringer, Erik J.

Article Type: Research Article

Abstract: Background: Emerging evidence demonstrates association of Alzheimer’s disease (AD) with impaired delivery of blood oxygen and nutrients to and throughout the brain. The cerebral circulation plays multiple roles underscoring optimal brain perfusion and cognition entailing moment-to-moment blood flow control, vascular permeability, and angiogenesis. With currently no effective treatment to prevent or delay the progression of AD, cerebrovascular microRNA (miRNA) markers corresponding to post-transcriptional regulation may distinguish phases of AD. Objective: We tested the hypothesis that cerebrovascular miRNA expression profiles indicate developmental stages of AD pathology. Methods: Total RNA was isolated from total brain vessel segments of …male and female 3xTg-AD mice [young, 1–2 mo; cognitive impairment (CI), 4–5 mo; extracellular amyloid-β plaques (Aβ), 6–8 mo; plaques+neurofibrillary tangles (AβT), 12–15 mo]. NanoString technology nCounter miRNA Expression panel for mouse was used to screen for 599 miRNAs. Results: Significant (p  < 0.05) downregulation of various miRNAs indicated transitions from young to CI (e.g., let-7g & miR-1944, males; miR-133a & miR-2140, females) and CI to Aβ (e.g., miR-99a, males) but not from Aβ to AβT. In addition, altered expression of select miRNAs from overall Pre-AD (young + CI) versus AD (Aβ+ AβT) were detected in both males (let-7d, let-7i, miR-23a, miR-34b-3p, miR-99a, miR-126-3p, miR-132, miR-150, miR-151-5p, miR-181a) and females (miR-150, miR-539). Altogether, at least 20 cerebrovascular miRNAs effectively delineate AD versus Pre-AD pathology. Conclusion: Using the 3xTg-AD mouse model, these data demonstrate that cerebrovascular miRNAs pertaining to endothelial function, vascular permeability, angiogenesis, inflammation, and Aβ/tau metabolism can track early development of AD. Show more

Keywords: 3xTg-AD, cerebrovasculature, non-coding RNAs, sex differences

DOI: 10.3233/JAD-215223

Citation: Journal of Alzheimer's Disease, vol. 85, no. 1, pp. 91-113, 2022