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The Journal of Alzheimer’s Disease is an international multidisciplinary journal to facilitate progress in understanding the etiology, pathogenesis, epidemiology, genetics, behavior, treatment and psychology of Alzheimer’s disease.
The journal publishes research reports, reviews, short communications, book reviews, and letters-to-the-editor. The journal is dedicated to providing an open forum for original research that will expedite our fundamental understanding of Alzheimer’s disease.
Authors: Li, Yaoru | Yang, Ziying | Zhang, Yanxin | Liu, Fang | Xu, Jing | Meng, Yaping | Xing, Gebeili | Ruan, Xuqin | Sun, Jun | Zhang, Nan
Article Type: Research Article
Abstract: Background: Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD) account for the vast majority of neurodegenerative dementias. AD and FTLD have different clinical phenotypes with a genetic overlap between them and other dementias. Objective: This study aimed to identify the genetic spectrum of sporadic AD and FTLD in the Chinese population. Methods: A total of 74 sporadic AD and 29 sporadic FTLD participants were recruited. All participants underwent whole-exome sequencing (WES) and testing for a hexanucleotide expansion in C9orf72 was additionally performed for participants with negative WES results. Results: Four known pathogenic or …likely pathogenic variants, including PSEN1 (p.G206D), MAPT (p.R5H), LRRK2 (p.W1434*), and CFAP43 (p.C934*), were identified in AD participants, and 1 novel pathogenic variant of ANXA11 (p.D40G) and two known likely pathogenic variants of MAPT (p.D177V) and TARDBP (p.I383V) were identified in FTLD participants. Twenty-four variants of uncertain significance as well as rare variants in risk genes for dementia, such as ABCA7, SORL1, TRPM7, NOS3, MPO , and DCTN1 , were also found. Interestingly, several variants in participants with semantic variant primary progressive aphasia were detected. However, no participants with C9orf72 gene variants were found in the FTLD cohort. Conclusions: There was a high frequency of genetic variants in Chinese participants with sporadic AD and FTLD and a complex genetic overlap between these two types of dementia and other neurodegenerative diseases. Show more
Keywords: Alzheimer’s disease, frontotemporal lobar degeneration, variant, whole-exome sequencing
DOI: 10.3233/JAD-231361
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-17, 2024
Authors: Chu, Yili | Xie, Qihui | Meng, Rongrong | Leng, Bing | Cao, Zhenxiang
Article Type: Research Article
Abstract: Background: With the increasing popularity of the internet, a growing number of patients and their companions are actively seeking health-related information online. Objective: The aim of this study was to assess the quality and readability of online information about Alzheimer’s disease (AD) in China. Methods: A total of 263 qualified AD-related web pages from different businesses, governments, and hospitals were obtained. The quality of the web pages was assessed using the DISCERN tool, and the readability of the web pages was assessed using a readability measurement website suitable for the Chinese language. The differences in readability …and quality between different types of web pages were investigated, and the correlation between quality and readability was analyzed. Results: The mean overall DISCERN score was 40.93±7.5. The government group scored significantly higher than the commercial and hospital groups. The mean readability score was 12.74±1.27, and the commercial group had the lowest readability score. There was a positive correlation between DISCERN scores and readability scores. Conclusions: This study presents an evaluation of the quality and readability of health information pertaining to AD in China. The findings indicate that there is a need to enhance the quality and readability of web pages about AD in China. Recommendations for improvement are proposed in light of these findings. Show more
Keywords: Alzheimer’s disease, internet, quality evaluation, readability evaluation
DOI: 10.3233/JAD-231339
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-12, 2024
Authors: Gale, Seth A.
Article Type: Article Commentary
Abstract: As the biological, biomarker-driven framework of Alzheimer’s disease (AD) becomes formalized through revised, consensus clinical criteria, clinicians will confront more and more patients in the earliest, asymptomatic stages of disease. The language and diction used by practitioners to characterize these early patients, whether they are diagnosed with AD, and how their condition is documented in medical and legal records have important implications for both their care and their medical-legal status outside of the health system. Investigation is needed urgently to better understand clinicians’ views and practices regarding early AD, as we adapt to new disease definitions in this unprecedented era …of care. Show more
Keywords: Alzheimer’s disease, asymptomatic Alzheimer’s disease, biomarkers, data privacy, language, legal liability, medical law, nosology, preclinical Alzheimer’s disease
DOI: 10.3233/JAD-240195
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-4, 2024
Authors: Horvath, Alexandra | Quinlan, Patrick | Eckerström, Carl | Åberg, N. David | Wallin, Anders | Svensson, Johan
Article Type: Research Article
Abstract: Background: Insulin-like growth factor-I (IGF-I) regulates myelin, but little is known whether IGF-I associates with white matter functions in subjective and objective mild cognitive impairment (SCI/MCI) or Alzheimer’s disease (AD). Objective: To explore whether serum IGF-I is associated with magnetic resonance imaging – estimated brain white matter volumes or cognitive functions. Methods: In a prospective study of SCI/MCI (n = 106) and AD (n = 59), we evaluated the volumes of the total white matter, corpus callosum (CC), and white matter hyperintensities (WMHs) as well as Mini-Mental State Examination (MMSE), Trail Making Test A and B (TMT-A/B), and …Stroop tests I–III at baseline, and after 2 years. Results: IGF-I was comparable in SCI/MCI and AD (113 versus 118 ng/mL, p = 0.44). In SCI/MCI patients, the correlations between higher baseline IGF-I and greater baseline and 2-year volumes of the total white matter and total CC lost statistical significance after adjustment for intracranial volume and other covariates. However, after adjustment for covariates, higher baseline IGF-I correlated with better baseline scores of MMSE and Stroop test II in SCI/MCI and with better baseline results of TMT-B and Stroop test I in AD. IGF-I did not correlate with WMH volumes or changes in any of the variables. Conclusions: Both in SCI/MCI and AD, higher IGF-I was associated with better attention/executive functions at baseline after adjustment for covariates. Furthermore, the baseline associations between IGF-I and neuropsychological test results in AD may argue against significant IGF-I resistance in the AD brain. Show more
Keywords: Alzheimer’s disease, attention, corpus callosum, executive function, insulin-like growth factor-I, magnetic resonance imaging, mild cognitive impairment, speed, subjective mild cognitive impairment, white matter hyperintensities
DOI: 10.3233/JAD-231026
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-14, 2024
Authors: Huang, Zhen
Article Type: Review Article
Abstract: Mounting evidence indicates that a physiological function of amyloid-β (Aβ) is to mediate neural activity-dependent homeostatic and competitive synaptic plasticity in the brain. I have previously summarized the lines of evidence supporting this hypothesis and highlighted the similarities between Aβ and anti-microbial peptides in mediating cell/synapse competition. In cell competition, anti-microbial peptides deploy a multitude of mechanisms to ensure both self-protection and competitor elimination. Here I review recent studies showing that similar mechanisms are at play in Aβ-mediated synapse competition and perturbations in these mechanisms underpin Alzheimer’s disease (AD). Specifically, I discuss evidence that Aβ and ApoE, two crucial players …in AD, co-operate in the regulation of synapse competition. Glial ApoE promotes self-protection by increasing the production of trophic monomeric Aβ and inhibiting its assembly into toxic oligomers. Conversely, Aβ oligomers, once assembled, promote the elimination of competitor synapses via direct toxic activity and amplification of “eat-me” signals promoting the elimination of weak synapses. I further summarize evidence that neuronal ApoE may be part of a gene regulatory network that normally promotes competitive plasticity, explaining the selective vulnerability of ApoE expressing neurons in AD brains. Lastly, I discuss evidence that sleep may be key to Aβ-orchestrated plasticity, in which sleep is not only induced by Aβ but is also required for Aβ-mediated plasticity, underlining the link between sleep and AD. Together, these results strongly argue that AD is a disease of competitive synaptic plasticity gone awry, a novel perspective that may promote AD research. Show more
Keywords: Alzheimer’s disease, amyloid-β, ApoE, dendritic spine, DNA damage repair, homeostatic plasticity, mGluR5, phosphatidylserine, sleep, synaptic competition
DOI: 10.3233/JAD-240042
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-24, 2024
Authors: Espay, Alberto J. | Herrup, Karl | Imbimbo, Bruno P. | Kepp, Kasper P. | Daly, Timothy
Article Type: Article Commentary
Abstract: Three recent anti-amyloid-β antibody trials for Alzheimer’s disease reported similar effect sizes, used non-reactive saline as placebo, and showed large numbers of adverse events including imaging anomalies (ARIA) that correlate with cognitive changes. Conversely, all previous antibody trials were less reactive and pronounced ineffective. We argue that these observations point to unblinding bias, inflating apparent efficacy and thus altering the risk-benefit balance. Further, we highlight data demonstrating that beyond reducing amyloid, monoclonal antibodies increase monomeric amyloid-β42 in cerebrospinal fluid, which may explain potential benefits. We should recalibrate the efficacy of these antibodies and devote more resources into strategies beyond …removing amyloid. Show more
Keywords: Alzheimer’s disease, ARIA, amyloid-β, Aβ42, placebo, RCT
DOI: 10.3233/JAD-240171
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-5, 2024
Authors: Xu, Jing | Chen, Yao | Shi, Yi | Sun, Anna | Yang, Yuedi | Boustani, Malaz | Su, Jing | Zhang, Pengyue
Article Type: Research Article
Abstract: Background: Early detection of Alzheimer’s disease (AD) is a key component for the success of the recently approved lecanemab and aducanumab. Patients with neuroinflammation-related conditions are associated with a higher risk for developing AD. Objective: Investigate the incidence of AD among patients with neuroinflammation-related conditions including epilepsy, hemorrhage stroke, multiple sclerosis (MS), and traumatic brain injury (TBI). Methods: We used Optum’s de-identified Clinformatics Data Mart Database (CDM). We derived covariate-matched cohorts including patients with neuroinflammation-related conditions and controls without the corresponding condition. The matched cohorts were: 1) patients with epilepsy and controls (N = 67,825 matched pairs); …2) patients with hemorrhage stroke and controls (N = 81,510 matched pairs); 3) patients with MS and controls (N = 9,853 matched pairs); and 4) patients TBI and controls (N = 104,637 matched pairs). We used the Cox model to investigate the associations between neuroinflammation-related conditions and AD. Results: We identified that epilepsy, hemorrhage stroke, and TBI were associated with increased risks of AD in both males and females (hazard ratios [HRs]≥1.74, p < 0.001), as well as in gender- and race-conscious subpopulations (HRs≥1.64, p < 0.001). We identified that MS was associated with increased risks of AD in both males and females (HRs≥1.47, p ≤0.004), while gender- and race-conscious subgroup analysis shown mixed associations. Conclusions: Patients with epilepsy, hemorrhage stroke, MS, and/or TBI are associated with a higher risk of developing AD. More attention on cognitive status should be given to older patients with these conditions. Show more
Keywords: Alzheimer’s disease, epilepsy, hemorrhagic stroke, multiple sclerosis, neuroinflammatory disease, traumatic brain injury
DOI: 10.3233/JAD-231286
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-14, 2024
Authors: Tuena, Cosimo | Serino, Silvia | Goulene, Karine Marie | Pedroli, Elisa | Stramba-Badiale, Marco | Riva, Giuseppe
Article Type: Research Article
Abstract: Background: Individuals with mild cognitive impairment (MCI) syndrome often report navigation difficulties, accompanied by impairments in egocentric and allocentric spatial memory. However, studies have shown that both bodily (e.g., motor commands, proprioception, vestibular information) and visual-cognitive (e.g., maps, directional arrows, attentional markers) cues can support spatial memory in MCI. Objective: We aimed to assess navigation cues for innovative spatial training in aging. Methods: Fifteen MCI patients were recruited for this study. Their egocentric and allocentric memory recall performances were tested through a navigation task with five different virtual reality (VR) assistive encoding navigation procedures (bodily, vision …only, interactive allocentric map, reduced executive load, free navigation without cues). Bodily condition consisted of an immersive VR setup to engage self-motion cues, vision only condition consisted of passive navigation without interaction, in the interactive allocentric map condition patients could use a bird-view map, in the reduced executive load condition directional cues and attentional markers were employed, and during free navigation no aid was implemented. Results: Bodily condition improved spatial memory compared to vision only and free navigation without cues. In addition, the interactive allocentric map was superior to the free navigation without cues. Surprisingly, the reduced executive load was comparable to vison only condition. Moreover, a detrimental impact of free navigation was observed on allocentric memory across testing trials. Conclusions: These findings challenge the notion of an amodal representation of space in aging, suggesting that spatial maps can be influenced by the modality in which the environment was originally encoded. Show more
Keywords: Alzheimer’s disease, dementia, embodied cognition, mild cognitive impairment, rehabilitation, spatial cognition
DOI: 10.3233/JAD-240122
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-12, 2024
Authors: Ghani, Zartashia | Saha, Sanjib | Jarl, Johan | Andersson, Martin | Sanmartin Berglund, Johan | Anderberg, Peter
Article Type: Correction
DOI: 10.3233/JAD-249009
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-12, 2024
Authors: Jiang, Xiaqing | Bahorik, Amber L. | Graff-Radford, Neill R. | Yaffe, Kristine
Article Type: Research Article
Abstract: Background: Plasma amyloid-β (Aβ) has emerged as an important tool to detect risks of Alzheimer’s disease and related dementias, although research in diverse populations is lacking. Objective: We compared plasma Aβ 42/40 by race with dementia risk over 15 years among Black and White older adults. Methods: In a prospective cohort of 997 dementia-free participants (mean age 74±2.9 years, 55% women, 54% Black), incident dementia was identified based on hospital records, medication, and neurocognitive test over 15 years. Plasma Aβ 42/40 was measured at Year 2 and categorized into low, medium, and high tertile. …We used linear regression to estimate mean Aβ 42/40 by race and race-stratified Cox proportional hazards models to assess the association between Aβ 42/40 tertile and dementia risk. Results: Black participants had a lower age-adjusted mean Aβ 42/40 compared to White participants, primarily among APOE ɛ4 non-carriers (Black: 0.176, White: 0.185, p = 0.035). Among Black participants, lower Aβ 42/40 was associated with increased dementia risk: 33% in low (hazard ratios [HR] = 1.77, 95% confidence interval 1.09–2.88) and 27% in medium tertile (HR = 1.67, 1.01–2.78) compared with 18% in high Aβ 42/40 tertile; Increased risks were attenuated among White participants: 21% in low (HR = 1.43, 0.81–2.53) and 23% in medium tertile (HR = 1.27, 0.68–2.36) compared with 15% in high Aβ 42/40 tertile. The interaction by race was not statistically significant. Conclusions: Among community-dwelling, non-demented older adults, especially APOE ɛ4 non-carriers, Black individuals had lower plasma Aβ 42/40 and demonstrated a higher dementia risk with low Aβ 42/40 compared with White individuals. Show more
Keywords: Amyloid, Alzheimer’s disease, Alzheimer’s disease and related dementias, cohort studies, race
DOI: 10.3233/JAD-240007
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-11, 2024
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