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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: Noori, Ayush | Jayakumar, Rojashree | Moturi, Vaishnavi | Li, Zhaozhi | Liu, Rongxin | Serrano-Pozo, Alberto | Hyman, Bradley T. | Das, Sudeshna
Article Type: Research Article
Abstract: Background: Recent Alzheimer’s disease (AD) discoveries are increasingly based on studies from a variety of omics technologies on large cohorts. Currently, there is no easily accessible resource for neuroscientists to browse, query, and visualize these complex datasets in a harmonized manner. Objective: Create an online portal of public omics datasets for AD research. Methods: We developed Alzheimer DataLENS, a web-based portal, using the R Shiny platform to query and visualize publicly available transcriptomics and genetics studies of AD on human cohorts. To ensure consistent representation of AD findings, all datasets were processed through a uniform bioinformatics …pipeline. Results: Alzheimer DataLENS currently houses 2 single-nucleus RNA sequencing datasets, over 30 bulk RNA sequencing datasets from 19 brain regions and 3 cohorts, and 2 genome-wide association studies (GWAS). Available visualizations for single-nucleus data include bubble plots, heatmaps, and UMAP plots; for bulk expression data include box plots and heatmaps; for pathways include protein-protein interaction network plots; and for GWAS results include Manhattan plots. Alzheimer DataLENS also links to two other knowledge resources: the AD Progression Atlas and the Astrocyte Atlas. Conclusions: Alzheimer DataLENS is a valuable resource for investigators to quickly and systematically explore omics datasets and is freely accessible at https://alzdatalens.partners.org . Show more
Keywords: Alzheimer’s disease, database, genetics, multiomics, single-cell RNA-seq, transcriptomics
DOI: 10.3233/JAD-230884
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-11, 2024
Authors: Wang, Yongchun | Jiang, Richeng | Li, Mingxi | Wang, Zicheng | Yang, Yu | Sun, Li
Article Type: Research Article
Abstract: Background: Alzheimer’s disease (AD) is the most common type of dementia, causing a huge socioeconomic burden. In parallel with the widespread uptake of single-cell RNA sequencing (scRNA-seq) technology, there has been a rapid accumulation of data produced by researching AD at single-cell resolution, which is more conductive to explore the neuroimmune-related mechanism of AD. Objective: To explore the potential features of T cells in the peripheral blood and cerebrospinal fluid of AD patients. Methods: Two datasets, GSE181279 and GSE134578, were integrated from GEO database. Seurat, Monocle, CellChat, scRepertoire, and singleR packages were mainly …employed for data analysis. Results: Our analysis demonstrated that in peripheral blood, T cells were significantly expanded, and these expanded T cells were possessed effector function, such as CD8+ TEMRA , CD4+ TEMRA , and CD8+ TEM . Interestingly, CD8+ TEMRA and CD4+ TEMRA cells positioned adjacently after dimensions reduction and clustering. Notably, we identified that the expanded T cells were developed from Naïve T cells and TCM cells, and TEM cells was in the intermediate state of this developing process. Additionally, in cerebrospinal fluid of AD patients, the amplified T cells were mainly CD8+ TEMRA cells, and the number and strength of communication between CD4+ TEM , CD8+ TEM , and CD8+ TEMRA were decreased in AD patients. Conclusions: Our comprehensive analyses identified the cells in cerebrospinal fluid from AD patients are expanded TEMRA or TEM cells and the TEMRA cells communicating with other immune cells is weakened, which may be an important immune feature that leads to AD. Show more
Keywords: Alzheimer’s disease, analysis of immune characteristics, immune cell subpopulation, single-cell RNA sequencing, TCR repertoire
DOI: 10.3233/JAD-230784
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-16, 2023
Authors: Snytnikova, Olga | Telegina, Darya | Savina, Ekaterina | Tsentalovich, Yuri | Kolosova, Nataliya
Article Type: Research Article
Abstract: Background: Alzheimer’s disease (AD) is the most common type of dementia in the elderly. Incomplete knowledge about the pathogenesis of this disease determines the absence of medications for the treatment of AD today. Animal models can provide the necessary knowledge to understand the mechanisms of biochemical processes occurring in the body in health and disease. Objective: To identify the most promising metabolomic predictors and biomarkers reflecting metabolic disorders in the development of AD signs. Methods: High resolution 1 H NMR spectroscopy was used for quantitative metabolomic profiling of the hippocampus of OXYS rats, an animal model …of sporadic AD, which demonstrates key characteristics of this disease. Animals were examined during several key periods: 20 days group corresponds to the “preclinical” period preceding the development of AD signs, during their manifestation (3 months), and active progression (18 months). Wistar rats of the same age were used as control. Results: Ranges of variation and mean concentrations were established for 59 brain metabolites. The main metabolic patterns during aging, which are involved in energy metabolism pathways and metabolic shifts of neurotransmitters, have been established. Of particular note is the significant increase of scyllo-inositol and decrease of hypotaurine in the hippocampus of OXYS rats as compared to Wistars for all studied age groups. Conclusions: We suggest that the accumulation of scyllo-inositol and the reduction of hypotaurine in the brain, even at an early age, can be considered as predictors and potential biomarkers of the development of AD signs in OXYS rats and, probably, in humans. Show more
Keywords: Aging, Alzheimer’s disease, hippocampal metabolome, hypotaurine, nuclear magnetic resonance spectroscopy, OXYS rats, scyllo-inositol
DOI: 10.3233/JAD-230706
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-18, 2023
Authors: Jehu, Deborah A. | Pottayil, Faheem | Dong, Yanbin | Zhu, Haidong | Sams, Richard | Young, Lufei
Article Type: Research Article
Abstract: Background: Physical activity preserves cognitive function in people without dementia, but the relationship between physical activity and cognitive domains among people living with dementia is unclear. Objective: The objective of this study was to explore the association between physical activity and cognition domains among people living with dementia. Methods: Participants living with dementia in residential care facilities (complete case analysis: n = 24/42) completed a battery of cognitive tests (global cognition : Montreal Cognitive Assessment; executive function : Trail-Making Test, Digit Span Forward Test; perception and orientation : Benton Judgement of Line Orientation Test; …language : Boston Naming Test; learning and memory : Rey Auditory Verbal Learning Test; complex attention : Digit Symbol Substitution Test). Participants wore an actigraphy monitor on their non-dominant wrist over seven days. We conducted a linear regression for total physical activity (independent variable) with race (white/black), fall risk (Morse Fall Scale), and the number of comorbidities (Functional Comorbidities Index) as covariates, and cognitive tests as variables of interest. Results: Participants were primarily male (75%), white (87.5%), and 50%had unspecified dementia (Alzheimer’s disease: 33%). Greater physical activity was associated with poorer global cognition, better executive function, and better learning and memory (p s < 0.05). Physical activity was not related to visuospatial perception, language, or complex attention. Conclusions: Physical activity may preserve executive function and learning and memory among people living with dementia. Wandering is more common in later stages of dementia, which may explain greater physical activity observed with lower global cognition. Regularly assessing physical activity may be useful in screening and monitoring cognitive changes. Show more
Keywords: Accelerometry, actigraphy, Alzheimer’s disease, cognition, cognitive domains, dementia, physical activity
DOI: 10.3233/JAD-230594
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-11, 2024
Authors: Gordon, Scott | Lee, Jong Soo | Scott, Tammy M. | Bhupathiraju, Shilpa | Ordovas, Jose | Kelly, Rachel S. | Tucker, Katherine L. | Palacios, Natalia
Article Type: Research Article
Abstract: Background: Recent studies have identified plasma metabolites associated with cognitive decline and Alzheimer’s disease; however, little research on this topic has been conducted in Latinos, especially Puerto Ricans. Objective: This study aims to add to the growing body of metabolomics research in Latinos to better understand and improve the health of this population. Methods: We assessed the association between plasma metabolites and global cognition over 12 years of follow-up in 736 participants of the Boston Puerto Rican Health Study (BPRHS). Metabolites were measured with untargeted metabolomic profiling (Metabolon, Inc) at baseline. We used covariable adjusted linear …mixed models (LMM) with a metabolite * time interaction term to identify metabolites (of 621 measured) associated with ∼12 years cognitive trajectory. Results: We observed strong inverse associations between medium-chain fatty acids, caproic acid, and the dicarboxylic acids, azelaic and sebacic acid, and global cognition. N-formylphenylalanine, a tyrosine pathway metabolite, was associated with improvement in cognitive trajectory. Conclusions: The metabolites identified in this study are generally consistent with prior literature and highlight a role medium chain fatty acid and tyrosine metabolism in cognitive decline. Show more
Keywords: Alzheimer’s disease, cognitive decline, Latinos, metabolomics, Puerto rican
DOI: 10.3233/JAD-230053
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-9, 2024
Authors: Beckers, Elise | Riphagen, Joost M. | Van Egroo, Maxime | Bennett, David A. | Jacobs, Heidi I.L.
Article Type: Short Communication
Abstract: Tau accumulation in and neurodegeneration of locus coeruleus (LC) neurons is observed in Alzheimer’s disease (AD). We investigated whether tangle and neuronal density in the rostral and caudal LC is characterized by an asymmetric pattern in 77 autopsy cases of the Rush Memory and Aging Project. We found left-right equivalence for tangle density across individuals with and without AD pathology. However, neuronal density, particularly in the caudal-rostral axis of the LC, is asymmetric among individuals with AD pathology. Asymmetry in LC neuronal density may signal advanced disease progression and should be considered in AD neuroimaging studies of LC neurodegeneration.
Keywords: Alzheimer’s disease, asymmetry, autopsy, brainstem, locus coeruleus, neurons, tangles
DOI: 10.3233/JAD-231328
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-7, 2024
Authors: Bini, Jason
Article Type: Article Commentary
Abstract: Excess cortisol is associated with more severe cognitive decline, Alzheimer’s disease, and related dementia phenotypes. The intracellular enzyme 11β-HSD1 regenerates active cortisol from inactive cortisone. In this current issue, high regional brain occupancy of Xanamemtrademark, determined by [11 C]TARACT PET imaging of 11β-HSD1, in cognitively normal individuals and mild cognitive impartment/Alzheimer’s disease (AD) patients is presented. In the future, comprehensive kinetic modeling using arterial sampling for occupancy studies, and whole-body PET imaging of 11β-HSD1 enzyme levels, in combination with stable isotope studies of cortisol metabolism, can provide broad insight into enzyme levels and activity in AD and other relevant diseases.
Keywords: Alzheimer’s disease, cortisol, positron emission tomography, 11β-hydroxysteroid dehydrogenase type 1
DOI: 10.3233/JAD-231463
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-3, 2024
Authors: Dorado-Martínez, Claudia | Montiel-Flores, Enrique | Ordoñez-Librado, Jose Luis | Gutierrez-Valdez, Ana Luisa | Garcia-Caballero, Cesar Alfonso | Sanchez-Betancourt, Javier | Reynoso-Erazo, Leonardo | Tron-Alvarez, Rocio | Rodríguez-Lara, Vianey | Avila-Costa, Maria Rosa
Article Type: Research Article
Abstract: Background: Previous work from our group has shown that chronic exposure to Vanadium pentoxide (V2 O5 ) causes cytoskeletal alterations suggesting that V2 O5 can interact with cytoskeletal proteins through polymerization and tyrosine phosphatases inhibition, causing Alzheimer’s disease (AD)-like hippocampal cell death. Objective: This work aims to characterize an innovative AD experimental model through chronic V2 O5 inhalation, analyzing the spatial memory alterations and the presence of neurofibrillary tangles (NFTs), amyloid-β (Aβ) senile plaques, cerebral amyloid angiopathy, and dendritic spine loss in AD-related brain structures. Methods: 20 male Wistar rats were divided into control …(deionized water) and experimental (0.02 M V2 O5 1 h, 3/week for 6 months) groups (n = 10). The T-maze test was used to assess spatial memory once a month. After 6 months, histological alterations of the frontal and entorhinal cortices, CA1, subiculum, and amygdala were analyzed by performing Congo red, Bielschowsky, and Golgi impregnation. Results: Cognitive results in the T-maze showed memory impairment from the third month of V2 O5 inhalation. We also noted NFTs, Aβ plaque accumulation in the vascular endothelium and pyramidal neurons, dendritic spine, and neuronal loss in all the analyzed structures, CA1 being the most affected. Conclusions: This model characterizes neurodegenerative changes specific to AD. Our model is compatible with Braak AD stage IV, which represents a moment where it is feasible to propose therapies that have a positive impact on stopping neuronal damage. Show more
Keywords: Alzheimer’s disease experimental model, Aβ plaques, cell death, dendritic spine loss, inhaled exposure, neurofibrillary tangles, Vanadium pentoxide
DOI: 10.3233/JAD-230818
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-23, 2024
Authors: Das, Sudeshna
Article Type: Introduction
DOI: 10.3233/JAD-240272
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-3, 2024
Authors: Zhang, Zheting | Lim, Mervyn Jun Rui
Article Type: Review Article
Abstract: Post-stroke cognitive impairment and dementia (PSCID) is a complication that affects long-term functional outcomes after stroke. Studies on dementia after long-term follow-up in stroke have focused predominantly on ischemic stroke, which may be different from the development of dementia after spontaneous intracerebral hemorrhage (ICH). In this review, we summarize the existing data and hypotheses on the development of dementia after spontaneous ICH, review the management of post-ICH dementia, and suggest areas for future research. Dementia after spontaneous ICH has a cumulative incidence of up to 32.0–37.4% at 5 years post-ICH. Although the pathophysiology of post-ICH dementia has not been fully …understood, two main theoretical frameworks can be considered: 1) the triggering role of ICH (both primary and secondary brain injury) in precipitating cognitive decline and dementia; and 2) the contributory role of pre-existing brain pathology (including small vessel disease and neurodegenerative pathology), reduced cognitive reserve, and genetic factors predisposing to cognitive dysfunction. These pathophysiological pathways may have synergistic effects that converge on dysfunction of the neurovascular unit and disruptions in functional connectivity leading to dementia post-ICH. Management of post-ICH dementia may include screening and monitoring, cognitive therapy, and pharmacotherapy. Non-invasive brain stimulation is an emerging therapeutic modality under investigation for safety and efficacy. Our review highlights that there remains a paucity of data and standardized reporting on incident dementia after spontaneous ICH. Further research is imperative for determining the incidence, risk factors, and pathophysiology of post-ICH dementia, in order to identify new therapies for the treatment of this debilitating condition. Show more
Keywords: Alzheimer’s disease, cognitive dysfunction, dementia, hemorrhagic stroke, intracerebral hemorrhage, stroke
DOI: 10.3233/JAD-240111
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-11, 2024
Authors: Tahami Monfared, Amir Abbas | Khachatryan, Artak | Hummel, Noemi | Kopiec, Agnieszka | Martinez, Marta | Zhang, Raymond | Zhang, Quanwu
Article Type: Research Article
Abstract: Background: Alzheimer’s disease (AD) and mild cognitive impairment (MCI) have negative quality of life (QoL) and economic impacts on patients and their caregivers and may increase along the disease continuum from MCI to mild, moderate, and severe AD. Objective: To assess how patient and caregiver QoL, indirect and intangible costs are associated with MCI and AD severity. Methods: An on-line survey of physician-identified patient-caregiver dyads living in the United States was conducted from June–October 2022 and included questions to both patients and their caregivers. Dementia Quality of Life Proxy, the Care-related Quality of Life, Work Productivity …and Activity Impairment, and Dependence scale were incorporated into the survey. Regression analyses investigated the association between disease severity and QoL and cost outcomes with adjustment for baseline characteristics. Results: One-hundred patient-caregiver dyads were assessed with the survey (MCI, n = 27; mild AD, n = 27; moderate AD, n = 25; severe AD, n = 21). Decreased QoL was found with worsening severity in patients (p < 0.01) and in unpaid (informal) caregivers (n = 79; p = 0.02). Dependence increased with disease severity (p < 0.01). Advanced disease severity was associated with higher costs to employers (p = 0.04), but not with indirect costs to caregivers. Patient and unpaid caregiver intangible costs increased with disease severity (p < 0.01). A significant trend of higher summed costs (indirect costs to caregivers, costs to employers, intangible costs to patients and caregivers) in more severe AD was observed (p < 0.01). Conclusions: Patient QoL and functional independence and unpaid caregiver QoL decrease as AD severity increases. Intangible costs to patients and summed costs increase with disease severity and are highest in severe AD. Show more
Keywords: Alzheimer’s disease, cost of illness, employer health costs, global burden of disease, health expenditure, indirect expenditure, intangible cost, mild cognitive impairment, quality of life
DOI: 10.3233/JAD-231259
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-16, 2024
Authors: Chong, Terence W.H. | Macpherson, Helen
Article Type: Article Commentary
Abstract: Dementia is a global public health priority. Physical activity has myriad health benefits, including for reducing dementia risk. To increase physical activity, detailed understanding of influencing factors is needed. Socioeconomic deprivation affects many aspects of health and wellbeing. Qualitative research with older people experiencing socioeconomic deprivation is needed to explore barriers and enablers to engaging in physical activity, with the view to co-designing interventions for implementation trials. A whole of society approach is pivotal to improving effectiveness of physical activity interventions for older adults with cognitive impairment, and target support for people experiencing socioeconomic deprivation, to improve their health outcomes.
Keywords: Alzheimer’s disease, cognitive health, cognitive impairment, dementia, physical activity, socioeconomic disadvantage
DOI: 10.3233/JAD-240095
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-4, 2024
Authors: Khaled, Mohamad | Al-Jamal, Hadi | Tajer, Layla | El-Mir, Reem
Article Type: Review Article
Abstract: Alzheimer’s disease (AD) is a neurodegenerative condition that displays a high prevalence in Lebanon causing a local burden in healthcare and socio-economic sectors. Unfortunately, the lack of prevalence studies and clinical trials in Lebanon minimizes the improvement of AD patient health status. In this review, we include over 155 articles to cover the different aspects of AD ranging from mechanisms to possible treatment and management tools. We highlight some important modifiable and non-modifiable risk factors of the disease including genetics, age, cardiovascular diseases, smoking, etc. Finally, we propose a hypothetical genetic synergy model between APOE4 and TREM2 genes …which constitutes a potential early diagnostic tool that helps in reducing the risk of AD based on preventative measures decades before cognitive decline. The studies on AD in Lebanon and the Middle East are scarce. This review points out the importance of genetic mapping in the understanding of disease pathology which is crucial for the emergence of novel diagnostic tools. Hence, we establish a rigid basis for further research to identify the most influential genetic and environmental risk factors for the purpose of using more specific diagnostic tools and possibly adopting a local management protocol. Show more
Keywords: Alzheimer’s disease, APOE, genetic factors, Lebanon, TREM2
DOI: 10.3233/JAD-231432
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-20, 2024
Authors: Choi, Yu Yong | Lee, Jang Jae | te Nijenhuis, Jan | Choi, Kyu Yeong | Park, Jongseong | Ok, Jongmyoung | Choo, IL Han | Kim, Hoowon | Song, Min-Kyung | Choi, Seong-Min | Cho, Soo Hyun | Chae, Youngshik | Kim, Byeong C. | Lee, Kun Ho
Article Type: Research Article
Abstract: Background: We previously demonstrated the validity of a regression model that included ethnicity as a novel predictor for predicting normative brain volumes in old age. The model was optimized using brain volumes measured with a standard tool FreeSurfer. Objective: Here we further verified the prediction model using newly estimated brain volumes from Neuro I, a quantitative brain analysis system developed for Korean populations. Methods: Lobar and subcortical volumes were estimated from MRI images of 1,629 normal Korean and 786 Caucasian subjects (age range 59–89) and were predicted in linear regression from ethnicity, age, sex, intracranial volume, …magnetic field strength, and scanner manufacturers. Results: In the regression model predicting the new volumes, ethnicity was again a substantial predictor in most regions. Additionally, the model-based z-scores of regions were calculated for 428 AD patients and the matched controls, and then employed for diagnostic classification. When the AD classifier adopted the z-scores adjusted for ethnicity, the diagnostic accuracy has noticeably improved (AUC = 0.85, Δ AUC = + 0.04, D = 4.10, p < 0.001). Conclusions: Our results suggest that the prediction model remains robust across different measurement tool, and ethnicity significantly contributes to the establishment of norms for brain volumes and the development of a diagnostic system for neurodegenerative diseases. Show more
Keywords: Alzheimer’s disease, brain aging, ethnic difference, magnetic resonance imaging, norm
DOI: 10.3233/JAD-231182
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-18, 2024
Authors: Boujelbane, Mohamed Ali | Trabelsi, Khaled | Salem, Atef | Ammar, Achraf | Glenn, Jordan M. | Boukhris, Omar | AlRashid, Maha M. | Jahrami, Haitham | Chtourou, Hamdi
Article Type: Research Article
Abstract: Background: Alzheimer’s disease and mild cognitive impairment (MCI) progress silently, making early diagnosis challenging, especially in less educated populations. The visual paired comparison (VPC) task, utilizing eye-tracking movement (ETM) technology, offers a promising alternative for early detection of memory decline. Objective: This systematic review and meta-analysis evaluated the efficacy of the VPC task, utilizing ETM as a tool for assessing age-related cognitive changes. Methods: A comprehensive search across five databases and grey literature focused on healthy and impaired memory participants assessed through the ETM-based VPC task. The primary outcomes were novelty preference scores and eye movement …metrics. The risk of bias of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). Random-effects meta-analyses calculated Hedges’ g effect size. Sensitivity and specificity of the VPC were meta-analytically pooled. Results: The systematic review included 12 articles, involving 1,022 participants (aged 18 to 90 years, with education ranging from 6.5 to 20.0 years), with a low risk of bias and minimal applicability concerns across all items. Five studies contributed to the meta-analysis, revealing a significant effect favoring the VPC task for recognition memory detection (k = 9, g = –1.03). Pooled sensitivity and specificity analyses demonstrated VPC effectiveness as a recognition memory assessment tool (0.84 and 0.75, respectively). Conclusions: The VPC task, utilizing ETM, may serve as a biomarker for early memory decline detection. Its use as a digital eye-tracking tool presents a possible alternative to traditional tests, warranting further research for application in neurodegenerative disease diagnosis. Show more
Keywords: Alzheimer’s disease, cognition, dementia, eye movements, novelty preference score, sensitivity, specificity
DOI: 10.3233/JAD-240028
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-15, 2024
Authors: Yoo, Han Soo | Kim, Han-Kyeol | Lee, Jae-Hoon | Chun, Joong-Hyun | Lee, Hye Sun | Grothe, Michel J. | Teipel, Stefan | Cavedo, Enrica | Vergallo, Andrea | Hampel, Harald | Ryu, Young Hoon | Cho, Hanna | Lyoo, Chul Hyoung
Article Type: Research Article
Abstract: Background: Degeneration of cholinergic basal forebrain (BF) neurons characterizes Alzheimer’s disease (AD). However, what role the BF plays in the dynamics of AD pathophysiology has not been investigated precisely. Objective: To investigate the baseline and longitudinal roles of BF along with core neuropathologies in AD. Methods: In this retrospective cohort study, we enrolled 113 subjects (38 amyloid [Aβ]-negative cognitively unimpaired, 6 Aβ-positive cognitively unimpaired, 39 with prodromal AD, and 30 with AD dementia) who performed brain MRI for BF volume and cortical thickness, 18 F-florbetaben PET for Aβ, 18 F-flortaucipir PET for tau, and detailed cognitive …testing longitudinally. We investigated the baseline and longitudinal association of BF volume with Aβ and tau standardized uptake value ratio and cognition. Results: Cross-sectionally, lower BF volume was not independently associated with higher cortical Aβ, but it was associated with tau burden. Tau burden in the orbitofrontal, insular, lateral temporal, inferior temporo-occipital, and anterior cingulate cortices were associated with progressive BF atrophy. Lower BF volume was associated with faster Aβ accumulation, mainly in the prefrontal, anterior temporal, cingulate, and medial occipital cortices. BF volume was associated with progressive decline in language and memory functions regardless of baseline Aβ and tau burden. Conclusions: Tau deposition affected progressive BF atrophy, which in turn accelerated amyloid deposition, leading to a vicious cycle. Also, lower baseline BF volume independently predicted deterioration in cognitive function. Show more
Keywords: Alzheimer’s disease, amyloid-beta, basal forebrain, cognition, tau
DOI: 10.3233/JAD-230975
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-15, 2024
Authors: Etekochay, Maudlyn O. | Amaravadhi, Amoolya Rao | González, Gabriel Villarrubia | Atanasov, Atanas G. | Matin, Maima | Mofatteh, Mohammad | Steinbusch, Harry Wilhelm | Tesfaye, Tadele | Praticò, Domenico
Article Type: Review Article
Abstract: Alzheimer’s disease (AD) is a chronic neurodegenerative disorder with a global impact. The past few decades have witnessed significant strides in comprehending the underlying pathophysiological mechanisms and developing diagnostic methodologies for AD, such as neuroimaging approaches. Neuroimaging techniques, including positron emission tomography and magnetic resonance imaging, have revolutionized the field by providing valuable insights into the structural and functional alterations in the brains of individuals with AD. These imaging modalities enable the detection of early biomarkers such as amyloid-β plaques and tau protein tangles, facilitating early and precise diagnosis. Furthermore, the emerging technologies encompassing blood-based biomarkers and neurochemical profiling exhibit …promising results in the identification of specific molecular signatures for AD. The integration of machine learning algorithms and artificial intelligence has enhanced the predictive capacity of these diagnostic tools when analyzing complex datasets. In this review article, we will highlight not only some of the most used diagnostic imaging approaches in neurodegeneration research but focus much more on new tools like artificial intelligence, emphasizing their application in the realm of AD. These advancements hold immense potential for early detection and intervention, thereby paving the way for personalized therapeutic strategies and ultimately augmenting the quality of life for individuals affected by AD. Show more
Keywords: Alzheimer’s disease, artificial intelligence, biomarker, machine learning, neuroimaging
DOI: 10.3233/JAD-231135
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-20, 2024
Authors: Nakanishi, Miharu | Yamasaki, Syudo | Nakashima, Taeko | Miyamoto, Yuki | Cooper, Claudia | Richards, Marcus | Stanyon, Daniel | Sakai, Mai | Yoshii, Hatsumi | Nishida, Atsushi
Article Type: Research Article
Abstract: Background: The emotional impact of the coronavirus disease 2019 (COVID-19) pandemic on people with dementia has been quantified. However, little is known about the impact of change in home-care use owing to the pandemic. Objective: To determine the longitudinal association between dementia, change in home-care use, and depressive symptoms during the pandemic. Methods: We included data of 43,782 home-dwelling older adults from the English Longitudinal Study of Ageing (ELSA), Study of health, Ageing and Retirement in Europe (SHARE), and National Health and Aging Trends Study (NHATS). This study considered the latest main wave …survey prior to the pandemic as the baseline, and the COVID-19 survey as follow-up. In a series of coordinated analyses, multilevel binomial logistic regression model was used to examine the association between baseline dementia, change in home-care use at follow-up, and presence of depressive symptoms. Results: Dementia, using the ELSA, SHARE, and NHATS datasets, was identified in 2.9%, 2.3%, and 6.5% of older adults, and home-care use reduced in 1.7%, 2.8%, and 1.1% of individuals with dementia, respectively. Dementia was significantly associated with the increased risk of depressive symptoms in all three cohorts. However, the interaction between dementia and period (follow-up) was non-significant in SHARE and NHATS. Across all three cohorts, home-care use during the pandemic, regardless of change in amount, was significantly associated with increased depressive symptoms, compared to the non-use of home care. Conclusions: These results highlight the need for tailoring dementia care at home to promote independence and provide sustainable emotional support. Show more
Keywords: Alzheimer’s disease, cohort studies, dementia, depression, home care services, SARS-CoV 2, social interaction
DOI: 10.3233/JAD-240097
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-13, 2024
Authors: Cai, Jie | Xie, Danni | Kong, Fanjing | Zhai, Zhenwei | Zhu, Zhishan | Zhao, Yanru | Xu, Ying | Sun, Tao
Article Type: Systematic Review
Abstract: Background: Alzheimer’s disease (AD), the most common form of dementia, remains long-term and challenging to diagnose. Furthermore, there is currently no medication to completely cure AD patients. Rapamycin has been clinically demonstrated to postpone the aging process in mice and improve learning and memory abilities in animal models of AD. Therefore, rapamycin has the potential to be significant in the discovery and development of drugs for AD patients. Objective: The main objective of this systematic review and meta-analysis was to investigate the effects and mechanisms of rapamycin on animal models of AD by examining behavioral indicators …and pathological features. Methods: Six databases were searched and 4,277 articles were retrieved. In conclusion, 13 studies were included according to predefined criteria. Three authors independently judged the selected literature and methodological quality. Use of subgroup analyses to explore potential mechanistic effects of rapamycin interventions: animal models of AD, specific types of transgenic animal models, dosage, and periodicity of administration. Results: The results of Morris Water Maze (MWM) behavioral test showed that escape latency was shortened by 15.60 seconds with rapamycin therapy, indicating that learning ability was enhanced in AD mice; and the number of traversed platforms was increased by 1.53 times, indicating that the improved memory ability significantly corrected the memory deficits. CONCLUSIONS: Rapamycin therapy reduced age-related plaque deposition by decreasing AβPP production and down-regulating β-secretase and γ-secretase activities, furthermore increased amyloid-β clearance by promoting autophagy, as well as reduced tau hyperphosphorylation by up-regulating insulin-degrading enzyme levels. Show more
Keywords: KeywordsAlzheimer’s disease, animal models, cholesterol metabolism, meta-analysis, oxidative stress, rapamycin, systematic review
DOI: 10.3233/JAD-231249
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-32, 2024
Authors: Sighinolfi, Giovanni | Mitolo, Micaela | Pizzagalli, Fabrizio | Stanzani-Maserati, Michelangelo | Remondini, Daniel | Rochat, Magali Jane | Cantoni, Elena | Venturi, Greta | Vornetti, Gianfranco | Bartiromo, Fiorina | Capellari, Sabina | Liguori, Rocco | Tonon, Caterina | Testa, Claudia | Lodi, Raffaele
Article Type: Research Article
Abstract: Background: Being able to differentiate mild cognitive impairment (MCI) patients who would eventually convert (MCIc) to Alzheimer’s disease (AD) from those who would not (MCInc) is a key challenge for prognosis. Objective: This study aimed to investigate the ability of sulcal morphometry to predict MCI progression to AD, dedicating special attention to an accurate identification of sulci. Methods: Twenty-five AD patients, thirty-seven MCI and twenty-five healthy controls (HC) underwent a brain-MR protocol (1.5T scanner) including a high-resolution T1-weighted sequence. MCI patients underwent a neuropsychological assessment at baseline and were clinically re-evaluated after a mean of 2.3 …years. At follow-up, 12 MCI were classified as MCInc and 25 as MCIc. Sulcal morphometry was investigated using the BrainVISA framework. Consistency of sulci across subjects was ensured by visual inspection and manual correction of the automatic labelling in each subject. Sulcal surface, depth, length, and width were retrieved from 106 sulci. Features were compared across groups and their classification accuracy in predicting MCI conversion was tested. Potential relationships between sulcal features and cognitive scores were explored using Spearman’s correlation. Results: The width of sulci in the temporo-occipital region strongly differentiated between each pair of groups. Comparing MCIc and MCInc, the width of several sulci in the bilateral temporo-occipital and left frontal areas was significantly altered. Higher width of frontal sulci was associated with worse performances in short-term verbal memory and phonemic fluency. Conclusions: Sulcal morphometry emerged as a strong tool for differentiating HC, MCI, and AD, demonstrating its potential prognostic value for the MCI population. Show more
Keywords: Alzheimer’s disease, brain sulci, cortical thickness, MCI conversion, mild cognitive impairment, sulcalmorphometry
DOI: 10.3233/JAD-231192
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-14, 2024
Authors: Chandrasekaran, Ganesh | Xie, Sharon X.
Article Type: Research Article
Abstract: Background: Missing data is prevalent in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). It is common to deal with missingness by removing subjects with missing entries prior to statistical analysis; however, this can lead to significant efficiency loss and sometimes bias. It has yet to be demonstrated that the imputation approach to handling this issue can be valuable in some longitudinal regression settings. Objective: The purpose of this study is to demonstrate the importance of imputation and how imputation is correctly done in ADNI by analyzing longitudinal Alzheimer’s Disease Assessment Scale –Cognitive Subscale 13 (ADAS-Cog 13) scores and their …association with baseline patient characteristics. Methods: We studied 1,063 subjects in ADNI with mild cognitive impairment. Longitudinal ADAS-Cog 13 scores were modeled with a linear mixed-effects model with baseline clinical and demographic characteristics as predictors. The model estimates obtained without imputation were compared with those obtained after imputation with Multiple Imputation by Chained Equations (MICE). We justify application of MICE by investigating the missing data mechanism and model assumptions. We also assess robustness of the results to the choice of imputation method. Results: The fixed-effects estimates of the linear mixed-effects model after imputation with MICE yield valid, tighter confidence intervals, thus improving the efficiency of the analysis when compared to the analysis done without imputation. Conclusions: Our study demonstrates the importance of accounting for missing data in ADNI. When deciding to perform imputation, care should be taken in choosing the approach, as an invalid one can compromise the statistical analyses. Show more
Keywords: Alzheimer’s disease, biomarkers, imputation, longitudinal study, missing data
DOI: 10.3233/JAD-231047
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-15, 2024
Authors: Wu, Yaxuan | Tan, Ming | Gao, Yanling | Geng, Na | Zhong, Weibin | Sun, Hairong | Li, Zhenguang | Wu, Chenxi | Li, Xuemei | Zhang, Jinbiao
Article Type: Research Article
Abstract: Background: The complement system plays crucial roles in cognitive impairment and acute ischemic stroke (AIS). High levels of complement proteins in plasma astrocyte-derived exosomes (ADEs) were proven to be associated with Alzheimer’s disease. We aimed to investigate the relationship of complement proteins in serum ADEs with poststroke cognitive impairment in type 2 diabetes mellitus (T2DM) patients. Methods: This study analyzed 197 T2DM patients who suffered AIS. The Beijing version of the Montreal Cognitive Assessment (MoCA) was used to assess cognitive function. Complement proteins in serum ADEs were quantified using ELISA kits. Results: Mediation analyses showed that …C5b-9 and C3b in serum ADEs partially mediate the impact of obstructive sleep apnea (OSA), depression, small vessel disease (SVD), and infarct volume on cognitive function at the acute phase of AIS in T2DM patients. After adjusting for age, sex, time, and interaction between time and complement proteins in serum ADEs, the mixed linear regression showed that C3b and complement protein Factor B in serum ADEs were associated with MoCA scores at three-, six-, and twelve-months after AIS in T2DM patients. Conclusions: Our study suggested that the impact of OSA, depression, SVD, and infarct volume on cognitive impairment in the acute stage of AIS may partially mediate through the complement proteins in serum ADEs. Additionally, the complement proteins in serum ADEs at the acute phase of AIS associated with MoCA scores at three-, six-, twelve months after AIS in T2DM patients. REGISTRATION: URL: http://www.chictr.org.cn/,ChiCTR1900021544 Show more
Keywords: Keywords: Alzheimer’s disease, astrocyte-derived exosomes, complement proteins, post stroke cognitive impairment, type 2 diabetes mellitus
DOI: 10.3233/JAD-231235
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-15, 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: Cetinsoy, Ozde | Anyanwu, Ijeoma | Krishnanand, Harikrishnan | Natarajan, Gokulakrishnan | Ramachandran, Naveen | Thomas, Alan | Brookes, Keeley J.
Article Type: Research Article
Abstract: Background: The role of the innate immune system has long been associated with Alzheimer’s disease (AD). There is now accumulating evidence that the soluble Urokinase Plasminogen Activator Receptor pathway, and its genes, PLAU and PLAUR may be important in AD, and yet there have been few genetic association studies to explore this. Objective: This study utilizes the DNA bank of the Brains for Dementia Research cohort to investigate the genetic association of common polymorphisms across the PLAU and PLAUR genes with AD. Methods: TaqMan genotyping assays were used with standard procedures followed …by association analysis in PLINK. Results: No association was observed between the PLAU gene and AD; however, two SNPs located in the PLAUR gene were indicative of a trend towards association but did not surpass multiple testing significance thresholds. Conclusions: Further genotyping studies and exploration of the consequences of these SNPs on gene expression and alternative splicing are warranted to fully uncover the role this system may have in AD. Show more
Keywords: Alzheimer’s disease, association, BDR, innate immune system, PLAUR , PLAU , suPAR
DOI: 10.3233/JAD-231383
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-10, 2024
Authors: Kim, Minjae | Song, Yoo Sung | Han, Kyunghwa | Bae, Yun Jung | Han, Ji Won | Kim, Ki Woong
Article Type: Research Article
Abstract: Background: Impaired glymphatic flow on the Alzheimer’s disease (AD) spectrum may be evaluated using diffusion tensor image analysis along the perivascular space (DTI-ALPS). Objective: We aimed to validate impaired glymphatic flow and explore its association with gray matter volume, cognitive status, and cerebral amyloid deposition on the AD spectrum. Methods: 80 participants (mean age, 76.9±8.5 years; 57 women) with AD (n = 65) and cognitively normal (CN) (n = 15) who underwent 3T brain MRI including DTI and/or amyloid PET were included. After adjusting for age, sex, apolipoprotein E status, and burden of white matter hyperintensities, the ALPS-index …was compared according to the AD spectrum. The association between the ALPS-index and gray matter volume, cognitive status, and quantitative amyloid from PET was assessed. Results: The ALPS-index in the AD was significantly lower (mean, 1.476; 95% CI, 1.395–1.556) than in the CN (1.784;1.615–1.952; p = 0.026). Volumes of the entorhinal cortex, hippocampus, temporal pole, and primary motor cortex showed significant associations with the ALPS-index (all, p < 0.05). There was a positive correlation between the ALPS-index and MMSE score (partial r = 0.435; p < 0.001), but there was no significant correlation between the ALPS-index and amyloid SUVRs (all, p > 0.05). Conclusions: Decreased glymphatic flow measured by DTI-ALPS in AD may serve as a marker of neurodegeneration correlating with structural atrophy and cognitive decline. Show more
Keywords: Alzheimer’s disease, amyloid PET, diffusion tensor, g;ymphatic function, volumetry
DOI: 10.3233/JAD-231131
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-12, 2024
Authors: Duff, Kevin | Hammers, Dustin B. | Koppelmans, Vincent | King, Jace B. | Hoffman, John M.
Article Type: Research Article
Abstract: Background: Practice effects on cognitive testing in mild cognitive impairment (MCI) and Alzheimer’s disease (AD) remain understudied, especially with how they compare to biomarkers of AD. Objective: The current study sought to add to this growing literature. Methods: Cognitively intact older adults (n = 68), those with amnestic MCI (n = 52), and those with mild AD (n = 45) completed a brief battery of cognitive tests at baseline and again after one week, and they also completed a baseline amyloid PET scan, a baseline MRI, and a baseline blood draw to obtain APOE ɛ4 …status. Results: The intact participants showed significantly larger baseline cognitive scores and practice effects than the other two groups on overall composite measures. Those with MCI showed significantly larger baseline scores and practice effects than AD participants on the composite. For amyloid deposition, the intact participants had significantly less tracer uptake, whereas MCI and AD participants were comparable. For total hippocampal volumes, all three groups were significantly different in the expected direction (intact > MCI > AD). For APOE ɛ4, the intact had significantly fewer copies of ɛ4 than MCI and AD. The effect sizes of the baseline cognitive scores and practice effects were comparable, and they were significantly larger than effect sizes of biomarkers in 7 of the 9 comparisons. Conclusion: Baseline cognition and short-term practice effects appear to be sensitive markers in late life cognitive disorders, as they separated groups better than commonly-used biomarkers in AD. Further development of baseline cognition and short-term practice effects as tools for clinical diagnosis, prognostic indication, and enrichment of clinical trials seems warranted. Show more
Keywords: Alzheimer’s disease, amyloid, biomarkers, brain imaging, effect sizes, mild cognitive impairment, neuropsychological testing, practice effects
DOI: 10.3233/JAD-231392
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-12, 2024
Authors: Peng, Lang | Xiang, Qingwei | Zhou, Yong | Yin, Renyi
Article Type: Research Article
Abstract: Background: The joint associations of handgrip strength (HGS) weakness and asymmetry with cognitive decline remain understudied in older adults. Objective: To investigate the associations between HGS weakness, asymmetry, and lower cognitive function in a nationally representative sample of older Americans. Methods: This cross-sectional study utilized data from the National Health and Nutrition Examination Survey 2011–2014. Weakness was defined as HGS <26 kg for men and <16 kg for women. Asymmetry was determined by calculating the ratio of dominant to non-dominant HGS. Participants with an HGS ratio <0.90 or >1.10 were classified as having any HGS …asymmetry. Those with an HGS ratio >1.10 exhibited dominant HGS asymmetry, while those with an HGS ratio <0.90 displayed nondominant HGS asymmetry, respectively. Lower cognitive functioning was defined as global cognitive composite scores more than 1 standard deviation below the mean. Covariate-adjusted logistic regression models were used to analyze the associations between HGS asymmetry/weakness and lower cognitive functioning. Results: Compared to individuals with non-weak and symmetric HGS, those with any HGS asymmetry alone and weakness alone had 1.017 (95% confidence interval [CI]: 0.707–1.463) and 1.391 (95% CI: 0.542–3.571) greater odds for cognitive decline, while co-occurrence of both HGS asymmetry and weakness was associated with 3.724 (95% CI: 1.711–8.107) greater odds for lower cognitive function after controlling for confounders. Cnclusions: Individuals exhibiting both diminished and asymmetrical HGS demonstrated an elevated susceptibility to cognitive impairment, thereby implying that the inclusion of HGS asymmetry assessment in conjunction with weakness evaluation may enhance the accuracy of prognosticating cognitive decline. Show more
Keywords: Alzheimer’s disease, cognitive dysfunction, cross-sectional study, geriatrics, handgrip strength
DOI: 10.3233/JAD-231375
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-10, 2024
Authors: Butler, Tracy | Wang, Xiuyuan | Chiang, Gloria | Xi, Ke | Niogi, Sumit | Glodzik, Lidia | Li, Yi | Razlighi, Qolamreza Ray | Zhou, Liangdong | Hojjati, Seyed Hani | Ozsahin, Ilker | Mao, Xiangling | Maloney, Thomas | Tanzi, Emily | Rahmouni, Nesrine | Tissot, Cécile | Lussier, Firoza | Shah, Sudhin | Shungu, Dikoma | Gupta, Ajay | De Leon, Mony | Mozley, P. David | Pascoal, Tharick | Rosa-Neto, Pedro
Article Type: Research Article
Abstract: Background: Alzheimer’s disease (AD) pathology is considered to begin in the brainstem, and cerebral microglia are known to play a critical role in AD pathogenesis, yet little is known about brainstem microglia in AD. Translocator protein (TSPO) PET, sensitive to activated microglia, shows high signal in dorsal brainstem in humans, but the precise location and clinical correlates of this signal are unknown. Objective: To define age and AD associations of brainstem TSPO PET signal in humans. Methods: We applied new probabilistic maps of brainstem nuclei to quantify PET-measured TSPO expression over the whole brain including brainstem …in 71 subjects (43 controls scanned using 11 C-PK11195; 20 controls and 8 AD subjects scanned using 11 C-PBR28). We focused on inferior colliculi (IC) because of visually-obvious high signal in this region, and potential relevance to auditory dysfunction in AD. We also assessed bilateral cortex. Results: TSPO expression was normally high in IC and other brainstem regions. IC TSPO was decreased with aging (p = 0.001) and in AD subjects versus controls (p = 0.004) In cortex, TSPO expression was increased with aging (p = 0.030) and AD (p = 0.033). Conclusions: Decreased IC TSPO expression with aging and AD—an opposite pattern than in cortex—highlights underappreciated regional heterogeneity in microglia phenotype, and implicates IC in a biological explanation for strong links between hearing loss and AD. Unlike in cerebrum, where TSPO expression is considered pathological, activated microglia in IC and other brainstem nuclei may play a beneficial, homeostatic role. Additional study of brainstem microglia in aging and AD is needed. Show more
Keywords: Alzheimer’s disease, inferior colliculus, inflammation, neuroinflammation, reticular formation, TSPO PET
DOI: 10.3233/JAD-231312
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-13, 2024
Authors: Kim, Donghyun | Jamrasi, Parivash | Li, Xinxing | Ahn, Soyoung | Sung, Yunho | Ahn, Seohyun | Kang, Yuseon | Song, Wook
Article Type: Research Article
Abstract: Background: Alzheimer-associated neuronal thread protein (AD7c-NTP) has been demonstrated to have high diagnostic accuracy in differentiating Alzheimer’s disease (AD) patients from healthy individuals. However, it is yet unclear whether exercise can lower the level of AD7c-NTP in urine among active Korean elderly. Objective: To assess the effect of exercise on AD7c-ntp levels in urine and cognitive function among active Korean elderly. Methods: In total, 40 Korean elderly (≥65 years) were divided into Active Control group (CG, n = 10), Aerobic exercise group (AG, n = 18), and combined Resistance/Aerobic exercise group (RAG, n = 12). A total of 12 …weeks of exercise intervention was implemented. At week 0 and 12, cognitive performance (Korean Mini-Mental State Examination, Korean-Color Word Stroop test), grip strength, and body composition (muscle mass and body fat percentage) were measured. Also, a morning urine sample was obtained from each subject. The level of AD7c-NTP was measured using competitive enzyme-linked immunosorbent assay (ELISA). Results: After 12 weeks of exercise intervention, there was a significant difference of AD7c-NTP levels between RAG and CG (p = 0.026), AG and CG (p = 0.032), respectively. Furthermore, the AD7c-NTP levels in urine showed negative correlation with K-MMSE scores (r = –0.390, p = 0.013) and grip strength (r = –0.376, p = 0.017), among all participants after exercise intervention. Conclusions: This is the first study to investigate urine biomarker through exercise intervention. In future stuides, participants who have low cognitive function and low activity levels need to be recruited to observe more significant ‘Exercise’ effect. Show more
Keywords: AD7C-NTP, Alzheimer’s disease, cognitive function, exercise, urine biomarker
DOI: 10.3233/JAD-230946
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-18, 2024
Authors: Thomas, Kelsey R. | Clark, Alexandra L. | Weigand, Alexandra J. | Edwards, Lauren | Durazo, Alin Alshaheri | Membreno, Rachel | Luu, Britney | Rantins, Peter | Ly, Monica T. | Rotblatt, Lindsay J. | Bangen, Katherine J. | Jak, Amy J.
Article Type: Research Article
Abstract: Background: Within older Veterans, multiple factors may contribute to cognitive difficulties. Beyond Alzheimer’s disease (AD), psychiatric (e.g., PTSD) and health comorbidities (e.g., TBI) may also impact cognition. Objective: This study aimed to derive subgroups based on objective cognition, subjective cognitive decline (SCD), and amyloid burden, and then compare subgroups on clinical characteristics, biomarkers, and longitudinal change in functioning and global cognition. Methods: Cluster analysis of neuropsychological measures, SCD, and amyloid PET was conducted on 228 predominately male Vietnam-Era Veterans from the Department of Defense-Alzheimer’s Disease Neuroimaging Initiative. Cluster-derived subgroups were compared on baseline …characteristics as well as 1-year changes in everyday functioning and global cognition. Results: The cluster analysis identified 3 groups. Group 1 (n = 128) had average-to-above average cognition with low amyloid burden. Group 2 (n = 72) had the lowest memory and language, highest SCD, and average amyloid burden; they also had the most severe PTSD, pain, and worst sleep quality. Group 3 (n = 28) had the lowest attention/executive functioning, slightly low memory and language, elevated amyloid and the worst AD biomarkers, and the fastest rate of everyday functioning and cognitive decline. CONCLUSIONS: Psychiatric and health factors likely contributed to Group 2’s low memory and language performance. Group 3 was most consistent with biological AD, yet attention/executive function was the lowest score. The complexity of older Veterans’ co-morbid conditions may interact with AD pathology to show attention/executive dysfunction (rather than memory) as a prominent early symptom. These results could have important implications for the implementation of AD-modifying drugs in older Veterans. Show more
Keywords: Alzheimer’s disease, amyloid, cognition, phenotypes, PTSD, Veterans
DOI: 10.3233/JAD-240077
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-11, 2024
Authors: Marr, Calum | McDowell, Bethany | Holmes, Clive | Edwards, Christopher J. | Cardwell, Christopher | McHenry, Michelle | Meenagh, Gary | Teeling, Jessica L. | McGuinness, Bernadette
Article Type: Research Article
Abstract: Background: Evidence suggests that TNF inhibitors (TNFi) used to treat rheumatoid arthritis (RA) may protect against Alzheimer’s disease progression by reducing inflammation. Objective: To investigate whether RA patients with mild cognitive impairment (MCI) being treated with a TNFi show slower cognitive decline than those being treated with a conventional synthetic disease-modifying anti-rheumatic drug (csDMARD). Methods: 251 participants with RA and MCI taking either a csDMARD (N = 157) or a TNFi (N = 94) completed cognitive assessments at baseline and 6-month intervals for 18 months. It was hypothesized that those taking TNFis would show less decline on the …primary outcome of Free and Cued Selective Reminding Test with Immediate Recall (FCSRT-IR) and the secondary outcome of Montreal Cognitive Assessment (MoCA). Results: No significant changes in FCSRT-IR scores were observed in either treatment group. There was no significant difference in FCSRT-IR between treatment groups at 18 months after adjusting for baseline (mean difference = 0.5, 95% CI = –1.3, 2.3). There was also no difference in MoCA score (mean difference = 0.4, 95% CI = –0.4, 1.3). Conclusions: There was no cognitive decline in participants with MCI being treated with TNFis and csDMARDs, raising the possibility both classes of drug may be protective. Future studies should consider whether controlling inflammatory diseases using any approach is more important than a specific therapeutic intervention. Show more
Keywords: Alzheimer’s disease, inflammation, mild cognitive impairment, rheumatoid arthritis, tumor necrosis factor-alpha
DOI: 10.3233/JAD-231329
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-15, 2024
Authors: Morrow, Christopher B. | Pontone, Gregory M.
Article Type: Article Commentary
Abstract: The following commentary discusses a review by Cressot et al. entitled: ‘Psychosis in Neurodegenerative Dementias: A Systematic Comparative Review’. The authors describe the epidemiology and phenomenology of psychosis across neurodegenerative dementias. Dementia with Lewy bodies had the highest reported prevalence of psychosis at 74% followed by Alzheimer’s disease, 54% and frontotemporal degeneration, 42% . Detailed characterization of psychosis shows differences in the types of hallucinations and delusions by dementia type. These findings suggest that different types of dementia related pathology are associated with high rates of psychosis with more specific symptom profiles than previously appreciated. Understanding the differences and variety …of psychotic experiences across dementia types may have diagnostic and therapeutic implications for treating hallucinations and delusions in populations suffering from neurodegenerative diseases. Show more
Keywords: Alzheimer’s disease, delusions, dementia, dementia with Lewy bodies, frontotemporal dementia, hallucinations, neurodegeneration, psychosis
DOI: 10.3233/JAD-240328
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-3, 2024
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