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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: 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
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