Journal of Alzheimer's Disease - Volume 99, issue 1

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. 99, no. 1, pp. 1-20, 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. 99, no. 1, pp. 21-40, 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. 99, no. 1, pp. 41-51, 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. 99, no. 1, pp. 53-84, 2024

Authors: Cressot, Coralie | Vrillon, Agathe | Lilamand, Matthieu | Francisque, Hélène | Méauzoone, Aurélie | Hourregue, Claire | Dumurgier, Julien | Marlinge, Emeline | Paquet, Claire | Cognat, Emmanuel

Article Type: Systematic Review

Abstract: Background: Psychosis, characterized by delusions and/or hallucinations, is frequently observed during the progression of Alzheimer’s disease (AD) and other neurodegenerative dementias (ND) (i.e., dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD)) and cause diagnostic and management difficulties. Objective: This review aims at presenting a concise and up-to-date overview of psychotic symptoms that occur in patients with ND with a comparative approach. Methods: A systematic review was conducted following the PRISMA guidelines. 98 original studies investigating psychosis phenotypes in neurodegenerative dementias were identified (40 cohort studies, 57 case reports). Results: Psychosis is a frequently …observed phenomenon during the course of ND, with reported prevalence ranging from 22.5% to 54.1% in AD, 55.9% to 73.9% in DLB, and 18% to 42% in FTD. Throughout all stages of these diseases, noticeable patterns emerge depending on their underlying causes. Misidentification delusions (16.6–78.3%) and visual hallucinations (50–69.6%) are frequently observed in DLB, while paranoid ideas and somatic preoccupations seem to be particularly common in AD and FTD, (respectively 9.1–60.3% and 3.10–41.5%). Limited data were found regarding psychosis in the early stages of these disorders. Conclusions: Literature data suggest that different ND are associated with noticeable variations in psychotic phenotypes, reflecting disease-specific tendencies. Further studies focusing on the early stages of these disorders are necessary to enhance our understanding of early psychotic manifestations associated with ND and help in differential diagnosis issues. Show more

Keywords: Alzheimer’s disease, delusion, dementia, dementia with Lewy bodies, frontotemporal degeneration, hallucinations, neurodegenerative disease, psychosis

DOI: 10.3233/JAD-231363

Citation: Journal of Alzheimer's Disease, vol. 99, no. 1, pp. 85-99, 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. 99, no. 1, pp. 101-103, 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. 99, no. 1, pp. 105-111, 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. 99, no. 1, pp. 113-115, 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. 99, no. 1, pp. 117-120, 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. 99, no. 1, pp. 121-143, 2024