Journal of Alzheimer's Disease Reports - Volume 8, issue 1

Authors: Krishna, Geethu | Thangaraju Sivakumar, Palanimuthu | Dahale, Ajit B. | Subramanian, Sarada

Article Type: Short Communication

Abstract: Blood tests are in need, in the clinical diagnosis of Alzheimer’s disease (AD) as minimally invasive and less expensive alternatives to cerebrospinal fluid and neuroimaging methods. On these lines, single molecule array (Simoa) analysis of amyloid-β (Aβ42 ), total tau (t-tau), phospho-tau (p-tau 181), and neurofilament L (NfL) in the plasma samples of AD subjects, healthy controls (HC), and non-AD subjects was conducted. Findings from this study suggest that a panel of multiple plasma biomarkers (NfL, Aβ42 , t-tau, and p-tau 181) combined with the clinical assessments could support differential diagnosis of AD and other dementias from healthy controls.

Keywords: Alzheimer’s disease, amyloid-β, neurofilament L, phospho tau 181, plasma biomarkers, total tau

DOI: 10.3233/ADR-230156

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 1-7, 2024

Authors: Li, Qin | Zhan, Jiehong | Feng, Yuxue | Liao, Zixuan | Li, Xiaofeng

Article Type: Research Article

Abstract: Background: The association of body mass index (BMI) with cognition and Alzheimer’s disease (AD) biomarkers of the elderly remains inconclusive. Objective: To investigate the relationship between BMI and cognition as well as AD biomarkers in the elderly with different cognitive status. Methods: Participants with cognitively normal (CN) were included as the CN group. Participants with mild cognitive impairment and mild dementia were included as the cognitive impairment (CI) group. The relationship between BMI and AD biomarkers (cerebrospinal fluid Aβ42 and p-tau181, hippocampal volume [HV]), global cognition (Mini-Mental State Examination [MMSE]), memory, and …executive function were explored. Results: In the CI group, BMI was associated with MMSE (β= 0.03, p  = 0.009), Aβ42 (β= 0.006, p  = 0.029), p-tau181/Aβ42 ratio (β= -0.001, p  = 0.011), and HV (β= 0.05, p  < 0.001). However in the CN group, BMI exhibited associations with p-tau181 (β= 0.012, p  = 0.014) and memory composite score (β= -0.04, p  = 0.038), but not with p-tau181/Aβ42 ratio and HV. Moreover, mediation analysis showed that in the CI group, the positive effect of BMI on HV and MMSE score was partially mediated by diastolic blood pressure. Conclusion: The association of BMI with cognition and AD biomarkers varies across different cognitive status. In particular, a lower BMI was associated with worse cognition, higher Aβ burden, and lower HV in individuals with CI. Clinical practice should strengthen the monitoring and management of BMI in patients with AD. Show more

Keywords: Alzheimer’s disease, body mass index, cognition, hippocampus

DOI: 10.3233/ADR-230163

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 9-24, 2024

Authors: Thomas, Jeremy L. | Nilaver, Benjamin I. | Lomniczi, Alejandro | Brown, Donald I. | Appleman, Maria-Luisa | Kohama, Steven G. | Urbanski, Henryk F.

Article Type: Short Communication

Abstract: Rhesus macaques develop amyloid-β (Aβ) plaques during old age, but it is unclear how extensively they express other pathological hallmarks of dementia. Here we used immunohistochemistry to examine expression of phosphorylated tau (pTau) protein and cytoplasmic inclusions of TAR DNA binding protein 43 kDa (TDP-43) within the amygdala of young and old males, and also in old surgically-menopausal females that were maintained on regular or obesogenic diets. Only one animal, a 23-year-old female, showed pTau expression and none showed TDP-43 inclusions. What genetic and/or environmental factors protect macaques from expressing more severe human neuro-pathologies remains an interesting unresolved question.

Keywords: Aging, amygdala, amyloid-β, pTau, rhesus macaque, TDP-43, western-style diet

DOI: 10.3233/ADR-230184

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 25-32, 2024

Authors: El Haj, Mohamad | Moustafa, Ahmed A. | Antoine, Pascal | Chapelet, Guillaume

Article Type: Research Article

Abstract: Background: Future thinking and prospective memory are two cognitive processes oriented toward the future and reliant on the ability to envision oneself in future scenarios. Objective: We explored the connection between future thinking and prospective memory in individuals with Alzheimer’s disease (AD). Methods: We invited both AD participants and control participants to engage in event-based prospective memory tasks (e.g., “please hand me this stopwatch when I inform you there are 10 minutes remaining”) and time-based prospective memory tasks (e.g., “close the book you are working on in five minutes”). Additionally, we asked participants …to engage in a future thinking task where they imagined upcoming events. Results: Analysis revealed that AD participants exhibited lower performance in both prospective memory tasks and future thinking compared to the control group. Importantly, we identified significant positive correlations between the performance on event- and time-based prospective memory tasks and future thinking abilities among AD participants. Conclusions: These findings underscore the connection between the decline in both prospective memory domains and the ability to envision future events in individuals with AD. Our results also shed light on the challenges AD individuals face when trying to project themselves into the future to mentally pre-experience upcoming events. Show more

Keywords: Alzheimer’s disease, event-based prospective memory, future thinking, prospective memory, time-based prospective memory

DOI: 10.3233/ADR-230144

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 33-42, 2024

Authors: Alavez-Rubio, Jessica Sarahi | Juarez-Cedillo, Teresa

Article Type: Review Article

Abstract: Dementia is a syndrome in which there is deterioration in memory, behavior, and the ability to perform everyday activities. Alzheimer’s disease and vascular dementia are the most common forms of dementia. There is evidence supporting the hypothesis that inflammatory and immune mechanisms are involved in dementia. Microglia, the resident macrophage tissues in the central nervous system, play a significant role in neuroinflammation and play an important role in amyloid-β clearance in the brain, and impaired microglial clearance of amyloid-β has also been shown to be involved in the pathogenesis of Alzheimer’s disease. However, there is also abundant evidence that microglia …have harmful actions in dementia. Once activated, they can mediate uptake at neuronal synapses. They can also exacerbate tau pathology and secrete deleterious inflammatory factors that can directly or indirectly damage neurons. Thus, depending on the stage of the disease, microglia can act both protectively and detrimentally. Therefore, it is still necessary to continue with studies to better understand the role of microglia in the pathology of dementia. Currently available drugs can only improve cognitive symptoms, have no impact on progression and are not curative, so identifying and studying new therapeutic approaches is important. Considering the role played by microglia in this pathology, it has been pointed out as a possible therapeutic approach. This manuscript aims to address the relationship between microglia and dementia and how this relationship could be used for therapeutic purposes. Show more

Keywords: Alzheimer’s disease, dementia, microglia, vascular dementia

DOI: 10.3233/ADR-230112

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 43-56, 2024

Authors: Keith, Cierra M. | Haut, Marc W. | D’Haese, Pierre-François | Mehta, Rashi I. | Vieira Ligo Teixeira, Camila | Coleman, Michelle M. | Miller, Mark | Ward, Melanie | Navia, R. Osvaldo | Marano, Gary | Wang, Xiaofei | McCuddy, William T. | Lindberg, Katharine | Wilhelmsen, Kirk C.

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD) and behavioral variant frontotemporal dementia (bvFTD) are typically associated with very different clinical and neuroanatomical presentations; however, there is increasing recognition of similarities. Objective: To examine memory and executive functions, as well as cortical thickness, and glucose metabolism in AD and bvFTD signature brain regions. Methods: We compared differences in a group of biomarker-defined participants with Alzheimer’s disease and a group of clinically diagnosed participants with bvFTD. These groups were also contrasted with healthy controls (HC). Results: As expected, memory functions were generally more impaired in AD, followed by bvFTD, …and both clinical groups performed more poorly than the HC group. Executive function measures were similar in AD compared to bvFTD for motor sequencing and go/no-go, but bvFTD had more difficulty with a set shifting task. Participants with AD showed thinner cortex and lower glucose metabolism in the angular gyrus compared to bvFTD. Participants with bvFTD had thinner cortex in the insula and temporal pole relative to AD and healthy controls, but otherwise the two clinical groups were similar for other frontal and temporal signature regions. Conclusions: Overall, the results of this study highlight more similarities than differences between AD and bvFTD in terms of cognitive functions, cortical thickness, and glucose metabolism. Further research is needed to better understand the mechanisms mediating this overlap and how these relationships evolve longitudinally. Show more

Keywords: Alzheimer’s disease, biomarkers, executive function, frontotemporal dementia, memory, MRI, PET

DOI: 10.3233/ADR-230049

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 57-73, 2024

Authors: Cai, Xiaoying | Wang, Yaqing | Li, Ying | Du, Zhanxin | Wang, Zhongxing

Article Type: Research Article

Abstract: Background: Observational studies have indicated the association of alteration of adipokines with Alzheimer’s disease (AD). However, it remains unclear whether the associations are causal. Objective: To determine the causal associations between adipokines and AD. Methods: A Mendelian randomization (MR) method was applied to investigate the causal relationships of adipokines, including adiponectin and resistin, with risk of AD. Genetic proxies from genome-wide association studies (GWAS) of adiponectin and resistin were selected as instrumental variables. GWAS summary statistics for AD were extracted as outcome. Results: In this study, we found evidence of the causal effects of …adiponectin on AD (OR: 0.850, 95% CI: 0.731-0.990, p  = 0.037). However, no relationship between resistin and AD (OR: 0.936, 95% CI: 0.851-1.029, p  = 0.171) was detected. In the reverse causation analysis, null associations of AD were found for adiponectin and resistin (all p  > 0.05). Conclusions: This study provides evidence of causality between adiponectin and risk of AD. However, no genetic susceptibility of resistin was discovered for AD. Show more

Keywords: Adiponectin, Alzheimer’s disease, association, mendelian randomization, resistin

DOI: 10.3233/ADR-230110

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 75-83, 2024

Authors: Garrido, Sandra | Markwell, Holly

Article Type: Research Article

Abstract: Background: Personalized music listening can be highly effective in supporting people experiencing changes in mood and behavior due to Alzheimer’s disease and other conditions causing dementia. However, a lack of staff education can be a barrier to effective use of music in residential aged care. Objective: This study investigates the usability, appeal and relevance of an online training course designed to help care staff develop personalized music programs for people living with dementia in their care. Methods: A mixed methods approach was taken in which 13 participants took part in a think-aloud session while using the …training. Qualitative data from the think-aloud session and interviews were triangulated with results of a survey evaluation of the training. Results: Themes relating to Engagement, Usability and Appeal, Pedagogical Design and Content, and Transfer, Impact and Barriers to Uptake were discussed. Results indicated that participants regarded the virtual environment and pedagogical design as of high quality, although some minor issues in navigability were identified. Participants also found the training to be highly relevant to their roles as caregivers and reported ways they would incorporate key concepts into care practices. However, ongoing barriers to implementation of such training were identified including systemic issues that contribute to a culture of focus on physical care. Conclusions: Consistency of navigation and clear instructions for interacting with content are important in training of time-poor care staff. Linking training to industry standards can provide important motivation for implementation of training, although systemic barriers can impede real-world change. Show more

Keywords: Aged care, Alzheimer’s disease, behavior support, dementia, music, personalized playlists, psychosocial

DOI: 10.3233/ADR-230082

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 85-94, 2024

Authors: Trigo, Arturo Nicolás | Muzzio, Marina | Figueroa, Marcelo Isidro | Alfaro-Gómez, Emma Laura | Bailliet, Graciela | Dopazo, Hernán Javier | Dipierri, José Edgardo

Article Type: Short Communication

Abstract: The pleiotropic nature of the apolipoprotein E (APOE ) gene is associated with complex diseases in different populations. We analyzed APOE polymorphisms in 76 individuals from Jujuy – Argentina using NGS technology. The observed genotypes align with the expected Hardy–Weinberg equilibrium. APOE3 was the most common allele, followed by APOE4 and APOE2 . The allele distribution pattern is consistent with findings in previously studied populations of Native Americans and Asians. The E4 allele’s low frequency, always observed in a heterozygous state, raises questions regarding its relevance in explaining dementia and longevity associated with this marker in the …Central Andes. Show more

Keywords: Allele frequency, Alzheimer’s disease, Andean population, APOE

DOI: 10.3233/ADR-230061

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 95-99, 2024

Authors: Wang, Hongqi | Yan, Xiaodong | Zhang, Yiming | Wang, Peifu | Li, Jilai | Zhang, Xia

Article Type: Research Article

Abstract: Background: The investigation of mitophagy in Alzheimer’s disease (AD) remains relatively underexplored in bibliometric analysis. Objective: To delve into the progress of mitophagy, offering a comprehensive overview of research trends and frontiers for researchers. Methods: Basic bibliometric information, targets, and target-drug-clinical trial-disease extracted from publications identified in the Web of Science Core Collection from 2007 to 2022 were assessed using bibliometric software. Results: The study encompassed 5,146 publications, displaying a consistent 16-year upward trajectory. The United States emerged as the foremost contributor in publications, with the Journal of Alzheimer ’s Disease being the …most prolific journal. P. Hemachandra Reddy, George Perry, and Xiongwei Zhu are the top 3 most prolific authors. PINK1 and Parkin exhibited an upward trend in the last 6 years. Keywords (e.g., insulin, aging, epilepsy, tauopathy, and mitochondrial quality control) have recently emerged as focal points of interest within the past 3 years. “Mitochondrial dysfunction” is among the top terms in disease clustering. The top 10 drugs/molecules (e.g., curcumin, insulin, and melatonin) were summarized, accompanied by their clinical trials and related targets. Conclusions: This study presents a comprehensive overview of the mitophagy research landscape in AD over the past 16 years, underscoring mitophagy as an emerging molecular mechanism and a crucial focal point for potential drug in AD. This study pioneers the inclusion of targets and their correlations with drugs, clinical trials, and diseases in bibliometric analysis, providing valuable insights and inspiration for scholars and readers of JADR interested in understanding the potential mechanisms and clinical trials in AD. Show more

Keywords: Alzheimer’s disease, bibliometric analysis, drug, mitochondrion, mitophagy

DOI: 10.3233/ADR-230139

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 101-128, 2024