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

Article Type: Correction

DOI: 10.3233/ADR-249001

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 849-850, 2024

Authors: Jang, Hyemin | Na, Duk L. | Kwon, Jay Cheol | Jung, Na-Yeon | Moon, Yeonsil | Lee, Jung Seok | Park, Kyung-Won | Lee, Ae Young | Cho, Hanna | Lee, Jae-Hong | Kim, Byeong C. | Park, Kee Hyung | Lee, Byung-Chul | Choi, Hojin | Kim, Jieun | Park, Mee Young

Article Type: Research Article

Abstract: Background: Predicting conversion to probable Alzheimer&s disease (AD) from amnestic mild cognitive impairment (aMCI) is difficult but important. A nomogram was developed previously for determining the risk of 3-year probable AD conversion in aMCI. Objective: To compare the probable AD conversion rates with cognitive and neurodegenerative changes for 2 years from high- and low risk aMCI groups classified using the nomogram. Methods: This prospective, multicenter, observational study was conducted in Korea. A total of patients were classified as high- or low-risk aMCI according to the nomogram and followed-up for 2 years to compare the annual conversion …rate to probable AD and brain structure changes between the two groups. Results: In total, 176 (high-risk, 85; low-risk, 91) and 160 (high-risk, 77; low-risk, 83) patients completed the 1-year and 2-year follow-up, respectively. The probable AD conversion rate was significantly higher in the high-risk (Year 1, 28.9%; Year 2, 46.1%) versus low-risk group (Year 1, 0.0%; Year 2, 4.9%, both p < 0.0001). Mean changes from baseline in Seoul Neuropsychological Screening Battery-Dementia Version, Clinical Dementia Rating-Sum of Box, and Korean version of the Instrumental Activities of Daily Living scores and cortical atrophy index at Years 1 and 2 were significantly greater in the high-risk group (p < 0.0001). Conclusions: The high-risk aMCI group, as determined by the nomogram, had a higher conversion rate to probable AD and faster cognitive decline and neurodegeneration change than the low-risk group. These real-world results have clinical implications that help clinicians in accurately predicting patient outcomes and facilitating early decision-making. Trial Registration: ClinicalTrials.gov (NCT03448445) Show more

Keywords: Alzheimer’s disease, amnestic mild cognitive impairment, conversion rate, neurodegeneration, neuropsychometry, nomogram

DOI: 10.3233/ADR-230189

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 851-862, 2024

Authors: Choe, Yeong Sim | Kim, Regina E.Y. | Kim, Hye Weon | Kim, JeeYoung | Lee, Hyunji | Lee, Min Kyoung | Lee, Minho | Kim, Keun You | Kim, Se-Hong | Kim, Ji-hoon | Lee, Jun-Young | Kim, Eosu | Kim, Donghyeon | Lim, Hyun Kook

Article Type: Research Article

Abstract: Background: Application of visual scoring scales for regional atrophy in Alzheimer’s disease (AD) in clinical settings is limited by their high time cost and low intra/inter-rater agreement. Objective: To provide automated atrophy scoring using objective volume driven from deep-learning segmentation methods for AD subtype classification using magnetic resonance imaging (MRI). Methods: We enrolled 3,959 participants (1,732 cognitively normal [CN], 1594 with mild cognitive impairment [MCI], and 633 with AD). The occupancy indices for each regional volume were calculated by dividing each volume by the size of the lateral and inferior ventricular volumes. MR images …from 355 participants (119 CN, 119 MCI, and 117 AD) from three different centers were used for validation. Two neuroradiologists performed visual assessments of the medial temporal, posterior, and global cortical atrophy scores in the frontal lobe using T1-weighted MR images. Images were also analyzed using the deep learning-based segmentation software, Neurophet AQUA. Cutoff values for the three scores were determined using the data distribution according to age. The scoring results were compared for consistency and reliability. Results: Four volumetric-driven scoring results showed a high correlation with the visual scoring results for AD, MCI, and CN. The overall agreement with human raters was weak-to-moderate for atrophy scoring in CN participants, and good-to-almost perfect in AD and MCI participants. AD subtyping by automated scores also showed usefulness as a research tool. Conclusions: Determining AD subtypes using automated atrophy scoring for late-MCI and AD could be useful in clinical settings or multicenter studies with large datasets. Show more

Keywords: Alzheimer’s disease, atrophy, cognitive dysfunction, magnetic resonance imaging, visual scoring

DOI: 10.3233/ADR-230105

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 863-876, 2024

Authors: Garcia, Ricardo Isaiah | Khemka, Sachi | Roghani, Aryan Kia | Reddy, Ruhananhad P. | Pattoor, Vasanthkumar | Jacob, Michael | Reddy, Aananya | Sehar, Ujala | Reddy, P. Hemachandra

Article Type: Review Article

Abstract:  A caregiver is a constantly evolving role that an individual most likely undertakes at some point in their lifetime. With discoveries and research in increasing life expectancy, the prevalence of neurological-related diseases, such as Alzheimer’s disease (AD) and dementia, is certainly likely to require more caregivers. The demand for AD caregivers is escalating as the prevalence of the disease continues to rise. The projected rise in AD within the Hispanic population in the United States over the next few decades is expected to be the most significant among all ethnic groups. The Hispanic population faces unique dementia risks due to …cultural factors like language barriers, lower education, and limited healthcare access. Higher rates of conditions such as diabetes and cardiovascular disease further elevate dementia risk. Family dynamics and caregiving responsibilities also differ, affecting dementia management within Hispanic households. Addressing these distinct challenges requires culturally sensitive approaches to diagnosis, treatment, and support for Hispanic individuals and their family’s facing dementia. With AD and other dementia becoming more prevalent, this article will attempt to expand upon the status of caregivers concerning their economic, health, and cultural statuses. We will attempt to focus on the Hispanic caregivers that live in Texas and more specifically, West Texas due to the lack of current literature that applies to this area of Texas. Lastly, we discuss the ramifications of a multitude of factors that affect caregivers in Texas and attempt to provide tools that can be readily available for Hispanics and others alike. Show more

Keywords: Alzheimer’s Association, Alzheimer’s disease, caregivers, culture, dementia, disparities, Hispanics, non-Hispanic whites, West Texas

DOI: 10.3233/ADR-240035

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 877-902, 2024

Authors: McKay, Mary | Gorai, Sukhamoy | Paidi, Ramesh K. | Mondal, Susanta | Pahan, Kalipada

Article Type: Research Article

Abstract: Background: Despite intense investigations, no effective treatment is yet available to reduce plaques and protect memory and learning in patients with Alzheimer’s disease (AD), the most common neurodegenerative disorder. Therefore, it is important to identify a non-toxic, but effective, treatment option for AD. Objective: Cinnamein, a nontoxic compound, is naturally available in Balsam of Peru and Tolu Balsam. We examined whether cinnamein treatment could decrease plaques and improve cognitive functions in 5XFAD mouse model of AD. Methods: We employed in silico analysis, time-resolved fluorescence energy transfer assay, thermal shift assay, primary neuron isolation, western …blot, immunostaining, immunohistochemistry, Barnes maze, T maze, and open field behavior. Results: Oral administration of cinnamein led to significant reduction in amyloid-β plaque deposits in the brain and protection of spatial learning and memory in 5XFAD mice. Peroxisome proliferator-activated receptor alpha (PPARα), a nuclear hormone receptor, is involved in plaque lowering and increase in hippocampal plasticity. While investigating underlying mechanisms, we found that cinnamein served as a ligand of PPARα. Accordingly, oral cinnamein upregulated the level of PPARα, but not PPARβ, in the hippocampus, and remained unable to decrease plaques from the hippocampus and improve memory and learning in 5XFAD mice lacking PPARα. While A disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) is one of the drivers of nonamyloidogenic pathway, transcription factor EB (TFEB) is considered as the master regulator of autophagy. Cinnamein treatment was found to upregulate both ADAM10 and TFEB in the brain of 5XFAD mice via PPARα. Conclusions: Our results suggest that this balsam component may have therapeutic importance in AD. Show more

Keywords: ADAM10, Alzheimer’s disease, cinnamein, cognitive function, plaque, PPARα , TFEB

DOI: 10.3233/ADR-230179

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 903-922, 2024

Authors: MohanaSundaram, ArunSundar | Patil, Bhushan | Praticò, Domenico

Article Type: Article Commentary

Abstract:  A recent article by El Haj et al. provided evidence that ChatGPT could be a potential tool that complements the clinical diagnosis of various stages of Alzheimer’s Disease (AD) as well as mild cognitive impairment (MCI). To reassess the accuracy and reproducibility of ChatGPT in the diagnosis of AD and MCI, we used the same prompt used by the authors. Surprisingly, we found that some of the responses of ChatGPT in the diagnoses of various stages of AD and MCI were different. In this commentary we discuss the possible reasons for these different results and propose strategies for future studies.

Keywords: Alzheimer’s disease, mild cognitive impairment, brain aging, diagnosis, artificial intelligence, ChatGPT

DOI: 10.3233/ADR-240069

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 923-925, 2024

Authors: Basta, Maria | Bouloukaki, Izolde | Skourti, Eleni | Zampetakis, Alexandros | Alexopoulou, Christina | Ganiaris, Andronikos | Aligizaki, Marina | Zaganas, Ioannis | Simos, ‘Panagiotis | Vgontzas, Alexandros

Article Type: Short Communication

Abstract:  We examined associations between objective sleep duration and cognitive status in older adults initially categorized as cognitively non-impaired (CNI, n  = 57) or diagnosed with mild cognitive impairment (MCI, n  = 53). On follow-up, 8 years later, all participants underwent neuropsychiatric/neuropsychological evaluation and 7-day 24-h actigraphy. On re-assessment 62.7% of participants were cognitively declined. Patients who developed dementia had significantly longer night total sleep time (TST) than persons with MCI who, in turn, had longer night TST than CNI participants. Objective long sleep duration is a marker of worse cognitive status in elderly with MCI/dementia and this association is very strong in …older adults. Show more

Keywords: Alzheimer’s disease, cognitive performance, dementia, long sleep duration, mild cognitive impairment, older adults

DOI: 10.3233/ADR-230203

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 927-934, 2024

Authors: Feng, Ziqian | Wang, Jiayu | Xu, Lisi | Wu, Jiajing | Li, Hongyi | Wang, Ziqi | Duan, Mingjun

Article Type: Research Article

Abstract: Background: Excessive daytime sleepiness (EDS) and caudate nucleus volume alterations have been linked to Alzheimer’s disease (AD), but their relationship remains unclear under the context of subjective cognitive decline (SCD). Objective: This study aimed to investigate the relationship between EDS and caudate nucleus volume in patients with SCD. Methods: The volume of entire brain was measured in 170 patients with SCD, including 37 patients with EDS and 133 non-EDS, from the Sino Longitudinal Study on Cognitive Decline (SILCODE). Participants underwent a comprehensive assessment battery, including neuropsychological and clinical evaluations, blood tests, genetic analysis for APOE …ɛ 4, and structural MRI scans analyzed using the fully automated segmentation tool, volBrain. Results: Patients with EDS had significantly increased volume in the total and left caudate nucleus compared to non-EDS. The most significant cognitive behavioral factor associated with caudate nucleus volume in the EDS was the Auditory Verbal Learning Test-recognition. Conclusions: These findings suggest that EDS may be associated with alterations in caudate nucleus volume, particularly in the left hemisphere, in the context of SCD. Further research is necessary to understand the underlying mechanisms of this relationship and its implications for clinical management. Show more

Keywords: Alzheimer’s disease, caudate nucleus, excessive daytime sleepiness, memory, subjective cognitive decline, volume

DOI: 10.3233/ADR-230101

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 935-944, 2024

Authors: Li, Cong | Qian, Haifeng | Feng, Lina | Li, Mingquan

Article Type: Research Article

Abstract: Background: There is now increasing evidence that type 2 diabetes mellitus (T2DM) is associated with Alzheimer’s disease (AD). However, it is unclear whether the two are causally related. Objective: To reveal the causal association between T2DM and AD, we performed a bidirectional Mendelian randomization (MR) analysis. Methods: Genetic instrumental variables were systematically screened, and inverse-variance weighting, MR—Egger regression, weighted median, simple mode, and weighted mode were applied to assess the pathogenic associations between the two diseases, and sensitivity analyses were used to further validate the robustness of the results. Results: The results of forward …MR analysis with T2DM as the exposure were [OR = 0.998, 95% CI (0.975∼1.021), p  = 0.857], and the results of reverse MR analysis with AD as the exposure were [OR = 0.966, 95% CI (0.934∼0.999), p  = 0.043]. The results showed no significant association between T2DM and AD at the gene level (p  < 0.025). Sensitivity analyses were consistent with the results of the main analysis, confirming the robustness of the study. Conclusions: T2DM and AD may not be genetically causally associated. Show more

Keywords: Alzheimer’s disease, causal association, Mendelian randomization, type 2 diabetes mellitus

DOI: 10.3233/ADR-240053

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 945-957, 2024

Authors: Abbate, Carlo | Gallucci, Alessia | Trimarchi, Pietro Davide | Piacquadio, Emanuela | Caramanti, Giulia | Parma, Anna | Fumagalli, Giorgio Giulio | Inglese, Silvia | Parisi, Paola Maria Rita | Tartarone, Federica | Giunco, Fabrizio

Article Type: Review Article

Abstract: We rediscovered a phenotype of AD known in the early 1900s as presbyophrenia, but then forgotten, and renamed as confabulation-misidentification phenotype. The phenotype includes diencephalic amnesia whose prototype is Korsakoff syndrome. The main features are anterograde and retrograde amnesia with marked disorientation and confabulation, executive impairments, reduced insight and attention deficits, misidentification, minor hallucination and other delusions, behavioral disturbances, and early anxiety. In this article, we summarize what we have discovered about the new phenotype and what is still missing to confirm this diencephalic variant of AD.

Keywords: Alzheimer’s disease, confabulation, diencephalic amnesia, Korsakoff syndrome, misidentification, presbyophrenia

DOI: 10.3233/ADR-230196

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 959-969, 2024