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

Authors: Lacerda, Isabel Barbeito | Baptista, Maria Alice Tourinho | Belfort, Tatiana | Mograbi, Daniel | Dourado, Marcia Cristina Nascimento

Article Type: Research Article

Abstract: Background: Awareness is a heterogeneous construct that requires accurate assessment. There is no consensus on the best methodology for capturing the phenomenon, thus leading to inconsistent results in this area. Objective: We aim to evaluate the reliability of clinicians’ ratings and a discrepancy assessment method, examining groups of people with Alzheimer’s disease (PwAD) according to their degree of awareness and demographic and clinical aspects. Methods: We cross-sectionally assessed 134 PwAD and their caregivers. Individuals’ level of awareness was assessed with two methods: clinicians’ ratings identified three groups (preserved awareness, impaired awareness, and absent awareness), while discrepancy …assessment identified four groups (preserved awareness, mildly impaired awareness, moderately impaired awareness, and absent awareness). Results: Clinicians’ ratings showed significant differences between PwAD with preserved, impaired, and absent awareness groups in cognition, functionality, and neuropsychiatric symptoms. There was a significant difference in caregivers’ anxiety between the impaired and absent awareness groups. Discrepancy assessment showed no clinical differences between the preserved and mildly impaired awareness groups or between the absent and moderately impaired awareness groups. A significant difference in functionality was observed between the other groups. Conclusions: Clinical aspects of each measure tended to differ between the chosen methods. Impairments in awareness fluctuate despite disease progression. Cognition and severity of disease cannot explain deficits in awareness. Show more

Keywords: Alzheimer’s disease, awareness, dementia, measures

DOI: 10.3233/ADR-230090

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 399-410, 2024

Authors: Liu, Jiahao | Roccati, Eddy | Chen, Yutong | Zhu, Zhuoting | Wang, Wei | He, Mingguang | Shang, Xianwen

Article Type: Research Article

Abstract: Background: Limited knowledge exists regarding the association between dementia incidence and vitamin D insufficiency/deficiency across seasons. Objective: This study aimed to evaluate the impact of seasonal serum vitamin D (25(OH)D) levels on dementia and its subtypes, considering potential modifiers. Methods: We analyzed 193,003 individuals aged 60–73 at baseline (2006–2010) from the UK Biobank cohort, with follow-up until 2018. 25(OH)D were measured at baseline, and incident dementia cases were identified through hospital records, death certificates, and self-reports. Results: Out of 1,874 documented all-cause dementia cases, the median follow-up duration was 8.9 years. Linear and nonlinear …associations between 25(OH)D and dementia incidence across seasons were observed. In multivariable-adjusted analysis, 25(OH)D deficiency was associated with a 1.5-fold (95% CIs: 1.2–2.0), 2.2-fold (1.5–3.0), 2.0-fold (1.5–2.7), and 1.7-fold (1.3–2.3) increased incidence of all-cause dementia in spring, summer, autumn, and winter, respectively. Adjusting for seasonal variations, 25(OH)D insufficiency and deficiency were associated with a 1.3-fold (1.1–1.4) and 1.8-fold (1.6–2.2) increased dementia incidence, respectively. This association remained significant across subgroups, including baseline age, gender, and education levels. Furthermore, 25(OH)D deficiency was associated with a 1.4-fold (1.1–1.8) and 1.5-fold (1.1–2.0) higher incidence of Alzheimer’s disease and vascular dementia, respectively. These associations remained significant across all subgroups. Conclusions: 25(OH)D deficiency is associated with an increased incidence of dementia and its subtypes throughout the year. Show more

Keywords: Alzheimer’s disease, dementia, moderation analysis, season, vitamin D

DOI: 10.3233/ADR-230077

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 411-422, 2024

Authors: Seifallahi, Mahmoud | Galvin, James E. | Ghoraani, Behnaz

Article Type: Research Article

Abstract: Background: Mild cognitive impairment (MCI) can be an early sign of Alzheimer’s disease and other types of dementia detectable through gait analysis. Curve walking, which demands greater cognitive and motor skills, may be more sensitive in MCI detection than straight walking. However, few studies have compared gait performance in older adults with and without MCI in these conditions. Objective: To compare the capability of curve and straight walking tests for the detection of MCI among older adults. Methods: We employed a Kinect v.2 camera to record the gait of 55 older adults (30 healthy controls, 25 …with MCI) during single-task straight and curve walking tests. We examined 50 gait markers and conducted statistical analyses to compare groups and conditions. The trail was approved with protocol No. IR.SEMUMS.REC.1398.237 by the ethics committee of Semnan University of Medical Sciences in Iran. Results: Older adults with MCI exhibited more compromised gait performance, particularly during curve walking. Curve walking outperformed straight walking in MCI detection, with several gait markers showing significant differences between healthy controls and MCI patients. These markers encompass average velocity, cadence, temporal markers (e.g., gait cycle subphase durations), spatial markers (e.g., foot position changes during gait subphases), and spatiotemporal markers (e.g., step and stride velocities). Conclusions: Our study suggests curve walking as a more informative and challenging test for MCI detection among older adults, facilitating early diagnosis using non-invasive, cost-effective tools like the Kinect v.2 camera, complementing cognitive assessments in early diagnosis, and tracking MCI progression to dementia. Show more

Keywords: Alzheimer’s disease, curve walking, gait analysis, Kinect v.2 camera, mild cognitive impairment, straight walking

DOI: 10.3233/ADR-230149

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 423-435, 2024

Authors: Wang, Hao | Shi, Lin | Luo, Shimei | Luo, Yishan | Xu, Chunyan | Qiu, Guozhen | Guo, Qiwen | Chen, Chunchun | Lu, Taikun | Liu, Kangding | Zhu, Feiqi

Article Type: Research Article

Abstract: Background: Increasing evidence suggests that both amyloid-β metabolism disorders in the liver and cerebral hypoperfusion play an important role in the pathogenesis of Alzheimer’s disease (AD). However, the relevance of liver function alterations to cerebral blood flow (CBF) of patients with AD remains unclear. Objective: We aimed to investigate the associations between liver function changes and CBF of patients with AD. Methods: We recruited 17 patients with sporadic AD. In addition to physical and neurological examinations, detection of AD biomarkers in cerebrospinal fluid by enzyme-linked immunosorbent assay and CBF assessment by arterial spin labeling sequence of …magnetic resonance image scans as well as measure of liver function markers in serum by routine laboratory testing were conducted. Neuropsychological tests were evaluated, including Mini-Mental State Examination and Montreal Cognitive Assessment. Linear and rank correlations were performed to test the associations of liver function alterations with regional CBF of AD. Results: We found that liver function markers, especially total protein, the ratio of albumin to globin, globin, alkaline phosphatase, and aspartate aminotransferase were significantly associated with regional CBF of AD patients. Conclusions: These findings demonstrated significant associations between perfusion in certain brain regions of AD and alterations of liver function markers, particularly proteins and liver enzymes, which might provide implications to the pathogenesis and treatment of AD. Show more

Keywords: Alzheimer’s disease, arterial spin labeling, cerebral blood flow, liver function markers

DOI: 10.3233/ADR-230102

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 437-445, 2024

Authors: Padala, Akshay P. | Ramakrishnan, Parameshwaran | Crawford, Christina G.

Article Type: Case Report

Abstract: Background: Social isolation is very common and has increased during the COVID-19 pandemic. Objective: To study if spiritual reconnection as part of a multi-component intervention can reduce social isolation in older adults with cognitive impairment. Methods: A longitudinal case study framework was used. A 68-year-old female with mild cognitive impairment presented with social isolation exacerbated by the COVID-19 pandemic. She participated in a telephone-based psychosocial intervention program called Connection Plans for 8 weeks. Motivational interviewing techniques were used to encourage the patient to pick goals to improve the mind, body, and connections. In her connections goal, …the patient expressed a desire to make spiritual reconnection. Connecting back to her spirituality was one of the key interventions in this patient. Social isolation, resilience, self-efficacy, and cognition were assessed using standardized rating scales before and after the intervention. Results: The patient was able to identify goals to enhance connections and physical and mental well-being. She successfully reconnected with her spirituality while maintaining COVID prevention measures. At an 8-week follow-up, compared to the baseline visit there was an improvement in measures of social isolation (22/30 to 14/30, a 36% reduction), resilience (12/20 to 20/20, a 67% improvement), and confidence (4/20 to 16/20, a 300% improvement). No improvement was noted in cognition. Conclusions: Spiritual reconnection as part of a multi-component intervention may protect against social isolation in older adults with cognitive impairment. Caution must be exercised in reaching this conclusion as this is a report of a single patient. Systematic studies are needed. Show more

Keywords: COVID pandemic, resilience, social isolation, spirituality

DOI: 10.3233/ADR-220028

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 447-452, 2024

Authors: Rohini, M. | Oswalt Manoj, S. | Surendran, D.

Article Type: Short Communication

Abstract: Alzheimer’s disease (AD) is an illness that affects the nervous system, leading to a loss in cognitive and logical abilities. Gene regulatory expressions, which are the complex language exhibited by DNA, serve several functionalities, including the physical and biological life cycle processes in the human body. The gene expression sequence affects the pathology experienced by an individual, its longevity, and potential for a cure. The transcription factors, from DNA to RNA conversion, and the binding process determine the gene expression, which varies for every human organ and disease. This study proposes Deep convolutional neural network model that reads the gene …regulatory expression sequence through various convolutional layers encoded to detect positive spikes in transcription factors. This results in the prediction of disease conversion probability from mild cognitive impairment to AD which is the key-requisite for affected geriatric cohorts. Show more

Keywords: Alzheimer’s disease, APOE, DNA, gene regulatory mechanism, rs429358, rs7412

DOI: 10.3233/ADR-230083

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 453-460, 2024

Authors: Ding, Yu | He, Jinrong | Kong, Fanli | Sun, Dongsheng | Chen, Weiqun | Luo, Bo | Wu, Jia | Zhang, Shaoying | Zhan, Peiyan | Peng, Caixia

Article Type: Research Article

Abstract: Background: Neuronal loss occurs early and is recognized as a hallmark of Alzheimer’s disease (AD). Promoting neurogenesis is an effective treatment strategy for neurodegenerative diseases. Traditional Chinese herbal medicines serve as a rich pharmaceutical source for modulating hippocampal neurogenesis. Objective: Gallic acid (GA), a phenolic acid extracted from herbs, possesses anti-inflammatory and antioxidant properties. Therefore, we aimed to explore whether GA can promote neurogenesis and alleviate AD symptoms. Methods: Memory in mice was assessed using the Morris water maze, and protein levels were examined via western blotting and immunohistochemistry. GA’s binding site in the promoter region …of transcription regulator nuclear factor erythroid 2-related factor 2 (Nrf2) was calculated using AutoDock Vina and confirmed by a dual luciferase reporter assay. Results: We found that GA improved spatial memory by promoting neurogenesis in the hippocampal dentate gyrus zone. It also improved synaptic plasticity, reduced tau phosphorylation and amyloid-β concentration, and increased levels of synaptic proteins in APP/PS1 mice. Furthermore, GA inhibited the activity of glycogen synthase kinase-3β (GSK-3β). Bioinformatics tools revealed that GA interacts with several amino acid sites on GSK-3β. Overexpression of GSK-3β was observed to block the protective effects of GA against AD-like symptoms, while GA promoted neurogenesis via the GSK-3β-Nrf2 signaling pathway in APP/PS1 mice. Conclusions: Based on our collective findings, we hypothesize that GA is a potential pharmaceutical agent for alleviating the pathological symptoms of AD. Show more

Keywords: Alzheimer’s disease, gallic acid, GSK-3β , neurogenesis, Nrf2, spatial memory

DOI: 10.3233/ADR-230171

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 461-477, 2024

Authors: Mondal, Tanmoy | Noreen, Zarish | Loffredo, Christopher A. | Johnson, Jheannelle | Bhatti, Attya | Nunlee-Bland, Gail | Quartey, Ruth | Howell, Charles D. | Moses, Gemeyel | Nnanabu, Thomas | Cotin, Sharleine T. | Clark, Marika | Chandra, Vijay | Jana, Siddhartha S. | Kwabi-Addo, Bernard | Korba, Brent E. | Shahzad, Sharoon | Bhatti, Muhammad Farrukh | Ghosh, Somiranjan

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder that is most prevalent in elderly individuals, especially in developed countries, and its prevalence is now increasing in developing countries like Pakistan. Objective: Our goal was to characterize key genes and their levels of expression and related molecular transcriptome networks associated with AD pathogenesis in a pilot case-control study in a Pakistani population. Methods: To obtain the spectrum of molecular networks associated with pathogenesis in AD patients in Pakistan (comparing cases and controls), we used high-throughput qRT-PCR (TaqMan Low-Density Array; n  = 33 subjects) coupled with Affymetrix Arrays …(n  = 8) and Ingenuity Pathway Analysis (IPA) to identify signature genes associated with Amyloid processing and disease pathways. Results: We confirmed 16 differentially expressed AD-related genes, including maximum fold changes observed in CAPNS2 and CAPN1 . The global gene expression study observed that 61% and 39% of genes were significantly (p -value 0.05) up- and downregulated, respectively, in AD patients compared to healthy controls. The key pathways include, e.g., Amyloid Processing , Neuroinflammation Signaling , and ErbB4 Signaling . The top-scoring networks in Diseases and Disorders Development were Neurological Disease , Organismal Injury and Abnormalities , and Psychological Disorders . Conclusions: Our pilot study offers a non-invasive and efficient way of investigating gene expression patterns by combining TLDA and global gene expression method in AD patients by utilizing whole blood. This provides valuable insights into the expression status of genes related to Amyloid Processing , which could play potential role in future studies to identify sensitive, early biomarkers of AD in general. Show more

Keywords: Alzheimer’s disease, amyloid processing, gene expression, pathogenesis, transcriptomic

DOI: 10.3233/ADR-230146

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 479-493, 2024

Authors: El Haj, Mohamad | Boutoleau-Bretonnière, Claire | Gallouj, Karim | Wagemann, Nathalie | Antoine, Pascal | Kapogiannis, Dimitrios | Chapelet, Guillaume

Article Type: Research Article

Abstract: Background: The potential of ChatGPT in medical diagnosis has been explored in various medical conditions. Objective: We assessed whether ChatGPT can contribute to the diagnosis of Alzheimer’s disease (AD). Methods: We provided ChatGPT with four generated cases (mild, moderate, or advanced stage AD dementia, or mild cognitive impairment), including descriptions of their complaints, physical examinations, as well as biomarker, neuroimaging, and neuropsychological data. Results: ChatGPT accurately diagnosed the test cases similarly to two blinded specialists. Conclusions: While the use of generated cases can be a limitation to our study, our findings demonstrate …that ChatGPT can be a useful tool for symptom assessment and the diagnosis of AD. However, while the use of ChatGPT in AD diagnosis is promising, it should be seen as an adjunct to clinical judgment rather than a replacement. Show more

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

DOI: 10.3233/ADR-230191

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 495-500, 2024

Authors: Turner, Michael | Belli, Antonio | Castellani, Rudolph J.

Article Type: Research Article

Abstract: Background: Cumulative effects of traumatic brain injury is of increasing concern, especially with respect to its role in the etiology and pathogenesis of neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Objective: Compare regional brain volume and connectivity between athletes with a history of concussion and controls. Methods: We evaluated whole-brain volumetric effects with Bayesian regression models and functional connectivity with network-based statistics, in 125 retired athletes (a mean of 11 reported concussions) and 36 matched controls. Results: Brain regions significantly lower in volume in the concussed group included the …middle frontal gyrus, hippocampus, supramarginal gyrus, temporal pole, and inferior frontal gyrus. Conversely, brain regions significantly larger included the hippocampal and collateral sulcus, middle occipital gyrus, medial orbital gyrus, caudate nucleus, lateral orbital gyrus, and medial postcentral gyrus. Functional connectivity analyses revealed increased edge strength, most marked in motor domains. Numerous edges of this network strengthened in athletes were significantly weakened with concussion. Aligned to meta-analytic neuroimaging data, the observed changes suggest functional enhancement within the motor, sensory, coordination, balance, and visual processing domains in athletes, attenuated by concussive head injury with a negative impact on memory and language. Conclusions: These findings suggest that engagement in sport may benefit the brain across numerous domains, but also highlights the potentially damaging effects of concussive head injury. Future studies with longitudinal cohorts including autopsy examination are needed to determine whether the latter reflects tissue loss from brain shearing, or the onset of a progressive Alzheimer’s disease like proteinopathy. Show more

Keywords: Alzheimer’s disease, brain imaging, brain structure and function, concussion, neurodegeneration, sport, traumatic brain injury

DOI: 10.3233/ADR-240021

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 501-516, 2024