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

Authors: Lombardi, Gemma | Berti, Valentina | Ginestroni, Andrea | Nacmias, Benedetta | Sorbi, Sandro

Article Type: Case Report

Abstract: Amyloid-β deposition is the pathological hallmark of both cerebral amyloid angiopathy and Alzheimer’s disease dementia, clinical conditions that can share cognitive decline and positive Amyloid-PET scan. A case is reported involving an 82-year-old Italian female who presented initially a memory deficit, later transient focal neurologic episodes, and finally two symptomatic lobar intracerebral hemorrhages. In light of these events, MRI and PET imaging findings, acquired before cerebral hemorrhages, are reconsidered and discussed, highlighting the utility of Amyloid-PET in supporting an in vivo diagnosis of cerebral amyloid angiopathy.

Keywords: Alzheimer’s disease, amyloid PET, cerebral amyloid angiopathy, lobar cerebral hemorrhage, superficial siderosis, FDG-PET

DOI: 10.3233/ADR-230183

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 281-288, 2024

Authors: Chithiramohan, Tamara | Santhosh, Smrithi | Threlfall, Grace | Hull, Louise | Mukaetova-Ladinska, Elizabeta B. | Subramaniam, Hari | Beishon, Lucy

Article Type: Systematic Review

Abstract: Background: Cognitive screening tools are important in the detection of dementia, including Alzheimer’s disease; however, they may contain cultural biases. Objective: This review examines culture-fair cognitive screening tools and evaluates their screening accuracy, strengths, and limitations. Methods: Medline, Embase, PsychINFO and CINAHL were searched. The protocol was registered on PROSPERO (CRD42021288776). Included studies used a culture-fair tool to assess cognition in older adults from varying ethnicities. Narrative synthesis was conducted. Results: 28 studies were included assessing eleven different tools. The Rowland Universal Dementia Assessment Scale (RUDAS) was as accurate as …the Mini-Mental State Examination (MMSE) (AUC 0.62-0.93), with a similar sensitivity (52–94%) and better specificity (70–98%), and the Multicultural Cognitive Examination (MCE) had improved screening accuracy (AUC 0.99) compared to RUDAS (AUC 0.92). The Visual Cognitive Assessment Test (VCAT) was equivalent to MMSE (AUC 0.84–0.91). The Kimberley Indigenous Cognitive Assessment tool (KICA) had AUC of 0.93–0.95; sensitivity of 90.6%, specificity 92.6%. Conclusions: The RUDAS, KICA and VCAT were superior to MMSE for screening dementia in ethnic minorities. Other tools also showed good screening accuracy. Further research should be done to validate tools in different populations. Show more

Keywords: Alzheimer’s disease, culture-fair, cognitive screening, dementia

DOI: 10.3233/ADR-230194

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 289-306, 2024

Authors: Shan, Guogen | Lu, Xinlin | Li, Zhigang | Caldwell, Jessica Z.K. | Bernick, Charles | Cummings, Jeffrey

Article Type: Research Article

Abstract: Background: Composite scores have been increasingly used in trials for Alzheimer’s disease (AD) to detect disease progression, such as the AD Composite Score (ADCOMS) in the lecanemab trial. Objective: To develop a new composite score to improve the prediction of outcome change. Methods: We proposed to develop a new composite score based on the statistical model in the ADCOMS, by removing duplicated sub-scales and adding the model selection in the partial least squares (PLS) regression. Results: The new AD composite S core with variable S election (ADSS) includes 7 …cognitive sub-scales. ADSS can increase the sensitivity to detect disease progression as compared to the existing total scores, which leads to smaller sample sizes using the ADSS in trial designs. Conclusions: ADSS can be utilized in AD trials to improve the success rate of drug development with a high sensitivity to detect disease progression in early stages. Show more

Keywords: ADCOMS, Alzheimer’s disease, cognitive outcome, composite score, mild cognitive impairment, model selection

DOI: 10.3233/ADR-230043

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 307-316, 2024

Authors: Dakdareh, Sara Ghasemi | Abbasian, Karim

Article Type: Research Article

Abstract: Background: Alzheimer’s disease and mild cognitive impairment are common diseases in the elderly, affecting more than 50 million people worldwide in 2020. Early diagnosis is crucial for managing these diseases, but their complexity poses a challenge. Convolutional neural networks have shown promise in accurate diagnosis. Objective: The main objective of this research is to diagnose Alzheimer’s disease and mild cognitive impairment in healthy individuals using convolutional neural networks. Methods: This study utilized three different convolutional neural network models, two of which were pre-trained models, namely AlexNet and DenseNet, while the third model was …a CNN1D-LSTM neural network. Results: Among the neural network models used, the AlexNet demonstrated the highest accuracy, exceeding 98%, in diagnosing mild cognitive impairment and Alzheimer’s disease in healthy individuals. Furthermore, the accuracy of the DenseNet and CNN1D-LSTM models is 88% and 91.89%, respectively. Conclusions: The research highlights the potential of convolutional neural networks in diagnosing mild cognitive impairment and Alzheimer’s disease. The use of pre-trained neural networks and the integration of various patient data contribute to achieving accurate results. The high accuracy achieved by the AlexNet neural network underscores its effectiveness in disease classification. These findings pave the way for future research and improvements in the field of diagnosing these diseases using convolutional neural networks, ultimately aiding in early detection and effective management of mild cognitive impairment and Alzheimer’s disease. Show more

Keywords: Alzheimer’s disease, AlexNet convolutional neural network, DenseNet convolutional neural network, mild cognitive impairment

DOI: 10.3233/ADR-230118

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 317-328, 2024

Authors: Pinjala, Poojitha | Tryphena, Kamatham Pushpa | Kulkarni, Amrita | Goswami, Prince Giri | Khatri, Dharmendra Kumar

Article Type: Research Article

Abstract: Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder linked to the loss of dopaminergic neurons in the substantia nigra. Mitophagy, mitochondrial selective autophagy, is critical in maintaining mitochondrial and subsequently neuronal homeostasis. Its impairment is strongly implicated in PD and is associated with accelerated neurodegeneration. Objective: To study the positive effect of dimethyl fumarate (DMF) on mitophagy via the NRF2/BNIP3/PINK1 axis activation in PD disease models. Methods: The neuroprotective effect of DMF was explored in in vitro and in vivo PD models. MTT assay was performed to determine the DMF …dose followed by JC-1 assay to study its mitoprotective effect in MPP+ exposed SHSY5Y cells. For the in vivo study, C57BL/6 mice were divided into six groups: Normal Control (NC), Disease Control (DC), Sham (Saline i.c.v.), Low Dose (MPP+ iodide+DMF 15 mg/kg), Mid Dose (MPP+ iodide+DMF 30 mg/kg), and High Dose (MPP+ iodide+DMF 60 mg/kg). The neuroprotective effect of DMF was assessed by performing rotarod, open field test, and pole test, and biochemical parameter analysis using immunofluorescence, western blot, and RT-PCR. Results: DMF treatment significantly alleviated the loss of TH positive dopaminergic neurons and enhanced mitophagy by increasing PINK1, Parkin, BNIP3, and LC3 levels in the MPP+ iodide-induced PD mice model. DMF treatment groups showed good locomotor activity and rearing time when compared to the DC group. Conclusions: DMF confers neuroprotection by activating the BNIP3/PINK1/Parkin pathway, enhancing the autophagosome formation via LC3, and improving mitophagy in PD models, and could be a potential therapeutic option in PD. Show more

Keywords: Alzheimer’s disease, autophagy, dimethyl fumarate, 1-methyl-4-phenyl pyridinium iodide, nuclear factor E2-related factor 2, Parkinson’s disease

DOI: 10.3233/ADR-230128

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 329-344, 2024

Authors: Teng, Zenghui

Article Type: Review Article

Abstract: Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease with cognitive decline and behavioral dysfunction. AD will become a global public health concern due to its increasing prevalence brought on by the severity of global aging. It is critical to understand the pathogenic mechanisms of AD and investigate or pursue a viable therapy strategy in clinic. Amyloid-β (Aβ) accumulation and abnormally hyperphosphorylated tau protein are the main regulating variables in the pathological phase of AD. And neuroinflammation brought on by activated microglia was found to be one risk factor contributing to changes in Aβ and tau pathology. It is important …to investigate the unique biomarkers of early diagnosis and advanced stage, which may help to elucidate the specific pathological process of AD and provide potential novel therapeutic targets or preventative measures. Show more

Keywords: Alzheimer’s disease, amyloid-β, biomarker, neuroinflammation, tau

DOI: 10.3233/ADR-230130

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 345-354, 2024

Authors: Ozsahin, Ilker | Zhou, Liangdong | Wang, Xiuyuan | Garetti, Jacob | Jamison, Keith | Xi, Ke | Tanzi, Emily | Jaywant, Abhishek | Patchell, Abigail | Maloney, Thomas | de Leon, Mony J. | Kuceyeski, Amy | Shah, Sudhin A. | Li, Yi | Butler, Tracy A.

Article Type: Short Communication

Abstract: Diffusion tensor imaging along perivascular spaces (DTI-ALPS) is a novel MRI method for assessing brain interstitial fluid dynamics, potentially indexing glymphatic function. Failed glymphatic clearance is implicated in Alzheimer’s disease (AD) pathophysiology. We assessed the contribution of age and female sex (strong AD risk factors) to DTI-ALPS index in healthy subjects. We also for the first time assessed the effect of head size. In accord with prior studies, we show reduced DTI-ALPS index with aging, and in men compared to women. However, head size may be a major contributing factor to this counterintuitive sex difference.

Keywords: Aging, Alzheimer’s disease, DTI-ALPS, glymphatic system, interstitial fluid dynamics, sex difference

DOI: 10.3233/ADR-230143

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 355-361, 2024

Authors: Perini, Giulia | Cotta Ramusino, Matteo | Conca, Francesca | Cosentino, Giuseppe | Farina, Lisa Maria | Costa, Alfredo | Farina, Elisabetta

Article Type: Case Report

Abstract: The prodromal stage of Lewy body dementia includes a mild cognitive impairment with visual processing and/or attention-executive deficits. A clinical presentation with progressive visual loss is indeed seldom reported and can be misleading with a posterior cortical atrophy disease. While the neurodegeneration at the occipital cortex can only partially explain the visual disturbances of Lewy body dementia, more recently a retinal dysfunction has been suggested by preliminary optical coherence tomography and autoptic findings. Herein, we present a case of a mild cognitive impairment with Lewy bodies, who presented initially with visual disturbances and signs of both retinal and cortical visual …processing dysfunction. A complete neuropsychological, neurophysiological and brain imaging assessment highlighted a prominent ventral visual pathway involvement. This report provides first that the prodromal stage of Lewy body dementia can manifest as a primarily progressive visual loss, second that the involvement of visual pathway, particularly the ventral stream, can be detectable from the retinal to the cortical level. Show more

Keywords: Alzheimer’s disease, Lewy body dementia, parvicellular system, prodromal stage, retinal involvement, visual perception deficits

DOI: 10.3233/ADR-230176

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 363-369, 2024

Authors: Singh, Anita | Maker, Matthew | Prakash, Jayant | Tandon, Raghav | Mitchell, Cassie S.

Article Type: Research Article

Abstract: Background: Amyloid-β plaques (Aβ) are associated with Alzheimer’s disease (AD). Pooled assessment of amyloid reduction in transgenic AD mice is critical for expediting anti-amyloid AD therapeutic research. Objective: The mean threshold of Aβ reduction necessary to achieve cognitive improvement was measured via pooled assessment (n  = 594 mice) of Morris water maze (MWM) escape latency of transgenic AD mice treated with substances intended to reduce Aβ via reduction of beta-secretase cleaving enzyme (BACE). Methods: Machine learning and statistical methods identified necessary amyloid reduction levels using mouse data (e.g., APP/PS1, LPS, Tg2576, 3xTg-AD, control, wild type, treated, untreated) …curated from 22 published studies. Results: K-means clustering identified 4 clusters that primarily corresponded with level of Aβ: untreated transgenic AD control mice, wild type mice, and two clusters of transgenic AD mice treated with BACE inhibitors that had either an average 25% “medium reduction” of Aβ or 50% “high reduction” of Aβ compared to untreated control. A 25% Aβ reduction achieved a 28% cognitive improvement, and a 50% Aβ reduction resulted in a significant 32% improvement compared to untreated transgenic mice (p  < 0.05). Comparatively, wild type mice had a mean 41% MWM latency improvement over untreated transgenic mice (p  < 0.05). BACE reduction had a lesser impact on the ratio of Aβ42 to Aβ40 . Supervised learning with an 80% –20% train-test split confirmed Aβ reduction was a key feature for predicting MWM escape latency (R2  = 0.8 to 0.95). Conclusions: Results suggest a 25% reduction in Aβ as a meaningful treatment threshold for improving transgenic AD mouse cognition. Show more

Keywords: Alzheimer’s disease, anti-amyloid therapy, artificial intelligence, BACE inhibitor, effect size, machine learning, transgenic mice

DOI: 10.3233/ADR-230174

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 371-385, 2024

Authors: Xia, Xuefei | Yuan, Pingqiao | Zhao, Xue | Jia, Fang Rong | Li, Bangyang | Cai, Peng

Article Type: Research Article

Abstract: Background: The development and popularization of the Internet provides an important opportunity to advance national strategies for healthy aging, particularly the impact of the Internet on cognitive function in middle-aged and older adults. Objective: This study aimed to quantify the impact of Internet use on the cognitive health of middle-aged and older adults (aged≥45 years). Methods: We used data from the Chinese Family Panel Study (CFPS) survey, tested the robustness of the baseline findings by variable substitution and instrumental variables methods, and analyzed heterogeneity. Subsequently, five purposes of Internet use that affect cognitive function were analyzed …in depth. Results: Internet use may improve cognitive function in middle-aged and older adults. The effect of Internet use on cognitive function was more pronounced in the lower age group (45–59 years), among males, in rural areas, and among middle-aged and older adults with higher levels of education. Cognitive functioning of middle-aged and older adults varied according to how often they used the Internet for entertainment, socialization, study, work, and business activities. Conclusions: The use of the Internet may be considered a practical non-pharmacological intervention to slow cognitive decline in middle-aged and older adults. Show more

Keywords: Alzheimer’s disease, cognitive function, Internet use, heterogeneity analysis, instrumental variable

DOI: 10.3233/ADR-230137

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 387-397, 2024