Journal of Alzheimer's Disease - Volume 97, issue 1

Authors: Lojo-Ramírez, Jose Antonio | Guerra-Gómez, Miriam | Marín-Cabañas, Alba Marta | Fernández-Rodríguez, Paula | Bernal Sánchez-Arjona, María | Franco-Macías, Emilio | García-Solís, David

Article Type: Research Article

Abstract: Background: Although the concordance between cerebrospinal fluid (CSF) Alzheimer’s disease (AD) biomarkers and amyloid-PET findings is well known, there are no data regarding the concordance of amyloid-PET with inconclusive CSF values of amyloid-β (Aβ)1 - 42 and p-tau for the diagnosis of AD. Objective: To investigate the relationship between the amyloid-PET results with discordant AD biomarkers values in CSF (Aβ1 - 42 +/p-tau–or Aβ1 - 42 –/p-tau+). Methods: An observational retrospective study, including 62 patients with mild cognitive impairment (32/62) or dementia (30/62), suspicious of AD who had undergone a lumbar puncture to determine CSF AD biomarkers, and presented discordant values …in CSF between Aβ1 - 42 and p-tau (Aβ1 - 42 +/p-tau–or Aβ1 - 42 –/p-tau+). All of them, underwent an amyloid-PET with 18 F-Florbetaben. An extensive neuropsychological testing as part of their diagnostic process (MMSE and TMA-93), was performed, and it was also obtained the Global Deterioration Scale. Results: Comparing the discordant CSF results of each patient with the cerebral amyloid-PET results, we found that in the group with Aβ1 - 42 + and p-tau–CSF values, the amyloid-PET was positive in 51.2% and negative in 48.8% of patients, while in the group with Aβ1 - 42 –and p-Tau+ CSF values, the amyloid-PET was positive in 52.6% of patients and negative in 47.4% of them. No significant association was found (p  = 0.951) between the results of amyloid-PET and the two divergent groups in CSF. Conclusions: No significant relationship was observed between the results of discordant AD biomarkers in CSF and the result of amyloid-PET. No trend in amyloid-PET results was observed in relation to CSF biomarker values. Show more

Keywords: Alzheimer’s disease, amyloid, biomarkers, cerebrospinal fluid, Florbetaben, PET

DOI: 10.3233/JAD-230744

Citation: Journal of Alzheimer's Disease, vol. 97, no. 1, pp. 447-458, 2024

Authors: Bapat, Rohan | Ma, Da | Duong, Tim Q.

Article Type: Research Article

Abstract: Background: Prognosis of future risk of dementia from neuroimaging and cognitive data is important for optimizing clinical management for patients at early stage of Alzheimer’s disease (AD). However, existing studies lack an efficient way to integrate longitudinal information from both modalities to improve prognosis performance. Objective: In this study, we aim to develop and evaluate an explainable deep learning-based framework to predict mild cognitive impairment (MCI) to AD conversion within four years using longitudinal whole-brain 3D MRI and neurocognitive tests. Methods: We proposed a two-stage framework that first uses a 3D convolutional neural …network to extract single-timepoint MRI-based AD-related latent features, followed by multi-modal longitudinal feature concatenation and a 1D convolutional neural network to predict the risk of future dementia onset in four years. Results: The proposed deep learning framework showed promising to predict MCI to AD conversion within 4 years using longitudinal whole-brain 3D MRI and cognitive data without extracting regional brain volumes or cortical thickness, reaching a balanced accuracy of 0.834, significantly improved from models trained from single timepoint or single modality. The post hoc model explainability revealed heatmap indicating regions that are important for predicting future risk of AD. Conclusions: The proposed framework sets the stage for future studies for using multi-modal longitudinal data to achieve optimal prediction for prognosis of AD onset, leading to better management of the diseases, thereby improving the quality of life. Show more

Keywords: Alzheimer’s disease, amyloid, artificial intelligence, deep learning, dementia, magnetic resonance imaging, mild cognitive impairment, tau

DOI: 10.3233/JAD-230893

Citation: Journal of Alzheimer's Disease, vol. 97, no. 1, pp. 459-469, 2024

Authors: Guo, Yun | Sun, Yan | Li, Meng | Qi, Wan-Yi | Tan, Lan | Tan, Meng-Shan

Article Type: Research Article

Abstract: Background: The associations between neuropsychiatric symptoms (NPSs) and Alzheimer’s disease (AD) have been well-studied, yet gaps remain. Objective: We aimed to examine the associations of four subsyndromes (hyperactivity, psychosis, affective symptoms, and apathy) of NPSs with cognition, neurodegeneration, and AD pathologies. Methods: Totally 1,040 non-demented elderly (48.07% males) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) were included. We assessed the relationships between NPSs and AD neuropathologies, cognition, neurodegeneration, and clinical correlates in cross-sectional and longitudinal via multiple linear regression, linear mixed effects, and Cox proportional hazard models. Causal mediation analyses were conducted to explore the mediation …effects of AD pathologies on cognition and neurodegeneration. Results: We found that individuals with hyperactivity, psychosis, affective symptoms, or apathy displayed a poorer cognitive status, a lower CSF amyloid-β (Aβ) level and a higher risk of clinical conversion (p  < 0.05). Hyperactivity and affective symptoms were associated with increasing cerebral Aβ deposition (p  < 0.05). Except psychosis, the other three subsyndromes accompanied with faster atrophy of hippocampal volume (p  < 0.05). Specific NPSs were predominantly associated with different cognitive domains decline through an 8-year follow-up (p  < 0.05). Moreover, the relationships between NPSs and cognitive decline, neurodegeneration might be associated with Aβ, the mediation percentage varied from 6.05% to 17.51% (p  < 0.05). Conclusions: NPSs could be strongly associated with AD. The influences of NPSs on cognitive impairments, neurodegeneration might be partially associated with Aβ. Show more

Keywords: Alzheimer’s disease, amyloid, cerebrospinal fluid, cognition, neurodegeneration, neuropsychiatric symptoms

DOI: 10.3233/JAD-230918

Citation: Journal of Alzheimer's Disease, vol. 97, no. 1, pp. 471-484, 2024

Authors: Jang, Yu Jung | Choi, Min Gyu | Yoo, Byung Jae | Lee, Kyeong Jae | Jung, Won Beom | Kim, Seong-Gi | Park, Sun Ah

Article Type: Research Article

Abstract: Background: Obesity is a modifiable risk factor for Alzheimer’s disease (AD). However, its relation with tau pathology (i.e., aberrant tau protein behavior in tauopathies such as AD) has been inconclusive. Objective: This study investigated the interaction between a high-fat diet (HFD) and tau pathology in adult male mice. Methods: Transgenic mice overexpressing human P301S Tau (those with the pathology) and wild-type (WT) littermates were subjected to behavioral tests, functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), and western blotting analysis to investigate the effects of prolonged HFD versus regular diet during adulthood. Results: …HFD increased body weight in both WT and P301S mice but had minimal effect on blood glucose levels. The brain response to HFD was tau genotype-specific. WT mice exhibited decreased recognition memory and enhanced network connectivity in fMRI, while P301S mice exhibited white matter tract disorganization in DTI as the sole significant finding. The reduction of insulin receptor β, insulin downstream signaling, neuronal nuclear protein, CD68-positive phagocytic activity, and myelin basic protein level were confined to the cortex of WT mice. In contrast to P301S mice, WT mice showed significant changes in the tau protein and its phosphorylation levels along with increased soluble neurofilament light levels in the hippocampus. Conclusions: HFD-induced brain dysfunction and pathological changes were blunted in mice with the pathology and more profound in healthy mice. Our findings highlight the need to consider this interaction between obesity and tau pathology when tailoring treatment strategies for AD and other tauopathies. Show more

Keywords: Alzheimer’s disease, diffusion tensor image, functional magnetic resonance image, high-fat diet, obesity, tau, transgenic mice, white matter integrity

DOI: 10.3233/JAD-230927

Citation: Journal of Alzheimer's Disease, vol. 97, no. 1, pp. 485-506, 2024

Authors: De Simone, Maria Stefania | Spalletta, Gianfranco | Vecchio, Daniela | Bassi, Andrea | Carlesimo, Giovanni Augusto | Piras, Fabrizio

Article Type: Research Article

Abstract: Background: Increasing evidence is demonstrating that degeneration of specific thalamic nuclei, in addition to the hippocampus, may occur in Alzheimer’s disease (AD) from the prodromal stage (mild cognitive impairment – MCI) and contribute to memory impairment. Objective: Here, we evaluated the presence of macro and micro structural alterations at the level of the anterior thalamic nuclei (ATN) and medio-dorsal thalamic nuclei (MDTN) in AD and amnestic MCI (aMCI) and the possible relationship between such changes and the severity of memory impairment. Methods: For this purpose, a sample of 50 patients with aMCI, 50 with AD, and …50 age- and education-matched healthy controls (HC) were submitted to a 3-T MRI protocol with whole-brain T1-weighted and diffusion tensor imaging and a comprehensive neuropsychological assessment. Results: At macro-structural level, both the ATN and MDTN were found significantly smaller in patients with aMCI and AD when compared to HC subjects. At micro-structural level, instead, diffusion alterations that significantly differentiated aMCI and AD patients from HC subjects were found only in the ATN, but not in the MDTN. Moreover, diffusion values of the ATN were significantly associated with poor episodic memory in the overall patients’ group. Conclusions: These findings represent the first in vivo evidence of a relevant involvement of ATN in the AD-related neurodegeneration and memory profile and strengthen the importance to look beyond the hippocampus when considering neurological conditions characterized by memory decline. Show more

Keywords: Alzheimer’s disease, anterior thalamic nuclei, diffusion tensor imaging, episodic memory, volumetry

DOI: 10.3233/JAD-230606

Citation: Journal of Alzheimer's Disease, vol. 97, no. 1, pp. 507-519, 2024

Authors: Nadeau, Patricia A. | Jobin, Benoît | Boller, Benjamin

Article Type: Correction

DOI: 10.3233/JAD-239013

Citation: Journal of Alzheimer's Disease, vol. 97, no. 1, pp. 521-521, 2024