Current Alzheimer Research - Volume 19, Issue 5, 2022

Background: There is a well-described mechanism of communication between the brain and gastrointestinal system in which both organs influence the function of the other. This bi-directional communication suggests that disease in either organ may affect function in the other. Objective: To assess whether the evidence supports gastrointestinal system inflammatory or degenerative pathophysiology as a characteristic of Alzheimer's disease (AD). Methods: A review of both rodent and human studies implicating gastrointestinal changes in AD was performed. Results: Numerous studies indicate that AD changes are not unique to the brain but also occur at various levels of the gastrointestinal tract involving both immune and neuronal changes. In addition, it appears that numerous conditions and diseases affecting regions of the tract may communicate to the brain to influence disease. Conclusion: Gastrointestinal changes represent an overlooked aspect of AD, representing a more system influence of this disease.

Background: Traumatic brain injury (TBI) has been associated with an increased likelihood of late-life dementia; however, the mechanisms driving this relationship are elusive. Bloodbased biomarkers may provide insight into these mechanisms and serve as useful prognostic indicators of cognitive recovery or decline following a TBI. Objective: The aim of this study was to examine blood biomarkers within one year of TBI and explore their relationship with cognitive decline. Methods: Service members and veterans (n=224) without injury (n=77), or with a history of bodily injury (n=37), uncomplicated mild TBI (n=55), or more severe TBI (n=55), underwent a blood draw and neuropsychological assessment within one year of their injury as part of a case-control study. A subsample (n=87) completed a follow-up cognitive assessment. Results: In the more severe TBI group, baseline glial fibrillary acidic protein (p=.008) and ubiquitin C-terminal hydrolase-L1 (p=.026) were associated with processing speed at baseline, and baseline ubiquitin C-terminal hydrolase-L1 predicted change in immediate (R²Δ=.244, p=.005) and delayed memory (R²Δ=.390, p=.003) over time. In the mild TBI group, higher baseline tau predicted greater negative change in perceptual reasoning (R²Δ=.188, p=.033) and executive functioning (R²Δ=.298, p=.007); higher baseline neurofilament light predicted greater negative change in perceptual reasoning (R²Δ=.211, p=.012). Conclusion: Baseline ubiquitin C-terminal hydrolase-L1 strongly predicted memory decline in the more severe TBI group, while tau and neurofilament light strongly predicted decline in the mild TBI group. A panel including these biomarkers could be particularly helpful in identifying those at risk for future cognitive decline following TBI.

Background: Caring for a family member with dementia is stressful and challenging. Family caregivers, as a vulnerable marginalized population and invisible backbone of the health care system, need accessible and effective interventions that are tailored to their particular needs. Objectives: The objective of this study was to evaluate the feasibility and effectiveness of a live online mindfulness-based cognitive therapy (tele-MBCT) intervention for family caregivers of individuals with dementia. Methods: Family caregivers were assigned to a tele-MBCT intervention or a usual care control group. Tele-MBCT participants attended eight weekly live online training and practiced mindfulness practices at home. All participants completed surveys at baseline, post-intervention, and 4-week follow-up. Results: 26 participants (age 60±13 years) were enrolled and randomized (14 in the intervention and 12 in the control group), and 92.3% completed the study. 88% of the participants were female, and 70% were caring for a parent for a mean of 5.12±2.88 years. 84% of the participants in the intervention group attended at least seven sessions and the average of daily practice was 23.58±45.71 minutes. All participants were satisfied with the intervention, and 88.8% were satisfied with the online delivery method. Participants in the intervention group showed Pre-Post improvement in self-compassion (t (11) = -2.49, p=0.03) and coping strategies (t (11) = 3.62, p=0.004) compared to the control group. Conclusion: Tele-MBCT is a feasible intervention and may improve psychological outcomes and adaptive coping in family caregivers of individuals with dementia. A larger controlled trial is warranted.

Background: The development of automatic speech recognition (ASR) technology allows the analysis of temporal (time-based) speech parameters characteristic of mild cognitive impairment (MCI). However, no information has been available on whether the analysis of spontaneous speech can be used with the same efficiency in different language environments. Objective: The main goal of this international pilot study is to address the question of whether the Speech-Gap Test® (S-GAP Test®), previously tested in the Hungarian language, is appropriate for and applicable to the recognition of MCI in other languages such as English. Methods: After an initial screening of 88 individuals, English-speaking (n = 33) and Hungarianspeaking (n = 33) participants were classified as having MCI or as healthy controls (HC) based on Petersen’s criteria. The speech of each participant was recorded via a spontaneous speech task. Fifteen temporal parameters were determined and calculated through ASR. Results: Seven temporal parameters in the English-speaking sample and 5 in the Hungarian-speaking sample showed significant differences between the MCI and the HC groups. Receiver operating characteristics (ROC) analysis clearly distinguished the English-speaking MCI cases from the HC group based on speech tempo and articulation tempo with 100% sensitivity, and on three more temporal parameters with high sensitivity (85.7%). In the Hungarian-speaking sample, the ROC analysis showed similar sensitivity rates (92.3%). Conclusion: The results of this study in different native-speaking populations suggest that changes in acoustic parameters detected by the S-GAP Test® might be present across different languages.

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease affecting the elderly, characterized by decreased cognitive function. Non-coding RNAs contribute to AD pathogenesis. Objective: To identify potential therapeutic targets for AD, competing endogenous RNA (ceRNA) networks were constructed using the hippocampus of 6-month-old amyloid precursor protein/ presenilin 1 double transgenic (APP/PS1) and wild-type mice. Methods: RNA-seq data (GSE158995), generated from the hippocampus of APP/PS1 and wild-type mice, were analyzed with the limma R package to identify significantly differentially expressed mRNAs and circRNAs (DEMs and DECs, respectively). DEM Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using Enrichr (https://maayanlab.cloud/Enrichr/). Correlations between DEMs and DECs were determined using the ggcorrplot R package. Main clusters and hub DEMs were selected using the STRING database and Cytoscape software. ceRNA interactions were predicted with the miRTarbase and Starbase tools and constructed with the ggalluvial R package and Cytoscape software. ceRNA networks were validated using the quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot. Results: 198 DEMs and 90 DECs were differentially expressed in APP/PS1 vs. wild-type hippocampus. DEM GO analysis revealed significant enrichment in transcription regulation, which was subdivided into three main clusters: transcription regulation, synaptic plasticity, and protein refolding. Within the transcription regulation cluster, AP-1 transcription factor components serve as hub genes. The mmu_circ_0001787(circGLCE)/miR-339-5p/Junb and mmu_circ_0001899(circFAM120C)/ miR-181a-5p/Egr1 ceRNA networks were established based on qRT-PCR and Western blot analysis. Conclusion: Two AP-1 transcription factor component-related ceRNA networks, circGLCE/miR- 339-5p/Junb and circFAM120C/miR-181a-5p/Egr1, were constructed using a mouse model of AD. These ceRNA networks may contribute to transcription regulation in AD and provide potential biomarkers for AD diagnosis and treatment.