Current Alzheimer Research - Volume 19, Issue 14, 2022

Alzheimer Disease (AD) pathology has been linked to brain accumulation of β amyloid (Aβ) and neurofibrillary tau tangles. An intriguing question is whether targeting factors independent of Aβ and tau pathologies could delay or even stop neurodegeneration. Amylin, a pancreatic hormone cosecreted with insulin, is believed to play a role in the central regulation of satiation and was shown to form pancreatic amyloid in persons with type-2 diabetes mellitus. Accumulating evidence demonstrates that amyloid-forming amylin secreted from the pancreas synergistically aggregates with vascular and parenchymal Aβ in the brain in both sporadic and early-onset familial AD. Pancreatic expression of amyloid-forming human amylin in AD-model rats accelerates AD-like pathology, whereas genetically suppressed amylin secretion protects against AD effects. Thus, current data suggest a role of pancreatic amyloid-forming amylin in modifying AD; further research is required to test whether lowering circulating amylin levels early during AD pathogenesis may curb cognitive decline.

Alzheimer’s disease (AD) is a progressive, multifactorial, chronic, neurodegenerative disease with high prevalence and limited therapeutic options, making it a global health crisis. Being the most common cause of dementia, AD erodes the cognitive, functional, and social abilities of the individual and causes escalating medical and psychosocial needs. As yet, this disorder has no cure and current treatment options are palliative in nature. There is an urgent need for novel therapy to address this pressing challenge. Digital therapeutics (Dtx) is one such novel therapy that is gaining popularity globally. Dtx provides evidence based therapeutic interventions driven by internet and software, employing tools such as mobile devices, computers, videogames, apps, sensors, virtual reality aiding in the prevention, management, and treatment of ailments like neurological abnormalities and chronic diseases. Dtx acts as a supportive tool for the optimization of patient care, individualized treatment and improved health outcomes. Dtx uses visual, sound and other non-invasive approaches for instanceconsistent therapy, reminiscence therapy, computerised cognitive training, semantic and phonological assistance devices, wearables and computer-assisted rehabilitation environment to find applications in Alzheimer's disease for improving memory, cognition, functional abilities and managing motor symptom. A few of the Dtx-based tools employed in AD include "Memory Matters", "AlzSense", "Alzheimer Assistant", "smart robotic dog", "Immersive virtual reality (iVR)" and the most current gamma stimulation. The purpose of this review article is to summarize the current trends in digital health in AD and explore the benefits, challenges, and impediments of using Dtx as an adjunctive therapy for the management of AD.

Background: Ketamine is a widely used anesthetic agent. Although the potential adverse effects of ketamine use in juvenile age are uncertain, certain studies reported that children exposed to recurrent anesthesia could face an increased risk of neurodevelopmental deficits in motor function and behavioral risks. We aimed to investigate the long-term effects of repeated exposure to various ketamine doses on anxious behavior and locomotor activity in juvenile rats. Objective: We aimed to investigate the long-term effects of repeated exposure to various ketamine doses on anxious behavior and locomotor activity in juvenile rats. Methods: Thirty-two Wistar Albino juvenile male rats were randomized into 5 mg/kg, 20 mg/kg, and 50 mg/kg ketamine (KET) and saline (Group C) Groups and KET was administered for 3 consecutive days at 3-hour intervals in 3 doses. Ten days after the last KET dose, behavioral parameters were analyzed with an open field test (OFT), elevated plus maze (EPM), and light-dark box (LDB). Satistical analysis was conducted with Kruskall-Wallis test followed by Dunn's Multiple Comparison Test. Results: Unsupported rearing behavior decreased in 50 mg/kg KET Groups when compared to Group C. Incorrect transition time, total grooming time, and transfer latency time increased significantly in the 50 mg/kg KET Group when compared to Group C. Conclusion: These results suggested that 50 mg/kg KET led to anxiety-like behavior and destroyed memory and spatial navigation. Ketamine doses were associated with late effects of ketamine on anxiety- like behavior in juvenile rats. Further studies are needed to determine the mechanisms that play a role in the different effects of ketamine doses on anxiety and memory.

Background: The hippocampus, entorhinal cortex, and fusiform gyrus are brain areas that deteriorate during early-stage Alzheimer’s disease (AD). The ApoE4 allele has been identified as a risk factor for AD development, is linked to an increase in the aggregation of amyloid β (Aβ) plaques in the brain, and is responsible for atrophy of the hippocampal area. However, to our knowledge, the rate of deterioration over time in individuals with AD, with or without the ApoE4 allele, has not been investigated. Methods: In this study, we, for the first time, analyze atrophy in these brain structures in AD patients with and without the ApoE4 using the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset. Results: It was found that the rate of decrease in the volume of these brain areas over 12 months was related to the presence of ApoE4. Further, we found that neural atrophy was not different for female and male patients, unlike prior studies, suggesting that the presence of ApoE4 is not linked to the gender difference in AD. Conclusion: Our results confirm and extend previous findings, showing that the ApoE4 allele gradually impacts brain regions impacted by AD.

Background: Sleep problems are very prevalent in older adults, especially in those at risk for dementia. But the relationships between sleep parameters and subjective or objective cognitive decline are still inconclusive. Aim: The study aimed to investigate the self-reported and objectively measured sleep characteristics in older adults with mild cognitive impairment (MCI) and subjective cognitive decline (SCD). Methods: This study adopted a cross-sectional design. We included older adults with SCD or MCI. Sleep quality was measured separately by the Pittsburgh sleep quality index (PSQI) and ActiGraph. Participants with SCD were divided into low, moderate, and high levels of SCD groups. Independent samples T-tests, one-way ANOVA, or nonparametric tests were used to compare the sleep parameters across groups. Covariance analyses were also performed to control the covariates. Results: Around half of the participants (45.9%) reported poor sleep quality (PSQI<7), and 71.3% of participants slept less than 7 hours per night, as measured by ActiGraph. Participants with MCI showed shorter time in bed (TIB) (p<0.05), a tendency of shorter total sleep time (TST) at night (p = 0.074) and for each 24-hour cycle (p = 0.069), compared to those with SCD. The high SCD group reported the highest PSQI total score and longest sleep latency than all the other three groups (p<0.05). Both the MCI and high SCD groups had shorter TIB and TST for each 24-hour cycle than the low or moderate SCD groups. Besides, participants with multiple-domain SCD reported poorer sleep quality than those with single-domain SCD (p<0.05). Conclusion: Sleep dysregulation is prevalent in older adults with a risk for dementia. Our findings revealed that objectively measured sleep duration might be an early sign of MCI. Individuals with high levels of SCD demonstrated poorer self-perceived sleep quality and deserved more attention. Improving sleep quality might be a potential target to prevent cognitive decline for people with a risk for dementia.

Background: Depression is one of the most common neuropsychiatric symptoms of Alzheimer’s disease (AD) which decreases the life quality of both patients and caregivers. There are currently no effective drugs. It is therefore important to explore the pathogenesis of depression in AD patients. Objective: The present study aimed to investigate the characteristics of the entorhinal cortex (EC) functional connectivity (FC) in the whole brain neural network of AD patients with depression (DAD). Methods: Twenty-four D-AD patients, 14 AD patients without depression (nD-AD), and 20 healthy controls underwent resting-state functional magnetic resonance imaging. We set the EC as the seed and used FC analysis. One-way analysis of variance was used to examine FC differences among the three groups. Results: Using the left EC as the seed point, there were FC differences among the three groups in the left EC-inferior occipital gyrus. Using the right EC as the seed point, there were FC differences among the three groups in the right EC-middle frontal gyrus, -superior parietal gyrus, -superior medial frontal gyrus, and -precentral gyrus. Compared with the nD-AD group, the D-AD group had increased FC between the right EC and right postcentral gyrus. Conclusion: Asymmetry of FC in the EC and increased FC between the EC and right postcentral gyrus may be important in the pathogenesis of depression in AD.