Current Alzheimer Research - Volume 19, Issue 2, 2022

Background/Objective: Although a large number of studies have been performed on the association between Alzheimer’s disease (AD) and type 2 diabetes mellitus (DM), the underlying pathophysiology of AD associated with DM has not been fully elucidated to date. We compared cognitive functions and brain imaging findings between AD patients with and without DM to characterize the association between cognition and imaging findings in AD patients with DM. Methods: Cognitive functions and brain imaging findings, including medial temporal lobe atrophy analyzed by magnetic resonance imaging, and hypoperfusion in the parietal, posterior cingulate, and frontal regions analyzed by single-photon emission computed tomography were compared between 126 AD patients without DM ([AD-DM]) and 51 AD patients with DM ([AD+DM]). Factors associated with cognitive-imaging associations, including education, occupation, leisure activity, comorbidity, frailty, and other demographics, were analyzed. Results: The [AD+DM] group showed significantly more severe cognitive dysfunction than the [ADDM] group, despite a similar degree of brain imaging abnormalities. Among the factors associated with cognitive-imaging associations, the level of leisure activity was significantly lower in the [AD+DM] group than in the [AD-DM] group, but no significant differences in other factors were observed between the 2 groups. Conclusion: The cognitive-imaging discrepancy observed in AD patients with DM may be associated with their low cognitive reserve, possibly caused by their low amount of leisure activities. Our findings suggest that lifestyle interventions, including physical, cognitive, and social activities, may reduce cognitive decline in AD patients with DM.

Alzheimer's disease (AD) is the most common type of dementia, pathologically characterized by the accumulation of senile plaques and neurofibrillary tangles. Chronic kidney disease (CKD) is highly prevalent in the elderly population closely associated with the occurrence of dementia. Recent epidemiological and experimental studies suggest a potential association of CKD with AD. Both diseases share a panel of identical risk factors, such as type 2 diabetes and hypertension. However, the relationship between CKD and AD is unclear. Lower clearance of a panel of uremic toxin including cystatin- C, guanidine, and adiponectin due to CKD is implied to contribute to AD pathogenesis. In this review, we summarize the current evidence from epidemiological, experimental, and clinical studies on the potential contribution of uremic toxins to AD pathogenesis. We describe outstanding questions and propose an outlook on the link between uremic toxins and AD.

Electronically generated electromagnetic fields (EMFs), including those used in wireless communication such as cell phones, Wi-Fi and smart meters, are coherent, producing very high electric and magnetic forces, which act on the voltage sensor of voltage-gated calcium channels to produce increases in intracellular calcium [Ca²⁺]i. The calcium hypothesis of Alzheimer’s disease (AD) has shown that each of the important AD-specific and nonspecific causal elements is produced by excessive [Ca²⁺]i. [Ca²⁺]i acts in AD via excessive calcium signaling and the peroxynitrite/oxidative stress/inflammation pathway, which are each elevated by EMFs.An apparent vicious cycle in AD involves amyloid-beta protein (Aβ) and [Ca²⁺]i. Three types of epidemiology suggest EMF causation of AD, including early onset AD. Extensive animal model studies show that low intensity EMFs cause neurodegeneration, including AD, with AD animals having elevated levels of Aβ, amyloid precursor protein and BACE1. Rats exposed to pulsed EMFs every day are reported to develop universal or near universal very early onset neurodegeneration, including AD; these findings are superficially similar to humans with digital dementia. EMFs producing modest increases in [Ca²⁺]i can also produce protective, therapeutic effects. The therapeutic pathway and peroxynitrite pathway inhibit each other. A summary of 18 different findings is provided, which collectively provide powerful evidence for EMF causation of AD. The author is concerned that smarter, more highly pulsed “smart” wireless communication may cause widespread very, very early onset AD in human populations.

Background: Considering the lack of direct comparison between cholinesterase inhibitors and memantine in patients with vascular cognitive impairment (VCI), determining how to choose the best treatment plan remains inconclusive. Hence, we conducted the network meta-analysis to compare the efficacy and acceptability of these drugs. Methods: PubMed, the Cochrane Central Register of Controlled Trials, Embase and Web of Science were searched for double-blind randomized controlled trials (RCTs) for the treatment of VCI, which involved donepezil, galantamine, rivastigmine, and memantine, from database inception to January 1, 2020. Then, a network meta-analysis based on the frequency method was conducted. Results: Eleven RCTs were included. Compared with the placebo, in terms of efficacy, donepezil 5 mg (standardized mean difference = -1.11, 95% confidence interval = -1.88 to -0.34), donepezil 10 mg (-1.44, -2.31 to -0.56), galantamine 24 mg (-1.99, -3.03 to -0.95), and memantine 20 mg (-1.89, -2.93 to -0.86) were more effective for the cognition of ADAS-cog, and donepezil 5 mg (0.46, 0.12 to 0.81), donepezil 10 mg (0.76, 0.34 to 1.17), and rivastigmine 12mg (0.60, 0.10 to 1.10) exhibited superior benefits for the cognition of MMSE. Donepezil 10 mg (-0.25, -0.44 to -0.06; -1.47, -2.79 to -0.15) exhibited improvements for CDR-SB and EXIT25, respectively. In terms of acceptability, memantine was found to be the best. Conclusion: Donepezil 5 mg, donepezil 10 mg, galantamine 24 mg, memantine 20 mg, and rivastigmine 12 mg exerted beneficial effects on cognition, and donepezil 10mg provided beneficial effects for executive function and global status. Based on the network meta-analysis, donepezil 10 mg might be the best choice, considering the benefits on cognition function, executive function and global status, but doserelated adverse reactions need to be noted. In the meantime, memantine is a better comprehensive choice in terms of efficacy and safety.

Background: Epileptic activity frequently occurs in patients with Alzheimer’s disease (AD), which may accelerate AD progression; however, the relationship between AD and epilepsy remains unclear. Objective: We aimed to investigate the molecular pathways and genes linking AD and epilepsy using bioinformatics approaches. Methods: Gene expression profiles of AD (GSE1297) and epilepsy (GSE28674) were derived from the Gene Expression Omnibus (GEO) database. The top 50% expression variants were subjected to weighted gene co-expression network analysis (WGCNA) to identify key modules associated with these diseases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses for the key modules were performed, and the intersected terms of functional enrichment and common genes within the key modules were selected. The overlapping genes were subjected to analyses of protein-protein interaction (PPI) network, transcription factor (TF)-mRNA network, microRNA (miRNA)-mRNA network, and drug prediction. Results: We identified 229 and 1187 genes in the AD-associated purple and epilepsy-associated blue modules, respectively. Six shared functional terms between the two modules included “calcium ion binding” and “calcium signaling pathway.” According to 17 common genes discovered, 130 TFmRNA pairs and 56 miRNA-mRNA pairs were established. The topological analyses of the constructed regulatory networks suggested that TF - FOXC1 and miRNA - hsa-mir-335-5p might be vital co-regulators of gene expression in AD and epilepsy. In addition, CXCR4 was identified as a hub gene, becoming the putative target for 20 drugs. Conclusion: Our study provided novel insights into the molecular connection between AD and epilepsy, which might be beneficial for exploring shared mechanisms and designing disease-modifying therapies.

In the next few years, the prevalence of diabetes mellitus (DM) is projected to dramatically increase globally, but most of the cases will occur in low-to-middle-income countries. Some of the major risk factors for diabetes accelerate the development of dementia in African-Americans, thus leading to a higher prevalence of dementia than Caucasians. Sub-Saharian Africa women have a disproportionately two-to-eight fold increased prevalence of dementia. In the eye of this storm, Nigeria holds the highest number of diabetics on the African continent, and its prevalence is rising in parallel to obesity, hypertension, and the population’s aging. The socio-economic impact of the rising prevalence of DM and dementia will be huge and unsustainable for the healthcare system in Nigeria, as has been recognized in developed economies. Here, we analyze the current situation of women's health in Nigeria and explore future perspectives and directions. The complex interplay of factors involved in diabetes and dementia in Nigerian women include key biological agents (metabolic syndrome, vascular damage, inflammation, oxidative stress, insulin resistance), nutritional habits, lifestyle, and anemia, that worsen with comorbidities. In addition, restricted resources, lack of visibility, and poor management result in a painful chain that increases the risk and burden of disease in Nigerian women from youth to old ages. Heath policies to increase the ratio of mental health professionals per number of patients, mostly in rural areas, foment of proactive primary care centers, and interventions targeting adolescents and adult women and other specific mothers-children pairs are strongly required for a sustainable development goal.

Introduction: In healthy elderly persons and patients with mild cognitive impairment, physical exercise can increase functional brain connectivity in the default mode network (DMN) measured by restingstate functional magnetic resonance imaging (rs-fMRI). However, no studies have so far investigated the effect of physical exercise on functional resting-state connectivity in the DMN in patients with Alzheimer’s disease (AD). Objective: In a single-blinded randomized controlled trial, we assessed the effects of an aerobic exercise intervention of 16 weeks of physical exercise on DMN connectivity using rs-fMRI in patients with AD. Methods: Forty-five patients were randomly assigned to either a control or exercise group. The exercise group performed 60-min of aerobic exercise three times per week for 16 weeks. All the patients underwent whole-brain rs-fMRI at 3 T, at baseline, and after 16 weeks. Since the posterior cingulate cortex (PCC) and adjacent precuneus constitute a central hub of the DMN, this parietal region was defined as region-ofinterest and used as the seed region for functional connectivity analysis of the rs-fMRI data treating age and gender as covariates. Results: Neither seed-based analysis, seeded in the PCC/precuneus region nor ICA-based analyses, focusing on components of the DMN network, showed any exercise-induced changes in functional resting-state connectivity from baseline to follow-up. Conclusion: 16 weeks of aerobic exercise does not modify functional connectivity of the PCC/precuneus region in patients with AD. A longer intervention may be needed to show the effect of exercise on brain connectivity.