Search Results (4,925)

Cannabis sativa is known for producing over 120 distinct phytocannabinoids, with Δ⁹-tetrahydrocannabinol (Δ⁹-THC) and cannabidiol (CBD) being the most prominent, primarily in their acidic forms. Beyond Δ⁹-THC and CBD, a wide array of lesser-known phytocannabinoids, along with terpenes, flavonoids, and alkaloids, demonstrate diverse pharmacological activities, interacting with the endocannabinoid system (eCB) and other biological pathways. These compounds, characterized by phenolic structures and hydroxyl groups, possess lipophilic properties, allowing them to cross the blood–brain barrier (BBB) effectively. Notably, their antioxidant, anti-inflammatory, and neuro-modulatory effects position them as promising agents in treating neurodegenerative disorders. While research has extensively examined the neuropsychiatric and neuroprotective effects of Δ⁹-THC, other minor phytocannabinoids remain underexplored. Due to the well-established neuroprotective potential of CBD, there is growing interest in the therapeutic benefits of non-psychotropic minor phytocannabinoids (NMPs) in brain disorders. This review highlights the emerging research on these lesser-known compounds and their neuroprotective potential. It offers insights into their therapeutic applications across various major neurological conditions. Full article

Identifying effective and accessible interventions for family caregivers of persons with dementia (PWD) is crucial as the prevalence of dementia increases in Asia. This study investigated the efficacy of a telephone-intervention on the reduction in caregiver burden, as well as depressive and anxiety symptoms among family caregivers (FCs) of PWD in Malaysia. A single-blinded randomized controlled trial was carried out with 121 FCs of PWD selected from memory or psychiatry clinics in three tertiary hospitals in Malaysia, who were randomly allocated into the intervention or control group. The intervention group received the psychoeducational intervention delivered by healthcare staff via telephone for 10 sessions over 12 weeks. The outcome of the intervention was measured by the Malay version of the Zarit Burden Interview and the Hospital Anxiety and Depression Scale at baseline and post-intervention. An intention to treat analysis shows that caregiver burden, anxiety symptoms, and psychological distress among FCs in the intervention group decreased by 7.57 units (p < 0.001), 2.46 units (p < 0.001), and 2.98 units (p = 0.011), respectively, at post-intervention, compared to the differences from baseline to post-intervention in the control group. Policies aimed at integrating the telephone-intervention into memory/psychiatry clinics in Malaysia may help FCs of PWD to reduce their caregiver burden and stress while caring for a family member with dementia. Full article

This review explores the potential health benefits and applications of phenolic secoiridoids derived from olive oil by-products in the prevention of Alzheimer’s disease (AD). As reviewed herein, polyphenols, such as epigallocatechin-3-gallate, epicatechin, and resveratrol, show in vitro and in vivo antioxidant, anti-inflammatory, and neuroprotective properties, and are particularly relevant in the context of AD, a leading cause of dementia globally. The olive oil industry, particularly in the Mediterranean region, produces significant amounts of waste, including leaves, pomace, and wastewater, which pose environmental challenges but also offer an untapped source of bioactive compounds. Despite promising in vitro and in vivo studies indicating that olive-derived polyphenols, such as oleuropein and hydroxytyrosol, may mitigate AD pathology, human clinical trials remain limited. The variability in extraction methods and the complex nature of AD further complicate research. Future studies should focus on standardizing the protocols and conducting robust clinical trials to fully assess the therapeutic potential of these compounds. This approach not only supports the development of new treatments for AD but also promotes environmental sustainability by valorizing olive oil industry waste. Full article

Background: Chronic kidney disease (CKD) is a risk factor for cognitive impairment (CI), and this risk is the highest in patients with end-stage kidney disease (ESKD). As a multifactorial disease, CI may be influenced by several potentially modifiable lifestyle and behavioral factors that may reduce or increase the risk of dementia. The aim of this study was to evaluate the associations between the known modifiable risk factors for dementia and the risk of CI in patients with ESKD treated with renal replacement therapy. The Charlson Comorbidity Index and the risk of CI in patients with ESKD were also assessed. Methods: In this cross-sectional study, 225 consecutive patients with ESKD treated with different modalities of renal replacement therapy were assessed for cognitive decline using the Addenbrooke’s Cognitive Examination (ACE III) test. Information was also collected on modifiable risk factors for dementia, medical history and demographics. Results: This study included 117 patients after kidney transplantation (KT) and 108 patients with ESKD undergoing peritoneal dialysis and hemodialysis. The prevalence of modifiable risk factors for dementia differed between the groups; KT patients were more likely to be physically active, residing in cities with populations of less than 500,000 inhabitants, and were less likely to suffer from depression. Furthermore, the KT group had a lower Charlson Comorbidity Index score, indicating less severe comorbidities, and a lower risk of CI (3.6 ± 1.67 vs. 5.43 ± 2.37; p = 0.001). In both the KT and dialysis groups, patients with CI were more likely to have a sedentary lifestyle (45% vs. 9%, p = 0.001 and 88% vs. 48%, p = 0.001, respectively), whereas lower educational attainment and depression had a significant negative impact on ACE III test results, but only in KT patients. Finally, cognitive function in dialysis patients was negatively affected by social isolation and living in urban areas. Conclusions: Modifiable risk factors for dementia, particularly a sedentary lifestyle, are associated with a higher risk of CI in patients treated with different renal replacement therapy modalities. As CI is an irreversible condition, it is important to identify lifestyle-related factors that may lead to dementia in order to improve or maintain cognitive function in patients with ESKD. Full article

Patients with Alzheimer’s disease and related dementia (ADRD) are faced with a formidable challenge of focal amyloid deposits and cerebral amyloid angiopathy (CAA). The treatment of amyloid deposits in ADRD by targeting only oxidative stress, inflammation and hyperlipidemia has not yielded significant positive clinical outcomes. The chronic high-fat diet (HFD), or gut dysbiosis, is one of the major contributors of ADRD in part by disrupted transport, epigenetic DNMT1 and the folate 1-carbon metabolism (FOCM) cycle, i.e., rhythmic methylation/de-methylation on DNA, an active part of epigenetic memory during genes turning off and on by the gene writer (DNMT1) and eraser (TET2/FTO) and the transsulfuration pathway by mitochondrial 3-mercaptopyruvate sulfur transferase (3MST)-producing H₂S. The repeat CAG expansion and m⁶A disorder causes senescence and AD. We aim to target the paradigm-shift pathway of the gut–brain microbiome axis that selectively inhibits amyloid deposits and increases mitochondrial transsulfuration and H₂S. We have observed an increase in DNMT1 and decreased FTO levels in the cortex of the brain of AD mice. Interestingly, we also observed that probiotic lactobacillus-producing post-biotic folate and lactone/ketone effectively prevented FOCM-associated gut dysbiosis and amyloid deposits. The s-adenosine-methionine (SAM) transporter (SLC25A) was increased by hyperhomocysteinemia (HHcy). Thus, we hypothesize that chronic gut dysbiosis induces SLC25A, the gene writer, and HHcy, and decreases the gene eraser, leading to a decrease in SLC7A and mitochondrial transsulfuration H₂S production and bioenergetics. Lactobacillus engulfs lipids/cholesterol and a tri-directional post-biotic, folic acid (an antioxidant and inhibitor of beta amyloid deposits; reduces Hcy levels), and the lactate ketone body (fuel for mitochondria) producer increases SLC7A and H₂S (an antioxidant, potent vasodilator and neurotransmitter gas) production and inhibits amyloid deposits. Therefore, it is important to discuss whether lactobacillus downregulates SLC25A and DNMT1 and upregulates TET2/FTO, inhibiting β-amyloid deposits by lowering homocysteine. It is also important to discuss whether lactobacillus upregulates SLC7A and inhibits β-amyloid deposits by increasing the mitochondrial transsulfuration of H₂S production. Full article

Informal caregivers play a crucial role in the care of individuals with dementia, and their caregiving may significantly impact their own health and well-being. This cross-sectional survey study focuses on the perceived importance of various types and characteristics of formal support in a convenience sample of caregivers aged 65 years or older (n = 175) caring for a spouse with dementia. Participants completed a questionnaire containing 17 items describing different types of support and 12 items describing different characteristics of support, rating their importance. The questionnaire also contained questions on various caregiving-related factors. Principle components analysis (PCA) was carried out on the importance ratings, separately, on the types of support items and the characteristics of support items. Each PCA produced three components. For types of support, they were Proficiency and Opportunity, Supportive Structures, Flexible Counselling. For characteristics of support, they included Respectful and Competent, Timely Support, and Accessible and Acceptable. The three characteristics of the support components all had higher mean importance ratings than the three types of support components. The content of some components indicated that while spouse caregivers rate support for their caregiving needs as important, they may not always differentiate their own needs from those of their partner with dementia. The negative impact of caregiving was the factor most strongly and consistently associated with the components’ importance ratings. This study emphasizes the need for health and social care providers to address the unique needs of spouse caregivers while simultaneously ensuring the delivery of quality care for individuals with dementia. Full article

Alzheimer’s disease (AD), the most prevalent form of dementia, is expected to rise dramatically in incidence due to the global population aging. Traditional diagnostic approaches, such as cerebrospinal fluid analysis and positron emission tomography, are expensive and invasive, limiting their routine clinical use. Recent advances in blood-based biomarkers, including amyloid-beta, phosphorylated tau, and neurofilament light, offer promising non-invasive alternatives for early AD detection and disease monitoring. This review synthesizes current research on these blood-based biomarkers, highlighting their potential to track AD pathology and enhance diagnostic accuracy. Furthermore, this review uniquely integrates recent findings on protein-protein interaction networks and microRNA pathways, exploring novel combinations of proteomic, genomic, and epigenomic biomarkers that provide new insights into AD’s molecular mechanisms. Additionally, we discuss the integration of these biomarkers with advanced neuroimaging techniques, emphasizing their potential to revolutionize AD diagnostics. Although large-scale validation is still needed, these biomarkers represent a critical advancement toward more accessible, cost-effective, and early diagnostic tools for AD. Full article

(1) Background: Plasmalogens are vinyl ether-type glycerophospholipids that are characteristically distributed in neural tissues and are significantly reduced in the brains of individuals with dementia compared to those in healthy subjects, suggesting a link between plasmalogen deficiency and cognitive decline. Hen eggs are expected to be a potential source of dietary plasmalogens, but the details remain unclear. (2) Methods: We evaluated the fresh weight, dry weight, total lipid, neutral lipids, glycolipids, and phospholipids in the egg yolk and egg white of hen egg. Then, the molecular species of plasmalogens were quantified using HPLC-ESI-MS/MS. (3) Results: In egg yolk, the total plasmalogen content was 1292.1 µg/100 g fresh weight and predominantly ethanolamine plasmalogens (PE-Pls), specifically 18:0/22:6-PE-Pls, which made up 75.6 wt% of the total plasmalogen. In egg white, the plasmalogen content was 31.4 µg/100 g fresh weight and predominantly PE-Pls, specifically 18:0/20:4-PE-Pls, which made up 49.6 wt% of the total plasmalogen. (4) Conclusions: Plasmalogens were found to be more enriched in egg yolk than in egg white. It was found that humans are likely to ingest almost 0.3 mg of total plasmalogens from one hen egg. These findings highlight the importance of plasmalogens in the daily diet, and it is recommended to explore the impact of long-term dietary plasmalogen intake to assess its effect on human health. This provides a viewpoint for the development of new food products. Full article

Background: Many studies have reported on the relationship between cognitive and masticatory functions. However, it remains unclear how the mandibular movements change during chewing in facility residents as dementia progresses. This study aimed to investigate the relationship between a kinematic analysis of mandibular movement during mastication and cognitive function in facility residents. Methods: Sixty-three participants were included from two long-term care facilities. The primary outcome variable was the kinematic data of mandibular movement during mastication. The participants chewed rice crackers, and their faces were recorded during this motion. The partial correlation coefficient between kinematic data and cognitive function was calculated. Furthermore, group comparisons were performed after dividing the participants into three groups based on their cognitive function. Results: Circular motion frequency was significantly correlated with the ABC dementia scale, even after adjusting for the appendicular skeletal muscle index, Eichner index, and short-form mini-nutritional assessment. The cycle and circular motion frequencies were markedly lower in the severe dementia group than in the mild dementia group. Conclusions: With declining cognitive function, mandibular movements during mastication decrease in circular motion and increase in linear motion. Additionally, our results suggested that residents with severe cognitive impairment had more linear mandibular motions during mastication than those with mild cognitive impairment. This may make it more difficult for residents with cognitive decline to ingest normal solid foods. Full article

Recently, an association between dysbiosis of the gut microbiota (GMB) and the development of several diseases, such as Alzheimer’s disease (AD), has been proposed. Dysbiosis involves changes in microbial diversity influenced by environmental factors, like diet or lifestyle. In this study, we investigated the role of GMB parameters in Spanish AD patients, assessing the impact of adherence to the Mediterranean lifestyle (ML), as well as to characterize these parameters in relation to neuropsychological, neuropsychiatric, emotional, and functionality parameters. A case–control study was conducted to investigate the association between the composition of the GMB and cognitive, emotional, neuropsychiatric, and functionality status in Spanish AD patients, along with a shotgun metagenomics approach. Richness and alpha-diversity were significantly lower in the AD group compared to the controls. PERMANOVA and ANOSIM tests of Bray–Curtis dissimilarity, Aitchison distance, and Jaccard similarity did not showed significant differences in beta-diversity between the two groups. Moreover, associations between various phyla of the AD group and orientation performance, food consumption, and activities of daily living were identified. Dysbiosis observed in Spanish AD patients is characterized by reductions in richness and alpha-diversity, alongside alterations in GMB composition, which may be linked to adherence to the ML and cognitive and functionality symptoms. Full article

This literature review explores the association between hypertension and major neurocognitive disorders, including delirium, Alzheimer’s disease, vascular dementia, Lewy body dementia, and frontotemporal dementia, which contribute significantly to global mortality and morbidity. Hypertension is a potentially modifiable risk factor for cognitive decline, as it contributes to the progression of neurodegenerative pathologies via vascular damage, inflammation, and the disruption of the blood–brain barrier. Despite this, the effectiveness of antihypertensive treatments in preventing or alleviating cognitive decline remains contentious. While some research highlights the potential benefits of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, other studies show inconsistent results, complicated by variations in hypertension definitions, diagnostic criteria for cognitive disorders, and confounding factors like medication adherence. Furthermore, the complex bidirectional relationship between hypertension and major neurocognitive disorders warrants more investigation, as cognitive decline can exacerbate cardiovascular risks through heightened inflammatory responses and compromised autonomic regulation. This review underscores the need for prospective, long-term studies to elucidate the relationships between hypertension and cognitive disorders and to evaluate the potential therapeutic benefits of antihypertensive treatments. Full article

Background: The aging population is associated with a net increase in the incidence and prevalence of chronic-degenerative diseases, particularly neurocognitive disorders. Therefore, the identification of preventative strategies to restrain the burden of such chronic conditions is of key relevance. Red wine and its components have accumulated evidence regarding their positive effects in terms of neurological pathologies associated with neurocognitive symptoms. Methods: Based on this background, the present narrative review aims to summarize the state-of-the-art evidence on the effects of red wine and its components on neurocognitive disorders in both preclinical and clinical settings. Results: The main findings highlight a protective effect of wine polyphenols present in red wine on dementia in different preclinical models of cognitive decline. The current translational clinical evidence remains uncertain, especially considering the risk-to-benefit ratio of alcohol consumption on brain health. Conclusions: Given the overall health risks associated with red wine consumption and consistent with the prevailing guidelines in the literature, there is insufficient evidence to support light-to-moderate red wine consumption as an effective strategy for preventing these diseases. However, the largely preclinical findings on polyphenols derived from red wine remain of significant interest in this context. Full article

Due to the continuous aging of the population and consequent increase in dementia, focus on its prevention is of growing importance for public health. Since effective pharmacological treatments are not yet available, other determinants of cognitive decline have become fundamental. Several studies have indicated that the Mediterranean diet (MedDiet) is associated with reduced incident cognitive decline and dementia, but few studies have been conducted in persons already diagnosed with Alzheimer’s disease (AD). We age-matched 73 patients with mild–moderate AD with 73 controls (mean age for the whole group = 76.5 ± 6.5; 67.5% women). The cases had a significantly lower adherence to the MedDiet and lower physical activity vs. controls, where only one participant (1.4%) had a high adherence to the MedDiet among cases compared to 5.5% among controls, while 52.5% of the cases had a moderate adherence to the MedDiet vs. 82.2% in controls. In multivariate analysis, only the presence of AD was significantly associated with a lower adherence to the MedDiet vs. controls. Other factors examined (gender, age, physical activity level, multimorbidity, and polypharmacy) were not significantly associated with adherence to the MedDiet. Thus, AD patients had a low adherence to the MedDiet and very low physical activity. Public health strategies aimed at promoting the Mediterranean diet and physical activity for older people should be a priority. Full article

FOXG1 syndrome is a rare neurodevelopmental disorder of the telencephalon, for which there is no cure. Underlying heterozygous pathogenic variants in the Forkhead Box G1 (FOXG1) gene with resulting impaired or loss of FOXG1 function lead to severe neurological impairments. Here, we report a patient with a de novo pathogenic single nucleotide deletion c.946del (p.Leu316Cysfs*10) of the FOXG1 gene that causes a premature protein truncation. To study this variant in vivo, we generated and characterized Foxg1 c946del mice that recapitulate hallmarks of the human disorder. Accordingly, heterozygous Foxg1 c946del mice display neurological symptoms with aberrant neuronal networks and increased seizure susceptibility. Gene expression profiling identified increased oligodendrocyte- and myelination-related gene clusters. Specifically, we showed that expression of the c946del mutant and of other pathogenic FOXG1 variants correlated with overexpression of proteolipid protein 1 (Plp1), a gene linked to white matter disorders. Postnatal administration of Plp1-targeting antisense oligonucleotides (ASOs) in Foxg1 c946del mice improved neurological deficits. Our data suggest Plp1 as a new target for therapeutic strategies mitigating disease phenotypes in FOXG1 syndrome patients. Full article

Introduction: Cognitive impairment, marked by a decline in memory and attention, is frequently underdiagnosed, complicating effective management. Cardiovascular risk factors (CVR) and anticholinergic burden (ACB) are significant contributors to dementia risk, with ACB often stemming from medications prescribed for neuropsychiatric disorders. This study evaluates cognitive profiles through three brief cognitive tests, analyzing the impact of CVR and ACB presence. Methods: This cross-sectional study was performed between 2019 and 2023 in community pharmacies and an outpatient clinic in Valencia, Spain. Eligible participants were patients with subjective memory complaints 50 years or older with clinical records of cardiovascular factors. Patients with conflicting information regarding diabetes diagnosis or not taking concomitant medications were excluded. Three brief cognitive tests (Memory Impairment Screening (MIS), Semantic Verbal Fluency Test, and SPMSQ) were assessed. CVR was calculated using the European SCORE2 table, and ACB was assessed using the CALS scale. Results: Among 172 patients with memory complaints and CVR factors, 60% failed at least one cognitive test. These patients were on significantly more medications and had higher blood pressure and HbA1c levels. An increase in CVR and ACB was associated with more failed tests. Additionally, elevated SCORE2 scores were associated with a greater failure rate on the MIS test, while patients with elevated ACB more frequently failed the SPMSQ test. Conclusions: Selecting an adequate brief cognitive test according to patients’ characteristics offers an opportunity to screen patients who are probably cognitively impaired. Whereas the MIS test may be helpful for patients with cardiovascular risk, SPMSQ stands out among patients with significant ACB. Full article