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Background: The population aged 80 or over has increased, which may predispose people to dementia. Validated scales are used to diagnose them. The study aimed to compare cognitive evolution and associated factors in individuals aged 80 or over. Method: The Research Ethics Committee from the University of Southern Santa Catarina (UNESC) authorized the study under 3,214,698. It was an observational, quantitative study with a cohort design. Individuals aged 80 or over were recruited for this study. One hundred twenty‐four participants were evaluated in 2016. After six years, they were reevaluated, with 102 participants lost to follow‐up, resulting in 22 participants for reapplication. In addition, 78 new participants entered the study, totaling 100 participants in 2022. Cognitive tests such as the Mini‐Mental State Examination (MMSE), Clock Test, Verbal Fluency, and Montreal Cognitive Assessment (MOCA) were applied. Result: When comparing the two times, there was a significant difference in the percentage of retirement and participation in some activities in the community. Compared to cognitive tests, a decrease in cognitive decline and verbal fluency was observed in 2022, assessed by the MMSE. When the 22 individuals were evaluated over six years, there was a significant change in participation in community activities. When asked about difficulty remembering things, people, or situations, there was a reduction in 2022. Unlike the MMSE and the verbal fluency test, the MOCA showed cognitive impairment in most individuals in 2022. Conclusion: It is concluded that the population of 2016 and 2022 showed some differences related to cognition, but this difference was not observed in the 22 individuals. These results indicate a divergence between the tests. Considering the many differences in the Brazilian population, it is necessary to standardize a cognitive test suitable for screening cognitive decline. [ABSTRACT FROM AUTHOR]

Background: Aging is a natural, irreversible process that can be successful or pathological, resulting in chronic degenerative diseases such as Alzheimer's disease. Low levels of estrogen characterize menopause. Research reveals that the lack of these hormones may be related to dementia and that vitamin D (vit D), when supplemented, has a neuroprotective and neuromodulator effect. Method: 60‐ or 120‐day‐old Wistar rats were subjected to ovariectomy (OVX) for either 1 or 8 months, treatment with oral administration of Vit D (42 or 420 IU/kg) and/or DONE (1 mg/kg) spanned 21 days. On the 22nd day of the protocol, 24 hours post the final administration, the prefrontal cortex and hippocampus were dissected for cytokine analysis, including interleukin 10 (IL‐10), IL‐1 β, and tumor necrosis factor α (TNF‐ α), conducted through enzyme immunoassay. Result: In 60‐day‐old rats undergoing one month of ovariectomy (OVX), elevated IL‐1β and TNF‐α levels were observed in the brain. The optimal dose for mitigating these effects was found to be vitamin D (Vit D) at 420 IU/kg, either alone or in combination with DONE. This dosage successfully reversed the increased IL‐1β levels in the frontal cortex and normalized the elevated TNF‐α levels in the hippocampus. Similarly, in rats subjected to OVX for eight months, the most effective dose for reversing increased IL‐1β levels in the frontal cortex and hippocampus was Vit D at 420 IU/kg. However, in this protocol, TNF‐α levels remained unchanged, emphasizing the selective impact of this particular dosage. Additionally, the optimal dose for modulating IL‐10 levels in the frontal cortex, particularly in the context of increased IL‐10 following OVX, was Vit D at 420 IU/kg. Conclusion: The administration of vitamin D either alone or in combination with DONE (a specific treatment) demonstrated favorable outcomes in the rats, effectively mitigating the inflammatory response. [ABSTRACT FROM AUTHOR]

Background: The increasing prevalence of neurodegenerative diseases, particularly among women post‐menopause, is linked to the decline in 17 β estradiol (E2). Vitamin D deficiency, common in older individuals, exacerbates this risk due to its anti‐inflammatory and neuroprotective properties. Hypovitaminosis D is associated with age‐related conditions, including cognitive decline. Donepezil, an acetylcholinesterase inhibitor used for Alzheimer's dementia, targets cholinergic dysfunction in normal aging and prodromal states of this disease, suggesting a potential intervention for early disease modification. Method: Adult female Wistar rats aged 60 or 120 days were used, submitted to ovariectomy (OVX) for 1, 4, or 8 months, supplemented with vit D, at doses of 42 and 420 IU/kg, or water or combined with DONE (1 mg/kg) orally by gavage for 21 days. The open field test (OFT) and Y‐maze test were performed. Result: Ovariectomized rats at 60 and 120 days of age exhibit deficits in short‐term spatial reference memory, as evidenced by performance in the Y‐maze task. In the OFT, 60‐day‐old rats subjected to OVX for four months displayed impairment, a trend also observed in rats of the same age undergoing OVX for eight months, both in the control and OVX groups. Notably, 120‐day‐old rats subjected to OVX for 4 and 8 months failed to learn, along with their respective control groups. However, the majority of interventions successfully reversed these memory impairments, with particular efficacy observed in treatments involving vitamin D at 42 IU/kg and the combination of vitamin D with DONE. Conclusion: Memory impairment occurs as a result of ovariectomy (OVX). This effect persists with aging, and vit D, either alone or in combination with DONE, emerges as a significant alternative for reversing or mitigating this cognitive decline. [ABSTRACT FROM AUTHOR]

D-galactose (D-gal) is a carbohydrate widely distributed in regular diets. However, D-gal administration in rodents is associated with behavioral and neurochemical alterations similar to features observed in aging. In this regard, this study aimed to investigate the effects of D-gal exposure, in different periods, in rats’ brain regions’ activities of creatine kinase (CK) and tricarboxylic acid (TCA) cycle enzymes. Male adult Wistar rats received D-gal (100 mg/kg, gavage) for 1, 2, 4, 6 or 8 weeks. CK and TCA enzymes’ activities were evaluated in rats’ prefrontal cortex and hippocampus. In general, the results showed an increase in citrate synthase (CS) and succinate dehydrogenase (SDH) activities in animals treated with D-gal compared to the control group in the prefrontal cortex and hippocampus. Also, in the fourth week, the malate dehydrogenase (MD) activity increased in the hippocampus of rats that received D-gal compared to control rats. In addition, we observed an increase in the CK activity in the prefrontal cortex and hippocampus in the first and eighth weeks of treatment in the D-gal group compared to the control group. D-gal administration orally administered modulated TCA cycle enzymes and CK activities in the prefrontal cortex and hippocampus, which were also observed in aging and neurodegenerative diseases. However, more studies using experimental models are necessary to understand better the impact and contribution of these brain metabolic abnormalities associated with D-gal consumption for aging. [ABSTRACT FROM AUTHOR]

Folic acid (FA) supplementation is important during pregnancy to avoid malformations in the offspring. However, it is unknown if it can affect the offspring throughout their lives. To evaluate the offspring, female mother rats (dams) were separated into 5 groups: Four groups received the AIN-93 diet, divided into control and FA (5, 10, and 50 mg/kg), and an additional group received a FA-deficient diet, and the diet was performed during pregnancy and lactation. We evaluated the female offspring of these dams (at 2 and 18 months old). The aged offspring fed with FA-deficient diet presented habituation, spatial and aversive memory impairment and the FA maternal supplementation prevented this. The natural aging caused an increase in the TNF-α and IL-1β levels in the hippocampus from 18-month-old offspring. FA maternal supplementation was able to prevent the increase of these cytokines. IL-4 levels decreased in the prefrontal cortex from aged control rats and FA prevented it. FA deficiency decreased the levels of IL-4 in the hippocampus of the young offspring. In addition, natural aging and FA deficiency decreased brain-derived neurotrophic factor levels in the hippocampus and nerve growth factor levels in the prefrontal cortex and FA supplementation prevented it. Thus, the present study shows for the first time the effect of FA maternal supplementation on memory, cytokines, and neurotrophins in the aged offspring. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease. The animal model of AD‐like dementia induced by the peptide β‐amyloid 1‐42 (Aβ1‐42) is widely used. However, the animals have to be anesthetized and no studies are evaluating which anesthetic causes less interference in this model. This study aimed to evaluate the interference of different anesthetics on behavioral and oxidative stress in a mice model of Aβ1‐42‐induced dementia. Method: Male and female BALB/c mice at 3‐ month‐old were used under three different protocols. Protocol 1 (inhalation): (1) 100% oxygen (isoflurane control); (2) artificial cerebrospinal fluid (ACSF) + isoflurane; (3) Aβ1‐42 + isoflurane. Protocol 2 (intraperitoneal): (1) saline; (2) ACSF + ketamine + xylazine; (3) ACSF + ketamine + dexmedetomidine; (4) Aβ1‐42 + ketamine + xylazine; (5) Aβ1‐42 + ketamine + dexmedetomidine. Protocol 3 (intraperitoneal): (1) saline; (2) ACSF + propofol; (3) Aβ1‐42 + propofol. After the anesthesia, mice were injected with Aβ1‐42 (400 pmol) free‐hand intracerebroventricular, then after 13 days, mice were submitted to the Y‐maze test (spatial memory), plus‐maze (anxiety), and open‐field (habituation memory); then, hippocampus were dissected to analysis. Result: Isoflurane per se (protocol 1) caused no memory impairment, but caused an anxiolytic effect in males, in addition, to increased sulfhydryl content in males. In protocol 2, ACSF + ketamine + xylazine induced spatial memory impairment in males and habituation memory impairment in females; the anesthetics of protocol 2 increased 2',7' dichlorodihydrofluorescein (DCF) levels in females, and ACSF + ket + dex reduced levels of glutathione (GSH) in males. In protocol 3, propofol per se caused an anxiolytic effect in males and increased DCF levels in males and females, increased superoxide dismutase activity in males, and reduction in females, in addition, increased sulfhydryl content in males. Conclusion: All anesthetic protocols evaluated caused alterations in the behavior and/or oxidative stress parameters; however, isoflurane seems to cause less interference in the animal model, followed by propofol. Protocol 3 seems to cause more interference, including in the Y‐maze (spatial memory), which is one of the main behavior tests to evaluate the mice model of Aβ1‐42‐induced dementia. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) and major depressive disorder (MDD) can share the same inflammatory theory in their pathophysiology, indicating that MDD may not only be a symptom, but a risk factor for AD. Therefore, the present study evaluated the levels of cytokines such as tumor necrosis factor alpha (TNF‐α), interleukin (IL) ‐1β, IL‐6 and IL‐10 in the frontal cortex and hippocampus of Wistar rats subjected to chronic mild stress protocol (CMS) for induction of an animal model of depression and administration of intra‐hippocampal β‐amyloid (βA) oligomers for induction of the dementia model. Method: 60‐day‐old Wistar rats went subjected to CMS protocol for 40 days. After the CMS, the animals were subjected to stereotaxic surgery for intra‐hippocampal administration of βA or artificial cerebrospinal fluid (ACSF). The next day, it was started the treatment with water, memantine, galantamine, donepezil and/or fluoxetine orally for 17 days. On the 59th day of the experimental protocol, euthanasia was performed, and the frontal cortex and hippocampus were dissected for later measurements of the TNF‐α, IL‐1β, IL‐6 and IL‐10. Result: The results of this study show that animals subjected to CMS and administration of βA showed increased levels of TNF‐α and IL‐1β in the frontal cortex and reduced IL‐10 level in the hippocampus. Fluoxetine reversed the levels of TNF‐α and IL‐1β in the frontal cortex. In addition, the fluoxetine + donepezil combination reversed the reduction of IL‐10 levels in the hippocampus. Galantamine was also effective in reversing TNF‐α levels in the cortex, as well as its association with fluoxetine and the association of donepezil with fluoxetine. The animals treated with memantine, as well as their association with fluoxetine, association of galantamine and fluoxetine and the association of donepezil with fluoxetine had levels of IL‐10 significantly increased in the frontal cortex. In the hippocampus, only treatments with donepezil were able to raise the levels of IL‐1β and IL‐10. Conclusion: The results obtained in the present study indicate that there is a pathophysiological interaction between diseases, and that the association of medications in the future may be a possible therapeutic strategy to reduce the inflammation, especially in association with fluoxetine. [ABSTRACT FROM AUTHOR]

The fetal brain is susceptible to programming effects during pregnancy, potentially leading to long-term consequences for offspring's cognitive health. Fructose intake is thought to adversely affect fetal brain development, whereas physical exercise before and during pregnancy may be protective. Therefore, this study aimed to assess biochemical and genotoxic changes in maternal hippocampi and behavioral, genotoxic, and biochemical alterations in offspring hippocampi. Seventy female mice were exposed to fructose (20%/L) and/or voluntary physical exercise (VPE) pre-pregnancy for eight weeks, and then mated and exposure was continued until weaning. Offspring were evaluated at 60 days old using behavioral test, genotoxic and biochemical markers. Fructose induced long-term memory impairment in male offspring, which was alleviated by VPE. VPE mitigated DNA damage from maternal fructose consumption in both maternal and offspring hippocampi in female offspring, VPE increased levels of APE-1, NRF2, and CREB proteins, whereas in males, OGG1 levels upregulate. Fructose consumption led to oxidative stress and antioxidant defense alterations in offspring, while VPE mitigated these effects. Telomere shortening was observed in male offspring from mothers who consumed fructose during pregnancy. Our findings suggest that exposure to fructose during (pre)pregnancy and lactation has adverse effects on offspring's hippocampi later in life, and VPE has a protective effect. Overall, the study underscores the significance of maternal dietary and physical habits on long term offspring health, with an emphasis on implications for adult cognitive function., (© The Author(s) 2025. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The human lifespan is increasing, and mankind is aging. It is estimated that, until the year 2050, this population worldwide will reach 22% of the total world population. Along with aging, the human immunologic system changes, a process called immunosenescence or even inflammaging. The aging immune system increases mortality and morbidity in the elderly mainly because it loses its capacity to react against internal and external aggressions. There is a decrease in B and T lymphocytes and CD4+ lymphocytes lose the CD28 protein expression that is needed for costimulation, leading to reduced response to viral infections. This could be responsible for more deleterious consequences of coronavirus disease infection in the elderly. Besides that, the human brain ages, being more susceptible to damage and viral infections, such as COVID-19 infection. There are several pathways that could explain the susceptibility to the COVID-19 infection in the elderly brain, one of them is binding to ACE 2 receptors in cerebral cells through the spike protein. It has been reported that glial cells and neurons, in addition to endothelial and arterial smooth muscle cells in the brain, express the ACE 2 receptor, which would justify the neurological symptoms and consequences of the disease. This infection can have several clinical manifestations such as hemorrhagic stroke, delirium and long-term cognitive complaints, such as brain fog, polyneuropathies, short time memory complaints and insomnia. Although none of the studies could prove that there is a long-term neuronal damage, there are clinical sequelae that should be taken into account and more studies are necessary to know the consequences of the infection in the elderly brain., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)