Age-related Memory Impairment Research Articles

Changes in Gene Expression Profile with Age in SAMP8: Identifying Transcripts Involved in Cognitive Decline and Sporadic Alzheimer’s Disease

Background: The senescence-accelerated mouse 8 (SAMP8) represents a model for Alzheimer’s disease (AD) research because it exhibits age-related learning and memory impairments consistent with early onset and rapid progression of senescence. To identify transcriptional changes during AD progression, in this study, we analyzed and compared the gene expression profiles involved in molecular pathways of neurodegeneration and cognitive impairment in senescence-accelerated resistant 1 (SAMR1) and SAMP8 mice. Methods: In total, 48 female SAMR1 and SAMP8 mice were randomly divided into six groups (SAMR1 and SAMP8 at 3, 7, and 9 months of age). Microarray analysis of 22,000 genes was performed, followed by functional analysis using Gene Ontology (NCBI) and examination of altered molecular pathways using the KEGG (Kyoto Encyclopedia of Genes and Genomes). Results: SAMP8 mice had 2516 dysregulated transcripts at 3 months, 2549 transcripts at 7 months, and 2453 genes at 9 months compared to SAMR1 mice of the same age. These accounted for 11.3% of the total number. This showed that with age, the gene expression of downregulated transcripts increases, and that of over-expressed transcripts decreases. Most of these genes were involved in neurodegenerative metabolic pathways associated with Alzheimer’s disease: apoptosis, inflammatory response, oxidative stress, and mitochondria. The qPCR results indicated that Ndufs4, TST/Rhodanese, Wnt3, and Sema6a expression was differentially expressed during aging. Conclusions: These results further revealed significant differences in gene expression profiles at different ages between SAMR1 and SAMP8 and showed alteration in genes involved in age-related cognitive decline and mitochondrial processes, demonstrating the relevance of the SAMP8 model as a model for sporadic AD.

Activation of the Gut-Brain Interaction by Urolithin A and Its Molecular Basis.

Background: Urolithin A (Uro-A), a type of polyphenol derived from pomegranate, is known to improve memory function when ingested, in addition to its direct effect on the skin epidermal cells through the activation of longevity gene SIRT1. However, the molI ecular mechanism by which orally ingested Uro-A inhibits cognitive decline via the intestine remains unexplored. Objectives: This study aimed to evaluate the role of Uro-A in improving cognitive function via improved intestinal function and the effect of Uro-A on the inflammation levels and gene expression in hippocampus. Methods: Research to clarify the molecular basis of the functionality of Uro-A was also conducted. Results: The results demonstrated that Uro-A suppressed age-related memory impairment in Aged mice (C57BL/6J Jcl, male, 83 weeks old) by reducing inflammation and altering hippocampal gene expression. Furthermore, exosomes derived from intestinal cells treated with Uro-A and from the serum of Aged mice fed with Uro-A both activated neuronal cells, suggesting that exosomes are promising candidates as mediators of the Uro-A-induced activation of gut-brain interactions. Additionally, neurotrophic factors secreted from intestinal cells may contribute to the Uro-A-induced activation of gut-brain interactions. Conclusions: This study suggests that Uro-A suppresses age-related cognitive decline and that exosomes and other secreted factors may contribute to the activation of the gut-brain interaction. These findings provide new insights into the therapeutic potential of Uro-A for cognitive health.

Lycopene alleviates age-related cognitive deficit via activating liver-brain fibroblast growth factor-21 signalling

Brain function is linked with many peripheral tissues, including the liver, where hepatic fibroblast growth factor 21 (FGF21) mediates communication between the liver and brain. Lycopene (LYC), a naturally occurring carotenoid, posses multiple health-promoting properties, including neuroprotective function. Here, we investigated the effects of LYC on age-related memory impairment and the relative contribution of liver-brain FGF21 signaling in these process. The results showed that after treatment with LYC for 3 months, brain aging and age-related cognitive deficits were effectively managed. In addition, LYC ameliorated neuronal degeneration, mitochondrial dysfunction and synaptic damage, and promoted synaptic vesicle fusion in 18-month-old mice. Notably, LYC activated liver-brain FGF21 signalling in aging mice. Whereas all these central effects of LYC were negated by blocking FGF21 via i. v. injection of adeno-associated virus in aging mice. Furthermore, recombinant FGF21 elevated mitochondrial ATP levels and enhanced synaptic vesicle fusion in mouse hippocampal HT-22 cells, which promoted neurotransmitter release. Additionally, we co-cultured hepatocytes and neurons in Transwell and found that LYC enhanced hepatocytes’ support for neurons. This support included improved cell senescence, enhanced mitochondrial function, and increased axon length in co-cultured neurons. In conclusion, LYC protects against age-related cognitive deficit, partly explained by activating liver-brain FGF21 signalling, hence promoting neurotransmitters release via increasing mitochondrial ATP levels and enhancing synaptic vesicle fusion. These findings revealed that FGF21 could be a potential therapeutical target in nutritional intervention strategies to improve cognitive damage caused by aging and age-related neurodegenerative diseases.

Unveiling citicoline's mechanisms and clinical relevance in the treatment of neuroinflammatory disorders.

Citicoline, a compound produced naturally in small amounts in the human body, assumes a pivotal role in phosphatidylcholine synthesis, a dynamic constituent of membranes of neurons. Across diverse models of brain injury and neurodegeneration, citicoline has demonstrated its potential through neuroprotective and anti-inflammatory effects. This review aims to elucidate citicoline's anti-inflammatory mechanism and its clinical implications in conditions such as ischemic stroke, head trauma, glaucoma, and age-associated memory impairment. Citicoline's anti-inflammatory prowess is rooted in its ability to stabilize cellular membranes, thereby curbing the excessive release of glutamate-a pro-inflammatory neurotransmitter. Moreover, it actively diminishes free radicals and inflammatory cytokines productions, which could otherwise harm neurons and incite neuroinflammation. It also exhibits the potential to modulate microglia activity, the brain's resident immune cells, and hinder the activation of NF-κB, a transcription factor governing inflammatory genes. Clinical trials have subjected citicoline to rigorous scrutiny in patients grappling with acute ischemic stroke, head trauma, glaucoma, and age-related memory impairment. While findings from these trials are mixed, numerous studies suggest that citicoline could confer improvements in neurological function, disability reduction, expedited recovery, and cognitive decline prevention within these cohorts. Additionally, citicoline boasts a favorable safety profile and high tolerability. In summary, citicoline stands as a promising agent, wielding both neuroprotective and anti-inflammatory potential across a spectrum of neurological conditions. However, further research is imperative to delineate the optimal dosage, treatment duration, and underlying mechanisms. Moreover, identifying specific patient subgroups most likely to reap the benefits of citicoline as a new therapy remains a critical avenue for exploration.

Antibodies to Glutamate Reduce the IL-6 Content in Cerebral Structures in Mice with Age-Related Memory Impairment.

Intranasal administration of antibodies to glutamate for 14 days improved passive avoidance conditioning and reduces the content of IL-6 within 7 days after their withdrawal in the prefrontal cortex and hippocampus of aging C57BL/6 mice.

Overexpression of TIAM2S, a Critical Regulator for the Hippocampal-Medial Prefrontal Cortex Network, Progresses Age-Related Spatial Memory Impairment.

TIAM Rac1-associated GEF 2 short-form protein (TIAM2S) is abundant in specific brain tissues, especially in the hippocampus, a brain region critical for processing and consolidation of spatial memory. However, how TIAM2S plasticizes the microstructure and circuits of the hippocampus to shape spatial memory as a neuroplastic regulator during aging remains to be determined. In this study, transgenic mice overexpressing human TIAM2S protein (TIAM2S-TG mice) were included, and interdisciplinary approaches, such as spatial memory tests and multiparametric magnetic resonance imaging sequences, were conducted to determine the role and the mechanism of TIAM2S in age-related spatial memory deficits. Despite no changes in their neural and glial markers and neuropathological hallmark expression of the hippocampus, behavioral tests showed that the TIAM2S-TG mice, and not wild-type (WT) mice, developed spatial memory impairment at 18 months old. The T2-weighted and diffusion tensor image analyses were performed to further study the possible role of TIAM2S overexpression in altering the hippocampal structure or neuronal circlets of the mice, increasing their vulnerability to developing spatial memory deficits during aging. The results revealed that the 12-month-old TIAM2S-TG mice had hippocampal dysplasticity, with larger volume, increased fiber numbers, and changed mean fractional anisotropy compared to those in the age-matched WT mice. The fiber tractography analysis exhibited significantly attenuated structural connectivity between the hippocampus and medial prefrontal cortex in the TIAM2S-TG mice. In conclusion, overexpression of TIAM2S, a detrimental factor affecting hippocampus plasticity, causes attenuation of the connectivity within hippocampus-mPFC circuits, leading to age-related spatial memory impairment.

IL-33 prevents age-related bone loss and memory impairment by suppression of Th17 response: evidence in a d-galactose-induced aging mouse model.

Cytokines are the primary mediators of age-related disorders. The IL-17/IL-10 axis plays a crucial role in bone destruction and neuro-inflammation. Additionally, a new Th2 cytokine-IL-33-has gained attention for its potential implications in aging-associated conditions. However, the involvement of IL-33 in aging-mediated bone loss and memory impairment remains unclear and needs further investigation. This study reveals the impact of IL-33 on various aspects of the immune system, bone health, and neural functions. To induce senescence, we used d-galactose for its convenience and fewer side effects. The experimental design involved treating 20-week-old C57BL/6J mice with d-galactose subcutaneously for 10weeks to induce aging-like effects. Thereafter, IL-33 recombinant protein was administered intraperitoneally for 15days to evaluate its impact on various immune, skeletal, and neural parameters. The results demonstrated that d-galactose-induced aging led to bone loss and compromised osteogenic parameters, accompanied by increased oxidative stress and neurodegeneration in specific brain regions. Behavioral activities were also affected. However, supplementation with IL-33 mitigated these effects, elevating osteogenic parameters and reducing senescence markers in osteoblast cells in an aging mouse model and exerted neuroprotective potential. Notably d-galactose-induced aging was characterized by high bone turnover, reflected by altered serum levels of CTX, PTH, beta-galactosidase, and P1NP. IL-33 treatment attenuated these effects, suggesting its role in regulating bone metabolism. Furthermore, d-galactose-induced aging was associated with increased differentiation of Th17 cells and upregulation of associated markers, such as STAT-3 and ROR-γt, while downregulating Foxp3, which antagonizes Th17 cell differentiation. IL-33 treatment countered these effects by suppressing Th17 cell differentiation and promoting IL-10-producing T-regulatory cells. Overall, these findings provide insights into the potential therapeutic implications of IL-33 in addressing aging-induced bone loss and memory impairment.

Digital Life Story Books: Intervention to maintain sense of self in older adults with memory difficulties

ABSTRACT The sharp increase in dementia and age-related memory impairments worldwide has made reminiscence-based interventions attractive. Past research is mixed with little focus on self-functioning. The aims of this study were (i) to develop and assess the implementation of a reminiscence-based intervention, Digital Life Story Books, grounded in evidence-based principles of autobiographical memory, and (ii) to evaluate its effectiveness in improving sense of self in older adults with memory difficulties. A remote reminiscence intervention, using multisensory Digital Life Story Books (DLSB), was developed. Using a short-term experimental, longitudinal design, 25 participants with memory difficulties were assigned to the DLSB condition (16 females; M = 73.96, SD = 8.8) and 23 to a Wait-List Control (16 females; M = 78.57, SD = 9.38). Informal caregivers (N = 34; M = 63.44, SD = 13.8) provided proxy-reports on the effects of the DLSB. The DLSB was successfully developed and positively evaluated by participants. In the DLSB condition, a strengthened sense of self, reflected directly in the memories selected for the DLSB was detected. No overall condition difference was detected pre- to post-therapy. The findings highlight the appeal of reminiscence activities but also the challenge of adequate measurement sensitivity to demonstrate effects.

Pharmacological HDAC3 inhibition alters memory updating in young and old male mice.

Long-term memories are not stored in a stable state but must be flexible and dynamic to maintain relevance in response to new information. Existing memories are thought to be updated through the process of reconsolidation, in which memory retrieval initiates destabilization and updating to incorporate new information. Memory updating is impaired in old age, yet little is known about the mechanisms that go awry. One potential mechanism is the repressive histone deacetylase 3 (HDAC3), which is a powerful negative regulator of memory formation that contributes to age-related impairments in memory formation. Here, we tested whether HDAC3 also contributes to age-related impairments in memory updating using the Objects in Updated Locations (OUL) paradigm. We show that blocking HDAC3 immediately after updating with the pharmacological inhibitor RGFP966 ameliorated age-related impairments in memory updating in 18-m.o. male mice. Surprisingly, we found that post-update HDAC3 inhibition in young (3-m.o.) male mice had no effect on memory updating but instead impaired memory for the original information, suggesting that the original and updated information may compete for expression at test and HDAC3 helps regulate which information is expressed. To test this idea, we next assessed whether HDAC3 inhibition would improve memory updating in young male mice given a weak, subthreshold update. Consistent with our hypothesis, we found that HDAC3 blockade strengthened the subthreshold update without impairing memory for the original information, enabling balanced expression of the original and updated information. Together, this research suggests that HDAC3 may contribute to age-related impairments in memory updating and may regulate the strength of a memory update in young mice, shifting the balance between the original and updated information at test.

Age-related enhancement of the association between episodic memory and gray matter volume in medial temporal and frontal lobes

BackgroundEpisodic memory (EM) deteriorates as a result of normal aging as well as Alzheimer’s disease. The neural underpinnings of such age-related memory impairments in older individuals are not well-understood. Although previous research has unveiled the association between gray matter volume (GMV) and EM in the elderly population, such findings exhibit variances across distinct age cohorts. Consequently, an investigation into the dynamic evolution of this relationship with advancing age is imperative.ResultThe present study utilized a sliding window approach to examine how the correlation between EM and GMV varied with age in a cross-sectional sample of 926 Chinese older adults. We found that both verbal EM (VEM) and spatial EM (SEM) exhibited positive correlations with GMV in extensive areas primarily in the temporal and frontal lobes and that these correlations typically became stronger with older age. Moreover, there were variations in the strength of the correlation between EM and GMV with age, which differed based on sex and the specific type of EM. Specifically, the association between VEM and GMVs in the insula and parietal regions became stronger with age for females but not for males, whereas the association between SEM and GMVs in the parietal and occipital regions became stronger for males but not for females. At the brain system level, there is a significant age-related increase in the correlations between both types of EM and the GMV of both the anterior temporal (AT) system and the posterior medial (PM) system in male group. In females, both types of EM show stronger age-related correlations with the GMV of the AT system compared to males.ConclusionsOur study revealed a significant positive correlation between GMV in most regions associated with EM and age, particularly in the frontal and temporal lobes. This discovery offers new insights into the connection between brain structure and the diminishing episodic memory function among older individuals.

A Longitudinal Study of the Effect of Memory on the Quality of life of European Adults and Older Adults

Among studies conceptualizing quality of life (QoL) as the subjective measure of one’s well-being, evidence suggests a link between cognitive impairment and diminished quality of life. However, the direction of the association is not clear, and most studies have employed a global measure of cognition, which can mask subtle domain-specific declines. In this study, we aim at examining the longitudinal associations between memory and QoL in a representative sample of adults and older adults in Europe and Israel, employing data from the Survey of Health, Ageing and Retirement in Europe (SHARE). The sample was composed by 56,616 respondents aged 50 or older at the beginning of the study period. A Parallel-Process Latent Growth Model (PP LGM) of memory and QoL conditioned on the effects of age, gender, educational level, physical inactivity, depressive symptomatology and social activity participation, was tested. Results displayed a trajectory of decline for both memory and QoL, with higher initial levels of memory associated with higher initial levels of QoL, and steeper decline in memory associated with steeper decline in QoL. Moreover, a positive effect of initial memory onto QoL trend over time was found, indicating that better memory is associated to better QoL in the future, but the opposite did not occur. Results also provide evidence of gender differences. All in all, this work found evidence supporting the longitudinal effect of memory on QoL, which may have consequences for intervention implementation, given that actions for alleviating age-related memory impairment could also have a positive impact onto older adults’ QoL.

Aging effects on the encoding/retrieval flip in associative memory: fMRI evidence from incidental contingency learning.

Associative memory is arguably the most basic memory function and therein constitutes the foundation of all episodic and semantic memory processes. At the same time, the decline of associative memory represents a core feature of age-related cognitive decline in both, healthy and pathological (i.e., dementia-related) aging. The neural mechanisms underlying age-related impairments in associative memory are still not fully understood, especially regarding incidental (i.e., non-intentional) learning. We investigated the impact of age on the incidental learning and memory retrieval of face-name combinations in a total sample of 46 young (N = 23; mean age = 23.39 years) and elderly (N = 22, mean age = 69.05 years) participants. More specifically, particular interest was placed in age-related changes in encoding/retrieval (E/R) flips, which denote a neural antagonism of opposed activation patterns in the same brain region during memory encoding and retrieval, which were assessed using fMRI. According to our hypothesis, the results showed a significant age-related decline in the retrieval performance in the old group. Additionally, at the neural level, we discovered an abolished E/R flip in the right anterior insula and a joint but reduced E/R flip activation magnitude in the posterior middle cingulate cortex in older subjects. In conclusion, the present findings suggest that the impaired neural modulation of the E/R flip in the right aIC might be a sensitive marker in the early detection of neural aging.

Bifidobacterium pseudocatenulatum NCU-08 ameliorated senescence via modulation of the AMPK/Sirt1 signaling pathway and gut microbiota in mice.

Aging is a degenerative disease in which organisms and neurological functions decline. Emerging research has underscored the vital role of the gut microbiota in age-related processes. However, the identification of aging-associated core microbiota remains limited. In this investigation, we isolated a strain of B. pseudocatenulatum NCU-08 from the feces of centenarians and assessed its impact on aging using a mouse model induced by D-gal. Our study revealed the exceptional probiotic attributes of B. pseudocatenulatum NCU-08. Administration of B. pseudocatenulatum NCU-08 significantly ameliorated age-related memory impairment, motor dysfunction, and anxiety-like behaviors in aging mice (p < 0.01). Moreover, tissue staining analysis demonstrated that B. pseudocatenulatum NCU-08 reduced the intensity of SA-β-gal-positive in the hippocampus of aging mice. It also reversed pathological damage and structural abnormalities in brain and intestinal tissue. B. pseudocatenulatum NCU-08 inhibited neuroinflammation induced by TLR4/NF-κB (p < 0.01) and preserved the blood-brain barrier integrity by activating the AMPK/Sirt1 pathway (p < 0.05). Furthermore, it mitigated neuronal apoptosis and oxidative stress by upregulating the PI3K/AKT signaling pathway (p < 0.01) and enhancing the activities of antioxidant enzymes, including GSH-Px (p < 0.01), SOD (p < 0.01), and CAT (p < 0.01). Besides, analysis of 16S rRNA sequencing data demonstrated that treatment with B. pseudocatenulatum NCU-08 restored intestinal microbiota homeostasis after senescence. It enhanced the abundance of beneficial bacteria while suppressing the growth of pathogenic microorganisms. In summary, our study unveiled that this novel strain of B. pseudocatenulatum NCU-08 exerts anti-aging effects through regulating the AMPK/Sirt1 pathway and intestinal microbiota. It holds promise as a functional food for promoting anti-aging effects and offers a novel approach to address aging and associated metabolic disorders.

Interpretative Assessment of Smriti w.s.r.to Mana and Buddhi in Ayurvedic Classical Texts

According to WHO estimations, India has 2443 disability-adjusted life years (DALYs) per 10,000 people who suffer from mental health issues. Also, the prevalence of age-related memory impairment was 3.6% in people 40 years of age and older, and 7.1% in people 65 years of age and older. In this world of gadgets, human beings are habitual in using devices for a lot of their work. Due to this, they are not in a habit of concentrating and memorizing things. Therefore, with time the human population keeps on losing their memory power. Many experts suggest that mentally challenging activities may help people with memory problems. Practicing yoga has also shown various health benefits, including improving memory and thus preventing memory impairment and related disorders. Numerous cognitive processes, including long-term memory, mental equilibrium, focus and concentration, attention span, processing speed, alternation ability, delayed and intermediate recall, executive function, verbal retention, and cognitive assessments are all improved by yoga.

Transcriptomics and biochemical evidence of trigonelline ameliorating learning and memory decline in the senescence-accelerated mouse prone 8 (SAMP8) model by suppressing proinflammatory cytokines and elevating neurotransmitter release

In recent years, exploring natural compounds with functional properties to ameliorate aging-associated cognitive decline has become a research priority to ensure healthy aging. In the present study, we investigated the effects of Trigonelline (TG), a plant alkaloid, on memory and spatial learning in 16-week-old senescence-accelerated mouse model SAMP8 using an integrated approach for cognitive and molecular biology aspects. After 30 days of oral administration of TG at the dose of 5 mg/kg/day, the mice were trained in Morris Water Maze task. TG-treated SAMP8 mice exhibited significant improvement in the parameters of escape latency, distance moved, and annulus crossing index. Next, we performed a whole-genome transcriptome profiling of the mouse hippocampus using microarrays. Gene ontology analyses showed that a wide range of biological processes, including nervous system development, mitochondrial function, ATP synthesis, and several signaling pathways related to inflammation, autophagy, and neurotransmitter release, were significantly enriched in TG-treated SAMP8 compared to nontreated. Further, a nonlinear dimensionality reduction technique, Uniform Manifold Approximation and Projection (UMAP), was applied to identify clusters of functions that revealed TG primarily regulated pathways related to inflammation, followed by those involved in neurotransmitter release. In addition, a protein–protein interaction network analysis indicated that TG may exert its biological effects through negatively modulating Traf6-mediated NF-κB activation. Finally, ELISA test showed that TG treatment significantly decreased proinflammatory cytokines- TNFα and IL6 and increased neurotransmitters- dopamine, noradrenaline, and serotonin in mouse hippocampus. Altogether, our integrated bio-cognitive approach highlights the potential of TG in alleviating age-related memory and spatial impairment.

Neuronal activation of Gαq EGL-30/GNAQ late in life rejuvenates cognition across species

Loss of cognitive function with age is devastating. EGL-30/GNAQ and Gαq signaling pathways are highly conserved between C.elegans and mammals, and murine Gnaq is enriched in hippocampal neurons and declines with age. We found that activation of EGL-30 in aged worms triples memory span, and GNAQ gain of function significantly improved memory in aged mice: GNAQ(gf) in hippocampal neurons of 24-month-old mice (equivalent to 70- to 80-year-old humans) rescued age-related impairments in well-being and memory. Single-nucleus RNA sequencing revealed increased expression of genes regulating synaptic function, axon guidance, and memory in GNAQ-treated mice, and worm orthologs of these genes were required for long-term memory extension in worms. These experiments demonstrate that C.elegans is a powerful model to identify mammalian regulators of memory, leading to the identification of a pathway that improves memory in extremely old mice. To our knowledge, this is the oldest age at which an intervention has improved age-related cognitive decline.

Phytochemical and Therapeutic Potential of Herbal Cognitive Enhancer

Memory is the most significant factor in distinguishing one person from another, as it is necessary to recognise one’s own self. The brain can encode, store, and retrieve information using three different types of memory. Individuals who lack these basic forms of memory are unable to create personal relationships, acquire new knowledge, and perform basic everyday duties. Memory refers to a person’s ability to encode, store, retain, and recall knowledge and past events in his or her brain. Memory gives a person the ability to learn from and adapt to previous experiences, as well as the ability to recall previously taught facts, skills, and habits. Today, poor memory, weak recall, and low retention are all typical issues. Memory deteriorates primarily because of stress and exhaustion. Memory loss, often known as age-related memory impairment, is frequent in those over the age of 40. This could be linked to the loss of hormones and proteins (growth factors) that repair brain cells as people get older. Herbs were employed to improve memory power in India throughout ancient times. Indian and Chinese cultures developed many traditional medicines from herbs to treat diminishing cognition, reverse memory loss, and improve learning power. Nootropic herbs are known for their brain-acting herbs and smart medications, which are derived from their isolated ingredients and aid to improve blood circulation in the brain. The focus of this review is on natural agents and herbs that work as memory enhancers. By using one of the herbs at a time, one can improve his or her memory.

Perspectives of older people with uncontrolled type 2 diabetes mellitus towards medication adherence: A qualitative study.

Better medication adherence among people with diabetes mellitus was found to be associated with improved glycaemic control. However, medication non-adherence is a significant concern in older people with uncontrolled type 2 diabetes mellitus. To explore the perspectives of older people with uncontrolled type 2 diabetes mellitus towards medication adherence. A qualitative descriptive exploratory study. A purposive sample of older people with uncontrolled type 2 diabetes mellitus living in the community was recruited. Snowball sampling was applied in community recruitment. In-depth telephone interviews were conducted using a semi-structured interview guide. Interviews were transcribed verbatim. Thematic analysis was used in data analysis. The consolidated criteria for reporting qualitative research (COREQ) guidelines were followed. The emerged six themes were: (a) impact of knowledge, attitudes and practices on medication adherence, (b) treatment-related barriers to medication adherence, (c) impact of age-related changes on medication adherence, (d) person-related barriers to medication adherence, (e) impact of COVID-19 on medication adherence and, (f) role of support systems in medication adherence. Knowledge of the disease process and medications, attitudes towards medication adherence, the practice of different treatment approaches, self-medication and dosing, negative experiences related to medications, polypharmacy, changes in lifestyle and roles, the influence of work-life, motivation, negligence, family support, support received from health workers, facilities available and financial capability are the main factors influence medication adherence. Age-related memory impairment, visual disturbances and physical weaknesses affect medication adherence in older people. Additionally, COVID-19-related guidelines imposed by the government and healthcare system-related issues during the COVID-19 pandemic also affected medication adherence. Adherence to medications among older people is hampered by a variety of factors, including their knowledge, attitudes and practices, person and treatment-related factors and age-related changes. The COVID-19 pandemic has brought additional challenges. Individualised patient care for older people with uncontrolled type 2 diabetes mellitus to improve medication adherence is timely. Strengthening support mechanisms for the above population is essential.

Phillyrin Ameliorates Oxidative Stress in D-Galactose-Induced Senescence in the Brain of Mice by Regulating the Nrf2/ HO-1 Signaling Pathway

Objective To investigate the effects of phillyrin on D-galactose (D-gal)-induced aging in the brain of mice and mechanism. Methods Institute of Cancer Research mice were intraperitoneally injected with D-gal 150 mg/kg to induce the aging model, and the mice were treated with phillyrin 5, 15, and 45 mg/kg once a day for 8 weeks. Results The memory impairment induced by D-gal in brain aging was ameliorated by phillyrin treatment, and the oxidative stress in the aging brain and serum was inhibited, as evidenced by increased superoxide dismutase, glutathione peroxidase enzyme activities, and decreased malondialdehyde levels. Additionally, the hippocampus damage has also been well improved by phillyrin. Moreover, the protein expressions of nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NADPH quinone oxidoreductase 1 (NQO1) were markedly up-regulated and the expression of Keap-1 was down-regulated in the phillyrin group than that in the aging model group. Conclusion These findings suggest that phillyrin is effective in the prevention of age-related memory impairment, and the attenuation oxidative stress by activating the Nrf2/HO-1 signaling pathway in the hippocampus may be one of the mechanisms.

Violation of the ultrastructural size principle in the dorsolateral prefrontal cortex underlies working memory impairment in the aged common marmoset (Callithrix jacchus).

Morphology and function of the dorsolateral prefrontal cortex (dlPFC), and corresponding working memory performance, are affected early in the aging process, but nearly half of aged individuals are spared of working memory deficits. Translationally relevant model systems are critical for determining the neurobiological drivers of this variability. The common marmoset (Callithrix jacchus) is advantageous as a model for these investigations because, as a non-human primate, marmosets have a clearly defined dlPFC that enables measurement of prefrontal-dependent cognitive functions, and their short (∼10 year) lifespan facilitates longitudinal studies of aging. Previously, we characterized working memory capacity in a cohort of marmosets that collectively covered the lifespan, and found age-related working memory impairment. We also found a remarkable degree of heterogeneity in performance, similar to that found in humans. Here, we tested the hypothesis that changes to synaptic ultrastructure that affect synaptic efficacy stratify marmosets that age with cognitive impairment from those that age without cognitive impairment. We utilized electron microscopy to visualize synapses in the marmoset dlPFC and measured the sizes of boutons, presynaptic mitochondria, and synapses. We found that coordinated scaling of the sizes of synapses and mitochondria with their associated boutons is essential for intact working memory performance in aged marmosets. Further, lack of synaptic scaling, due to a remarkable failure of synaptic mitochondria to scale with presynaptic boutons, selectively underlies age-related working memory impairment. We posit that this decoupling results in mismatched energy supply and demand, leading to impaired synaptic transmission. We also found that aged marmosets have fewer synapses in dlPFC than young, though the severity of synapse loss did not predict whether aging occurred with or without cognitive impairment. This work identifies a novel mechanism of synapse dysfunction that stratifies marmosets that age with cognitive impairment from those that age without cognitive impairment. The process by which synaptic scaling is regulated is yet unknown and warrants future investigation.