cognitive function

Overview

Cognitive function refers to the ensemble of mental processes by which an organism acquires, processes, stores, and acts upon information. It encompasses domains including memory, attention, executive function, language, processing speed, and visuospatial ability, all of which depend on the structural and functional integrity of neural circuits distributed across the cerebral cortex, hippocampus, prefrontal cortex, and subcortical regions. At the cellular level, cognitive function emerges from the coordinated activity of neurons, astrocytes, and microglia, with glial cells playing increasingly recognized roles in synaptic maintenance, neuroinflammation, and metabolic support. Disruptions to these cellular interactions — through accumulation of Beta amyloid, neuroinflammatory cascades, oxidative stress, or vascular insufficiency — underlie the cognitive decline observed in conditions ranging from Alzheimer's disease (AD) and mild cognitive impairment (MCI) to traumatic brain injury, HIV-associated neurocognitive disorder, and metabolic disease.

As a biological process and clinical outcome measure, cognitive function sits at the intersection of neuroscience, gerontology, immunology, and pharmacology. Its assessment spans standardized neuropsychological batteries, computerized paradigms, and emerging biomarker approaches, while its modulation is pursued through pharmacological agents, lifestyle interventions, dietary modifications, and novel delivery technologies. The progressive identification of molecular mediators — including Brain-derived neurotrophic factor, interleukin-6, anti-inflammatory cytokines, and Serum glial fibrillary acidic protein — has expanded the translational toolkit for measuring and restoring cognitive capacity across disease states.

Focus of Latest Publications

Neuroinflammation, Glial Biology, and Amyloid Pathology

Recent investigation has focused on the contribution of astrocyte–microglia crosstalk to cognitive decline in AD. A 2026 study in Immunity (PMID: 41962542) demonstrated that the astrocytic calcium-dependent enzyme PAD2 governs microglial activity to exacerbate amyloid pathology through citrullinated vimentin. Pharmacological inhibition of PAD2 normalized glial transcriptomic signatures and rescued cognition in 5×FAD mice, directly linking astrocyte enzymatic activity to the behavioral readout of cognitive function. Complementing this, a study in Materials Today Bio (PMID: 41696149) showed that an anti-inflammatory neuroenhancer targeting Beta amyloid pathology enabled AD mice to efficiently recover memory and cognition, underscoring the therapeutic potential of simultaneously addressing neuroinflammation and Alzheimer's disease. A further study in Journal of Ethnopharmacology (PMID: 41791622) employed systems pharmacology to reveal that gastrodiae rhizoma improves stress-induced cognitive impairment by protecting hippocampal synapses from excessive microglia-mediated pruning, demonstrating that microglial synaptic activity is a convergence point for both pathological and therapeutic modulation of cognition.

Extracellular Vesicles and Exosome-Based Therapies

Extracellular vesicles have emerged as a promising vehicle for cognitive recovery. A comparative study in Behavioural Brain Research (PMID: 41912089) assessed astrocyte-derived exosomes across neurobehavioral, molecular, and electrophysiological dimensions in a mouse model of AD, finding restoration of cognitive function. Similarly, a study in Stem Cell Reviews and Reports (PMID: 41729433) showed that intravenously administered human umbilical cord mesenchymal stem cell-derived exosomes displayed sustained brain retention and significantly restored motor coordination and cognitive function in a rat model of moderate-to-severe cerebral palsy. These findings position stem cell- and astrocyte-derived extracellular vesicles as mechanistically distinct but convergent strategies for neuroprotection and cognitive rescue.

Novel Drug Delivery: Intranasal mRNA Lipid Nanoparticles

A study in ACS Nano (PMID: 42157518) introduced an intranasal blood-brain barrier-bypassing lipid nanoparticle (LNP) platform for mRNA delivery. Co-delivery of mRNAs encoding Brain-derived neurotrophic factor and interleukin-10 via this platform significantly reduced neuroinflammation, inhibited neuronal death, and improved cognition in a repetitive mild traumatic brain injury mouse model. This work highlighted LNP surface charge optimization and nasal administration as critical parameters for achieving therapeutic brain concentrations sufficient to influence cognitive outcomes.

Gut–Brain Axis and Microbiome

The gut–brain axis has been implicated as a modifiable determinant of post-injury cognition. A 2026 study in Neurochemical Research (PMID: 42171840) used fecal microbiota transplantation from exercise-preconditioned mice to attenuate post-stroke cognitive impairment, assessing cognitive function alongside gut microbiome composition, fecal short-chain fatty acid levels, inflammation, and gut-blood-brain barrier integrity. This positions the microbiome as both a biomarker and a therapeutic lever for cognitive outcomes following cerebrovascular events.

Metabolic and Dietary Modulators

Several investigations have examined metabolic perturbations and their cognitive sequelae. A study in Behavioural Brain Research (PMID: 41713597) demonstrated that linagliptin attenuates hippocampal oxidative stress and cognitive dysfunction induced by a high-sugar diet in rats, linking dietary hyperglycemia and the resulting oxidative stress to measurable cognitive impairment. A longitudinal study in CNS Neuroscience & Therapeutics (PMID: 42201257) investigated how DL-methionine, DL-homocysteine, and methylation levels predict cognitive decline in AD, calling for further elucidation of the precise interactions among these one-carbon Metabolites and their impact on cognitive function. A cross-sectional analysis in Australasian Journal on Ageing (PMID: 42159347) found that while calcium supplementation is widely used in older adults, its long-term effects on cognitive function remain unclear, underscoring the need for rigorous longitudinal study of mineral supplementation.

HIV, Infectious Disease, and Pharmacological Interventions

Cognitive function has been an endpoint in infectious disease trials. A randomized controlled trial published in Clinical Infectious Diseases (PMID: 41098140) investigated the effect of semaglutide on cognitive function in people with HIV (PWH), examining whether its benefit is mediated by changes in adiposity or inflammation. Separately, a longitudinal brain imaging study in Journal of Infectious Diseases (PMID: 41542974) analyzed the effects of aging, HIV serostatus, and viral load on cognition and brain volumes across PWH with undetectable and detectable HIV type 1, establishing that viral suppression mitigates but does not fully normalize cognitive and structural brain trajectories.

Environmental, Sensory, and Behavioral Interventions

Nature exposure, hearing rehabilitation, mindfulness, and social interventions have each been investigated as cognitive modulators. A randomized protocol in JMIR Research Protocols (PMID: 42172624) compared real versus virtual nature exposure on cognition and brain activity in adults with and without ADHD, grounded in attentional restoration theory. A family-supported hearing aid intervention trial (SOUND; PMID: 42156151) examined whether behavioral support guided by self-determination theory, technology acceptance models, and family social support theory could improve cognitive function in older Chinese adults with hearing loss and MCI. A randomized controlled trial in Psychology of Sport and exercise (PMID: 41577062) assessed the effects of a 12-week mindfulness-based intervention on executive functioning, brain oxygenation, and biomarkers of cognitive function in baseball players. Together, these trials reflect growing interest in non-pharmacological pathways to cognitive enhancement, with attention, motor control, and electrophysiological responses serving as mechanistic readouts.

Biomarkers and Epidemiological Findings

Blood-based biomarkers have been validated against cognitive outcomes in community and clinical cohorts. A study in Nature Communications (PMID: 42091863) showed that Alzheimer's disease blood biomarkers — including Serum glial fibrillary acidic protein — measured through remote capillary sampling correlate well with venous biomarkers and with cognition and function in individuals ranging from cognitively normal to those with MCI or AD. Epidemiological associations have also implicated serum cotinine levels (a nicotine metabolite) in cognitive function in US adults aged 60 and older (Medicine, PMID: 42175434), and a longitudinal study using the English Longitudinal Study of Ageing (PMID: 41620179) mapped change trajectories of cognitive function before and after the onset of loneliness, revealing accelerated decline following new-onset social isolation. Hearing loss was independently associated with cognitive function alongside activities of daily living and nutritional status in a Chinese population cohort (Maturitas, PMID: 41819712).

Key Publications

• Jun Healthful plant-based diet, gut enterotype, and cognition in a rural Chinese elderly cohort: A longitudinal multi-omics study. (Cell reports. Medicine, 2026, PMID 42127905): "higher mHPDI is associated with better global cognition, with stronger benefits in participants with non-Prevotella-dominant enterotypes."
• Jun Targeting HIF-1α rescues microglial efferocytosis via the SLC7A11-TAM pathway to ameliorate Sepsis-associated encephalopathy. (International immunopharmacology, 2026, PMID 41990706): "KC7F2 restored efferocytosis, shifted cytokines toward anti-inflammatory profiles, improved cognition and survival, and normalized metabolomic signatures, while DMOG produced opposite effects."
• Jun Targeting diaschisis to alleviate memory deficits after experimental stroke. (Neurobiology of disease, 2026, PMID 41999925): "Moreover, this study suggests that anti-seizure drugs can reduce abnormal excitability and improve cognition after experimental stroke."
• Jun Systems pharmacology reveals the mechanism underlying gastrodiae rhizoma in improving stress-induced cognitive impairment: Protecting hippocampal synapses from excessive microglia-mediated pruning. (Journal of ethnopharmacology, 2026, PMID 41791622): "As a valuable traditional Chinese herb in both medical and dietary applications, GR is known for its neuroprotective effects and use in improving cognitive function."
• Jun Astrocytic calcium-dependent enzyme PAD2 governs microglia activity to exacerbate amyloid pathology via citrullinated vimentin. (Immunity, 2026, PMID 41962542): "Pharmacological PAD2 inhibition mimicked the genetic rescue, normalizing glial signatures and cognition."
• Jun Astrocyte-derived exosomes in cognitive recovery: A comparative assessment of neurobehavioral, molecular, and electrophysiological dimensions. (Behavioural brain research, 2026, PMID 41912089): "...in restoring cognitive function in a mouse model of AD."
• Jun Association Between Calcium Supplement Use and Cognitive Impairment in Ageing Women: A Longitudinal Analysis. (Australasian journal on ageing, 2026, PMID 42159347): "Calcium supplementation is widely used in older adults, but its long-term effects on cognitive function remain unclear."
• Jun Rationale and study design for the first precision medicine randomized placebo-controlled trial in the 16p11.2 deletion syndrome. (Expert review of neurotherapeutics, 2026, PMID 42080302): "Secondary outcomes included objective dysarthria indices, memory, motor control, and cognitive function, assessed with both standardized clinical measures and novel, computer-based assessments with automated scoring."
• Jun Methionine, Homocysteine, and Methylation Levels Predict Cognitive Decline in Alzheimer's Disease. (CNS neuroscience & therapeutics, 2026, PMID 42201257): "However, the precise interactions among these factors and their impact on cognitive function in AD require further elucidation."
• May Association between serum cotinine levels and cognitive function in Americans aged 60 and older: A cross-sectional study. (Medicine, 2026, PMID 42175434): "This study examined the association between serum cotinine levels and cognitive function in US adults aged ≥60 years."