Cognition In Adults Research Articles

Family Size across the Life Course and Cognitive Decline in Older Mexican Adults.

A growing body of research has identified associations between family size and cognition in older adults. These studies largely focus on older adults' own fertility history instead of sibship size, defined as one's number of siblings. Sibship size may impact cognitive development during early childhood, creating differences that may persist into late-life. Using a gendered life course framework, this study evaluates how family size across the life course (both sibship size and number of children) relates with cognitive aging among older Mexican adults. Data comes from the 2012, 2015, 2018, and 2021 waves of the Mexican Health and Aging Study (n=14,872 adults age 50+). We use latent growth curve models to evaluate how family size (sibship size and fertility history) relates with levels of latent general cognitive ability and nine-year cognitive decline and variation across gender. Small sibship size related to higher levels of cognitive ability among men, but not women. This benefit was somewhat reduced when educational attainment was accounted for. Regarding fertility history, we observed an inverse U-shaped relationship with level of cognitive ability, regardless of gender, that remained significant even after accounting for sibship size and other confounders. Neither family size measure predicted the rate of cognitive decline. This research broadens our understanding of family size and cognition associations in the context of Mexico's changing demographics that challenge the reliance on family support in late-life and highlights potential gender differences.

An online multidomain lifestyle intervention to prevent cognitive decline in at-risk older adults: a randomized controlled trial.

Effective, scalable dementia prevention interventions are needed to address modifiable risk factors given global burden of dementia and challenges in developing disease-modifying treatments. A single-blind randomized controlled trial assessed an online multidomain lifestyle intervention to prevent cognitive decline over 3 years. Participants were dementia-free community-dwelling Australians aged 55-77 years with modifiable dementia risk factors. Eligible participants (n = 6,104, 64% female) were randomized 1:1 to a personalized schedule of online coaching in two to four modules (targeting physical activity, nutrition, cognitive activity and depression or anxiety) or a control group that received module-eligible information only. At 3 years, the mean change in a global cognitive composite, the primary outcome, was met. The mean changes in z scores were 0.28 (95% confidence interval (CI): 0.25-0.32) for intervention, 0.10 (95% CI: 0.07-0.13) for control and 0.18 (95% CI: 0.13-0.23, P < 0.001) for the between-group difference. Trial-related adverse events occurred in 19 (0.60%) intervention and 1 (0.03%) control participant. Randomization of this internet-delivered lifestyle intervention tailored to individual dementia risk factors resulted in significantly better cognition in older adults over 3 years. This intervention is scalable with the potential for population-level rollout that may delay cognitive decline in the general community. Australian New Zealand ClinicalTrials.gov registration: ACTRN12618000851268.

Dietary intakes of flavonoids in relation to cognitive function among middle-aged and older adults: results from the Chinese Square Dance Cohort.

Objective: The study aims to explore the association between intake of dietary flavonoids and global cognition, domain-specific cognition and mild cognitive impairment (MCI) in middle-aged and older adults in China. Design: A cross-sectional study. Methods: This study used baseline data collected during 2021-2023 from the Chinese Square Dance Cohort. Dietary information was collected using a semi-quantitative food frequency questionnaire, and flavonoid intakes were calculated. Cognitive function was evaluated using a battery of neuropsychological tests, and global cognition was assessed using the composite z-score. Participants with MCI were diagnosed by Petersen's criteria. The relationship between flavonoid intake and cognitive score was determined using multiple linear regression and presented as β values with 95%CIs. The association of flavonoid intake with MCI was evaluated using logistic regression models and presented as odds ratios (ORs) with 95%CIs. Results: Among 3990 middle-aged and older participants, the median (P25-P75) age was 63 (59-67) years, and 85.05% were females. After adjusting for various covariates, compared to the lowest quartile (Q1), the highest intakes (Q4) of total flavonoids, anthocyanidins and flavan-3-ols, flavanones, flavones, flavonols, procyanidins, and isoflavones were associated with higher composite z-scores, with β values (95%CIs) of 0.12 (0.06, 0.17), 0.15 (0.10, 0.21), 0.09 (0.04, 0.15), 0.11 (0.06, 0.17), 0.08 (0.02, 0.13), 0.09 (0.03, 0.14), and 0.09 (0.04, 0.15), respectively. In addition, higher dietary intakes of anthocyanidins and isoflavones were associated with lower odds of MCI, where the corresponding ORs (95%CIs) for Q4 were 0.69 (0.51, 0.94) and 0.72 (0.54, 0.97), respectively. Conclusion: Higher flavonoid intakes were related to better cognitive function. These findings suggest a beneficial effect of flavonoid intake on the cognitive aging process.

The social self in the developing brain.

The notion that the self is fundamentally social in nature and develops through social interactions has a long tradition in philosophy, sociology, and psychology. However, to date, the early development of the social self and its brain bases in infancy has received relatively little attention. This presents a review and synthesis of existing neuroimaging research, showing that infants recruit brain systems, involved in self-processing and social cognition in adults, when responding to self-relevant cues during social interactions. Moreover, this review draws on recent research, demonstrating the early developmental emergence and social embeddedness/dependency of the default-mode network in infancy, a brain network considered of critical importance to the sense of self and social cognition. This stands in contrast to research pointing to the relatively late ontogenetic emergence of the conceptual self, by about 18-24 months of age, as seen in the mirror-self recognition test. Based on this review and synthesis, the social self first hypothesis (SSFH) is formulated, presenting an integrated view, arguing for the early ontogenetic emergence of the social self and its brain basis. This developmental account informs and extends existing evolutionary thinking, emphasizing the primary role that social interdependence has played in the evolution of the human mind.

Assessing the health implications of anticholinergic drugs in older people

In this narrative review, we analyzed the existing literature on the pros and cons of anticholinergic medications, focusing on their prevalence, underlying mechanisms, and methods of assessment. Our review underscores the significant adverse effects of anticholinergic drugs, particularly on cognition and functional abilities in older adults. These effects include the exacerbation of various cognitive states, increased psychiatric symptoms, heightened risk of delirium, functional decline, elevated hospitalization rates, greater likelihood of institutionalization, and increased mortality. While anticholinergic medications provide therapeutic benefits, their use in older adults requires careful evaluation due to these considerable risks. Discontinuation of anticholinergic therapy offers both benefits and challenges. We propose practical guidelines for their use in clinical contexts such as dementia, schizophrenia, depression, anxiety, Parkinson’s disease, cardiovascular conditions, and urinary incontinence.

Multidimensional sleep health and cognitive function across adulthood.

Sleep is essential for proper function of the mind and body. Studies report the effect of sleep problems on cognition but focus on only a single or limited number of sleep indicators or on clinical populations (e.g., sleep apnea), and/or provide only cross-sectional results. This study examined cross-sectional and longitudinal associations between multidimensional assessment of sleep health and cognitive function. 3398 adults (Mage=56years) provided self-reported sleep and objective cognitive data for the Midlife in the United States study. A subsample of 2119 participants also provided sleep and cognitive data at follow-up approximately 9years later. A multidimensional, composite measure of sleep health composed of regularity, satisfaction, alertness, efficiency, and duration based on the Ru-SATED model was utilized (higher score=better sleep health) to evaluate self-reported sleep, and cognitive function was assessed using the Brief Test of Adult Cognition by Telephone. Cross-sectionally, better sleep health was associated with better cognition (B=0.121, SE=0.017, p<.001). This relationship remained significant even after adjusting for sociodemographic and health covariates (B=0.039, SE=0.014, p=.006). Longitudinally, improvement in sleep health from baseline to follow-up was associated with better cognitive performance at follow-up (B=0.031, SE=0.011, p=.004); however, this relationship did not remain significant after adjusting for covariates (B=0.015, p=.139). Findings suggest better sleep health measured across multiple domains is associated with higher cognitive function. Future studies may want to examine potential mechanisms by which better sleep health relates to better cognitive function over time, such as reduction in stress or inflammation.

Blood Pressure Variability and Cognition in Black and White Older Adults Over 18 Years of Follow-up: A Population-Based Cohort Study.

Hypertension is a well-established cardiovascular risk factor for cognitive function. As blood pressure fluctuates because of aging-related changes, we examined the association between visit-to-visit blood pressure variability (BPV) and cognition in older adults. This prospective observational cohort study included 4,770 individuals aged older than 65 years with repeated blood pressure assessment participating in the Chicago Health and Aging Project, a bi-racial population-based study lasting from 1993 to 2012. Blood pressure was measured by research staff every 3 years over 18 of follow-up. Systolic and diastolic BPV was calculated as the sum of the absolute difference in blood pressure between successive measurements, divided by the number (n - 1) of assessments. Cognition was assessed by standardized cognitive tests, and z-scores for the composite cognitive score were computed. Multivariable adjusted linear regression models were used to evaluate the association of systolic and diastolic BPV during the study period with cognition at the last visit. Of 4,770 individuals, 2,998 (62.9%) were women, 3,146 (66.0%) were Black, and the mean (SD) age at baseline was 71.3 (5.3) years. The mean systolic BPV was 17.7 mm Hg in Black individuals and 16.0 mm Hg in White participants. Higher systolic and diastolic BPV was associated with lower cognitive scores at the end of follow-up. Compared with individuals in the first tertile of systolic BPV (lower BPV), participants with third tertile (higher BPV) had lower cognitive scores by 0.074 standardized units (β -0.074; 95% CI -0.131 to -0.018), corresponding to 1.8 years older in cognitive age. This relationship differed by race, being significant only in older Black adults. Black individuals in the third tertile of systolic BPV had lower cognitive scores by 0.115 standardized units (β -0.115; 95% CI -0.183 to -0.047) compared with those in the first tertile, corresponding to 2.8 years older in cognitive age. Similar findings were observed for diastolic BPV. Elevated BPV, particularly in older Black adults, was associated with a lower cognitive score, suggesting routine assessment for blood pressure to identify and mitigate the adverse role of BPV in cognitive functioning in older adults.

Effect of exogenous β-hydroxybutyrate on BDNF signaling, cognition, and amyloid precursor protein processing in humans with T2D and insulin-resistant rodents.

People with type 2 diabetes (T2D) have a greater risk of developing neurodegenerative diseases, like Alzheimer's disease, in later life. Exogenous ketone supplements containing the ketone body β-hydroxybutyrate (β-OHB) may be a strategy to protect the brain as β-OHB can support cerebral metabolism and promote neuronal plasticity via expression of brain-derived neurotrophic factor (BDNF). Parallel human (ClinicalTrials.gov ID NCT04194450, ClinicalTrials.gov ID NCT05155410) and rodent trials were conducted to characterize the effect of acute and short-term exogenous ketone supplementation on indices of brain health. First, we aimed to investigate the effect of acute and short-term supplementation of exogenous ketone monoester on circulating BDNF and cognition in adults with T2D. There were no effects of ketone supplementation on plasma BDNF or cognition. Second, we aimed to investigate the mechanistic effects of acute and chronic β-OHB supplementation on cortical BDNF content and recognition memory in C57BL/6J mice with and without insulin resistance. Acutely, β-OHB did not alter recognition memory or BDNF content. Similarly, chronic β-OHB supplementation did not alter recognition memory or BDNF content. Collectively, our data demonstrates that ketone supplementation does not elevate BDNF content in humans or mice. Furthermore, our data does not support the involvement of BDNF in the potential cognitive benefits of β-OHB supplementation.NEW & NOTEWORTHY Ketone supplementation does not alter circulating BDNF levels or cognition in humans with T2D. Acute and chronic ketone supplementation in C57BL/6J mice did not change BDNF protein content or improve recognition memory. Ketone supplementation in C57BL/6J mice positively modulated β-site amyloid precursor protein cleaving enzyme 1 (BACE1) activity, providing a potential future therapeutic strategy.

Abdominal myosteatosis is associated with lower processing speed in a multiethnic cohort of older adults.

Prior research linking myosteatosis with cognition in older adults has been conducted in relatively homogenous populations with narrow age ranges. We evaluated if abdominal myosteatosis was associated with processing speed in a multiethnic cohort of middle aged and older adults. The analytical sample included 1,268 adults (46-86 years old, mean 63±9 years, 53% female of 41% White, 20% Black, 14% Chinese, and 25% Hispanic), a subset from the Multi-Ethnic Study of Atherosclerosis (MESA). Bivariate analyses were performed between abdominal computed tomography derived muscle densities (a myosteatosis measure) at year 3 with Digit Symbol Coding (DSC) with cytokines. Multivariable models were first adjusted for demographics, education, and general cognition, and further adjusted for other known predictors of dementia: APOE -4, physical activity, diabetes, cholesterol, smoking, and blood pressure. We further assessed whether central adiposity, general adiposity, and cytokines modified this association. We tested interactions by ethnicity, sex, and age. Rectus abdominis myosteatosis was significantly associated with worse DSC (B= -0.247, 95% CI: 0.098,0.396, p=0.001) independent of demographics, education, general cognition, and dementia risk factors. Adjustment for central adiposity, and cytokines did not attenuate the associations. Tests for interactions by ethnicity, sex, and age were not statistically significant. Rectus abdominis myosteatosis is associated with worse processing speed in this middle and older aged multiethnic population of men and women, independent of other known predictors of cognition. Longitudinal studies should assess the interplay of myosteatosis with other markers of adiposity, inflammation, and circulating mediators and their combined impact on processing speed. Abdominal myosteatosis correlated with lower cognitive processing speed in older adults.Myosteatosis links muscle density to cognitive function beyond dementia risk factors.Pro-inflammatory cytokines do not mediate the muscle-cognition association.Ethnicity, sex, and adiposity measures do not modify myosteatosis-cognition links.Abdominal CT scans could serve as diagnostic tools for cognitive health insights.

Age-associated differences in FIRES: Characterizing prodromal presentation and long-term outcomes via the web-based NORSE/FIRES Family Registry.

Febrile infection-related epilepsy syndrome (FIRES) is a rare clinical presentation of refractory status epilepticus following a febrile infection. This study analyzes data from the NORSE/FIRES Family Registry, an international web-based registry available in six languages with data entered by patients, families, and clinicians to explore clinical presentations, survivorship, and long-term outcomes in adult and pediatric FIRES patients. We characterize and examine differences in demographics, prodromal symptoms, seizure frequency, anti-seizure medications (ASMs), quality of life, cognition, mood, and anxiety in adults vs pediatric populations with FIRES. Eighty-six participants were included in the study. Pediatric patients (n = 54) were predominantly male (77.8%) and experienced a significantly higher post-FIRES seizure burden than adult survivors (67.7% ≥12 seizures/month in pediatrics vs 11.8% in adults, p <.001). Adults (n = 32) were more likely to be female (59.4%) and have flu-like prodromal symptoms (90.6%). At ≥6 months post-FIRES, both groups exhibited high ASM use, with the majority (87.5%) taking three or more medications. Pediatric patients reported worse mood and anxiety outcomes compared to adults (p <.005). Self-reported quality of life and cognition were rated as moderate across in adults (5.2/10) and pediatric(4.7/10) patients, although pediatric patients indicated poorer cognition. Our findings highlight the challenges in managing post-FIRES outcomes across different age groups, particularly in pediatric patients who face a higher seizure burden and report worse cognitive outcomes.

Relationship between severe hypoglycemia or impaired awareness of hypoglycemia and diabetes-related health status, global cognition and executive functions in adults with type 1 diabetes without severe anxiety or depression.

To explore the relationship between impaired awareness of hypoglycemia (IAH) or severe hypoglycemia (SH), and health status and cognition in adults with type 1 diabetes (T1D). T1D adults attending a tertiary diabetes service were recruited into this cross-sectional study. People screening positive for severe anxiety or depression were not included. Hypoglycemia awareness status was assessed using the full-scale and factor 1 of the Minimally Modified Clarke Hypoglycemia Survey (MMCHS; ≥4 and ≥ 2 = IAH); and data collected on health status (Diabetes Health Profile: barriers to activity, BA; psychological distress, PD; disinhibited eating); global cognition (Montreal Cognitive Assessment); and executive functions (EF; INECO Frontal Screening, IFS). A score of reduced awareness in item 3 and/or 4 of the MMCHS defined experience of ≥1 SH in past 6-12 months. In 165 T1D adults, prevalences of SH, IAH by MMCHS full-scale and factor 1 were 35 %, 13 % and 28 %. Participants with IAH by factor 1 had higher scores for PD (p = 0.008). Participants with SH and IAH (full-scale or factor 1) had higher BA scores (all p < 0.05) but no impairment of global cognition or EF. Participant Z-score IFS was lower than in non-diabetic individuals (p < 0.001). In our cohort, executive dysfunction in T1D was not associated with SH or IAH. IAH was associated with PD, and both SH and IAH were related to behavioral dysfunction.

Cognitive Trajectory Before and After Cataract Surgery: A Population-Based Approach.

Cataract surgery is the most common surgical procedure performed for older US adults. Cataracts are associated with poor cognition and higher rates of dementia, but whether cataract surgery improves cognition for US older adults is not known. We examined the relationship between cataract surgery and long-term change in cognition in the Health and Retirement Study, a population-based study of older US adults linked with Medicare billing data. We analyzed community-dwelling participants who underwent cataract surgery between 2000 and 2018, propensity-matched on age, sex, education (four levels), diabetes status (four levels), pre-procedural latent cognition, vision impairment, and interview timing and mode to older adults who did not have cataract surgery during the study period. Cataract surgery date was ascertained using Medicare billing data. We calculated latent value of cognition using biennial self/proxy cognitive assessments, and used linear mixed effects models adjusting for demographic and health factors to model cognition from 5 years before, to 5 years after, cataract surgery (or a simulated event, for controls). The primary measure was difference-in-differences estimate of latent cognition comparing the year prior, to the year after, cataract surgery or a simulated event. We analyzed 4384 older adults who underwent cataract surgery and 4384 matched controls (mean [SD] age 76.1 [6.8] years, 62.0% women, 83.9% non-Hispanic white). Across the first postoperative year, cataract surgical participants declined 0.002 (-0.002 to 0.006) units faster than nonsurgical controls (p = 0.37), equivalent to 8 (-10 to 26) days more cognitive aging. Post hoc subgroup analyses also found no difference in cognition for groups stratified by pre-procedural latent cognition (i.e., normal vs. cognitively impaired) or vision (i.e., vision-impaired vs. intact). Under typical United States practice, cataract surgery for older patients was not significantly associated with cognitive improvement or decline in the year after, compared with the year before, surgery.

The impact of brain-systemic oxygenation coupling in sleep-disordered breathing on cognitive function in elderly

Background: Intermittent hypoxia, a consequence of sleep-disordered breathing (SDB), may contribute to an increased risk of cognitive decline. However, the association between SDB and cognition remains highly variable. Methods: Fifty-two community-dwelling healthy older adults (28 women) were recruited. All participants underwent neuropsychiatric evaluations, simultaneous ambulatory polysomnography (PSG), and near-infrared spectroscopy (NIRS) recordings. We quantified the average coherence between oxy-Hb and SpO2 signals during SDB events to determine whether it could predict cognitive outcomes in healthy older adults, where higher coherence indicates reduced protection against systemic hypoxia. Results: The mean (SD) coherence of oxy-Hb and SpO2 was 0.16 (0.07). Linear regression analysis showed a significant association between mean coherence and worse Stroop Color Word Test scores (t=-0.304, p = .004). In contrast, oxy-Hb reduction alone and conventional SDB parameters did not show a significant association with cognition. Conclusion: This is the first report to demonstrate an association between a novel parameter of brain-systemic oxygenation coherence in SDB and cognition in older adults. A higher coherence rate of cortical oxy-Hb and systemic SpO2 during SDB may reflect a loss of compensatory mechanisms against systemic hypoxia and could help stratify older adults with a higher risk for cognitive decline.

The added value of metadata on test completion time for the quantification of cognitive functioning in survey research.

Information on the time spent completing cognitive testing is often collected, but such data are not typically considered when quantifying cognition in large-scale community-based surveys. We sought to evaluate the added value of timing data over and above traditional cognitive scores for the measurement of cognition in older adults. We used data from the Longitudinal Aging Study in India-Diagnostic Assessment of Dementia (LASI-DAD) study (N = 4,091), to assess the added value of timing data over and above traditional cognitive scores, using item-specific regression models for 36 cognitive test items. Models were adjusted for age, gender, interviewer, and item score. Compared to Quintile 3 (median time), taking longer to complete specific items was associated (p < 0.05) with lower cognitive performance for 67% (Quintile 5) and 28% (Quintile 4) of items. Responding quickly (Quintile 1) was associated with higher cognitive performance for 25% of simpler items (e.g., orientation for year), but with lower cognitive functioning for 63% of items requiring higher-order processing (e.g., digit span test). Results were consistent in a range of different analyses adjusting for factors including education, hearing impairment, and language of administration and in models using splines rather than quintiles. Response times from cognitive testing may contain important information on cognition not captured in traditional scoring. Incorporation of this information has the potential to improve existing estimates of cognitive functioning.

Obstructive sleep apnea and polysomnographic predictors of neuropsychological performance two years after injury in a prospective cohort of adults with traumatic brain injury

Objective: Obstructive sleep apnea (OSA) has been associated with structural and functional brain changes and cognitive impairment in sleep clinic samples. Persons with traumatic brain injury (TBI) are at increased risk of OSA compared to community samples, and many experience chronic cognitive disability. However, the impact of OSA on cognitive outcome after TBI is unknown. The purpose of this study was to examine the relationship between polysomnographic sleep parameters on neuropsychological performance 2 years following TBI. We hypothesized that oxygen desaturation, sleep fragmentation, and sleep depth would predict neuropsychological performance. Method: Participants (N = 123) were persons with moderate-to-severe TBI who underwent Type 1 Polysomnography during acute neurorehabilitation. At 2 years post-TBI, participants completed telephone-based neuropsychological testing (the Brief Test of Adult Cognition by Telephone). General linear models were fit to investigate the relationship between sleep parameters and neuropsychological performance, controlling for demographics and posttraumatic amnesia. Results: When controlling for demographics, injury characteristics, and other sleep parameters, greater percent of Stage 1 sleep time predicted poorer cognitive performance (Overall BTACT composite, p = 0.0078, ηp2 = 6.6%; Verbal Memory composite, p = 0.0407, ηp2 = 3.9%; Executive Function composite, p = 0.0215, ηp2 = 4.9%). Oxygen desaturation, cortical arousals, Stage 3 sleep, and the obstructive apnea-hypopnea index were not significantly associated with cognitive outcome. Conclusions: Reduced sleep depth was associated with cognitive outcome in persons with TBI; these findings require replication. Future research should examine whether improving sleep (e.g. increasing deep sleep) during acute recovery can improve cognitive recovery following TBI.

Insulin resistance, cognition, and functional brain network topology in older adults with obesity.

Cross-sectional data from a sample of older adults with obesity was used to determine how peripheral and neuronal insulin resistance (IR) relate to executive function and functional brain network topology. Older adults (n=71) with obesity but without type 2 diabetes were included. Peripheral IR was quantified by HOMA2-IR. Neuronal IR was quantified according to a proposed neuron-derived exosome-based method (NDE-IR). An executive function composite score, summed scores to the Auditory Verbal Learning Test (AVLT) trials 1-5, and functional brain networks generated from resting-state functional magnetic resonance imaging were outcomes in analyses. We used general linear models and a novel regression framework for brain network analysis to identify relationships between IR measures and brain-related outcomes. HOMA2-IR, but not NDE-IR, was negatively associated with executive function. Neither IR measure was associated with AVLT score. Peripheral IR was also related to hippocampal network topology in participants who had undergone functional neuroimaging. Neither peripheral nor neuronal IR were significantly related to network topology of the central executive network. Cognitive and functional imaging effects were observed from HOMA2-IR, but not NDE-IR. The hippocampus may be particularly vulnerable to effects of peripheral IR.

Effects of acute PM2.5 purification on cognitive function and underlying mechanisms: Evidence from integrating alternative splicing into multi-omics.

The relationship between fine particulate matter (PM2.5) and cognition has been extensively investigated. However, the causal impact of acute PM2.5 purification on cognition improvement and the underlying biological mechanisms remain relatively opaque. Our double-blinded randomized controlled trial assessed the impact of acute PM2.5 purification on executive function, underpinned by multi-omics approaches including alternative splicing (AS) analysis. A total of 93 participants experienced a two-hour exposure to either reduced and normal PM2.5 levels. We measured the cognition of healthy young adults, collected peripheral blood before and after intervention, and performed multi-omics analysis including transcriptomics, metabolomics, and proteomics. Results indicated that reducing PM2.5 by 1 μg/m3 was associated with a 0.10 % (95 % CI: [0.18 %, 0.01 %]; p = 0.031) improvement in executive function. Notably, we identified 96 AS events without concurrent transcriptional amount alterations. Multi-layered omics analyses revealed disrupted pathways in hypoxia, mitochondrial function and energy metabolism, and immune responses, validated by ELISA and biochemical assay. These findings demonstrated short-term improvements of cognition following PM2.5 purification and provide mechanistic understandings of PM2.5-induced cognition alterations. This study underscores the significance of incorporating AS in the molecular framework of multi-omics research by exploring variable exon splicing, which could enrich multi-omics analysis methodologies and expose to broader audience.

Effectiveness of Distant/Remote Blessing Treatment on Cognitive-motor Function: A Randomized Double-blind Placebo-controlled Trial.

Biofield therapies can be administered in person (hands-on treatment) or remotely, and this study focuses on the latter. A literature review did not find any reports on the effectiveness of remote biofield energy /blessing therapy in enhancing cognition and motor function performance in adults. The aim of this study was to examine the effect of distant/remote blessing (biofield energy) therapy on the cognitive and motor functions in adults with self-reported neuropsychological impairments using NIH Toolbox®. The present study was a randomized, double-blind clinical trial involving 117 participants with self-reported neuropsychological impairments. These participants were stratified into three distinct groups: control, sham control, and blessing/biofield treatment as the intervention. At baseline (day 0), day 90, and day 180, NIH Toolbox® was employed to evaluate all participants' cognitive and motor function scores. In the blessing treatment group, language function score (p <0.01), working memory (p <0.0001), and episodic memory (p <0.0001) scores exhibited statistically significant differences compared to both the naïve control and sham control groups. Moreover, in the blessing intervention group, a substantial improvement was observed in locomotion (p <0.0001), standing balance (p <0.01), dexterity (p <0.01), grip strength (p <0.05), and muscle endurance (p <0.05) compared to the naïve control and sham control groups. Importantly, no adverse effects were reported during the study period. The study outcomes revealed that distant/remote blessing/biofield energy therapy is safe, non-invasive, and less expensive. It enhances cognitive-motor functions in adults with perceived neuropsychological impairments. CTRI/2022/07/043736.

Cognitive and Alzheimer's disease biomarker effects of oral nicotinamide riboside (NR) supplementation in older adults with subjective cognitive decline and mild cognitive impairment.

Age-associated depletion in nicotinamide adenine dinucleotide (NAD+) concentrations has been implicated in metabolic, cardiovascular, and neurodegenerative disorders. Supplementation with NAD+ precursors, such as nicotinamide riboside (NR), offers a potential therapeutic avenue against neurodegenerative pathologies in aging, Alzheimer's disease, and related dementias. A crossover, double-blind, randomized placebo (PBO) controlled trial was conducted to test the safety and efficacy of 8 weeks' active treatment with NR (1 g/day) on cognition and plasma AD biomarkers in older adults with subjective cognitive decline and mild cognitive impairment. The primary efficacy outcome was the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Secondary outcomes included plasma phosphorylated tau 217 (pTau217), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL). Exploratory outcomes included Lumosity gameplay (z-scores) for cognition and step counts from wearables. Mixed model for repeated measures was used for between-group comparisons; paired t-tests were used for within-individual comparisons. Forty-six participants aged over 55 were randomized to NR-PBO or PBO-NR groups; 41 completed baseline visits, and 37 completed the trial. NR supplementation was safe and well tolerated with no differences in adverse events reported between NR and PBO treatment phases. For the between-group comparison, there was a 7% reduction in pTau217 concentrations after taking NR, while an 18% increase with PBO (p = 0.02). No significant between-group differences were observed for RBANS, other plasma biomarkers(GFAP and NfL), Lumosity gameplay scores or step counts. For the within-individual comparison, pTau217 concentrations significantly decreased during the NR phase compared to the PBO (p = 0.02), while step counts significantly increased during the NR phase than PBO (p = 0.04). Eight weeks NR supplementation is safe and lowered pTau217 concentrations but did not alter cognition as measured by conventional or novel digital assessments. Further research is warranted to validate NR's efficacy in altering pathological brain aging processes. The integrated study design combines a two-arm parallel trial with a crossover phase, offering the opportunity to enhance sample size for within-individual analysis and assess carryover effects.NR is safe but did not alter cognition as measured by multi-modal assessments in SCD/MCI.For between-group comparison, pTau217 levels decreased with NR and increased with PBO at 8-week follow-up.For within-individual comparison, step counts increased after NR and decreased after PBO.A larger, longer study with pharmacodynamic and pathophysiological biomarkers is needed to assess NR's disease-modifying effects.

Lactate shuttling links histone lactylation to adult hippocampal neurogenesis in mice.

Lactate has emerged as a central metabolic fuel and an important signaling molecule. Its availability participates in various brain functions. Although lactate homeostasis is vital for adult hippocampal neurogenesis and cognition, it is still unknown how shuttles lactate across the plasma membrane of neural stem cells (NSCs) to control their activity and neurogenic potential. In this study, we show that monocarboxylate transporter (MCT)1 and MCT2, respectively, control efflux and influx of lactate in the murine NSCs, thereby maintaining intracellular lactate homeostasis. Mechanistically, lactate shuttling links histone lactylation to govern NSC proliferation through MDM2-p53 signaling pathway. Notably, genetic ablation of MCT2 from NSCs or pharmacological inhibition of MDM2-P53 interaction prevents voluntary running-induced NSC proliferation in the murine adult hippocampus. Taken together, our findings demonstrate that lactate shuttling controls histone lactylation, which acts as a nexus for controlling adult hippocampal neurogenesis.