Factors associated with brain ageing - a systematic review.

BACKGROUND: Brain age is a biomarker that predicts chronological age using neuroimaging features. Deviations of this predicted age from chronological age is considered a sign of age-related brain changes, or commonly referred to as brain ageing. The aim of this systematic review is to identify and synthesize the evidence for an association between lifestyle, health factors and diseases in adult populations, with brain ageing. METHODS: This systematic review was undertaken in accordance with the PRISMA guidelines. A systematic search of Embase and Medline was conducted to identify relevant articles using search terms relating to the prediction of age from neuroimaging data or brain ageing. The tables of two recent review papers on brain ageing were also examined to identify additional articles. Studies were limited to adult humans (aged 18 years and above), from clinical or general populations. Exposures and study design of all types were also considered eligible. RESULTS: A systematic search identified 52 studies, which examined brain ageing in clinical and community dwelling adults (mean age between 21 to 78 years, ~ 37% were female). Most research came from studies of individuals diagnosed with schizophrenia or Alzheimer's disease, or healthy populations that were assessed cognitively. From these studies, psychiatric and neurologic diseases were most commonly associated with accelerated brain ageing, though not all studies drew the same conclusions. Evidence for all other exposures is nascent, and relatively inconsistent. Heterogenous methodologies, or methods of outcome ascertainment, were partly accountable. CONCLUSION: This systematic review summarised the current evidence for an association between genetic, lifestyle, health, or diseases and brain ageing. Overall there is good evidence to suggest schizophrenia and Alzheimer's disease are associated with accelerated brain ageing. Evidence for all other exposures was mixed or limited. This was mostly due to a lack of independent replication, and inconsistency across studies that were primarily cross sectional in nature. Future research efforts should focus on replicating current findings, using prospective datasets. TRIAL REGISTRATION: A copy of the review protocol can be accessed through PROSPERO, registration number CRD42020142817 .

Social connectedness and mortality after prostate cancer diagnosis: A prospective cohort study.

Men with prostate cancer experience side effects for which a supportive social environment may be beneficial. We examined the association between four measures of social connectedness and mortality after a prostate cancer diagnosis. Male participants in the Melbourne Collaborative Cohort Study in 1990-1994, who developed incident prostate cancer and attended follow-up in 2003-2007, were eligible for the study. Information on social connectedness, collected at follow-up, included (i) living arrangement; (ii) frequency of visits to friends/relatives and (iii) from friends/relatives; (iv) weekly hours of social activities. A total of 1,421 prostate cancer cases was observed (338 all-cause deaths, 113 from prostate cancer), including 867 after follow-up (150 all-cause deaths, 55 from prostate cancer) and 554 before follow-up (188 all-cause deaths, 58 from prostate cancer). Cox models stratified by tumour Gleason score and stage, and sequentially adjusted for socioeconomic, health- and lifestyle-related confounders, were used to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) for the association between social connectedness and all-cause mortality after prostate cancer. Men who reported living alone before diagnosis had higher overall mortality (HR = 1.6, 95% CI: 1.0-2.5), after adjustment for socioeconomic, health and lifestyle confounders. Lower mortality was observed for men with more social activities (p-trend = 0.07), but not in comprehensively adjusted models. Consistent with these findings, men living alone after prostate cancer diagnosis had higher mortality (HR = 1.3, 95% CI: 0.9-1.9). Lower mortality was observed with increasing socializing hours in the age-adjusted model (p-trend = 0.06) but not after more comprehensive adjustment. Our findings suggest that living with someone, but not other aspects of social connectedness, may be associated with decreased mortality for men with prostate cancer.

Non-uniformity correction for medium wave infrared focal plane array-based compressive imaging.

As a super-resolution imaging method, high-resolution medium wave infrared (MWIR) images can be obtained from a low-resolution focal plane array-based (FPA) sensor using compressive imaging (CI) technology. As a common problem in MWIR FPA imaging, the non-uniformity reduces image quality, which is turning worse in MWIR FPA CI. This paper investigates the source of the non-uniformity of MWIR FPA CI, both in the captured low-resolution MWIR images and in the reconstructed high-resolution ones. According to the system model and the image super-resolution computation process of FPA CI, we propose a calibration-based non-uniformity correction (NUC) method for MWIR FPA CI. Based on the actual MWIR FPA CI system, the effectiveness and practicability of the proposed NUC method are verified, obtaining better results than the traditional method. According to the theoretical analysis and experimental results, the particularities of the non-uniformity in MWIR FPA CI are discovered and discussed, which have certain great guiding significance and practical value.

Stray light correction for medium wave infrared focal plane array-based compressive imaging.

With focal plane array-based (FPA) compressive imaging (CI), high-resolution medium wave infrared (MWIR) images can be reconstructed by a low-resolution FPA sensor. However, in MWIR FPA CI system, the stray light is inevitable, which reduces the image contrast and increases the blocky structural artifacts of the reconstructed images. In this work, we focus on the stray light in MWIR FPA CI system. This paper investigates the sources of stray light in MWIR FPA CI system and modifies the systematic radiation model. According to the systematic computation model, we illustrate that stray light impedes the accurate sampling of compressive measurements in the MWIR FPA CI system, which may increase the blocky structural artifacts in the reconstructed high-resolution images. With the help of digital micro-mirror device modulation, we propose an operational method to substantially correct the effect of the stray light in MWIR FPA CI system, which can improve the image contrast and reduce the blocky structural artifacts of the reconstructed images, while not significantly increasing the cost of image acquisition and computation. Based on the experimental results obtained from the actual MWIR FPA CI system, we have verified the effectiveness and practicability of the proposed stray light correction method.

Association between NAFLD and risk of prevalent chronic kidney disease: why there is a difference between east and west?

BACKGROUNDS: There is a discrepancy between west and east on the relationship between non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD). This study aimed to find out the possible reason for this and to clarify the association between NAFLD and CKD by analyzing two population-based datasets from the US and China. METHODS: Two health examination datasets from China and the US were used. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2 or and/or abnormal albuminuria and/or overt proteinuria. Binary logistic regression was used to examine the association between NAFLD and CKD. RESULTS: A total of 60,965 participants were analyzed, including 11,844 from the US and 51,229 from China. The prevalence of NAFLD was 27.12% in the Chinese population and 36.08% in the US population (p < 0.001). The proportions of CKD and late stage CKD (stages 3-5) were higher in the US population than the Chinese one. NAFLD was independently associated with an increased risk of CKD in Chinese population, whereas in the US population, the NAFLD was not an independent risk factor of CKD. In subgroup analyses which excluded late stages CKD (stages 3-5), the risks of mild renal function decline became consistent: NAFLD was associated with early stages of CKD but not the late stages of CKD in both populations. CONCLUSION: NAFLD increased the risk of early stages of CKD in both Chinese and the US population. The conflicting results reported by previous studies might result from the different proportion of late stages of CKD.

DMD Mask Construction to Suppress Blocky Structural Artifacts for Medium Wave Infrared Focal Plane Array-Based Compressive Imaging.

With medium wave infrared (MWIR) focal plane array-based (FPA) compressive imaging (CI), high-resolution images can be obtained with a low-resolution MWIR sensor. However, restricted by the size of digital micro-mirror devices (DMD), aperture interference is inevitable. According to the system model of FPA CI, aperture interference aggravates the blocky structural artifacts (BSA) in the reconstructed images, which reduces the image quality. In this paper, we propose a novel DMD mask design strategy, which can effectively suppress BSA and maximize the reconstruction efficiency. Compared with random binary codes, the storage space and computation cost can be significantly reduced. Based on the actual MWIR FPA CI system, we demonstrate the proposed DMD masks can effectively suppress the BSA in the reconstructed images. In addition, a new evaluation index, blocky root mean square error, is proposed to indicate the BSA in FPA CI.

Focal plane array-based compressive imaging in medium wave infrared: modeling, implementation, and challenges.

As a super-resolution imaging method, compressive imaging (CI) has become a research hotspot in recent years. However, most researchers focus on the visible light and near-infrared regime. Further, most experimental studies are confined to a single-pixel camera, and there are comparatively few reports of the experimental studies about CI in the field of focal plane array-based (FPA) CI in the medium-wave infrared (MWIR). This paper derives the system model for an FPA CI system, describes the generation process of DMD masks, and modifies the block-based compressive sensing algorithm to be applicable to the FPA CI system. Based on the actual FPA CI system in MWIR, high-resolution MWIR images are obtained from a low-resolution MWIR sensor, realizing 16 times MWIR image super-resolution. However, imaging quality is not as ideal as that in visible light FPA CI system because of the particularities of MWIR. We analyze the particularities of an FPA CI system in MWIR and provide suggestions on how to solve them to improve performance. This work could provide guidance for researchers to build an experimental FPA CI system in MWIR.

Associations between body mass index and mortality in acute-on-chronic liver failure patients.

INTRODUCTION AND OBJECTIVES: The association between the level of body mass index (BMI) and the mortality of patients with critical liver disease remains unclear. This study aimed to examine the association between BMI and hospital mortality of patients with acute-on-chronic liver failure (ACLF). METHODS: Clinical data from 146 ACLF patients were collected and analyzed. BMI was categorized into three groups: lower BMI (<18.5kg/m2), normal BMI (18.5-24.9kg/m2), and overweight (25.0-32.0kg/m2). BMI and laboratory parameters were measured one day before, or on the day of the start of the treatment. Values of BMI and laboratory parameters were compared between survivors and non-survivors, and then hospital mortality rates were compared among patients with different BMI levels. RESULTS: The prognosis of ACLF patients was significantly correlated with international normalized ratio (INR), albumin and BMI. The ACLF patients with low albumin level and high INR values tend to have a high mortality rate. Also, survival time was significantly shorter in the ACLF patients with lower BMI, while patients with normal and overweight values had longer survival time. CONCLUSIONS: A graded association between BMI and hospital mortality with a strong significant trend was found in ACLF patients in China.

Time-dependence of NIHSS in predicting functional outcome of patients with acute ischemic stroke treated with intravenous thrombolysis.

OBJECTIVES: The National Institute of Health Stroke Scale (NIHSS) is a predictor for the prognosis of acute ischaemic stroke (AIS) and its prediction is time-dependent. We examined the performance of NIHSS at different timepoints in predicting functional outcome of patients with thrombolysed AIS. METHODS: This prospective study included 269 patients with AIS treated with recombinant tissue plasminogen activator (rt-PA). Unfavourable functional outcome was defined as modified Rankin Scale score 4-6 at 3 months after rt-PA treatment. Receiver operating characteristic curves were used to examine the predictive power of NIHSS score at admission and 2 hours/24 hours/7 days/10 days after rt-PA treatment. Youden's index was used to select the threshold of NIHSS score. Logistic regression was used to estimate the ORs of unfavourable functional outcome for patients with NIHSS score higher than the selected thresholds. RESULTS: The threshold of NIHSS score at admission was 12 (sensitivity: 0.51, specificity: 0.84) with an acceptable predictive power (area under curve [AUC] 0.74) for unfavourable functional outcome. The threshold changed to 5 at 24 hours after rt-PA treatment (sensitivity: 0.83, specificity: 0.65) and remained unchanged afterwards. The predictive power and sensitivity sequentially increased over time and peaked at 10 days after rt-PA treatment (AUC 0.92, sensitivity: 0.85, specificity: 0.80). NIHSS scores higher than the thresholds were associated with elevated risk of unfavourable functional outcome at all timepoints (all p<0.001). CONCLUSIONS: NIHSS is time-dependent in predicting AIS prognosis with increasing predictive power over time. Since patients whose NIHSS score ≥ 12 are likely to have unfavourable functional outcome with rt-PA treatment only, mechanical thrombectomy should be largely taken into consideration for these patients.

Geriatric syndromes, multimorbidity, and disability overlap and increase healthcare use among older Chinese.

BACKGROUND: Geriatric syndromes, multimorbidity, and disability are prevalent among ageing population. However, no study empirically examined their additive or synergistic effect on healthcare use. The present study aims to estimate overlapping prevalence of geriatric syndromes, multimorbidity, and disability; and to examine associations of these three conditions with healthcare use. METHODS: A cross-sectional study was conducted in community-dwelling older adults aged 60 and above in 12 Hong Kong districts. Pearson's chi-squared test for trend was performed to examine prevalence of geriatric syndromes, multimorbidity, and disability across three age groups (60-69, 70-79, and ≥ 80). Multiple logistic regression was conducted to explore associations of these three conditions with three types of healthcare use (hospital admission, general outpatient clinic and specialist outpatient clinic attendance) respectively. RESULTS: Among 2618 participants, 75.3, 41.8, and 22.5% had geriatric syndromes, multimorbidity, and disability respectively, and 10.4% had all the three conditions. Prevalence of the three conditions and their coexistence significantly increased with age (p for trend < .001). Each condition was independently associated with at least two out of three types of healthcare use. Interestingly, the associations of multimorbidity and disability with specialist outpatient clinic attendance were weakened at older age, while the associations of geriatric syndromes with hospital admission and specialist outpatient clinic attendance were strengthened. Furthermore, the odds of all the three types of healthcare use increased with the number of conditions present (p for trend < .001). CONCLUSIONS: Our findings support that the three conditions overlap and increase healthcare use. Early identification, prevention and intervention targeting older adults living with multiple healthcare needs are necessary.

Epigenetic age acceleration and cognitive performance over time in older adults.

INTRODUCTION: This study investigated whether epigenetic age acceleration (AA) is associated with the change in cognitive function and the risk of incident dementia over 9 years, separately in males and females. METHODS: Six epigenetic AA measures, including GrimAge, were estimated in baseline blood samples from 560 Australians aged ≥70 years (50.7% female). Cognitive assessments included global function, episodic memory, executive function, and psychomotor speed. Composite cognitive scores were also generated. Dementia (Diagnostic and Statistical Manual for Mental Disorders - IV [DSM-IV] criteria) was adjudicated by international experts. RESULTS: Associations between epigenetic AA and cognitive performance over-time varied by sex. In females only, GrimAA/Grim2AA was associated with worse delayed recall, composite cognition, and composite memory (adjusted-beta ranged from -0.1372 to -0.2034). In males only, GrimAA/Grim2AA was associated with slower processing speed (adjusted-beta, -0.3049) and increased dementia risk (adjusted hazard ratios [HRs], 1.78 and 2.00, respectively). DISCUSSION: Epigenetic AA is associated with cognitive deterioration in later life but with evidence of sex-specific associations. Highlights: Epigenetic age acceleration was associated with cognitive deterioration over time.However, these associations differed by sex.In females, accelerated GrimAge appeared to be a better marker of decline in memory.In males, accelerated GrimAge was associated with slower processing speed over time.Association between accelerated GrimAge and dementia risk was found only in males.

Associations of body habitus and its changes with incident dementia in older adults.

BACKGROUND: This study examined the associations of body mass index (BMI) and waist circumference (WC), as well as their short- and long-term changes over time, with incident dementia in older individuals. METHODS: Data came from 18,837 community-dwelling individuals aged 65+ years from Australia and the United States, who were relatively healthy without major cognitive impairment at enrolment. Anthropometric measures were prospectively assessed at baseline, as well as change and variability from baseline to year two (three time-points). In a subgroup (n = 11,176), self-reported weight at age 18 and 70+ years was investigated. Dementia cases satisfied DSM-IV criteria. Cox regression was used to examine the associations between anthropometric measures and incident risk of dementia. RESULTS: Compared to normal weight, an overweight (HR: 0.67, 95%CI: 0.57-0.79, p < 0.001) or obese BMI (HR: 0.73, 95%CI: 0.60-0.89, p = 0.002), or a larger WC (elevated, HR: 0.71, 95%CI: 0.58-0.86, p < 0.001; highly elevated, HR: 0.65, 95%CI: 0.55-0.78, p < 0.001; relative to low) at baseline was associated with lower dementia risk. In contrast, substantial increases in BMI (>5%) over 2 years after baseline were associated with higher dementia risk (HR: 1.49, 95% CI: 1.17-1.91, p = 0.001). Increased dementia risk was also seen with an underweight BMI at baseline and a 2-year BMI decrease (>5%), but these associations appeared only in the first 4 years of follow-up. Compared to normal weight at both age 18 and 70+ years, being obese at both times was associated with increased dementia risk (HR: 2.27, 95%CI: 1.22-4.24, p = 0.01), while obesity only at age 70+ years was associated with decreased risk (HR: 0.70, 95%CI: 0.51-0.95, p = 0.02). CONCLUSIONS: Our findings suggest that long-term obesity and weight gain in later life may be risk factors for dementia. Being underweight or having substantial weight loss in old age may be early markers of pre-clinical dementia.

Adverse events in older adults and the risk of dementia and cognitive decline.

Background: Increasing evidence suggests that stress could be a risk factor for dementia but this might vary by gender. This study investigated whether adverse life events were associated with cognitive decline and dementia in later-life, separately in men and women. Methods: Participants were 12,789 community-dwelling Australians aged ≥ 70 years. Ten common adverse events in later-life were self-reported. Cognitive decline was defined as a 1.5 SD decline from participants' baseline score in tests of global cognition, psychomotor speed, episodic memory, and executive functioning, which were assessed regularly over a maximum of 10.3 years. Dementia was diagnosed according to DSM-IV criteria. Results: An increased risk of dementia was observed in participants who experienced the death of a spouse/partner (HR: 1.72, 95% CI: 1.17 - 2.52) and for individuals who experienced major financial problems (HR: 1.53, 95% CI: 1.05 - 2.23). The latter also increased the risk of cognitive decline in men specifically (HR: 1.43, 95% CI: 1.10 - 1.86). In contrast, some events for women were associated with a reduced risk of dementia (e.g. close family or friends lost their job/retired (HR: 0.62, 95% CI: 0.40-0.95)). Limitations: Events including major money problems may result from prodromal dementia symptoms, thus reverse causation needs to be considered. Conclusions: Adverse life events may influence dementia risk in older adults, but associations vary depending on the nature of the event, and across genders. These findings support the need for early interventions in older people who have experienced adversities, particularly for the death of a loved one.

Lifestyle Enrichment in Later Life and Its Association With Dementia Risk.

Importance: Lifestyles enriched with socially and mentally stimulating activities in older age may help build cognitive reserve and reduce dementia risk. Objective: To investigate the association of leisure activities and social networks with dementia risk among older individuals. Design, Setting, and Participants: This longitudinal prospective cohort study used population-based data from the ASPREE Longitudinal Study of Older Persons (ALSOP) for March 1, 2010, to November 30, 2020. Community-dwelling individuals in Australia aged 70 years or older who were generally healthy and without major cognitive impairment at enrollment were recruited to the ALSOP study between March 1, 2010, and December 31, 2014. Data were analyzed from December 1, 2022, to March 31, 2023. Exposures: A total of 19 measures of leisure activities and social networks assessed at baseline were classified using exploratory factor analysis. Main Outcomes and Measures: Dementia was adjudicated by an international expert panel according to Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria. Cox proportional hazards regression examined dementia risk over 10 years, adjusting for education, socioeconomic status, and a range of health-related factors. Results: This study included 10 318 participants. Their median age was 73.8 (IQR, 71.6-77.2) years at baseline, more than half (52.6%) were women, and most self-identified as White (98.0%). In adusted analyses, more frequent engagement in adult literacy activities (eg, writing letters or journaling, using a computer, and taking education classes) and in active mental activities (eg, playing games, cards, or chess and doing crosswords or puzzles) was associated with an 11.0% (adjusted hazard ratio [AHR], 0.89 [95% CI, 0.85-0.93]) and a 9.0% (AHR, 0.91 [95% CI, 0.87-0.95]) lower risk of dementia, respectively. To a lesser extent, engagement in creative artistic activities (craftwork, woodwork, or metalwork and painting or drawing) (AHR, 0.93 [95% CI, 0.88-0.99]) and in passive mental activities (reading books, newspapers, or magazines; watching television; and listening to music or the radio) (AHR, 0.93 [95% CI, 0.86-0.99]) was also associated with reduced dementia risk. In contrast, interpersonal networks, social activities, and external outings were not associated with dementia risk in this sample. Conclusions and Relevance: These results suggest that engagement in adult literacy, creative art, and active and passive mental activities may help reduce dementia risk in late life. In addition, these findings may guide policies for geriatric care and interventions targeting dementia prevention for older adults.

Grip strength, gait speed, and trajectories of cognitive function in community-dwelling older adults: A prospective study.

Introduction: This study investigated whether grip strength and gait speed predict cognitive aging trajectories and examined potential sex-specific associations. Methods: Community-dwelling older adults (n = 19,114) were followed for up to 7 years, with regular assessment of global function, episodic memory, psychomotor speed, and executive function. Group-based multi-trajectory modeling identified joint cognitive trajectories. Multinomial logistic regression examined the association of grip strength and gait speed at baseline with cognitive trajectories. Results: High performers (14.3%, n = 2298) and low performers (4.0%, n = 642) were compared to the average performers (21.8%, n = 3492). Grip strength and gait speed were positively associated with high performance and negatively with low performance (P-values < 0.01). The association between grip strength and high performance was stronger in women (interaction P < 0.001), while gait speed was a stronger predictor of low performance in men (interaction P < 0.05). Discussion: Grip strength and gait speed are associated with cognitive trajectories in older age, but with sex differences. Highlights: There is inter-individual variability in late-life cognitive trajectories.Grip strength and gait speed predicted cognitive trajectories in older age.However, sex-specific associations were identified.In women, grip strength strongly predicted high, compared to average, trajectory.In men, gait speed was a stronger predictor of low cognitive performance trajectory.

Epigenetic aging as a biomarker of dementia and related outcomes: a systematic review.

Background: Biological aging may be a robust biomarker of dementia or cognitive performance. This systematic review synthesized the evidence for an association between epigenetic aging and dementia, mild cognitive impairment and cognitive function. Methods: A systematic search was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: 30 eligible articles were included. There was no strong evidence that accelerated epigenetic aging was associated with dementia/mild cognitive impairment (n = 7). There was some evidence of an association with poorer cognition (n = 20), particularly with GrimAge acceleration, but this was inconsistent and varied across cognitive domains. A meta-analysis was not performed due to high study heterogeneity. Conclusion: There is insufficient evidence to indicate that current epigenetic aging clocks can be clinically useful biomarkers of dementia or cognitive aging.

As individuals get older, changes in cognitive performance are common, including some degree of cognitive decline. Dementia is a symptom characterized by significant decline in cognitive function that affects daily living, and age is the biggest risk factor. Researchers have now identified ways to estimate a person's biological age from a blood sample (referred to as 'epigenetic aging'), and this measure is thought to better estimate an individual's rate of aging than his or her chronological age. This study brought together all of the previous studies, 30 in total, that have investigated links between biological aging and cognitive performance, as well as dementia risk. Synthesizing all of this evidence, the authors found no strong evidence that the individuals with dementia had accelerated aging. However, there was some evidence, although inconsistent, indicating that accelerated aging was associated with worse cognitive performance.

Pre-thrombectomy prognostic prediction of large-vessel ischemic stroke using machine learning: A systematic review and meta-analysis.

Introduction: Machine learning (ML) methods are being increasingly applied to prognostic prediction for stroke patients with large vessel occlusion (LVO) treated with endovascular thrombectomy. This systematic review aims to summarize ML-based pre-thrombectomy prognostic models for LVO stroke and identify key research gaps. Methods: Literature searches were performed in Embase, PubMed, Web of Science, and Scopus. Meta-analyses of the area under the receiver operating characteristic curves (AUCs) of ML models were conducted to synthesize model performance. Results: Sixteen studies describing 19 models were eligible. The predicted outcomes include functional outcome at 90 days, successful reperfusion, and hemorrhagic transformation. Functional outcome was analyzed by 10 conventional ML models (pooled AUC=0.81, 95% confidence interval [CI]: 0.77-0.85, AUC range: 0.68-0.93) and four deep learning (DL) models (pooled AUC=0.75, 95% CI: 0.70-0.81, AUC range: 0.71-0.81). Successful reperfusion was analyzed by three conventional ML models (pooled AUC=0.72, 95% CI: 0.56-0.88, AUC range: 0.55-0.88) and one DL model (AUC=0.65, 95% CI: 0.62-0.68). Conclusions: Conventional ML and DL models have shown variable performance in predicting post-treatment outcomes of LVO without generally demonstrating superiority compared to existing prognostic scores. Most models were developed using small datasets, lacked solid external validation, and at high risk of potential bias. There is considerable scope to improve study design and model performance. The application of ML and DL methods to improve the prediction of prognosis in LVO stroke, while promising, remains nascent. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021266524, identifier CRD42021266524.

Potential modifiable factors associated with late-life cognitive trajectories.

Objective: There is variability across individuals in cognitive aging. To investigate the associations of several modifiable factors with high and low cognitive performance. Methods: Data came from 17,724 community-dwelling individuals aged 65-98 years. Global cognition, verbal fluency, episodic memory, and psychomotor speed were assessed over up to seven years. Group-based multi-trajectory modeling identified distinct cognitive trajectories. Structural equation modeling examined the direct/indirect associations of social/behavioral factors and several chronic conditions with cognitive trajectories. Results: Seven trajectory subgroups were identified. In the structural equation modeling we compared two subgroups-participants with the highest (14.2%) and lowest (4.1%) cognitive performance with the average subgroup. Lower education, never alcohol intake, and frailty directly predicted increased risk of low performance, and decreased likelihood of high performance. Hypertension (RR: 0.69, 95%CI: 0.60-0.80), obesity (RR: 0.84, 95%CI: 0.73-0.97), diabetes (RR: 0.69, 95%CI: 0.56-0.86) and depression (RR: 0.68, 95%CI: 0.54-0.85) only predicted lower likelihood of high cognitive performance, while dyslipidemia was only associated with low performance (RR: 1.30, 95%CI: 1.07-1.57). Living alone predicted increased risk of low cognitive performance and several comorbidities. Smoking did not predict cognitive trajectories but was associated with increased risk of diabetes, obesity and frailty. Findings were similar when examining the direct associations between modifiable risk factors and all seven cognitive subgroups. Conclusions: Although several modifiable factors were associated with high performance, and reversely with low performance, this was not observed for obesity, hypertension and dyslipidemia. Further, health behaviors may affect cognitive function indirectly, via geriatric conditions. This indicates that strategies to promote healthy cognitive aging, may be distinct from those targeting dementia prevention.

Cognitive Trajectories in Community-Dwelling Older Adults and Incident Dementia, Disability and Death: A 10-Year Longitudinal Study.

Objective: The inter-individual variability in cognitive changes may be early indicators of major health events. We aimed to determine whether late-life cognitive trajectories were associated with incident dementia, persistent physical disability and all-cause mortality. Methods: Data came from a cohort of older community-dwelling individuals aged 70 years or above in Australia and the United States. Global cognition, verbal fluency, episodic memory and psychomotor speed were assessed regularly at up to seven waves between 2010 and 2017. Dementia, disability in activities of daily living, and death were adjudicated between 2017 and 2020. Latent classes of cognitive trajectories over seven years were determined using group-based trajectory modeling. Multivariable logistic regression was used for the prospective associations between cognitive trajectories and these outcomes. Results: Cognitive trajectories were defined for 16,174 participants (mean age: 78.9 years; 56.7% female) who were alive and without incident dementia or disability by 2017, among which 14,655 participants were included in the association analysis. Between three and five trajectory classes were identified depending on the cognitive test. Cognitive trajectories were strongly associated with the risk of dementia. For example, compared to those in the highest-functioning trajectory, the worst performers of episodic memory had a 37-fold increased risk of dementia (95% CI: 17.23-82.64). The lowest trajectories of both global cognition and episodic memory also predicted increased mortality risk (OR: 1.80, 95% CI: 1.28-2.52; OR: 1.61, 95% CI: 1.09-2.36, respectively), while only slow psychomotor speed was marginally associated with physical disability (OR: 2.39, 95% CI: 0.99-5.77). Conclusions: In older individuals, cognitive trajectories appear to be early indicators of clinically relevant health outcomes. Systematic cognitive assessments as part of routine geriatric evaluation may facilitate early identification and interventions for those individuals at highest risk.

Circular RNA circPHC3 Promotes Cell Death and Apoptosis in Human BMECs After Oxygen Glucose Deprivation via miR-455-5p/TRAF3 Axis in vitro.

OBJECTIVE: Brain microvascular endothelial cells (BMECs) are involved in brain vascular dysfunction in ischemic stroke. Abnormal expression of circular RNAs regulate physiological and pathophysiological processes in the central nervous system. The aim of the present study was to investigate profile circRNAs in human BMECs after oxygen glucose deprivation (OGD), which was an in vitro model of ischemic stroke, and find promising biomarkers in ischemic stroke. METHODS: RNA sequencing (RNA-seq) technology was conducted to analyze the differential expression of circRNAs between BMECs after OGD and non-OGD treated BMECs. RT-qPCR, cell proliferation, cell apoptosis and dual-luciferase assay, and so on, were used to investigate the functions and molecular mechanisms of hsa_circ_0001360 (named circPHC3 in this study) in ischemic stroke. RESULTS: CircPHC3 was highly expressed in human BMECs after OGD. Knockdown of circPHC3 inhibited cell death and apoptosis in human BMECs treated with OGD. Mechanistically, circPHC3 acted as miR-455-5p sponge to activate TRAF3 to promote cell death and apoptosis in human BMECs after OGD. CONCLUSION: In short, circPHC3 promotes cell death and apoptosis in ischemic stroke in vitro model, which might be a novel molecular target for acute cerebrovascular protection.