Gestational diabetes mellitus is associated with greater incidence of dementia during long-term post-partum follow-up.

BACKGROUND: The impact of gestational diabetes mellitus (GDM) on incident dementia is unknown. Our aim was to evaluate the relationship between GDM and all-cause dementia and the mediating effects of chronic diseases on this relationship. METHODS: This prospective cohort study included women from the UK Biobank who were grouped based on GDM history. Multivariate Cox proportional hazard models were used to explore the associations between GDM and dementia. We further analysed the mediating effects of chronic diseases on this relationship and the interactions of covariates. RESULTS: A total of 1292 women with and 204,171 women without a history of GDM were included. During a median follow-up period of 45 years after first birth, 2921 women were diagnosed with dementia. Women with a GDM history had a 67% increased risk of incident dementia (hazard ratio 1.67, 95% confidence interval: 1.03-2.69) compared with those without a GDM history. According to mediation analyses, type 2 diabetes, coronary heart disease, chronic kidney disease and comorbidities (diagnosed with any two of the three diseases) explained 34.5%, 8.4%, 5.2% and 18.8% of the mediating effect on the relationship. Subgroup analyses revealed that physical activity modified the association between GDM history and dementia (p for interaction = 0.030). Among physically inactive women, GDM was significantly associated with incident dementia; however, this association was not observed among physically active women. CONCLUSIONS: A history of GDM was associated with a greater risk of incident dementia. Type 2 diabetes partially mediated this relationship. Strategies for dementia prevention might be considered for women with a history of GDM.

Association between Age at Diagnosis of Hyperlipidemia and Subsequent Risk of Dementia.

OBJECTIVES: The relationship between age at diagnosis of hyperlipidemia and dementia remains unclear. We examined whether younger age at diagnosis of hyperlipidemia is associated with higher risk of subsequent dementia. DESIGN: A longitudinal population-based study with a median follow-up of 12.8 years. SETTING AND PARTICIPANTS: We analyzed data on a sample of 489,642 participants in the United Kingdom. METHODS: This study was based on the UK Biobank. Information on hyperlipidemia and dementia diagnoses was collected at baseline (2006-2010) and follow-up [median = 12.8 years, interquartile range (IQR): 12.1-13.6 years]. Propensity score matching method and Cox proportional hazards models were used to assess the association between age at diagnosis of hyperlipidemia and dementia. RESULTS: Among 489,642 participants (mean age: 56.9 ± 8.1 years; female: 54.7%), 114,112 (23.3%) were diagnosed with hyperlipidemia. Younger age at diagnosis of hyperlipidemia (per 10-year decrease) was significantly associated with higher risks of all-cause dementia [hazard ratio (HR), 1.12; 95% CI, 1.07-1.18; P < .001], Alzheimer's disease (AD) (HR, 1.22; 95% CI, 1.14-1.31; P < .001), and vascular dementia (VD) (HR, 1.16; 95% CI, 1.05-1.27; P < .001). After propensity score matching, patients with hyperlipidemia diagnosed before 50 years had the highest HR for all-cause dementia (HR, 1.46; 95% CI, 1.15-1.86; P = .002), followed by patients diagnosed between 50 and 69 years (HR, 1.21; 95% CI, 1.12-1.31; P < .001) and then patients diagnosed aged 70 years and older (HR, 0.94; 95% CI, 0.84-1.06; P = .302). Similar results were observed for AD and VD. CONCLUSIONS AND IMPLICATIONS: A dose-response relationship between age at hyperlipidemia diagnosis and risk of dementia was found in the longitudinal cohort study, with younger age at diagnosis of hyperlipidemia being associated with higher subsequent risk.

Associations between onset age of orthostatic hypotension and incident myocardial infarction, stroke, and dementia: a prospective cohort study.

BACKGROUND: The associations of age at orthostatic hypotension onset with incident myocardial infarction (MI), stroke, and dementia remain unknown. This study aimed to examine whether younger onset age of orthostatic hypotension was associated with higher risks of incident MI, stroke, and dementia. METHODS: Data were obtained from the UK Biobank. Information on the diagnosis of orthostatic hypotension, MI, stroke, and dementia was collected at baseline (2006-2010) and follow-ups (median=13 years). The propensity score matching method and the Cox proportional hazard models were employed. RESULTS: A total of 448 374 adults (mean age: 56.8±8.1 years), of whom 3795 had orthostatic hypotension, were included. orthostatic hypotension patients exhibited higher risks of developing MI, stroke, and dementia than non-orthostatic hypotension participants. Importantly, among orthostatic hypotension patients, younger onset age (per 10-year decrement) was significantly associated with high risks of MI (HR=3.15, 95% CI: 2.54 to 3.90, P<0.001), stroke (HR=1.72, 95% CI: 1.33 to 2.23, P<0.001), and dementia (HR=1.26, 95% CI: 1.02 to 1.57, P=0.034). After propensity score matching, orthostatic hypotension patients had significantly higher risks of MI, stroke, and dementia than matched controls among all onset age groups, and the HRs gradually increased with descending onset age. CONCLUSIONS: Younger onset age of orthostatic hypotension was associated with higher risks of incident MI, stroke, and dementia, underscoring the necessity to pay additional attention to the cardiovascular health and neurocognitive status of individuals diagnosed with orthostatic hypotension at younger ages to attenuate subsequent risks of incident cardiovascular diseases and dementia.

Time in target range of systolic blood pressure and cognitive outcomes in patients with hypertension.

BACKGROUND: Blood pressure (BP) is a dynamic measure that fluctuates over time. However, conventional BP control indicators may not adequately reflect the variability of BP during a period of time. METHODS: We performed a secondary analysis of the Systolic Blood Pressure Intervention Trial (SPRINT), which compared systolic blood pressure (SBP) targets of <120 mmHg (intensive) and <140 mmHg (standard) among patients with hypertension and high cardiac risks. The target ranges were defined as 110 to 130 mmHg in intensive treatment arm and 120 to 140 mmHg in standard treatment arm, respectively. Time in target range (TTR) was calculated based on SBP measurements recorded during the first 3-month follow-up using linear interpolation method. The Fine-Gray competing risk regression models were used to evaluate the association between TTR and cognitive outcomes. RESULTS: A total of 7965 patients with the mean (SD) age of 68.0 (9.2) years were included, and 35% were female. Patients with higher TTR were younger, more likely to be male and take <3 BP-lowering agents. Compared to the last quartile, the first quartile of TTR was significantly associated with a higher risk of probable dementia (HR: 1.74; 95% CI: 1.22-2.46; p = 0.002) and the composite of probable dementia or mild cognitive impairment (HR: 1.26; 95% CI: 1.03-1.55; p = 0.025). The risk of probable dementia and the composite outcome increased with per quartile decrease of TTR (HR: 1.18; 95% CI: 1.06-1.30; p = 0.002 and HR: 1.07; 95% CI: 1.00-1.14; p = 0.036). Sensitivity analyses showed similar results after adjusting mean SBP during the first 3-month follow-up. CONCLUSIONS: In this secondary analysis of SPRINT data, TTR was independently associated with probable dementia among patients with hypertension, suggesting that TTR could be used as a practical metric of BP control to evaluate the risk of dementia in older adults. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Identifier: NCT01206062.

Association of Cardiovascular Health With Risk of Incident Depression and Anxiety.

OBJECTIVE: To investigate the association between cardiovascular health (CVH), defined by the American Heart Association's Life's Essential 8 (LE8) score, and incident depression and anxiety. DESIGN: A prospective cohort study using data from UK Biobank. SETTING: Participants were enrolled from March 2006 to October 2010. PARTICIPANTS: Participants without cardiovascular diseases and common mental disorders at baseline and having complete data on metrics of LE8 were included. MEASUREMENTS: CVH was assessed by LE8 score including eight components. The overall CVH was categorized as low (LE8 score <50), moderate (50≤ LE8 score <80), and high (LE8 score ≥80). RESULTS: We included 115,855 participants (mean age: 55.7 years; female: 52.6%). During a median follow-up of 12.4 years, 3,194 (2.8%) and 4,005 (3.5%) participants had incident depression and anxiety, respectively. Compared with participants having low CVH, those having moderate and high CVH had 37% (HR = 0.63, 95% CI: 0.57-0.70) and 52% (HR = 0.48, 95% CI: 0.41-0.55) lower risk of incident depression. Similarly, moderate and high CVH were related to a lower risk of incident anxiety (HR = 0.81, 95% CI: 0.73-0.89 and HR = 0.68, 95% CI: 0.60-0.78). Restricted cubic spline showed that LE8 score was inversely related to incident depression and anxiety in a linear manner, and the risk of incident depression and anxiety decreased by 17% (HR = 0.83, 95% CI: 0.80-0.85) and 10% (HR = 0.90, 95% CI: 0.88-0.92) for 10-point increment in LE8 score, respectively. CONCLUSIONS: Higher CVH, evaluated by LE8 score, is strongly associated with a lower risk of incident depression and anxiety, suggesting the significance of optimizing CVH by adopting LE8.

Association Between Onset Age of Coronary Heart Disease and Incident Dementia: A Prospective Cohort Study.

BACKGROUND: The association of age at coronary heart disease (CHD) onset with incident dementia remains unexplored. This study aimed to examine whether younger onset age of CHD is associated with a higher risk of incident dementia. METHODS AND RESULTS: Data were obtained from the UK Biobank. Information on the diagnosis of CHD and dementia was collected at baseline and follow-ups. Propensity score matching method and Cox proportional hazards models were used to evaluate the association between different ages at CHD onset and incident dementia. A total of 432 667 adults (mean±SD age, 56.9±8.1 years) were included, of whom 11.7% had CHD. Compared with participants without CHD, participants with CHD exhibited higher risks of developing all-cause dementia, Alzheimer's disease, and vascular dementia. More importantly, younger age at CHD onset (per 10-year decrease) was significantly associated with elevated risks of all-cause dementia (hazard ratio [HR], 1.25 [95% CI, 1.20-1.30]; P<0.001), Alzheimer's disease (HR, 1.29 [95% CI, 1.20-1.38]; P<0.001), and vascular dementia (HR, 1.22 [95% CI, 1.13-1.31]; P<0.001). After propensity score matching, patients with CHD had significantly higher risks of all-cause dementia, Alzheimer's disease, and vascular dementia than matched controls among all onset age groups, and the HRs gradually elevated with decreasing age at CHD onset. CONCLUSIONS: Younger onset age of CHD is associated with higher risks of incident all-cause dementia, Alzheimer's disease, and vascular dementia, underscoring the necessity to pay attention to the neurocognitive status of individuals diagnosed with CHD at younger age to conduct timely interventions to attenuate subsequent risk of incident dementia.

Age at Diagnosis of Atrial Fibrillation and Incident Dementia.

Importance: Epidemiological evidence regarding the association between atrial fibrillation (AF) onset age and risk of incident dementia remains unexplored. Objective: To examine whether age at AF diagnosis is associated with risk of incident dementia and its subtypes. Design, Setting, and Participants: This prospective, population-based cohort study used data from UK Biobank, a public, open-access database in the UK with baseline information collected from 2006 to 2010. A total of 433 746 participants were included in the main analysis after excluding participants with a diagnosis of dementia or AF at baseline, missing data on covariates, or having dementia before AF onset during a median follow-up of 12.6 years. Data were analyzed from October to December 2022. Exposures: AF diagnosis and age at AF diagnosis according to age groups (<65 years, 65-74 years, or ≥75 years). Main Outcomes and Measures: Incident dementia, ascertained through linkage from multiple databases until December 31, 2021. Cox proportional hazards models and the propensity score matching method were adopted to estimate the association between AF onset age and incident dementia. Results: Of 433 746 included participants, 236 253 (54.5%) were female, the mean (SD) age was 56.9 (8.1) years, and 409 990 (94.5%) were White. Compared with individuals without AF, 30 601 individuals with AF had a higher risk of developing all-cause dementia (adjusted hazard ratio [HR], 1.42; 95% CI, 1.32-1.52) and vascular dementia (VD; adjusted HR, 2.06; 95% CI, 1.80-2.36), but not Alzheimer disease (AD; adjusted HR, 1.08; 95% CI, 0.96-1.21). Among participants with AF, younger age at AF onset was associated with higher risks of developing all-cause dementia (adjusted HR per 10-year decrease, 1.23; 95% CI, 1.16-1.32), AD (adjusted HR per 10-year decrease, 1.27; 95% CI, 1.13-1.42), and VD (adjusted HR per 10-year decrease, 1.35; 95% CI, 1.20-1.51). After propensity score matching, individuals with AF diagnosed before age 65 years had the highest HR of developing all-cause dementia (adjusted HR, 1.82; 95% CI, 1.54-2.15), followed by AF diagnosed at age 65 to 74 years (adjusted HR, 1.47; 95% CI, 1.31-1.65) and diagnosed at age 75 years or older (adjusted HR, 1.11; 95% CI, 0.96-1.28). Similar results can be seen in AD and VD. Conclusions and Relevance: In this prospective cohort study, earlier onset of AF was associated with an elevated risk of subsequent all-cause dementia, AD, and VD, highlighting the importance of monitoring cognitive function among patients with AF, especially those younger than 65 years at diagnosis.

Age at Onset of Heart Failure and Subsequent Risk of Dementia: A Longitudinal Cohort Study.

BACKGROUND: The average age at onset of heart failure (HF) shows a progressive decrease in recent years; however, the association between age at onset of HF and risk of subsequent dementia remains undetermined. OBJECTIVES: The study sought to examine whether younger onset age of HF is associated with a higher risk of incident dementia. METHODS: Individual-level data from the UK Biobank cohort study were analyzed in the present study. Cox regression models and the propensity score matching method were used to analyze the associations of HF and its onset age with subsequent all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VD). RESULTS: Compared with 442,791 participants without HF, those with HF had a higher risk of all-cause dementia (HR: 1.14). Among 14,413 participants with HF, multivariable-adjusted HRs for all-cause dementia, AD, and VD were 1.18, 1.64, and 1.27, respectively, per 10-year decrease in age at HF onset. The propensity score matching analyses found that the strength of association between HF and all-cause dementia increased with decreasing onset age of HF (≥75 years, HR: 1.05; 65-74 years, HR: 1.10; <65 years, HR: 1.67) after multivariable adjustment. Similarly, participants with onset age of HF <65 years had the greatest HRs for incident AD and VD, compared with their matched control subjects. CONCLUSIONS: Younger age at HF onset was associated with increased risk of dementia. Individuals with an onset age of HF before 65 years of age may represent a particularly vulnerable population for dementia irrespective of subtypes and need careful monitoring and timely intervention to attenuate subsequent risk of incident dementia.

Altered functional connectivity in anterior cingulate cortex subregions in treatment-resistant schizophrenia patients.

BACKGROUND: The anterior cingulate cortex (ACC) plays a key role in motor control, attention, and cognitive control. It is well established that schizophrenia is associated with impaired functional connectivity (FC) of the ACC pathway. So far, however, there has been little discussion about the ACC subregions function in patients with treatment-resistant schizophrenia (TRS). AIM: This study aims to characterize resting-state functional connectivity (rs-FC) profiles of ACC subregions in patients with TRS. The association between these FC and clinical symptoms, neurocognitive function, and grey matter volume (GMV) was studied as well. METHODS: A total of 81 patients with schizophrenia (40 patients with TRS = 40, 41 patients with non-treatment-resistant schizophrenia (NTRS)) and 39 age- and gender-matched healthy controls (HC) were enrolled, and underwent structural magnetic resonance imaging (MRI), resting-state functional MRI (rs-fMRI), clinical evaluation. The ACC subregions, including subgenual ACC (sgACC), pregenual ACC (pgACC), and dorsal ACC (dACC), were selected as seed regions from the automated anatomical labelling atlas 3 (AAL3). The GMV of the ACC subregions were calculated and seed-based FC maps for all ACC subregions were generated and compared between the TRS and NTRS, HC group. Additionally, correlations between altered FC and clinical symptoms, GMV, and neurocognitive functions in the TRS patients were explored. RESULT: Compared with HC, increased FC was observed in TRS and NTRS groups between bilateral sgACC and left cuneus, right cuneus, and left lingual gyrus, while decreased FC was found between bilateral dACC and thalamic. Additionally, compared with NTRS, the TRS group showed increased FC between bilateral dACC and right cuneus and decreased FC between bilateral dACC and thalamic. The TRS group showed decreased GMV in all ACC subregions than the HC group, and there is no significant difference between the TRS group and the NTRS group. CONCLUSION: The findings in this study suggest that disrupted FC of subregional ACC has the potential as a marker for TRS. The dysconnectivity of bilateral dACC- right cuneus and bilateral dACC-thalamus, are likely to be the unique FC profiles of TRS. These findings further our understanding of the neurobiological impairments in TRS.

Increased Functional Connectivity Involving the Parahippocampal Gyrus in Patients with Schizophrenia during Theory of Mind Processing: A Psychophysiological Interaction Study.

BACKGROUND: Theory of Mind (ToM) is an ability to infer the mental state of others, which plays an important role during social events. Previous studies have shown that ToM deficits exist frequently in schizophrenia, which may result from abnormal activity in brain regions related to sociality. However, the interactions between brain regions during ToM processing in schizophrenia are still unclear. Therefore, in this study, we investigated functional connectivity during ToM processing in patients with schizophrenia, using functional magnetic resonance imaging (fMRI). METHODS: A total of 36 patients with schizophrenia and 33 healthy controls were recruited to complete a ToM task from the Human Connectome Project (HCP) during fMRI scanning. Psychophysiological interaction (PPI) analysis was applied to explore functional connectivity. RESULTS: Patients with schizophrenia were less accurate than healthy controls in judging social stimuli from non-social stimuli (Z = 2.31, p = 0.021), and displayed increased activity in the right inferior frontal gyrus and increased functional connectivity between the bilateral middle temporal gyrus and the ipsilateral parahippocampal gyrus during ToM processing (AlphaSim corrected p < 0.05). CONCLUSIONS: Here, we showed that the brain regions related to sociality interact more with the parahippocampal gyrus in patients with schizophrenia during ToM processing, which may reflect a possible compensatory pathway of ToM deficits in schizophrenia. Our study provides a new idea for ToM deficits in schizophrenia, which could be helpful to better understand social cognition of schizophrenia.

Onset age of diabetes and incident dementia: A prospective cohort study.

BACKGROUND: Relationship between age at diagnosis of diabetes and dementia is lacking. The aim of the study was to investigate whether diabetes onset at a younger age was associated with a higher incidence of dementia. METHODS: 466,207 participants free of dementia in the UK biobank (UKB) were included in the analysis. Propensity score matching (PSM) was adopted to match diabetic and non-diabetic participants in different onset age of diabetes groups to evaluate onset age of diabetes and incident dementia. RESULTS: Compared with non-diabetic participants, diabetes participants had an adjusted hazard ratio (HR) of 1.87 (95 % confidence interval [CI]: 1.73-2.03) for all-cause dementia, 1.85 (95 % CI: 1.60-2.04) for Alzheimer's disease (AD), and 2.86 (95 % CI: 2.47-3.32) for vascular dementia (VD). Among diabetic participants who reported onset age, the adjusted HRs for incident all-cause dementia, AD, and VD were 1.20 (95 % CI: 1.14-1.25), 1.19 (95 % CI: 1.10-1.29), and 1.19 (95 % CI: 1.10-1.28), respectively, per 10 years decrease in age at diabetes onset. After PSM, strength of association between diabetes and all-cause dementia increased with decreasing onset age of diabetes (≥60 years: HR = 1.47, 95 % CI: 1.25-1.74; 45-59 years: HR = 1.66, 95 % CI: 1.40-1.96; <45 years: HR = 2.92, 95 % CI: 2.13-4.01) after multivariable adjustment. Similarly, diabetic participants with onset age <45 years had greatest HRs for incident AD and VD, compared with their matched controls. LIMITATIONS: Our results only reflect the characteristics of UKB participants. CONCLUSIONS: Younger age at diabetes onset was significantly associated with a higher risk of dementia in this longitudinal cohort study.

Cognitive Decline Before and During COVID-19 Pandemic Among Older People With Multimorbidity: A Longitudinal Study.

OBJECTIVE: To investigate whether older people living with multimorbidity would suffer an accelerated decline in cognition during the COVID-19 pandemic, compared with prepandemic data. DESIGN: A 5-year cohort conducting surveys from year 2016 to 2021, with 2016 to 2019 as the control period and 2019 to 2021 the pandemic period. SETTING AND PARTICIPANTS: In total, 9304 cognitively healthy older participants age ≥50 years were included from the Health and Retirement Study (HRS). METHODS: Multimorbidity was defined as the concurrent presence of 2 or more chronic diseases. A global cognition z score was calculated using memory (immediate and delayed word recall tests) and executive function (counting backwards and the serial sevens tests). Incident dementia was defined using either the reported physician diagnosis or an alternative approach based on cognition summary score. Linear mixed models were used to assess longitudinal changes, while modified Poisson regression models were used to analyze the risk of incident dementia. RESULTS: Of the 9304 participants included, 3649 (39.2%) were men, with a mean age of 65.8 ± 10.8 years. Participants with multimorbidity (n = 4375) suffered accelerated declines of 0.08 standard deviation (95% confidence interval 0.03, 0.13, P = .003) in global cognition and an elevated dementia risk (risk ratio 1.66, 95% confidence 1.05 to 2.61, P = .029), compared with individuals without morbidity (n = 1818) during the pandemic period. After further adjusting sociodemographic characteristics and prepandemic cognitive measurements, these differences remained evident. In contrast, no significant differences in cognitive declines were observed during the control period. CONCLUSIONS AND IMPLICATIONS: During the COVID-19 pandemic, older people with multimorbidity suffered an accelerated decline in cognition and elevated incident dementia risk, while no evident differences in cognitive decline rates were observed before the pandemic. Measures targeting vulnerable older people with multimorbidity could be significant for assisting these individuals to tackle neurocognitive challenges during the pandemic.

Sex differences in changes of depressive symptoms among older adults before and during the COVID-19 pandemic: evidence from two longitudinal cohorts.

BACKGROUND: Major concerns about the adverse mental health impact of the rapidly spread COVID-19 pandemic have been raised. Previous studies on changes of depressive symptoms during the COVID-19 pandemic have yielded inconsistent results regarding the sex differences. Since women have higher depressive symptoms even without the pandemic, it is essential to consider the pre-existing change of depressive symptoms of a similar period to discern the effect of the pandemic on depression. This study aimed to evaluate sex differences in depressive symptoms before and during the pandemic. METHODS: Data from the Health and Retirement Study (HRS; waves 13 to 15) and the English Longitudinal Study of Ageing (ELSA; wave 8 to COVID-19 wave 2) were analyzed. Depressive symptoms were assessed by the 8-item Center for Epidemiological Studies Depression (CES-D) scale. According to the time of COVID-19 outbreak in the US and the UK, the intervals from waves 13 to 14 surveys of the HRS and from waves 8 to 9 surveys of the ELSA were employed as pre-pandemic periods to control for the pre-existing depressive symptoms, respectively. Changes of CES-D scores during the pre-pandemic and pandemic periods were assessed by linear mixed models. RESULTS: Nine thousand, seven hundred thirty-seven participants (mean age: 66.7 ± 10.7 years) from the HRS and 5,098 participants (mean age: 68.7 ± 10.0 years) from the ELSA were included. CES-D scores among women were significantly higher than those among men at all waves in both cohorts. During the pre-pandemic period, no significant sex difference on changes of CES-D scores was detected in either the HRS or the ELSA. During the pandemic period, CES-D scores were increased in both men and women and the sex differences in CES-D increments of the two cohorts were both significant. Enlarged sex differences were demonstrated in increments of CES-D scores during the pandemic period. CONCLUSIONS: Our results suggest women suffered from worse depressive symptoms in response to the pandemic, although the changes of depression were similar between men and women before the pandemic. These findings underscore the necessity to support the vulnerable populations, especially women, to manage the distress brought by the pandemic and maintain optimal mental health status.

Reduced grid-like theta modulation in schizophrenia.

The hippocampal formation has been implicated in the pathophysiology of schizophrenia, with patients showing impairments in spatial and relational cognition, structural changes in entorhinal cortex and reduced theta coherence with medial prefrontal cortex. Both the entorhinal cortex and medial prefrontal cortex exhibit a 6-fold (or 'hexadirectional') modulation of neural activity during virtual navigation that is indicative of grid cell populations and associated with accurate spatial navigation. Here, we examined whether these grid-like patterns are disrupted in schizophrenia. We asked 17 participants with diagnoses of schizophrenia and 23 controls (matched for age, sex and IQ) to perform a virtual reality spatial navigation task during magnetoencephalography. The control group showed stronger 4-10 Hz theta power during movement onset, as well as hexadirectional modulation of theta band oscillatory activity in the right entorhinal cortex whose directional stability across trials correlated with navigational accuracy. This hexadirectional modulation was absent in schizophrenia patients, with a significant difference between groups. These results suggest that impairments in spatial and relational cognition associated with schizophrenia may arise from disrupted grid firing patterns in entorhinal cortex.

Progression of depressive symptoms after early exposure to famine: The China Health and Retirement Longitudinal Study.

BACKGROUND: The effect of early exposure to famine on progression of depressive symptoms has not been studied and the Chinese Famine offers a unique opportunity to explore this association with its long duration and widespread influence. OBJECTIVE: To investigate the longitudinal association of early famine exposure with subsequent depressive symptoms and whether there existed a critical exposure period. METHODS: Data from the China Health and Retirement Longitudinal Study (CHARLS) were analysed. Famine exposure was evaluated retrospectively in 2014 and severe famine exposure was defined as starvation to death of family members. Depressive symptoms were assessed prospectively from wave 1 (2011-2012) to wave 4 (2018) using the 10-item Center for Epidemiological Studies Depression Scale (CES-D). Linear mixed model and Cox proportional hazards model were applied to evaluate associations of famine exposure with progression or occurrence of depressive symptoms. RESULTS: A total of 7053 participants were included. Compared with no famine exposure, severe famine exposure was associated with a faster growth in CES-D score (0.169 point/year, 95 % CI 0.035 to 0.304, P = 0.013) and an elevated risk of occurrence of depressive symptoms (HR 1.360, 95 % CI 1.069 to 1.729, P = 0.012). Further analysis revealed that famine exposure during middle childhood was associated with a faster growth in CES-D score (0.404 point/year, 95 % CI 0.164 to 0.644, P = 0.001). LIMITATIONS: This is an observational study therefore causal relationship cannot be concluded. CONCLUSIONS: Early exposure to severe famine was associated with aggravation of depressive symptoms. Middle childhood might be a critical time window for depression prevention.

Utility of SCORE2 risk algorithm for predicting life course accelerated frailty and physical function decline.

BACKGROUND: Frailty is a dynamic process that increases with ageing, while it remains unclear whether cardiovascular disease (CVD) risk algorithm could predict life course dynamic frailty trajectories, for example, the longitudinal patterns of how frailty evolves with time. We intended to examine the predictive utility of the Systemic Coronary Risk Estimation 2 (SCORE2) algorithm for life course accelerated frailty and physical function decline, in comparison with the precedent SCORE algorithm. METHODS: Longitudinal data regarding accumulation of deficits frailty index (FI) and physical function (grip strength, gait speed, peak expiratory flow and timed chair rises) were drawn from the English Longitudinal Study of Ageing (ELSA) and Health and Retirement Study (HRS), two nationally representative cohorts with community-dwelling adults aged ≥50 years. SCORE and SCORE2 were calculated at baselines following European Society of Cardiology guidelines. A group-based trajectory modelling approach was used for identifying potential life course frailty trajectories, based on 14- and 12-year FI data in the ELSA and HRS. Modified Poisson regression and linear mixed model were applied for analysing associations between SCORE2 with accelerated frailty trajectory and physical function decline, respectively. Receiver operating characteristic curve (ROC) analysis was conducted to evaluate predictive utility for accelerated frailty increase trajectory of SCORE and SCORE2, with the area under the curve (AUC) compared using the paired DeLong's test. RESULTS: A total of 4834 participants from the ELSA and 7815 participants from the HRS were included (mean age: 64.0 ± 9.2 and 65.4 ± 9.9 years; men: 44.3% and 41.4%, respectively). Three frailty trajectories were consistently identified in both cohorts: (1) stable frailty increase (n = 3026 in ELSA and 4004 in HRS); (2) moderate frailty increase (n = 1325 in ELSA and 2955 in HRS); (3) accelerated frailty increase (n = 483 in ELSA and 856 in HRS). Each 10% increment in SCORE2 risk was associated with the higher risk of accelerated frailty increase (risk ratio [RR]: 3.58, 95% confidence interval [CI] [3.22, 3.98], P < 0.001 in ELSA; RR: 1.61, 95% CI [1.56, 1.67], P < 0.001 in HRS) and faster declines in all physical function measurements. SCORE2 algorithm showed good accuracy for predicting accelerated frailty increase (area under the curve [AUC] in ELSA: 0.759; HRS: 0.744), with better performance than the SCORE (AUC in ELSA: 0.729; HRS: 0.700) in both cohorts (P < 0.001 for comparison). CONCLUSIONS: SCORE2 algorithm could serve good utility for predicting life course accelerated frailty increase and physical function decline among community-dwelling non-frail adults aged ≥50 years.

Prediction Abilities of SCORE2 Risk Algorithms for Incident Dementia and All-Cause Mortality: Results From the UK Biobank Cohort Study.

BACKGROUND: Whether the updated Systematic COronary Risk Evaluation (SCORE2) risk algorithm is suitable for the prediction of incident dementia and all-cause mortality and whether its discrimination abilities for these outcomes are higher than those of the SCORE and Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) risk algorithms are unclear. METHODS: The present study included 429 033 participants (mean age: 57.1 ± 8.1 years; male: 46.2%; White: 94.1%) free of dementia from the UK Biobank at baseline, with a median follow-up of 12.8 years. Cox regression models were adopted to investigate the longitudinal relationships of SCORE2 risk categories with outcomes, and receiver operating characteristic curve analyses were used to compare the discrimination abilities of the 3 algorithms. RESULTS: During 5 376 778 person-years of follow-up, 6 477 all-cause dementia, 2 726 Alzheimer's disease (AD), 1 439 vascular disease (VD), and 31 981 all-cause deaths were identified. We found that higher SCORE2 risk was associated with higher risks of all-cause dementia, AD, VD, and all-cause mortality. The C-indices of SCORE2 risk for discriminating incident all-cause dementia, AD, VD, and all-cause death were 0.750 (95% confidence interval [CI]: 0.745 to 0.755), 0.750 (95% CI: 0.743 to 0.757), 0.800 (95% CI: 0.791 to 0.809), and 0.721 (95% CI: 0.718 to 0.724), respectively, which were significantly improved in comparison to those of the SCORE and CAIDE risk algorithms. CONCLUSION: The SCORE2 risk algorithm is applicable in predicting incident all-cause dementia, AD, VD, and all-cause mortality in European populations, and its discrimination abilities for dementia and death are significantly higher than those of the SCORE and CAIDE risk algorithms. Further validations in other populations are warranted.

Relationships of Residential Distance to Major Traffic Roads with Dementia Incidence and Brain Structure Measures: Mediation Role of Air Pollution.

Background: Uncertainty exists regarding the operating pathways between near-roadway exposure and dementia incidence. We intend to examine relationships between proximity to major roadways with dementia incidence and brain MRI structure measures, and potential mediation roles of air and noise pollution. Methods: The cohort study was based on the UK Biobank. Baseline survey was conducted from 2006 to 2010, with linkage to electronic health records conducted for follow-up. Residential distance to major roadways was ascertained residential address postcode. A land use regression model was applied for estimating traffic-related air pollution at residence. Dementia incidence was ascertained using national administrative databases. Brain MRI measures were derived as image-derived phenotypes, including total brain, white matter, gray matter, and peripheral cortical gray matter. Results: We included 460,901 participants [mean (SD) age: 57.1 (8.1) years; men: 45.7%]. Compared with individuals living >1,000 m from major traffic roads, living ≤1,000 m was associated with a 13% to 14% higher dementia risk, accounting for 10% of dementia cases. Observed association between residential distance and dementia was substantially mediated by traffic-related air pollution, mainly nitrogen dioxide (proportion mediated: 63.6%; 95% CI, 27.0 to 89.2%) and PM2.5 (60.9%, 26.8 to 87.0%). The shorter residential distance was associated with smaller volumes of brain structures, which was also mediated by traffic-related air pollutants. No significant mediation role was observed of noise pollution. Conclusions: The shorter residential distance to major roads was associated with elevated dementia incidence and smaller brain structure volumes, which was mainly mediated by traffic-related air pollution.

Targeting Mitochondrial Oxidative Stress: Potential Neuroprotective Therapy for Spinal Cord Injury.

Spinal cord injury (SCI) is a serious central nervous system (CNS) injury disease related to hypoxia-ischemia and inflammation. It is characterized by excessive reactive oxygen species (ROS) production, oxidative damage to nerve cells, and mitochondrial dysfunction. Mitochondria serve as the primary cellular origin of ROS, wherein the electron transfer chain complexes within oxidative phosphorylation frequently encounter electron leakage. These leaked electrons react with molecular oxygen, engendering the production of ROS, which culminates in the occurrence of oxidative stress. Oxidative stress is one of the common forms of secondary injury after SCI. Mitochondrial oxidative stress can lead to impaired mitochondrial function and disrupt cellular signal transduction pathways. Hence, restoring mitochondrial electron transport chain (ETC), reducing ROS production and enhancing mitochondrial function may be potential strategies for the treatment of SCI. This article focuses on the pathophysiological role of mitochondrial oxidative stress in SCI and evaluates in detail the neuroprotective effects of various mitochondrial-targeted antioxidant therapies in SCI, including both drug and non-drug therapy. The objective is to provide valuable insights and serve as a valuable reference for future research in the field of SCI.

Associations of physical activity participation trajectories with subsequent motor function declines and incident frailty: A population-based cohort study.

Background: Maintaining physical function and delaying frailty are of significant importance in both quality of life and health longevity for successful aging. The objective of this study is to investigate whether different trajectories of long-term physical activity (PA) participation are associated with subsequent motor function declines and incident frailty in middle-aged and elderly adults. Materials and methods: Data from 8,227 aged ≥ 50 years adults enrolled in the English Longitudinal Study of Aging were analyzed. Long-term PA participation trajectories were assessed using group-based trajectory modeling over the first 6-year period from wave 1 (2002-2003) to wave 4 (2008-2009). The longitudinal associations of PA trajectories with motor function declines and incident frailty were evaluated by a linear mixed model and Cox regression model, respectively, with follow-up of 10 years from wave 4 to wave 9 (2018-2019). Results: Five distinct trajectories of long-term PA participation were identified in the aging cohort, including persistently low-active trajectory (N = 2,039), increasing active trajectory (N = 1,711), declining active trajectory (N = 216), persistently moderate-active trajectory (N = 2,254), and persistently high-active trajectory (N = 2,007). Compared with the persistently low-active group, the participants in persistently moderate- and high-active groups experienced significantly decelerated grip strength decline, decreased gait speed decline, and faster chair rises after multiple-adjustment. Similarly, participants maintaining moderate- and high-active PA were also associated with a lower risk of incident frailty (multiple-adjusted hazard ratio: 0.70, 95% confidence interval: 0.62-0.80, and 0.42, 95% CI: 0.36-0.49, respectively), compared with those with persistently low PA. Notably, the participants with the increasing active trajectory got similar health benefits as those with persistently moderate and high levels of PA. Conclusion: In addition to persistent PA, increasing PA was linked to a slower decline in motor function and lower risk of incident frailty in the cohort. Our findings suggest that regular PA is never too late.