Social Health and Cognitive Change in Old Age: Role of Brain Reserve.

OBJECTIVE: Individual aspects of social health (SH; eg, network, engagement, support) have been linked to cognitive health. However, their combined effect and the role of the structural properties of the brain (brain reserve [BR]) remain unclear. We investigated the interplay of SH and BR on cognitive change in older adults. METHODS: Within the Swedish National Study on Aging and Care-Kungsholmen, 368 dementia-free adults aged ≥60 years with baseline brain magnetic resonance imaging were followed over 12 years to assess cognitive change. A measure of global cognition was computed at each of the 5 waves of assessment by averaging domain-specific Z scores for episodic memory, perceptual speed, semantic memory, and letter and category fluency. An SH composite score was computed at baseline by combining leisure activities and social network. BR was proxied by total brain tissue volume (TBTV). Linear mixed models (adjusted for sociodemographic, vascular, and genetic factors) were used to estimate cognitive trajectories in relation to SH and TBTV. Interaction analysis and stratification were used to examine the interplay between SH and TBTV. RESULTS: Moderate-good SH (n = 245; vs poor, ß-slope = 0.01, 95% confidence interval [CI] = 0.002-0.02, p = 0.018) and moderate-to-large TBTV (n = 245; vs small, ß-slope = 0.03, 95% CI = 0.02-0.04, p < 0.001) were separately associated with slower cognitive decline. In stratified analysis, moderate-good SH was associated with higher cognitive levels (but not change) only in participants with moderate-to-large TBTV (ß-intercept = 0.21, 95% CI = 0.06-0.37, p < 0.01; interaction SH * TBTV, p < 0.05). INTERPRETATION: Our findings highlight the interplay between SH and BR that likely unfolds throughout the entire life course to shape old-age cognitive outcomes. ANN NEUROL 2023;93:844-855.

Biopolymer Hydrogel-Based Salt-Resistant Evaporator for Solar-Energy-Driven Desalination and Water Purification.

Interfacial solar steam generation (ISSG) has recently received much attention as a low-carbon-footprint and high-energy-efficient strategy for seawater desalination and wastewater treatment. However, achieving the goals of a high evaporation rate, ecofriendliness, and high tolerance to salt ions in brine remains a bottleneck. Herein, a novel hydrogel-based evaporator for effective solar desalination was synthesized on the basis of sodium alginate (SA) and carboxymethyl chitosan (CMCS) incorporating a carbon nanotube (CNT)-wrapped melamine sponge (MS) through a simple dipping-drying-cross-linking process. The hydrogel-based evaporator reaches a high evaporation rate of 2.18 kg m-2 h-1 in 3.5 wt % brine under 1 sun irradiation. Furthermore, it demonstrated excellent salt ion rejection in high-concentration salt water. Simultaneously, it exhibits excellent purification functionality toward heavy metals and organic dyes. This study provides a simple and efficient strategy for seawater desalination and wastewater treatment.

LncRNA JHDM1D-AS1 promotes osteogenic differentiation of periodontal ligament cells by targeting miR-532-5p to activate IGF1R signaling.

OBJECTIVE: The aim of this study was to explore the mechanism underlying periodontal ligament cells (PDLCs) osteogenic differentiation. BACKGROUND: Periodontitis causes damage to tooth-supporting apparatus and eventually leads to tooth loss. PDLCs hold great promise in periodontal regeneration due to their osteogenic features. METHODS: The expression of osteogenic markers, lncRNA JHDM1D-AS1, miR-532-5p and IGF1R was examined. For osteogenic differentiation, primary human PDLCs (hPDLCs) were cultured in an osteogenic medium, and it was assessed by ALP activity and Alizarin Red staining. The interaction between JHDM1D-AS1, miR-532-5p and IGF1R was analyzed via dual luciferase, RIP and RNA pull-down assays. RESULTS: JHDM1D-AS1 was up-regulated during osteogenic differentiation and its silencing inhibited hPDLC osteogenic differentiation. JHDM1D-AS1 worked as a miR-532-5p sponge in hPDLCs. miR-532-5p directly targeted IGF1R to suppress its expression, and miR-532-5p knockdown facilitated osteogenic differentiation of hPDLCs. Overexpression of IGF1R promoted osteogenic differentiation of hPDLCs via activating Notch/HES1 signaling in hPDLCs. CONCLUSION: JHDM1D-AS1 promotes osteogenic differentiation of hPDLCs via sponging miR-532-5p to facilitate IGF1R expression and activate Notch/HES1 signaling.

The mediating effect of perceived social support between family resilience and meaning in life in breast cancer patients.

PURPOSE: The beneficial effects of family resilience and meaning in life on patients are established, but limited is known for the effect of perceived social support. We aim to investigate the impact of family resilience on the meaning of life among Chinese patients with breast cancer (BC) and to further detect whether perceived social support mediated this association. METHODS: From February to June 2022, we conducted this cross-sectional study with 276 women who were diagnosed with BC in a tertial hospital in Guangdong province, China. The Chinese version of Meaning in Life Scale (C-MiLS) was used to measure the meaning in life. The Chinese version of the family resilience assessment scale (C-FRAS) and the perceived social support scale (PSSS) were adopted to obtain the family resilience and perceived social support, respectively. The mediating effect of perceived spousal support was estimated using the bootstrapped confidence interval (CI) via IBM SPSS AMOS 22.0. RESULTS: The mean scores were 60.79 ± 11.63 for meaning in life, 82.08 ± 11.48 for family resilience, and 62.72 ± 12.19 for perceived social support, respectively. Our results indicated the positive correlations of meaning in life with family resilience (ß = 0.822, P < 0.05) and perceived social support (ß = 0.886, P < 0.05). The perceived social support exerted the mediating effect in the relationship between family resilience and meaning in life (ß = 0.368 [95%CI, 0.274, 0.450], P < 0.001), accounting for 54.6% of the variance in meaning in life. CONCLUSIONS: Our findings highlight that family resilience and perceived social support should be enhanced for BC patients to improve their meaning in life. In particular, the association between family resilience and meaning in life was positively mediated by perceived social support. Thus, interventions for improving family resilience and perceived social support might be useful in easing psychological distress and improving meaning in life in individuals with BC.

Dentoperiodontal and skeletal changes induced by miniscrew-assisted rapid maxillary expansion (C-expander) treatment in adults: A retrospective clinical trial.

INTRODUCTION: The objective of this study was to evaluate the dental periodontal and skeletal response to ≥5 mm of expansion width achieved by C-expander treatment with posterior miniscrews placed between the first and second molars in adults. METHODS: A total of 28 patients aged 21.91 ± 3.20 years with maxillary transverse deficiency underwent C-expander treatment. Anterior miniscrews were positioned between the first and second premolars, whereas posterior miniscrews were positioned between the first and second molars. Cone-beam computed tomography records were obtained before expansion and 3 months after expansion. The dental periodontal and skeletal changes for all patients were recorded. RESULTS: The C-expander treatment expanded the palatal suture with slight buccal alveolar bone inclination. An increase in the nasal cavity width and a greater increase in the maxillary base bone width were observed after maxillary expansion. The expansion at the posterior nasal spine (3.78 mm) was approximately 85.7% of that at the anterior nasal spine (4.41 mm). No significant buccal dehiscence occurred after expansion, whereas the mesiobuccal alveolar bone thickness of the first molars was decreased at the 8 mm level with respect to the cementoenamel junction. The first molar showed decreased inclination (right, -0.45°; left, -0.38°, P >0.05), whereas the expansion at the apical level was less than that at the crown level. Age and the skeletal/dental expansion ratio had no discernible relationship. CONCLUSIONS: Miniscrew-assisted C-expander treatment can be effective for adults with maxillary transverse deficiency. Rearward placement of the miniscrews may create an approximately parallel expansion. Most maxillary expansion was derived from skeletal expansion with slight alveolar bone buccal inclination.

Interactive association between insomnia symptoms and sleep duration for the risk of dementia-a prospective study in the Swedish National March Cohort.

OBJECTIVE: Given the importance of sleep in maintaining neurocognitive health, both sleep duration and quality might be component causes of dementia. However, the possible role of insomnia symptoms as risk factors for dementia remain uncertain. METHODS: We prospectively studied 22,078 participants in the Swedish National March Cohort who were free from dementia and stroke at baseline. Occurrence of dementia was documented by national registers during a median follow-up period of 19.2 years. Insomnia symptoms and sleep duration were ascertained by Karolinska Sleep Questionnaire. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: Compared to participants without insomnia at baseline, those who reported any insomnia symptom experienced a greater incidence of dementia during follow-up (HR 1.08, 95% CI: 1.03, 1.35). Difficulty initiating sleep versus non-insomnia (HR 1.24, 95% CI: 1.02, 1.52), but not difficulty maintaining sleep or early morning awakening was associated with an increased risk of dementia. Short sleep duration was associated with increased risk of dementia (6 h vs. 8 h, HR 1.29, 95% CI: 1.11-1.51; 5 h vs. 8 h, HR 1.26, 95% CI: 1.00-1.57). Stratified analyses suggested that insomnia symptoms increased the risk of dementia only amongst participants with ≥7 h sleep (vs. non-insomnia HR 1.24, 95% CI: 1.00-1.54, P = 0.05), but not amongst short sleepers (<7 h). Short sleep duration also did not further inflate the risk of dementia amongst insomniacs. CONCLUSION: Insomnia and short sleep duration increase the risk of dementia amongst middle-aged to older adults.

Mechanical Thrombectomy for Mild Acute Ischemic Stroke with Large-Vessel Occlusion: A Systematic Review and Meta-Analysis.

BACKGROUND: The functional prognosis of mechanical thrombectomy (MT) for mild acute ischemic stroke (AIS) with large-vessel occlusion (LVO) is controversial. To explore a more precise estimation, a meta-analysis was conducted. METHODS: The relevant studies were identified by searching PubMed, Embase, Web of Science, and Cochrane Collaboration Database until October 2021. The pooled analysis, subgroup analysis, sensitivity analysis, and publication bias examination were all conducted. The meta-analysis was performed by using Stata 12.0. RESULTS: Eleven studies were included with a total of 1,929 subjects, including 794 patients receiving MT and 1,135 patients receiving medical management. The pooled analysis showed that MT might be not associated with functional prognosis among mild AIS with LVO (excellent functional prognosis: risk ratio (RR) = 1.07, 95% confidence interval (CI) = 0.94-1.21, p = 0.294; favorable functional prognosis: RR = 1.01, 95% CI = 0.96-1.06, p = 0.823). The statistical stability and reliability were demonstrated by the sensitivity analysis and publication bias outcomes. CONCLUSION: Our meta-analysis suggests that MT may be not associated with functional prognosis of mild AIS with LVO.

circSKIL promotes osteoblastic differentiation of periodontal ligament cells by sponging miR-532-5p to activate Notch signaling.

BACKGROUND AND OBJECTIVE: Periodontal ligament cells (PDLCs) possess the capacity to differentiate into a variety of cell types to benefit periodontal regeneration. In this study, we examined the circSKIL/miR-532-5p/Notch1 axis in controlling the osteoblastic differentiation of PDLCs. METHODS: Primary human PDLCs (hPDLCs) were isolated and induced to differentiate into osteoblasts. Osteogenic responses were assessed for the expressions of osteoblast-related marker proteins (including alkaline phosphatase (ALP), osteocalcin (OCN), bone morphogenetic protein-2 (BMP2), and runt-related transcription factor 2 (RUNX2) by RT-PCR. The formation of mineralized nodules was examined by Alizarin Red S (ARS) staining and ALP activity. Expressions of circSKIL, miR-532-5p, and Notch1 were measured by RT-PCR and western blotting, and their regulations by combining bioinformatic analysis and luciferase reporter assay. Notch signaling was assessed for the expressions of hairy and enhancer of split-1 (HES1) and Notch intracellular domain (NICD). RESULTS: During osteoblastic differentiation of hPDLCs, circSKIL, and Notch1 were up-regulated, while miR-532-5p down-regulated. By sponging miR-532-5p, circSKIL activated Notch signaling, increasing levels of Notch1, HES1, and NICD. Functionally, knocking down circSKIL or overexpressing miR-532-5p inhibited osteoblastic differentiation of PDLCs, down-regulating ALP, OCN, BMP2, and RUNX2, and reducing ARS staining or ALP activity. The impacts of circSKIL knockdown were rescued by miR-532-5p inhibitor or overexpressing Notch1, while those caused by up-regulating miR-532-5p were reversed by overexpressing Notch1. CONCLUSION: By targeting miR-532-5p and up-regulating Notch1, circSKIL critically controls osteoblastic differentiation of hPDLCs. Therefore, modulating this axis may maximize the differentiation of PDLCs into osteoblasts and benefit periodontal regeneration.

A Chewing Gum Residue-Based Gel with Superior Mechanical Properties and Self-Healability for Flexible Wearable Sensor.

Chewing gum residue is hard to decompose and easy to cause pollution, which is highly desirable to realize recycling. In this paper, a chewing gum gel with enhanced mechanical properties and self-healing properties is prepared by using polyvinyl alcohol (PVA) as the backbone in chewing gum residue. The hydrogen bond and the borax ester bond are employed to construct reversible interaction to enhance the self-healing ability. The physical crosslinking is realized by further freeze-thaw treatment to improve its mechanical properties. The gel demonstrates high elongation at break of 610% and strength of 0.11 MPa, as well as excellent self-healing performance and recyclable properties. In particular, the gel with a fast signal response is successfully applied as a wearable strain sensor to monitor different types of human motion. The gel as a sensor exhibits self-healing properties suggesting superior safety and stability, and displays wide linear sensitivity (the gauge factor is 0.417 and 0.170). The gel can be further served to explore temperature changes, implying the application in temperature monitoring. This study develops a novel approach for the recycle and reuse of chewing gum residue. The obtained gel may be a promising candidate for the fabrication of flexible wearable sensor.

Identification and Pharmacological Characterization of Two Serotonin Type 7 Receptor Isoforms from Mythimna separata.

Serotonin (5-hydroxytryptamine, 5-HT) is an important neuroactive molecule, as neurotransmitters regulate various biological functions in vertebrates and invertebrates by binding and activating specific 5-HT receptors. The pharmacology and tissue distribution of 5-HT receptors have been investigated in several model insects, and these receptors are recognized as potential insecticide targets. However, little is known about the pharmacological characterization of the 5-HT receptors in important agricultural pests. In this study, we investigated the sequence, pharmacology, and tissue distribution of 5-HT7 receptors from oriental armyworm Mythimna separata (Walker) (Lepidoptera: Noctuidae), an important migratory and polyphagous pest species. We found that the 5-HT7 receptor gene encodes two molecularly distinct transcripts, Msep5-HT7L and Msep5-HT7S, by the mechanism of alternative splicing in M. separata. Msep5-HT7S differs from Msep5-HT7L based on the deletion of 95 amino acids within the third intracellular loop. Two Msep5-HT7 receptor isoforms were activated by 5-HT and synthetic agonists α-methylserotonin, 8-hydroxy-DPAT, and 5-methoxytryptamine, resulting in increased intracellular cAMP levels in a dose-dependent manner, although these agonists showed much poorer potency and efficacy than 5-HT. The maximum efficacy of 5-HT compared to the two 5-HT isoforms was equivalent, but 5-HT exhibited 2.63-fold higher potency against the Msep5-HT7S than the Msep5-HT7L receptor. These two isoforms were also blocked by the non-selective antagonist methiothepin and the selective antagonists WAY-100635, ketanserin, SB-258719, and SB-269970. Moreover, two distinct mRNA transcripts were expressed preferentially in the brain and chemosensory organs of M. separata adults, as determined by qPCR assay. This study is the first comprehensive characterization of two splicing isoforms of 5-HT7 receptors in M. separata, and the first to demonstrate that alternative splicing is also the mechanism for producing multiple 5-HT7 isoforms in insects. Pharmacological and gene expression profiles offer important information that could facilitate further exploration of their function in the central nervous system and peripheral chemosensory organs, and may even contribute to the development of new selective pesticides.

Influence of protein ion charge state on 213 nm top-down UVPD.

Ultraviolet photodissociation (UVPD) is a powerful and rapidly developing method in top-down proteomics. Sequence coverages can exceed those obtained with collision- and electron-induced fragmentation methods. Because of the recent interest in UVPD, factors that influence protein fragmentation and sequence coverage are actively debated in the literature. Here, we performed top-down 213 nm UVPD experiments on a 7 T Fourier-transform ion cyclotron resonance mass spectrometer (FT-ICR MS) for the model proteins ubiquitin, myoglobin and cytochrome c that were electrosprayed from native, denaturing and supercharging solutions in order to investigate the effect of protein charge states on UVPD fragments. By performing UVPD in ultrahigh vacuum, factors associated with collisional cooling and any ion activation during transfer between mass analyzers can be largely eliminated. Sequence coverage increased from <10% for low charge states to >60% for high charge states for all three proteins. This trend is influenced by the overall charge state, i.e., charges per number of amino acid residues, and to a lesser degree by associated structural changes of protein ions of different charge states based on comparisons to published collision-cross section measurements. To rationalize this finding, and correlate sequence ion formation and identity with the number and location of protons, UVPD results were compared to protonation sites predicted based on electrostatic modelling. Assuming confined protonation sites, these results indicate the presence of two general fragmentation types; i.e., charge remote and charge directed. For moderately high protein charge states, fragment ions mostly originate in regions between likely protonation sites (charge remote), whereas sequence ions of highly charge protein ions occur either near backbone amide protonation sites at low-basicity residues (charge directed) or at charge remote sites (i.e., high-basicity residues). Overall, our results suggest that top-down 213 UVPD performance in the zero-pressure limit depends strongly on protein charge states and protonation sites can influence the location of backbone cleavages.

Shared risk and protective factors between Alzheimer's disease and ischemic stroke: A population-based longitudinal study.

INTRODUCTION: Stroke, especially ischemic stroke's (IS) link with Alzheimer's disease (AD) remains unclear. METHODS: This prospective cohort study included 2459 AD- and cerebrovascular disease-free older adults at baseline (mean age 71.9 ± 10.3 years, Stockholm, Sweden). Using Cox regressions, shared risk factors (SRFs) and shared protective factors (SPFs) between AD and IS were recognized when their hazard ratios in both AD and IS models were significant and in the same direction. RESULTS: During the follow-up period of up to 15 years, 132 AD and 260 IS mutually exclusive cases were identified. SRFs were low education, sedentary lifestyle, and heart diseases. High levels of psychological well-being, actively engaging in leisure activities, and a rich social network were SPFs. Having ≥1 SPF reduced 47% of AD and 28% of IS risk among people with a low risk profile (<2 SRFs), and 38% of AD and 31% of IS risk with a high risk profile (≥2 SRFs). In total, 57.8% of AD/IS cases could be prevented if individuals have ≥1 SPF and no SRF. DISCUSSION: AD and IS share risk/protective profiles, and SPFs seem to counteract the adverse effects of SRFs on both AD and IS.

Sex differences in dementia and response to a lifestyle intervention: Evidence from Nordic population-based studies and a prevention trial.

INTRODUCTION: Evidence on sex differences in the risk for dementia has been mixed. The goal was to assess sex differences in the development of dementia, and in the effects of a lifestyle intervention. METHODS: Two strategies were adopted, one using combined data from three large Nordic population-based cohort studies (n = 2289), adopting dementia as outcome, and 2-year multidomain lifestyle intervention (n = 1260), adopting cognitive change as outcome. RESULTS: There was higher risk for dementia after age 80 years in women. The positive effects of the lifestyle intervention on cognition did not significantly differ between men and women. Sex-specific analyses suggested that different vascular, lifestyle, and psychosocial risk factors are important for women and men in mid- and late-life. CONCLUSION: Women had higher risk for dementia among the oldest individuals. Lifestyle interventions may be effectively implemented among older men and women.

Mechanism for the Binding of Netropsin to Hairpin DNA Revealed Using Nanoscale Ion Emitters in Native Mass Spectrometry.

Netropsin is one of the first ligands to be discovered that selectively binds to the minor groove of DNA and is actively used as a scaffold for developing potential anticancer and antibiotic agents. The mechanism by which netropsin binds to hairpin DNA remains controversial with two competing mechanisms having been proposed. In one mechanism, netropsin binding induces a hairpin-to-duplex DNA transition. Alternatively, netropsin binds in two thermodynamically different modes at a single duplexed AATT site. Here, results from native mass spectrometry (MS) with nanoscale ion emitters indicate that netropsin can simultaneously and sequentially bind to both hairpin and duplex DNA. Duplex DNA was not detected using conventional MS with larger emitters because nanoscale emitters significantly reduce the extent of salt adduction to ligand-DNA complex ions, including in the presence of relatively high concentrations of nonvolatile salts. Based on native MS and polyacrylamide gel electrophoresis results, the abundances of hairpin and duplex DNA are unaffected by the addition of netropsin. By native MS, the binding affinities for five ligand-DNA and DNA-DNA interactions can be rapidly obtained simultaneously. This research indicates a "simultaneous binding mechanism" for the interactions of netropsin with DNA.

Nontargeted Identification of Plasma Proteins O-, N-, and S-Transmethylated by O-Methyl Organophosphates.

Organophosphates (OPs) are used worldwide as pesticides. However, acute and chronic exposure to OPs can cause serious adverse health effects. The mechanism of delayed OP toxicity is thought to involve off-target inhibition of serine proteases, although the precise molecular details remain unclear owing to the lack of an analytical method for global detection of protein targets of OPs. Here, we report the development of a mass spectrometry method to identify OP-adducted proteins from complex mixtures in a nontargeted manner. Human plasma was incubated with the OP dichlorvos that was 50% isotopically labeled and 50% unlabeled. Proteins and protein adducts were extracted, digested, and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to detect "twin ions" of peptides that were covalently modified by a chemical reaction with dichlorvos. The LC-MS/MS data were processed by a blended data analytics software (Xenophile) to detect the amino acid residue sites of proteins that were covalently modified by exposure to OPs. We discovered that OPs can transmethylate the N, S, and O side chains of His, Cys, Glu, Asp, and Lys residues. For model systems, such transmethylation reactions were confirmed by LC-MS, nuclear magnetic resonance (NMR), and rationalized using electronic structure calculations. Methylation of the ubiquitous antioxidant glutathione by dichlorvos can decrease the reducing/oxidizing equilibrium of glutathione in liver extracts, which has been implicated in diseases and pathological conditions associated with delayed OP toxicity.

Genetic risk of dementia mitigated by cognitive reserve: A cohort study.

OBJECTIVE: We investigated whether cognitive reserve modifies the risk of dementia attributable to apolipoprotein ε4 (APOE-ε4), a well-known genetic risk factor for dementia. METHODS: We followed 2,556 cognitively intact participants aged ≥60 years from the ongoing prospective community-based Swedish National Study on Aging and Care in Kungsholmen (SNAC-K). Dementia was ascertained through clinical and neuropsychological assessments and diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria. Structural equation modeling was used to generate a cognitive reserve indicator from 4 previously validated contributors: early life education, midlife substantive work complexity, late life leisure activities, and late life social networks. Cox proportional hazard models estimated dementia risk in relation to cognitive reserve indicator. The interaction between the cognitive reserve indicator and APOE-ε4 was assessed on multiplicative and additive scales. RESULTS: After an average of 6.3 years (range = 2.1-10.7) of follow-up, 232 dementia cases were ascertained. Relative to individuals in the lowest tertile of cognitive reserve indicator, those with moderate and high reserve were at a reduced risk of dementia. There was no multiplicative interaction between APOE-ε4 status and cognitive reserve indicator (p = 0.113). Additive interaction was statistically significant. Relative to APOE-ε4 carriers with low cognitive reserve, ε4 carriers with high reserve had a reduced risk of dementia (hazard ratio [HR] = 0.28, 95% confidence interval [CI] = 0.13-0.59). The magnitude of risk reduction was similar in ε4 noncarriers with a high cognitive reserve indicator (HR = 0.24, 95% CI = 0.15-0.40). INTERPRETATION: Lifelong engagement in reserve-enhancing activities attenuates the risk of dementia attributable to APOE-ε4. Promoting cognitive reserve might be especially effective in subpopulations with high genetic risk of dementia. ANN NEUROL 2019.

Low Mood and Risk of Dementia: The Role of Marital Status and Living Situation.

OBJECTIVE: This study aims to explore whether low mood is related to an increased dementia risk in two cohorts of older adults of different generations, and whether marital status and living situation modify this association. METHODS: Participants (≥70 years), free from dementia and living at home, were identified from two population-based studies: the Kungsholmen Project (KP; n = 1,197) and the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K; n = 1,402). Low mood was obtained by self-report (KP and SNAC-K) at baseline in 1987-89 (KP) and 2001-04 (SNAC-K). Incident dementia cases were ascertained over 9 years, using the same diagnostic procedures and comparable criteria for the two cohorts (DSM-III-R in KP and DSM-IV-TR in SNAC-K). Hazard ratios (HR) were derived from Cox proportional hazards models. RESULTS: Those having low mood at baseline were at higher risk of dementia in both cohorts combined (HR: 1.2, 95% confidence interval (CI): 1.0-1.4) than those without low mood. However, an increased risk was detected only in those who did not have a partner (HR: 1.5, 95% CI: 1.2-1.9), or lived alone (HR: 1.5, 95% CI: 1.2-1.9), but not among those who had a partner or lived with someone (HR: 0.8, 95% CI: 0.5-1.2). CONCLUSION: Marital status and living situation have the potential to buffer the detrimental effects of low mood on dementia onset. Thus, specific attention from health care should target individuals having low mood and who do not have a partner or live alone.

Association of diabetes with stroke and post-stroke dementia: A population-based cohort study.

INTRODUCTION: The impact of prediabetes and diabetes on stroke and the development of dementia after a stroke remain unclear. METHODS: A total of 2655 dementia-free participants (including a stroke-free cohort and a prevalent stroke cohort) were followed-up for 12 years. Dementia and post-stroke dementia were determined by clinical examinations and national registry data. Diabetes was ascertained via medical examination, medication use, medical records, or glycated hemoglobin (HbA1c) ≥6.5%. Prediabetes was defined as HbA1c ≥5.7% in diabetes-free participants. RESULTS: In the stroke-free cohort, 236 participants developed ischemic stroke, and 47 developed post-stroke dementia. Diabetes was associated with ischemic stroke (hazard ratio [HR] 1.76, 95% confidence interval [CI] 1.16 to 2.67) and post-stroke dementia (HR 2.56, 95% CI 1.04 to 6.25). In the prevalent stroke cohort, diabetes was also related to dementia risk. Prediabetes was not significantly related to stroke or post-stroke dementia. DISCUSSION: Diabetes, but not prediabetes, is associated with an increased risk of ischemic stroke and post-stroke dementia.

Mid- to late-life migraine diagnoses and risk of dementia: a national register-based follow-up study.

BACKGROUND: Previous studies found an association between migraine and dementia, which are two leading causes of disability. However, these studies did not differentiate between migraine types and did not investigate all prevalent dementia subtypes. The main objective of this national register-based study was to investigate whether migraine was a risk factor for dementia. Additionally, we explored potential differences in dementia risk for migraine with and without aura. METHODS: We obtained data on birth cohorts born between 1935 and 1956 (n = 1,657,890) from Danish national registers. Individuals registered with migraine before age 59 (n = 18,135) were matched (1:5) on sex and birthdate with individuals without migraine (n = 1,378,346). Migraine was defined by International Classification of Diseases (ICD) diagnoses and dementia was defined by ICD diagnoses and anti-dementia medication. After matching, 62,578 individuals were eligible for analysis. For the statistical analyses, we used Cox regression models and adjusted for socio-demographic factors and several psychiatric and somatic morbidities. RESULTS: During a median follow-up time of 6.9 (IQR: 3.6-11.2) years, 207 individuals with migraine developed dementia. Compared with individuals without migraine, we found a 50% higher rate of dementia among individuals with migraine (HR = 1.50; 95% CI: 1.28-1.76). Individuals without aura had a 19% higher rate of dementia (HR = 1.19; 95% CI: 0.84-1.70), and individuals with aura had a two times higher rate of dementia (HR = 2.11; 95% CI: 1.48-3.00). CONCLUSIONS: Our findings support the hypothesis that migraine is a midlife risk factor for dementia in later life. The higher rate of dementia in individuals with a hospital-based diagnosis of migraine with aura emphasizes the need for studies on pathological mechanisms and potential preventative measures. Furthermore, given that only hospital-based migraine diagnoses were included in this study, future research should also investigate migraine cases derived from the primary healthcare system to include less severe migraine cases.

Psychosocial working conditions, trajectories of disability, and the mediating role of cognitive decline and chronic diseases: A population-based cohort study.

BACKGROUND: Unfavorable psychosocial working conditions have been associated with cognitive decline and chronic diseases, both of which may subsequently accelerate functional dependence. This study aimed to investigate the association between job demand-control-support combinations and trajectories of disability in later life and to further explore the role of cognitive decline and the co-occurrence of chronic diseases in mediating this association. METHODS AND FINDINGS: In this cohort study, 2,937 community dwellers aged 60+ years (mean age 73 ± 10.6; 62.9% female) residing in the Kungsholmen District of Stockholm, Sweden, participated in the baseline survey (2001-2004) and were followed up to 12 years. Lifelong occupational history was obtained through a standardized interview; job demands, job control, and social support at work in the longest-held occupation were graded with a psychosocial job-exposure matrix. Job control, demands, and social support were dichotomized using the median values from the matrix, respectively, to further generate demand-control-support combinations. Disability was measured by summing the number of impaired basic and instrumental activities of daily living. Global cognitive function was assessed by Mini-Mental State Examination. Chronic conditions were ascertained by clinical examinations, medical history, and patient clinical records; the total number of chronic diseases was summed. Data were analyzed using linear mixed-effects models and mediation analysis. Age, sex, education, alcohol consumption, smoking, leisure activity engagement, early-life socioeconomic status, occupational characteristic and physical demands, and baseline cognitive function and number of chronic diseases were adjusted for in the analyses. Compared with active jobs (high control/high demands; n = 1,807), high strain (low control/high demands; n = 328), low strain (high control/low demands; n = 495), and passive jobs (low control/low demands; n = 307) were all associated with a faster rate of disability progression (ß = 0.07, 95% CI 0.02-0.13, p = 0.01; ß = 0.10, 95% CI 0.06-0.15, p < 0.001; ß = 0.11, 95% CI 0.05-0.18, p < 0.001). The association between high strain and disability progression was only shown in people with low social support at work (ß = 0.13, 95% CI 0.07-0.19, p < 0.001), but not in those with high social support (ß = 0.004, 95% CI -0.09 to 0.10, p = 0.93). Moreover, we estimated that the association between demand-control status and disability trajectories was mediated 38.5% by cognitive decline and 18.4% by accumulation of chronic diseases during the follow-up period. The limitations of this study include unmeasured confounding, self-reported work experience, and the reliance on a psychosocial job-exposure matrix that does not consider variabilities in individuals' perception on working conditions or job characteristics within occupations. CONCLUSIONS: Our findings suggest that negative psychosocial working conditions during working life may accelerate disability progression in later life. Notably, social support at work may buffer the detrimental effect of high strain on disability progression. Cognitive decline and chronic-disease accumulation, and especially the former, partially mediate the association of psychosocial working conditions with trajectories of disability. Further studies are required to explore more mechanisms that underlie the association between psychosocial working conditions and disability trajectories.