Effect of FOXO3 and Air Pollution on Cognitive Function: A Longitudinal Cohort Study of Older Adults in China from 2000 to 2014

Forkhead Box O 3 (FOXO3) genotype is strongly associated with human longevity and may be protective against neurodegeneration. Air pollution is a risk factor for cognitive decline and dementia. We aimed to study the individual and combined effects of FOXO3 and air pollution on cognitive function in a large prospective cohort with up to 14 years of follow-up. We measured cognitive function and impairment using the Mini-Mental State Examination (MMSE). We used tagging SNPs rs2253310, rs2802292, and rs4946936 to identify the FOXO3 gene, of which roughly half of the population had the longevity associated polymorphism. We matched annual average fine particulate matter (PM2.5) concentrations within 1 km^2 grid. We conducted cross-sectional and longitudinal analyses using multivariable linear and logistic regression models and generalized estimating equation. At baseline, carriers of the longevity associated homozygous minor alleles of FOXO3 SNPs had a higher MMSE score than the carriers of homozygous major alleles. In the longitudinal follow-up, carriers of FOXO3 homozygous minor alleles had lower odds of cognitive impairment compared to non-carriers. Higher PM2.5 was associated with a lower MMSE score and higher odds of cognitive impairment. The positive effects of FOXO3 were the strongest in females, older people, and residents in areas with lower air pollution.

The Effectiveness of Non-clozapine Antipsychotics Combined with Electroconvulsive Therapy versus Clozapine Combined with Electroconvulsive Therapy for Treatment-resistant Schizophrenia

The study aimed to compare the effectiveness and safety of other atypical antipsychotics (non-clozapine) plus electroconvulsive therapy (ECT) (NC+ECT) versus clozapine plus ECT (C+ECT) for treating treatment-resistant schizophrenia (TRS). Data of 32 patients with TRS who was receiving ECT were analysed. We compared clinical characteristics, response to treatment [defined as an improvement of 40% in the Brief Psychotic Rating Scale (BPRS) psychotic symptom subscale from pretreatment scores], change of Mini-mental Status Exam (MMSE) scores, and other adverse effects between the NC+ECT group (N= 16) and C+ECT group (N =16). We found that the overall response rate was 65.6% (75.8% for the NC+ECT group and 56.3% for the C+ECT group, p=0.26). The overall BPRS score in both groups decreased significantly. The mean difference in total BPRS psychotic subscale score between pre-ECT and after last ECT was 10.4 + 5.8 (p<0.001) for the NC+ECT group and 6.6 + 7.3 (p = 0.002) for the C+ECT group. When comparing the NC+ECT group to the C+ECT group, the mean difference in total BPRS psychotic subscale score was not significant. (p = 0.104). The mean difference in MMSE score between pre-ECT and after the last ECT was -1.1 + 5.1 (p =0.45) for the NC+ECT group and 0.2 + 4.3 (p=0.855) for the C+ECT group. The change of MMSE score in the NC+ECT group was not significant different compare to the C+ECT group (p = 0.461). We concluded the combination of antipsychotics and ECT is an effective and safe treatment option for patients with TRS. Other NC+ECT groups’ efficacy may be comparable to that of clozapine plus ECT.

Preliminary Exploration of the Sequence of Nerve Fiber Bundles Involvement for Idiopathic Normal Pressure Hydrocephalus: A Correlation Analysis Using Diffusion Tensor Imaging

The study preliminarily explored the sequence and difference of involvement in different neuroanatomical structures in idiopathic normal pressure hydrocephalus (INPH). We retrospectively analyzed the differences in diffusion tensor imaging (DTI) parameters in 15 ROIs [including the bilateral centrum semiovale (CS), corpus callosum (CC) (body, genu, and splenium), head of the caudate nucleus (CN), internal capsule (IC) (anterior and posterior limb), thalamus (TH), and the bilateral frontal horn white matter hyperintensity (FHWMH)] between 27 INPH patients and 11 healthy controls and the correlation between DTI indices and clinical symptoms, as evaluated by the INPH grading scale (INPHGS), the Mini-Mental State Examination (MMSE), and the timed up and go test (TUG-t), before and 1 month after shunt surgery. Significant differences were observed in DTI parameters from the CS (pFA1 = 0.004, pADC1 = 0.005) and the genu (pFA2 = 0.022; pADC2 = 0.001) and body (pFA3 = 0.003; pADC3 = 0.002) of the CC between the groups. The DTI parameters from the CS were strongly correlated with the MMSE score both pre-operatively and post-operatively. There was association between apparent diffusion coefficient (ADC) values of anterior and posterior limbs of the IC and MMSE. The DTI parameters of the head of the CN were correlated with motion, and the ADC value was significantly associated with the MMSE score. The FA value from TH correlated with an improvement in urination after shunt surgery. We considered that different neuroanatomical structures are affected differently by disease due to their positions in neural pathways and characteristics, which is further reflected in clinical symptoms and the prognosis of shunt surgery.

Association between baseline Mini-Mental State Examination score and dementia incidence in a cohort of oldest old

ABSTRACT Background: The Brazilian population has aged rapidly. The oldest old, defined as persons aged 80 years or older, is the fastest growing segment of the Brazilian population. Several instruments have been used to assess the cognitive performance of the older people and predict dementia. One of the most commonly used is the Mini-Mental State Examination (MMSE). Objective: The aim of this study was to investigate the relationship between baseline MMSE score and the incidence of dementia in a Brazilian cohort of independent oldest old. Methods: Sociodemographic data and serial cognitive assessment of 248 older adults were analyzed. Results: Mean follow-up time of subjects was 4.0(±1.9) years, 71.4% were women, and mean MMSE score at entry was 25(±3.5). Mean MMSE scores at baseline were significantly higher (p=0.001) in the cognitively intact group than in those who developed dementia. The logistic regression showed that for a one point increase in MMSE score at baseline there was a 10% reduction in the probability of dementia. Conclusions: In the Brazilian scenario of a rapidly growing population of oldest old, the extensive use of the MMSE gives rise to the need not only to determine its effectiveness for screening dementia, but also to interpret its score in terms of future conversion to dementia.

The effect of intraoperative dexmedetomidine on cognitive dysfunction after surgery: a updated meta-analysis

Background Postoperative cognitive dysfunction (POCD) is one of the most common. Neuroprotective effects of dexmedetomidine (DEX) are reported in previous studies but evidence regarding the POCD is still unclear. In order to gain latest evidence, the present study analyzes the outcomes of randomized controlled trials (RCTs) which utilized DEX with general anaesthesia perioperatively. Method Four online databases (PubMed, Embase, the Cochrane Library, and CNKI) were used to find relevant RCTs to conduct systematic analysis. All studies comparing the incidence of POCD or MMSE score between the DEX group and the placebo or comparator group in patients undergoing general anaesthetic surgery were eligible for inclusion. Based on the inclusion and exclusion criteria, the studies were selected. This meta-analysis was performed using odds ratios (ORs) with 95% confidence intervals (CIs) for dichotomous data and standardized mean difference (SMD) and 95% CIs for continuous data as effective measures. Results In total of 21 studies were included in this meta-analysis. The results showed that the incidence of POCD in DEX group was significantly lower than the control group on the first (OR = 0.36, 95% CI 0.24–0.54),third (OR = 0.45,95% CI 0.33–0.61) and seventh (OR = 0.40,95% CI 0.26–0.60) postoperative days; the MMSE scores in DEX group were higher than the control group on the first (SMD = 1.24, 95% CI 1.08–1.41), third(SMD = 1.09, 95%CI 0.94–1.24) and seventh (SMD = 3.28, 95% CI 1.51–5.04) postoperative days. Conclusions Intraoperative DEX use can ameliorate the POCD of patients who received surgical operations under general anesthesia, and effectively reduce the incidence of POCD and improve MMSE score.

Involvement in Decision-Making for Daily Care and Cognitive Decline among Older Adults Who Need Care in Japan

Effective decision-making regarding daily care for older adults with needs could reduce the risk of dementia by preventing loss of motivation and improving care quality. However, empirical studies are scarce, particularly in non-Western countries with different socio-cultural backgrounds. By using 2-year longitudinal data of older Japanese adults aged 65 years and above who were receiving care at home, as well as of their family caregivers, we examined the association of involvement in decision-making with the onset of cognitive decline among older Japanese adults requiring care. The analysis included 219 cases of individuals with normal cognition and no missing variables at baseline and responded to the follow-up survey. An MMSE score of 23 or lower at follow-up was defined as the onset of cognitive decline. The level of involvement in decision-making was assessed by one item and dichotomized (not involved/involved). The covariates were age, gender, education, MMSE score, eligibility level for long-term care, and others at baseline. At baseline, 67.1% were 75 years or older, 58.9% were female, and 91.8% responded being “involved” in the decision-making. The incidence of cognitive decline at follow-up was 30.6%. The multivariable logistic regression analysis showed that involvement in decision-making (OR=0.298 [95% CI: 0.10-0.88], p=0.029) was negatively and significantly associated with the onset of cognitive decline. Our findings show the importance of involvement in the decision-making for daily care to reduce the risk of subsequent cognitive decline in older adults requiring care, even in a culture of familism.

Post-stroke cognitive impairment: screening with MMSE and MoCA and predictors of their persistence after treatment at the Stroke Center

Objective — to analyze the results of screening for post‑stroke cognitive impairment (PCI) in patients with cerebral stroke (CS) admitted to the Stroke Center (SC) in different disease phases, and to determine independent predictors of the PCI persistence at discharge. Methods and subjects. 399 patients were enrolled, including 242 (60.7 %) men and 157 (39.3 %) women with the median age was 66.2 years (IQR 58.5 — 76.3). IS was diagnosed in 331 (82.9 %), and ICH in 68 (17.1 %) patients. Among patients with IS, 137 (41.4 %) had an atherothrombotic subtype, 152 (46.0 %) had a cardioembolic subtype, 21 (6.3 %) had a lacunar subtype, another 21 (6.3 %) had another or unknown cause of stroke. Patients were screened for PCI using the Mini‑Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) on admission and at discharge. Participants with MMSE score of 0 — 24 or a MoCA score of 0 — 25 were considered having PCI. Upon admission, all patients were assessed using the National Institutes of Health Stroke Scale (NIHSS), Bartel Index, and Modified Rankine Scale (mRS). The method of constructing and analyzing logistic regression models was used to determine independent predictors of the preservation of PCI at discharge. The analysis was carried out using the MedCalc v. 19.1. Results. The baseline NIHSS score ranged from 0 to 39 (median 11, IQR 6 — 18). The majority (64.2 %) of the subjects were hospitalized within the first 30 days from the CS onset. The MMSE score on admission ranged from 0 to 30 (median 20, IQR 2 — 27), and in 179 (44.9 %) of the patients the initial score was 0 to 17 (severe PCI), whereas in 61 (15 3 %) of the participants it was 18 to 24 (moderately severe PCI) and only 159 (39.8 %) persons scored 25 to 30 (no PCI). The baseline MoCA score ranged from 0 to 30 (median 15, IQR 1 — 24), and 356 (89.2 %) patients were shown to have PCI (score 0 to 25). According to screening with MMSE at discharge, 125 (31.4 %) patients had severe PCI, and 67 (16.8 %) had moderately severe PCI. The MoCA assessment before discharge indicated PCI in 324 (81.2 %) patients. According to both MMSE and MoCA, the rate of PCI on admission was significantly higher than at discharge (p < 0.001). Among the 240 patients who had PCI according to MMSE score, 239 (99.6 %) had PCI according to the MoCA score. However, among 159 patients who screened negative for PCI with MMSE at admission, 117 (73.6 %) screened positive with MoCA. Screening results using both MMSE and MoCA were not significantly associated with affected hemisphere. ICH was associated with lower (p < 0.0001) MMSE and MoCA scores compared with IS. Predictors of PCI according to MMSE score at discharge were a longer time interval from CS onset to SC admission, and a lower baseline MMSE score. However, with MoCA, the predictors were AT subtype IS, lesions in the distribution of the right or both middle cerebral arteries, older patient age, and a lower baseline MoCA score. Conclusions. In patients with MI, a high rate of PCI was documented on admission, but was significantly lower at discharge. In patients with established PCI, according to MMSE score, the use of MoCA for screening seems useless, however, screening with MoCA identified PCI in 3/4 in patients with a normal MMSE score. The independent predictors of scores on these two scales, indicating PCI, were significantly different, so they should not be considered interchangeable.

The Relationships Between Lipid Accumulation Product Levels and Cognitive Decline Over 4 Years in a Rural Area of Xi’an, China

Background and Aims: The relationships between blood lipid levels and obesity and cognitive impairment have not been fully determined. Considering that the lipid accumulation product (LAP) is a composite index of blood lipid levels and obesity, we investigated the relationships between LAP levels at baseline and cognitive decline over 4 years.Methods: A total of 983 subjects (≥40 years) from a longitudinal cohort in a village of Xi’an, China, who completed the baseline survey were followed-up for 4 years. All participants underwent face-to-face interviews and cognitive assessments at baseline and at the 4-year follow-up. The Mini-Mental State Examination (MMSE) was used to assess cognitive function, and an MMSE score dropping ≥ 2 points from baseline was defined as cognitive decline. The relationships between LAP and cognitive decline were analyzed by linear regression models.Results: During the 4-year follow-up, 172 patients exhibited cognitive decline (17.5%). Univariate analysis showed that the rate of change in MMSE score was significantly different between the low-LAP group and the high-LAP group (t = −2.26, p = 0.024). Multiple linear regression indicated that a high LAP was positively associated with cognitive decline (β = 0.564, p = 0.012). Stratified multivariate analysis showed that LAP was positively associated with cognitive decline in the normal blood pressure female subgroup (β = 1.29, p = 0.002) but not in the high blood pressure group or the male group.Conclusions: High LAP is associated with cognitive decline in females with normal blood pressure but not in those with high blood pressure or males. This indicates that the relationships between blood lipid levels and obesity and cognitive impairment may be affected by blood pressure and sex.

AWAKENING CHARACTERISTICS AND RECOVERY OF COGNITIVE FUNCTION IN PATIENTS UNDERGOING SHORT SURGICAL PROCEDURES: COMPARISON BETWEEN DESFLURANE AND PROPOFOL

Objectives: Early awakening and recovery of the cognitive function improves post-operative outcome and early discharge of the patients. Desflurane and Propofol offer rapid emergence from anesthesia. We compared the awakening and recovery of cognitive function between these two agents. Methods: A total of 50 patients aged 30–60 years belonging to ASA 1 and 2 were studied. In both the groups baseline, Mini Mental State Examination (MMSE) score was recorded and were induced with Target controlled infusion (TCI) of Propofol to achieve plasma site concentration (Cp) of 6 mcg/ml. Group P continued with TCI Propofol Cp 3 mcg ml-1 and in group D, TCI was stopped and started Desflurane 6% end tidal concentration followed by Desflurane 3%. Hemodynamic variables were noted and after stopping the agent, time to eye open, squeeze hands, removal of laryngeal mask airway, state name, and modified Aldrete score were noted. MMSE score was recorded 1, 6, and 24 h postoperatively. Results: Awakening time was significantly shorter in duration in Desflurane group compared to Propofol. The mean time to eye open in the Propofol group was 10.41±2:31 min and Desflurane group was 06.21±01.42 min (***p=0.000). There was an increase in the mean MMSE score postoperatively at 6 h and 24 h interval when compared to the baseline within the groups. However, there was no difference in recovery of cognitive function between the two groups. Conclusion: The use of inhalational agent Desflurane provided shorter awakening time than intravenous Propofol in short surgical procedures but the recovery of cognitive function was comparable. There were no significant side effects.