Sex Differences in the Association Between LDL/HDL with Cognitive Decline in Older Adults: National Health and Nutrition Examination Survey.

Background: Lipids have a significant impact on the development and functioning of the nervous system, but the sex differences between the association of LDL/HDL, which reflects lipid metabolic status, and cognitive impairment remains unclear. Objective: We aimed to determine if there were sex differences between the association of LDL/HDL and cognitive function in US older adults. Methods: This population-based cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) 2011-2012 and 2013-2014 cycles. The main outcome was poor cognitive performance defined by the Digit Symbol Substitution Test (DSST) <  34 based on published literature. Results: A total of 1,225 participants were included in the study, with a cognitive impairment incidence of 25.6% (314/1,225). Multivariate regression models demonstrated a significant association between cognitive decline and each 1-unit increase in LDL/HDL, after adjusting for all covariates (adjusted odds ratio [OR] = 1.36, 95% confidence interval [CI]: 1.11-1.67). Furthermore, subgroup analysis revealed an interaction between LDL/HDL and cognitive impairment in sex subgroups. Conclusions: LDL/HDL was associated with cognitive impairment in the US older adult population in adjusted models, although the significance of this association was not observed in females.

Biomarker Changes during 20 Years Preceding Alzheimer's Disease.

BACKGROUND: Biomarker changes that occur in the period between normal cognition and the diagnosis of sporadic Alzheimer's disease have not been extensively investigated in longitudinal studies. METHODS: We conducted a multicenter, nested case-control study of Alzheimer's disease biomarkers in cognitively normal participants who were enrolled in the China Cognition and Aging Study from January 2000 through December 2020. A subgroup of these participants underwent testing of cerebrospinal fluid (CSF), cognitive assessments, and brain imaging at 2-year-to-3-year intervals. A total of 648 participants in whom Alzheimer's disease developed were matched with 648 participants who had normal cognition, and the temporal trajectories of CSF biochemical marker concentrations, cognitive testing, and imaging were analyzed in the two groups. RESULTS: The median follow-up was 19.9 years (interquartile range, 19.5 to 20.2). CSF and imaging biomarkers in the Alzheimer's disease group diverged from those in the cognitively normal group at the following estimated number of years before diagnosis: amyloid-beta (Aß)42, 18 years; the ratio of Aß42 to Aß40, 14 years; phosphorylated tau 181, 11 years; total tau, 10 years; neurofilament light chain, 9 years; hippocampal volume, 8 years; and cognitive decline, 6 years. As cognitive impairment progressed, the changes in CSF biomarker levels in the Alzheimer's disease group initially accelerated and then slowed. CONCLUSIONS: In this study involving Chinese participants during the 20 years preceding clinical diagnosis of sporadic Alzheimer's disease, we observed the time courses of CSF biomarkers, the times before diagnosis at which they diverged from the biomarkers from a matched group of participants who remained cognitively normal, and the temporal order in which the biomarkers became abnormal. (Funded by the Key Project of the National Natural Science Foundation of China and others; ClinicalTrials.gov number, NCT03653156.).

Association between healthy lifestyle and memory decline in older adults: 10 year, population based, prospective cohort study.

OBJECTIVE: To identify an optimal lifestyle profile to protect against memory loss in older individuals. DESIGN: Population based, prospective cohort study. SETTING: Participants from areas representative of the north, south, and west of China. PARTICIPANTS: Individuals aged 60 years or older who had normal cognition and underwent apolipoprotein E (APOE) genotyping at baseline in 2009. MAIN OUTCOME MEASURES: Participants were followed up until death, discontinuation, or 26 December 2019. Six healthy lifestyle factors were assessed: a healthy diet (adherence to the recommended intake of at least 7 of 12 eligible food items), regular physical exercise (≥150 min of moderate intensity or ≥75 min of vigorous intensity, per week), active social contact (≥twice per week), active cognitive activity (≥twice per week), never or previously smoked, and never drinking alcohol. Participants were categorised into the favourable group if they had four to six healthy lifestyle factors, into the average group for two to three factors, and into the unfavourable group for zero to one factor. Memory function was assessed using the World Health Organization/University of California-Los Angeles Auditory Verbal Learning Test, and global cognition was assessed via the Mini-Mental State Examination. Linear mixed models were used to explore the impact of lifestyle factors on memory in the study sample. RESULTS: 29 072 participants were included (mean age of 72.23 years; 48.54% (n=14 113) were women; and 20.43% (n=5939) were APOE ε4 carriers). Over the 10 year follow-up period (2009-19), participants in the favourable group had slower memory decline than those in the unfavourable group (by 0.028 points/year, 95% confidence interval 0.023 to 0.032, P<0.001). APOE ε4 carriers with favourable (0.027, 95% confidence interval 0.023 to 0.031) and average (0.014, 0.010 to 0.019) lifestyles exhibited a slower memory decline than those with unfavourable lifestyles. Among people who were not carriers of APOE ε4, similar results were observed among participants in the favourable (0.029 points/year, 95% confidence interval 0.019 to 0.039) and average (0.019, 0.011 to 0.027) groups compared with those in the unfavourable group. APOE ε4 status and lifestyle profiles did not show a significant interaction effect on memory decline (P=0.52). CONCLUSION: A healthy lifestyle is associated with slower memory decline, even in the presence of the APOE ε4 allele. This study might offer important information to protect older adults against memory decline. TRIAL REGISTRATION: ClinicalTrials.gov NCT03653156.

The Effect of APOE ɛ4 on the Functional Connectivity in Frontoparietal Network in Hypertensive Patients.

Allele 4 of the apolipoprotein E gene (APOE ε4) and hypertension are considered risk factors for Alzheimer's Disease (AD). The detection of differences in cognitive function and brain networks between hypertensive patients who are APOE ε4 carriers and non-carriers may help in understanding how hypertension and risk genes cumulatively impair brain function, which could provide critical insights into the genetic mechanism by which hypertension serves as a potential risk factor for cognitive decline and even AD. Using behavioral data from 233 elderly hypertensive patients and neuroimaging data from 38 of them from Beijing, China; the study aimed to assess the effects of APOE ε4 on cognition and to explore related changes in functional connectivity. Cognitively, the patients with APOE ε4 showed decreased executive function, memory and language. In the MRI sub-cohort, the frontoparietal networks in the APOE ε4 carrier group exhibited an altered pattern, mainly in the left precentral regions, inferior frontal lobe and angular gyrus. More importantly, the decline of cognitive function was correlated with abnormal FC in the left precentral regions in APOE ε4 carriers. APOE ε4 aggravated the dysfunction in frontal and parietal regions in hypertensive patients. This highlights the importance of brain protection in hypertensive patients, especially those with a genetic risk of AD.

Recommendations for the diagnosis and treatment of paroxysmal kinesigenic dyskinesia: an expert consensus in China.

Paroxysmal dyskinesias are a group of neurological diseases characterized by intermittent episodes of involuntary movements with different causes. Paroxysmal kinesigenic dyskinesia (PKD) is the most common type of paroxysmal dyskinesia and can be divided into primary and secondary types based on the etiology. Clinically, PKD is characterized by recurrent and transient attacks of involuntary movements precipitated by a sudden voluntary action. The major cause of primary PKD is genetic abnormalities, and the inheritance pattern of PKD is mainly autosomal-dominant with incomplete penetrance. The proline-rich transmembrane protein 2 (PRRT2) was the first identified causative gene of PKD, accounting for the majority of PKD cases worldwide. An increasing number of studies has revealed the clinical and genetic characteristics, as well as the underlying mechanisms of PKD. By seeking the views of domestic experts, we propose an expert consensus regarding the diagnosis and treatment of PKD to help establish standardized clinical evaluation and therapies for PKD. In this consensus, we review the clinical manifestations, etiology, clinical diagnostic criteria and therapeutic recommendations for PKD, and results of genetic analyses in PKD patients performed in domestic hospitals.

Concordance between the assessment of Aß42, T-tau, and P-T181-tau in peripheral blood neuronal-derived exosomes and cerebrospinal fluid.

INTRODUCTION: Neuronal-derived exosomal Aß42, T-tau, and P-T181-tau have been demonstrated to be biomarkers of Alzheimer's disease (AD). However, no study has assessed the association of Aß42, T-tau, and P-T181-tau between exosomes and CSF. METHODS: This was a multicenter study with two-stage design. The subjects included 28 AD patients, 25 aMCI patients, and 29 controls in the discovery stage; the results of which were confirmed in the validation stage (73 AD, 71 aMCI, and 72 controls). RESULTS: The exosomal concentrations of Aß42, T-tau, and P-T181-tau in AD group were higher than those in aMCI and control groups (all P < .001). The level of each exosomal biomarker was highly correlated with that in CSF. DISCUSSION: This study verified the agreement between CSF and blood exosomal biomarkers and confirmed that exosomal Aß42, T-tau, and P-T181-tau have the same capacity as those in CSF for the diagnosis of AD and aMCI.

The cost of Alzheimer's disease in China and re-estimation of costs worldwide.

INTRODUCTION: The socioeconomic costs of Alzheimer's disease (AD) in China and its impact on global economic burden remain uncertain. METHODS: We collected data from 3098 patients with AD in 81 representative centers across China and estimated AD costs for individual patient and total patients in China in 2015. Based on this data, we re-estimated the worldwide costs of AD. RESULTS: The annual socioeconomic cost per patient was US $19,144.36, and total costs were US $167.74 billion in 2015. The annual total costs are predicted to reach US $507.49 billion in 2030 and US $1.89 trillion in 2050. Based on our results, the global estimates of costs for dementia were US $957.56 billion in 2015, and will be US $2.54 trillion in 2030, and US $9.12 trillion in 2050, much more than the predictions by the World Alzheimer Report 2015. DISCUSSION: China bears a heavy burden of AD costs, which greatly change the estimates of AD cost worldwide.

Combined application of dexamethasone and hyperbaric oxygen therapy yields better efficacy for patients with delayed encephalopathy after acute carbon monoxide poisoning.

BACKGROUND: Delayed encephalopathy after acute carbon monoxide (CO) poisoning (DEACMP) commonly occurs after recovering from acute CO poisoning. This study was performed to assess the efficacy of the combined application of dexamethasone and hyperbaric oxygen (HBO) therapy in patients with DEACMP. PATIENTS AND METHODS: A total of 120 patients with DEACMP were recruited and randomly assigned into the experimental group (receiving dexamethasone 5 mg/day or 10 mg/day plus HBO therapy) and control group (HBO therapy as monotherapy). Meanwhile, the conventional treatments were provided for all the patients. We used the Mini-Mental State Examination (MMSE) scale to assess the cognitive function, the National Institutes of Health Stroke Scale (NIHSS) to assess the neurological function and the remission rate (RR) to assess the clinical efficacy. Myelin basic protein (MBP) in the cerebrospinal fluid (CSF) was also measured. RESULTS: After 4 weeks of treatment, compared to the control group, the experimental group had a significantly higher remission rate (P=0.032), a significantly higher average MMSE score (P=0.037) and a significantly lower average NIHSS score (P=0.002). Meanwhile, there was a trend toward better improvement with dexamethasone 10 mg/day, and the level of MBP in the CSF of patients was significantly lower in the experimental group than in the control group (P<0.0001). The addition of dexamethasone did not significantly increase the incidence of adverse events. CONCLUSION: These results indicate that the combined application of dexamethasone and HBO therapy could yield better efficacy for patients with DEACMP and should be viewed as a potential new therapy.

Decreased plasma levels of soluble low density lipoprotein receptor-related protein-1 (sLRP) and the soluble form of the receptor for advanced glycation end products (sRAGE) in the clinical diagnosis of Alzheimer's disease.

Soluble low density lipoprotein receptor-related protein-1 (sLRP) and the soluble form of the receptor for advanced glycation end products (sRAGE) may reflect some peripheral plasma features of the pathophysiological process of Alzheimer's disease (AD). Decreased plasma levels of sLRP and sRAGE in patients with AD have been documented. However, whether different levels of these proteins can differentiate AD from other types of dementia has not been described. In the present study we assessed the concentrations of these two proteins in 126 patients with AD, 96 with vascular dementia (VaD), 30 with non-AD neurodegenerative dementias (NND) and 98 cognitively normal controls (NC). Plasma sLRP was significantly lower in the group with AD compared with any of the other three groups (p<0.001). Sensitivity of sLRP was 77.8% for AD, whereas specificity was 93.3% for NND, 85.7% for the NC and 58.3% for those with VaD. Plasma sRAGE showed a significantly lower concentration in the group with AD compared with those in the VaD or NC group, but there were no significant differences between the AD compared to the NND group or the VaD compared to the NND group. Sensitivity of sRAGE was 82.5% for patients with AD, whereas specificity was 53.5% for NND, 73.5% for the NC group and 43.8% for those with VaD. The receiving operator characteristic analysis of combined sLRP and sRAGE showed a higher diagnostic accuracy (area under the curve, 0.88; 95% confidence interval, 0.84-0.93) than that of either sLRP or sRAGE considered singly. The results support the possibility that these two biomarkers may help with the diagnosis of AD.