Higher Risk Of Cognitive Dysfunction Research Articles

Investigation of the Effects of Maternal Nutrition during Pregnancy on Cognitive Functions of Toddlers: A Systematic Review

Abstract Background: Growing the human brain requires all necessary nutrients to form and maintain, so the development of cognitive functions of infants and children depends on adequate nutrition. Children whose mothers had inadequate nutrition are at high risk for cognitive dysfunction. The objective of the present study was to review the studies conducted on “the relationship between nutrient intake during pregnancy and the development of cognitive functions in toddlers”. The present study was conducted by systematic review method using PRISMA checklist items. Methods: To conduct this study, the keywords “maternal nutrition”, “pregnancy diet”, “pregnancy supplement”, “IQ”, “intelligence quotient”, “neurodevelopment”, “cognitive function”, “toddler”, “early years” and “infant” were searched based on the Mesh database in scientific databases including Scopus, SID, Google Scholar, PubMed, and Science Direct to find articles related to the effect of nutrition during pregnancy on the development of the cognitive function of toddlers and its components in Persian and English. Finally, 17 articles were selected for review in this study. Results: The results showed that taking a supplement of iron, saturated fatty acids, vitamins B and D, and folic acid improved the cognitive functions of toddlers. On the other hand, taking supplements containing iodine and zinc had no significant effect on the development of cognitive functions. Diets containing seafood during pregnancy had a beneficial effect on the cognitive functions of children. Conclusions: The study results highlighted the importance of adequate nutrition during pregnancy and showed that maternal nutrition played an important role in the development of cognitive functions of toddlers.

Acromegalic Rat Model Presented Cognitive Impairments and Tau Hyperphosphorylation in Hippocampus.

Acromegaly patients, in addition to the most prominent physical and endocrine changes, also exhibit a higher risk of cognitive dysfunction. However, the reasons and mechanisms underlying cognitive impairments in acromegaly patients remain unknown. Acromegalic rats were induced by subcutaneous injection of tumor cells, with continuous monitoring of body weight and hormonal to confirm the occurrence of acromegaly. Behavioral assessments, including Open Field Test, Novel Object Recognition Test, and Barnes maze Test, were conducted to evaluate the animals' cognitive function. Western blotting, immunohistochemistry, and immunofluorescence techniques were employed to examine changes in hippocampal tau protein, Aβ, and associated signaling pathways. The tumor cells secreting growth hormone increased the secretion of growth hormone, resulting in changes in body size and endocrine functions, thus causing acromegaly. The acromegaly model showed deficiencies in working memory and spatial memory. Hyperphosphorylation of tau protein was observed in the hippocampus of the acromegaly model, but no Aβ deposition was observed. The acromegaly model exhibits hippocampal growth hormone (GH) resistance, decreased expression of GH receptors, and subsequently reduced expression activity of the PI3K-Akt-GSK3β signaling pathway, which is responsible for the hyperphosphorylation of tau protein. The prolonged elevation of GH and insulin-like growth factor 1 (IGF-1) levels caused by acromegaly may lead to abnormalities in the SD rat's PI3K-Akt-GSK3β signaling pathway, subsequently resulting in hyperphosphorylation of hippocampal tau protein and cognitive impairment.

Impact of Coexisting Dementia on Inpatient Outcomes for Patients Admitted with a COPD Exacerbation.

PurposePeople with COPD are at a higher risk of cognitive dysfunction than the general population. However, the additional impact of dementia amongst such patients is not well understood, particularly in those admitted with a COPD exacerbation. We assessed the impact of coexisting dementia on inpatient mortality and length of stay (LOS) in patients admitted to hospital with a COPD exacerbation, using the United States based National Inpatient Sample database.Patients and MethodsPatients aged over 40 years and hospitalised with a primary diagnosis of COPD exacerbation from 2011 to 2015 were included. Cases were grouped into patients with and without dementia. Multivariable logistic regression analysis, stratified by age, was used to assess risk of inpatient deaths. Cox regression was carried out to compare death rates and competing risk analysis gave estimates of discharge rates with time to death a competing variable.ResultsA total of 576,381 patients were included into the analysis, of which 35,372 (6.1%) had co-existent dementia. There were 6413 (1.1%) deaths recorded. The odds of inpatient death were significantly greater in younger patients with dementia (41–64 years) [OR (95% CI) dementia vs without: 1.75 (1.04–2.92), p=0.03]. Cases with dementia also had a higher inpatient mortality rate in the first 4 days [HR (95% CI) dementia vs without: 1.23 (1.08–1.41), p=0.002] and a longer LOS [sub-hazard ratio (95% CI) dementia vs without: 0.93 (0.92–0.94), p<0.001].ConclusionDementia as a comorbidity is associated with worse outcomes based on inpatient deaths and LOS in patients admitted with COPD exacerbations.

Diabetic retinopathy and cognitive dysfunction: a systematic review and meta-analysis.

This study aims to determine the relationship between diabetic retinopathy (DR) and cognitive dysfunction as well as explores the effects of DR on different cognitive domains. A systematic search of PubMed, Embase, Web of Science, Wanfang data, CBM, CNKI, and VIP databases from their inception to October 2021. The pooled odds ratio (ORs), hazard ratio (HRs), and 95% confidence interval (CIs) were calculated. Twenty-two studies met the inclusion criteria and meta-analysis included 15 studies. The presence of DR reflects a higher risk of cognitive dysfunction (OR = 2.45; 95% CI: 1.76-3.41; HR = 1.34 95% CI: 1.10-1.62). Cohort study combined risk was 2.62 (95% CI: 1.93-3.56), in cross-sectional study was 2.07 (95% CI: 1.11-3.88). The pooled OR was 2.38 (95% CI: 1.83-3.10) and 3.11 (95% CI: 1.15-8.40) in Asia and Oceania. No such association was found in North America (OR = 2.22; 95% CI: 0.77-6.38). The pooled risk was 2.47 (95% CI: 1.76-3.48) in patients with T2DM, while did not identify an association between these two conditions in T1DM. The combined unadjusted and adjusted ORs were 2.72 (95% CI: 1.99-3.73) and 2.06 (95% CI: 1.49-2.85). DR severity and the risk of cognitive impairment showed a positive correlation and mainly impaired the speeds of psychomotor and information processing. DR can help to identify people at high risk of cognitive dysfunction. Further studies are indispensable for exploring the relationship between DR and cognitive impairment in the patients for different age, gender and race, as well as to assess the risk of cognitive impairment in different populations.

Serum 25-hydroxy vitamin D level is associated with cognitive impairment in people aged 65 years and older.

Vitamin D deficiency is prevalent in the population, especially in older people. In recent years, studies have revealed an association between a low vitamin D level and cognitive decline. The present research aimed to investigate the relationship of serum 25-hydroxyvitamin D (25-OH-D) level with cognitive function in senior patients. We recruited 299 patients aged 65 years and older. The patients were grouped based on their serum 25-OH-D levels into group A (<10.0 ng/mL), B (10.0-19.9 ng/mL), and C (≥20.0 ng/mL). Cognitive function was assessed with the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Clinical Dementia Rating (CDR) scale, and Activities of Daily Living (ADL) scale. MMSE and MoCA scores were significantly lower in group A (26.02±3.99 and 21.56±5.59, respectively) than in group B (27.34±2.79 and 23.94±4.74, respectively) and group C (27.65±2.54 and 24.95±4.45, respectively). The proportion of patients with cognitive impairment was increased in group A (71.1%) compared to group B (55.3%) and group C (43.9%), and the difference was statistically significant (both P<0.01). Spearman's correlation analysis showed that MMSE and MoCA had a positive relationship with serum 25-OH-D level (β=0.173 and 0.243, both P<0.01) with adjustments for factors as age, sex, and education level. Stepwise regression analysis indicated that MMSE and MoCA scores were correlated with serum 25-OH-D level, age, and education level. A lower level of 25-OH-D is common in senior patients and is associated with cognitive impairment. Patients with severe deficiency of vitamin D (serum 25-OH-D level <10 ng/mL) have lower MMSE and MoCA scores and a higher risk of cognitive dysfunction.

Prediction of Neurocognitive Outcome after Moderate-Severe Traumatic Brain Injury Using Serum Neuron-Specific Enolase and S100 biomarkers.

Seric biomarkers have been tested in a large number of studies on traumatic brain injuries (TBI) patients in order to predict severity, especially related to the short-term outcome. However, TBI patients have a high risk of developing long-term complications such as physical disability, cognitive impairment, psychiatric pathology, epilepsy, and others.The aim of this study was to assess the correlation between protein biomarkers S100 and neuron-specific enolase (NSE) and neurocognitive status at 10- and 90-days post-injury.Both biomarkers were tested in the first 4h and after 72h post-injury in 62 patients with moderate-severe TBI. The patients were evaluated by a series of neurocognitive tests: Early Rehabilitation Barthel Index (ERBI), Glasgow Outcome Scale-Extended (GOSE), The Mini-Mental State Examination (MMSE), Processing Speed Index (PSI), and Stroop Test, at 10 and 90 days post-injury and supplementary by the Hospital Anxiety and Depression Scale at 90 days. For evaluating the whole neurocognitive status instead of every scale separately, we used Structural Equation Modeling (SEM), while for anxiety and depressive symptoms, we used multiple regression analyses. SEM showed that NSE values at 4 hours were significant predictors of the cognitive status at 10 (p=0.034) and 90 days (p= 0.023). Also, there were found significant correlations between NSE at 4h and the anxiety level. This study demonstrated a significant correlation between NSE at 4h and short and medium-term neuropsychological outcomes, which recommends using this biomarker for selecting patients with a higher risk of cognitive dysfunction.

Analysis of Risk Factors Associated with Cognitive Dysfunction in Patients with Atrial Fibrillation

Objective: To discuss the risk factors of cognitive dysfunction in patients with atrial fibrillation. Methods: The 150 cases of patients with atrial fibrillation were analyzed in the first affiliated hospital of Nanchang University who were treated in the cardiovascular department, general medicine department and gerontology department from August 2018 to June 2019. We used Mini-Mental State Examination (MMSE) score to evaluate cognitive function of patients with atrial fibrillation. According to the level of education and MMSE score, patients with atrial fibrillation were divided into three groups: normal cognitive function group, mild cognitive impairment group (MCI) and dementia group. And then the demographic data, the previous use of taking drugs, the results of ultrasonic cardiogram (UCG) and laboratory test were analyzed. Results: 1) The basic situation of research object: a total of 150 patients with atrial fibrillation were enrolled in the study, and the average age of these patients was 65.05 ± 8.74 years old, which included 78 males (52%) and 72 females (48%). The mean MMSE score was 23.42 ± 4.65. According to MMSE score, 86 cases (57.3%) of cognitive dysfunction occurred in 150 patients with atrial fibrillation, which included 41 cases (27.3%) of mild cognitive impairment and 45 cases (30%) of dementia. 2) The comparison of general clinical data: there were significant differences in age, smoking, level of education, left ventricular ejection fraction, left atrial diameter, D-dimer, fibrinogen, homocysteine, platelet and previous use of taking warfarin, dabigatran, CCB, statins among the three groups (P < 0.05). 3) The linear correlational analysis between risk factors of cognitive function and MMSE score in patients with atrial fibrillation: there was a positive correlation between left ventricular ejection fraction and MMSE score, but age, left atrial diameter, homocysteine, low density lipoprotein, platelet, BMI, NT-proBNP, D-dimer were negatively correlated with MMSE score. 4) The risk factors with statistical significance in ANOVA were analyzed by ordinal and multinomial logistic regression, which showed that age (OR = 1.174, 95% CI: 0.091 - 0.231), the level of education (illiteracy OR = 4.162, 95% CI: -0.032 - 2.955, primary school OR = 2.751, 95% CI: -0.172 - 2.197, junior high school OR = 3.539, 95% CI: -0.048 - 2.577, senior high school and special secondary school OR = 1.332, 95% CI: -1.080 - 1.655), no CCB (OR = 1.174, 95% CI: 0.091 - 0.231), no warfarin (OR = 13.749, 95% CI: 1.480 - 3.762), no dabigatran (OR = 16.395, 95% CI: 1.462 - 4.131), D-dimer (OR = 2.745, 95% CI: -0.611 - 2.631), fibrinogen (OR = 3.228, 95% CI: 0.399 - 1.946) were related to the high occurrence of cognitive dysfunction. Conclusions: 1) Patients with atrial fibrillation had a higher risk of cognitive dysfunction (the incidence of 57.4%). 2) There was a positive correlation between left ventricular ejection fraction and MMSE score, but age, left atrial diameter, homocysteine, low density lipoprotein, platelet, BMI, NT-proBNP, and D-dimer were negatively correlated with MMSE score. 3) High level of education, previous use of taking warfarin and dabigatran etexilate were protective factors for cognitive function in patients with atrial fibrillation; but age, previous use of taking CCB, D-dimer and fibrinogen were the risk factors in patients with atrial fibrillation.

The impact of anorexigenic peptides in experimental models of Alzheimer's disease pathology.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder in the elderly population. Numerous epidemiological and experimental studies have demonstrated that patients who suffer from obesity or type 2 diabetes mellitus have a higher risk of cognitive dysfunction and AD. Several recent studies demonstrated that food intake-lowering (anorexigenic) peptides have the potential to improve metabolic disorders and that they may also potentially be useful in the treatment of neurodegenerative diseases. In this review, the neuroprotective effects of anorexigenic peptides of both peripheral and central origins are discussed. Moreover, the role of leptin as a key modulator of energy homeostasis is discussed in relation to its interaction with anorexigenic peptides and their analogs in AD-like pathology. Although there is no perfect experimental model of human AD pathology, animal studies have already proven that anorexigenic peptides exhibit neuroprotective properties. This phenomenon is extremely important for the potential development of new drugs in view of the aging of the human population and of the significantly increasing incidence of AD.

Gastrodin Ameliorates Cognitive Dysfunction in Diabetes Rat Model via the Suppression of Endoplasmic Reticulum Stress and NLRP3 Inflammasome Activation.

Patients with diabetes mellitus (DM) are at high risk for cognitive dysfunction. Endoplasmic reticulum stress (ERS) and inflammation play crucial roles in DM. Gastrodin (Gas), the main component of Gastrodia elata, possesses anti-oxidative stress, anti-inflammatory, and neuroprotective effects. This present study aims to investigate whether Gas could ameliorate cognitive dysfunction in DM and to explore its underlying mechanisms. Rats with streptozotocin-induced type 2 DM were used in this study. After administration of Gas for 5 weeks, the levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) in serum, TNF-α, IL-1β, MDA and SOD in the hippocampus were measured. Morris water maze, hematoxylin and eosin (HE) and Nissl staining were performed to assess the effects of Gas on cognitive function and hippocampal neuronal apoptosis. Protein levels of GLUT3, brain derived neurotrophic factor (BDNF), GRP78, PERK, P-PERK, TXNIP, ASC, NLRP3, CHOP, Bcl-2 and Bax were measured by using Western blot. The results showed that Gas could improve hyperglycemia and dyslipidemia in DM rats, as the levels of TC, TG LDL-C in serum were decreased. TNF-α, IL-1β, MDA contents in the hippocampus were decreased, and SOD contents was increased in the hippocampus of DM rats. Inflammation, oxidative stress, ERS, and apoptosis were observed in the hippocampus of DM rats, accompanied with decreased expression of BDNF and GLUT3. Gas improved the cognitive deficits caused by diabetes and inhibited inflammation, oxidative stress, ERS, and apoptosis in the hippocampus. Furthermore, Gas substantially increased the expression of GLUT3, and inhibited hippocampal ERS and ERS-mediated apoptosis. Additionally, Gas increased the expression of BDNF and decreased the activation of NLRP3 inflammasome. These results suggested that by inhibiting ERS and NLRP3 inflammasome activation and increasing the expression of BDNF and GLUT3, Gas exhibits neuroprotective effects against cognitive dysfunction in DM.

Effect of Area-Level Socioeconomic Deprivation on Risk of Cognitive Dysfunction in Older Adults.

To investigate the relationship between area-level deprivation and risk of cognitive dysfunction. Cross-sectional analysis. The Trinity, Ulster, and Department of Agriculture (TUDA) study from 2008 to 2012. Community-dwelling adults aged 74.0 ± 8.3 without dementia (N = 5,186; 67% female). Adopting a cross-jurisdictional approach, geo-referenced address-based information was used to map and link participants to official socioeconomic indicators of deprivation within the United Kingdom and the Republic of Ireland. Participants were assigned an individual deprivation score related to the smallest administrative area in which they lived. These scores were categorized into comparable quintiles, that were then used to integrate the datasets from both countries. Cognitive health was assessed using the Mini-Mental State Examination (MMSE); cognitive dysfunction was defined as a MMSE score of 24 or less. Approximately one-quarter of the cohort resided within the most-deprived districts in both countries. Greater area-level deprivation was associated with significantly lower MMSE scores; fewer years of formal education; greater anxiety, depression, smoking and alcohol use, and obesity; and more adverse outcomes, including higher blood pressure and diabetes risk. After adjustment for relevant covariates, area deprivation was associated with significantly higher risk of cognitive dysfunction (odds ratio = 1.40, 95% confidence interval = 1.05-1.87, P = .02, for most vs least deprived). This analysis combining data from two health systems shows that area deprivation is an independent risk factor for cognitive dysfunction in older adults. Adults living in areas of greatest socioeconomic deprivation may benefit from targeted strategies aimed at improving modifiable risk factors for dementia. Further cross-national analysis investigating the impact of area- level deprivation is needed to address socioeconomic disparities and shape future policy to improve health outcomes in older adults.© 2018 American Geriatrics Society and Wiley Periodicals, Inc.

Reduction of Cognitive Decline in Patients with or at High Risk for Diabetes.

The incidence of Alzheimer's disease and related disorders is expected to triple by 2050. People with type 2 diabetes and prediabetes have a higher risk of cognitive dysfunction, including Alzheimer's disease and vascular dementia. Controversy remains about when and how to prevent and treat cognitive dysfunction in people with or at high risk of diabetes. In our review of ongoing clinical trials, we have found that there has been an increase in the number of studies assessing the efficacy of pharmacological and non-pharmacological approaches to prevent or slow down cognitive impairment among people with or at high risk of diabetes. Despite the considerable risk of cognitive impairment in people with diabetes and prediabetes, there is not enough evidence to support a specific treatment to prevent or slow mild cognitive impairment, or progression to Alzheimer's disease or related disorders. Several ongoing trials are attempting to identify the usefulness of several compounds, as well as lifestyle changes including exercise and diet. Direct mechanisms linking diabetes to cognitive decline have not been elucidated.

Chronic Obstructive Pulmonary Disease as a Risk Factor for Cognitive Dysfunction: A Meta-Analysis of Current Studies.

Cognitive dysfunction has been shown to be associated with many risk factors, such as smoking, diabetes, and body mass index. Chronic obstructive pulmonary disease (COPD), a common disease within the elderly population, has also been found to be related to cognitive decline. However, whether COPD is a risk factor of cognitive dysfunction is not well established. The purpose of this meta-analysis is to investigate the role COPD plays in cognitive dysfunction. PubMed, Cochrane library and Web of Science databases were searched. Three cohort studies and eleven cross-sectional studies were found to be eligible. According to our results, COPD patients had a higher risk of cognitive dysfunction than controls (OR [odds ratio]: 1.72; 95% CI, 1.12-2.65; p = 0.01). The exacerbation of COPD was strongly correlated with cognitive decline. COPD patients performed worse than controls on the Mini- Mental State Examination test, but the results were not statistically significant (OR: -0.79; 95% CI, [-1.78, 0.19]; p = 0.11). Thus, more attention should be given to the occurrence of cognitive decline in COPD patients. The prevention and control of COPD exacerbation are critical.

Medico-legal Implications of Changes in Handwriting of Some Hemodialysis Egyptian Patients (A Prospective Study)

Little attention has been paid to the possibility of cognitive deficits in patients with major organs   failure   such as  the  liver,  kidney,  or  heart.  Hemodialysis     patients    are   at high   risk   for   cognitive dysfunction,     psychometric     deficits   and metabolic    alternations    than   chronic   kidney disease    alone   that   can   affect   the   quality   of hand   writing    and   impair   its proper recognition. Aim  of  the  study  it aims to : Structurally  analyze changes in handwriting characteristics  among some  hemodialysis  Egyptian   patients and to assess their medico-legal  implications of the handwriting . Thirty seven stable hemodialysis patients were included in this study. All the patients were asked to write a sample.  Typing tool, writing surface, writing mode and time for filling the form were standardized for all the patients. Qualitative data were presented as frequencies and percentages. Results:  Handwriting   analysis  showed,  There was a statistically  significant  difference  (P<  0.001)  regarding Writing   speed  (slow speed (81.1%), medium (13.5%), and very slow speed (5.4%),  Pen  pressure   grades  (light pressure (62.2%),heavy  pressure  (24.3%) and medium pressure (13.5%»,  word  size (large word size (46%), medium word size (40.5%) and small word size   (13.5%), Interrupted stroke (97.3%), Curved (zigzag) stroke   (100%), Extra stroke (100%)  and      Stiff  stroke(100%), dirtiness(78.4%), spacing represented (97.3%)over-Writing (73%) defined as number of over-writings done by each subject / total number of words written by each subject x  100. Conclusion: hemodialysis patients had a characteristic impairment in handwriting skills which may indicate cognitive deficit that cannot be elicited by clinical examination and investigations. These changes may carry great medico legal implications, and should be considered when analyzing their hand writings.

Cognitive training in Parkinson's disease reduces cognitive decline in the long term

Patients with Parkinson's disease (PD) are at high risk for cognitive dysfunction. Non-pharmacological interventions have attracted increasing interest for enhancing PD patients' cognitive functions. One-year follow-up data (T2 ) of a randomized controlled trial evaluating two 6-week cognitive trainings - a structured (NEUROvitalis, NV) and an unstructured (mentally fit, MF) program - compared with a waiting list control group (CG) in non-demented PD patients (Hoehn and Yahr I-III) are presented. Forty-seven PD patients were examined at T2 . Effects on overall cognitive functions (Mini-Mental State Examination and DemTect) were compared between all groups with repeated measurement analyses of variance. A combined score of the percentage change value from baseline (T0 ) to T2 was calculated to identify patients who retained or improved their cognitive state (responders). The risk of developing mild cognitive impairment (MCI) was analyzed. Significant time × treatment effects on overall cognitive functions were found for both training groups, each compared separately to the CG (DemTect, P<0.05). Nine patients (56.3%) of the NV group, seven (41.2%) of the MF group and three (21.4%) of the CG were responders. Comparing NV to CG the odds ratio was 4.7 [95% confidence interval (0.8; 33.3)], and comparing MF to CG it was 2.6 [95% confidence interval (0.4; 17.4)]. MCI risk for patients without prior MCI was 40.0% in CG, 18.2% in MF and 18.2% in NV. The odds ratio was 3 comparing NV to CG, MF to CG. This study gives evidence that cognitive training may be effective to prevent cognitive decline and onset of MCI in PD patients.

Rationale and clinical data supporting nutritional intervention in Alzheimer’s disease

Adequate nutrition plays an important role in the maintenance of cognitive function, particularly during aging. Malnutrition is amongst the risk factors for developing mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Epidemiological studies have associated deficiencies in some nutrients with a higher risk of cognitive dysfunction and/or AD.Cognitive decline in AD is correlated with synaptic loss and many of the components required to maintain optimal synaptic function are derived from dietary sources. As synapses are part of the neuronal membrane and are continuously being remodelled, the availability of sufficient levels of nutritional precursors (mainly uridine monophosphate, choline and omega-3 fatty acids) to make the phospholipids required to build neuronal membranes may have beneficial effects on synaptic degeneration in AD. In addition, B-vitamins, phospholipids and other micronutrients act as cofactors to enhance the supply of precursors required to make neuronal membranes and synapses. Despite this, no randomized controlled trial has hitherto provided evidence that any single nutrient has a beneficial effect on cognition or lowers the risk for AD. However, a multi-target approach using combinations of (micro)nutrients might have beneficial effects on cognitive function in neurodegenerative brain disorders like AD leading to synaptic degeneration.Here we review the clinical evidence for supplementation, based on a multi-target approach with a focus on key nutrients with a proposed role in synaptic dysfunction. Based on preclinical evidence, a nutrient mixture, Souvenaid® (Nutricia N.V., Zoetermeer, The Netherlands) was developed. Clinical trials with Souvenaid® have shown improved memory performance in patients with mild AD. Further clinical trials to evaluate the effects of nutritional intervention in MCI and early dementia due to AD are on-going.

Examination of the FDA Warning for Statins and Cognitive Dysfunction

Background: The ACC/AHA released new guidelines in December of 2013 for treatment of high blood cholesterol to simplify identification and treatment of patients most likely to benefit from statins. These guidelines may result in more patients receiving statin therapy, and at younger ages. In 2012, the U.S. Food and Drug Administration (FDA) mandated warnings for all statin drugs for possible adverse effects on cognitive performance. Statins can be classified as having greater lipophilic or hydrophilic solubility properties with lipophilic statins more readily crossing the blood brain barrier, and possibly differentially inducing detrimental cognitive effects. Objective: We sought to analyze generalizability of the FDA statin class warning. Methods: De-identified publicly-available data were analyzed from the FDA Adverse Event Reporting System (AERS) in relation to reports of cognitive dysfunction (primary outcome), and by type of statin (lipophilic, hydrophilic) versus “control” drugs used in the general population. Results: Significantly higher proportional reporting ratios (PRRs) were observed for lipophilic statins, which more readily cross the blood-brain barrier, (range: 1.47-3.51) compared to hydrophilic statins (range: 0.69-1.64). However, fluvastatin, lovastatin, and pitavastatin (lipophilic) had relatively few adverse reports. The signal of higher risk of cognitive dysfunction was observed for the lipophilic statin atorvastatin (PRR = 2.59, 95% confidence interval: 2.44-2.75) followed by simvastatin (PRR = 2.22, 95% confidence interval: 2.04-2.31). Hydrophilic statins (rosuvastatin, pravastatin) showed essentially no evidence suggestive of heightened risk of cognitive dysfunction. Fluvastatin, lovastatin, and pitavastatin had relatively few adverse reports, and no evidence of a higher proportion of cognitive dysfunction reports compared to the control drugs in aggregate (PRR range: 0.22 to 1.48). Conclusions: Inconsistent with the FDA class warning, highly lipophilic statins with specific pharmacokinetic properties (atorvastatin, simvastatin) appear to confer a significantly greater risk of adverse cognitive effects compared to other lipophilic statins and those with hydrophilic solubility properties.

Apolipoprotein E-ε4 polymorphism and cognitive dysfunction after carotid endarterectomy

Approximately 25% of patients undergoing carotid endarterectomy (CEA) exhibit cognitive dysfunction (CD) 1day and 1month after CEA. The apolipoprotein E (apoE)-ε4 polymorphism has been previously identified as a robust independent risk factor for CD 1month after CEA. We aimed to determine whether the apoE-ε4 polymorphism is also an independent risk factor for CD as early as 1day after CEA and to confirm the previous findings at 1month. Patients undergoing elective CEA (n=411) were enrolled with written informed consent in this follow-up observational study. CD was evaluated via an extensive neuropsychometric battery. apoE-ε4 carriers exhibited significantly more CD 1day (30.1% versus 17.9%, p=0.01) and 1month (25.7% versus 9.8%, p=0.001) after CEA compared to non-carriers. Multivariate regression models were generated to determine independent predictors of CD. At 1day, apoE-ε4 was significantly associated with higher risk of CD (odds ratio [OR]: 2.24 [95% confidence interval 1.29–3.84], p=0.004), while statin use was significantly associated with lower risk (OR: 0.40 [0.24–0.67], p<0.001). At 1month, apoE-ε4 was significantly associated with higher risk of CD (OR: 3.14 [1.53–6.38], p=0.002), while symptomatic status was significantly associated with lower risk (OR: 0.45 [0.20–0.94], p=0.03). The apoE-ε4 polymorphism is an independent risk factor for CD as early as 1day after CEA and is confirmed to be an independent risk factor for CD at 1month as well.

Pentamethylquercetin Protects Against Diabetes-Related Cognitive Deficits in Diabetic Goto-Kakizaki Rats

Diabetic patients have a signifiantly higher risk of developing all forms of dementia. Pentamethylquercetin (PMQ) has been proven to have potential as an anti-diabetic agent. Nevertheless, whether PMQ can improve diabetes-induced cognitive dysfunction has not been investigated. To address this, we evaluated the effectiveness and underlying mechanisms of PMQ for ameliorating diabetes-related cognitive dysfunction in vivo and in vitro. Our results showed that Goto-Kakizaki (GK) rats displayed impairment in their learning abilities and memory capabilities. Furthermore, GK rats reflected cognitive dysfunction in proportion to the intensity of insulin resistance index. In addition, dendritic spine density and the % cell viability significantly decreased in hippocampus neurons. High glucose conditions induced hippocampal neurons damage, inflicted dendritic spine dysontogenesis, and reduced Akt/cAMP response element-binding protein activation. Treatment with PMQ in GK rats significantly ameliorated cognitive deficits and neuronal damage and increased dendritic spine density, at least in part, by improving insulin resistance and metabolic disorders. Furthermore, PMQ significantly activated the Akt/cAMP response element-binding protein pathway and increased the expression of memory-related proteins in the downstream part of the Akt/cAMP response element-binding protein pathway, such as synaptophysin and glutamate receptor 1. In addition, PMQ inhibited high glucose-induced cellular toxicity. LY294002 appeared to partly inhibit PMQ-mediated protective effects in hippocampal neurons. The results suggest that insulin resistance could predominantly reduce Akt/cAMP response element-binding protein activation in the brain, which is associated with a higher risk of cognitive dysfunction. PMQ could provide a new potential option for the prevention of cognitive dysfunction in diabetes.

Independent association of cognitive dysfunction with cardiac hypertrophy irrespective of 24-h or sleep blood pressure in older hypertensives

Our aim was to assess whether cardiac hypertrophy is associated with cognitive function independently of office, 24-h, or sleep blood pressure (BP) levels in older hypertensive patients treated with antihypertensive medications. In this cross-sectional study, we recruited 443 hypertensive patients aged over 60 years (mean age: 73.0 years; 41% men) who were ambulatory, lived independently, and were without clinically overt dementia. They underwent measurements of 24-h BP monitoring, echocardiographic left ventricular mass index (LVMI), and cognitive function (mini-mental state examination, MMSE). MMSE score was inversely associated with office, 24-h, awake, and sleep systolic BP (SBP) (each, P < 0.05). There was a close association between MMSE score and LVMI (ρ = -0.32; P < 0.001). Using multiple logistic regression analysis including numerous covariates (i.e., age, sex, obesity, current smoking, educational level, duration of antihypertensive medications, renal dysfunction, statin use, and previous history of cardiovascular disease), the odds ratio (OR) for the presence of cognitive dysfunction, defined as the lowest quartile of MMSE score (median MMSE score: 23 points; n = 115), was estimated; the presence of cardiac hypertrophy (LVMI ≥125 kg/m(2) in men and ≥110 kg/m(2) in women) as well as uncontrolled 24-h BP (mean 24-h SBP/diastolic BP (DBP) ≥130/80 mm Hg) or sleep BP (mean sleep SBP/DBP ≥120/70 mm Hg), but not uncontrolled office BP (mean office SBP/DBP ≥140/90 mm Hg), were independently associated with cognitive dysfunction (all P < 0.05). Among older hypertensive patients with antihypertensive medications, those who had echocardiographically determined cardiac hypertrophy may be at high risk for cognitive dysfunction, irrespective of their office BP and 24-h BP levels.

Progression of Cognitive Dysfunction in Elderly Chronic Kidney Disease Patients in a Veteran's Institution in Central Taiwan: a 3-Year Longitudinal Study

A strong positive correlation between estimated glomerular filtration rate (eGFR) multiplied by follow-up time and memory function has been demonstrated previously. The purpose of this study was to investigate the factors affecting progression of cognitive dysfunction in the elderly with different levels of kidney function. In April 2002, a prospective study on progression of cognitive function was conducted on 356 elderly people. All participants received a comprehensive geriatric assessment, serum biochemical test, homeostasis model assessment (HOMA), and a genetic polymorphism study, including polymorphism of apolipoprotein E (APOE), Cystatin, C-reactive protein (CRP) and tumor necrosis factor (TNF). Lean body mass-adjusted eGFR was used to evaluate severity of chronic kidney disease (CKD), and a clinical dementia rating scale was used to assess cognitive dysfunction. Patients were stratified according to eGFR (≥49 mL/min and <49 mL/min). Using multivariate logistic regression models, older age (OR=1.27, 95% CI=1.00-1.61) was associated with a high risk for progression of cognitive function in patients with a relatively low eGFR. In patients with lower eGFR, higher mini-mental state examination (MMSE) scores (OR=0.23, 95% CI=0.10-0.54) were correlated with a low risk for progression of cognition, while in patients with higher eGFR, higher MMSE scores (OR=0.39, 95% CI=0.23-0.65) were less correlated with cognitive dysfunction. However, elevated serum plasminogen activator inhibitor-1 (PA1-1) was associated with a high risk for cognitive dysfunction (OR=1.06, 95% CI=1.01-1.11) in patients with a better eGFR. Age, MMSE score and serum PAI-1 were found to be factors that predicted cognitive dysfunction at different functional levels of CKD.