Cognitive Impairment In Elderly Individuals Research Articles

A non-linear relationship between blood pressure and mild cognitive impairment in elderly individuals: A cohort study based on the Chinese longitudinal healthy longevity survey (CLHLS).

Hypertension is an established risk factor for mild cognitive impairment (MCI) in elderly individuals. Nevertheless, the impact of different levels of blood pressure on the progression of MCI remains uncertain. This study aims to investigate the non-linear relationship between blood pressure and MCI in the elderly and detect the critical blood pressure threshold, thus, improving blood pressure management for individuals at high risk of MCI. Data was obtained from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) cohort. We chose normal cognitive elderly individuals who entered the cohort in 2014 for a 5-year follow-up to observe the progression of MCI. Subsequently, we utilized the Cox regression model to identify risk factors for MCI and conducted a Cox-based restricted cubic spline regression (RCS) model to examine the non-linear relationship between systolic blood pressure (SBP) and diastolic blood pressure (DBP) with MCI, determining the critical blood pressure threshold for MCI progression. In the elderly population, female (HR = 1.489, 95% CI: 1.017-2.180), lacking of exercise in the past (HR = 1.714, 95% CI: 1.108-2.653), preferring animal fats (HR = 2.340, 95% CI: 1.348-4.061), increased age (HR = 1.061, 95% CI: 1.038-1.084), increased SBP (HR = 1.036, 95% CI: 1.024-1.048), and increased DBP (HR = 1.056, 95% CI: 1.031-1.081) were associated with MCI progression. After adjusting factors such as gender, exercise, preferred types of fats, and age, both SBP (P non-linear < 0.001) and DBP (P non-linear < 0.001) in elderly individuals exhibited a non-linear association with MCI. The risk of MCI rose when SBP exceeded 135mmHg and DBP was in the range of 80-88mmHg. However, when DBP exceeded 88mmHg, there was a declining trend in MCI progression, although the HR remained above 1. The identified critical blood pressure management threshold for MCI was 135/80mmHg. In this study, we discovered that risk factors affecting the progression of MCI in elderly individuals comprise gender (female), preferring to use animal fat, lack of exercise in the past, increased age, increased SBP, and increased DBP. Additionally, a non-linear relationship between blood pressure levels and MCI progression was confirmed, with the critical blood pressure management threshold for MCI onset falling within the prehypertensive range.

Prediction model for mild cognitive impairment in patients with type 2 diabetes using the autonomic function test.

Type 2 diabetes mellitus (T2DM) is a risk factor for cognitive impairment, and reduced heart rate variability (HRV) has been correlated with cognitive impairment in elderly individuals. This study investigated risk factors and validated a predictive model for mild cognitive impairment (MCI) in patients with T2DM using an autonomic function test. Patients with T2DM, 50-85years of age, who attended the diabetes clinic at Gyeongsang National University Hospital between March 2018 and December 2019, were included. A total of 201 patients had been screened; we enrolled 124 patients according to the inclusion and exclusion criteria in this study. Cognitive function was assessed using the Montreal Cognitive Assessment-Korean version (MOCA-K); MCI was defined as a total MOCA-K score ≤ 23. Risk factors for MCI in patients with T2DM, including demographic- and diabetes-related factors, and autonomic function test results, were analyzed. Based on multivariate logistic regression, a nomogram was developed as a prediction model for MCI. Thirty-nine of 124 patients were diagnosed with MCI. Age, education, and decreased cardiovagal function were associated with a high risk for MCI, with cardiovagal function exerting the greatest influence. However, diabetes-related factors, such as glycemic control, duration of diabetes, or medications, were not associated with the risk for MCI. The nomogram demonstrated excellent discrimination (area under the curve, 0.832) and was well calibrated. Approximately one-third of patients had MCI; as such, carefully evaluating cognitive function in elderly T2DM patients with reduced HRV is important to prevent progression to dementia.

Sex and age disparities in multi-metal mixture exposure and cognitive impairment in urban elderly individuals: The mediation effect and biological function of metabolites

Studies on the relationships between metal mixtures exposure and cognitive impairment in elderly individuals are limited, particularly the mechanism with metabolite. Few studies are available on the potential sex and age specific associations between metal exposure, metabolites and cognitive impairment. We examined plasma metal and blood metabolite concentrations among 1068 urban elderly participants. Statistical analysis included a battery of variable selection approaches, logistic regression for metal/metabolite associations, and Bayesian kernel machine regression (BKMR) to identify mixed effects of metals/metabolites on cognitive impairment risk. Our results showed that As was positively associated with cognitive impairment in the female (OR 95 % CI = 2.21 (1.36, 3.57)) and 60- to 70-year-old (OR 95 % CI = 2.60 (1.54, 4.41)) groups, Cr was positively associated with cognitive impairment in the male (OR 95 % CI = 2.15 (1.27, 3.63)) and 60- to 70-year-old (OR 95 % CI = 2.10 (1.24, 3.57)) groups, and Zn was negatively associated with cognitive impairment, especially in the female (OR 95 % CI = 0.46 (0.25, 0.84)), 60- to 70-year-old (OR 95 % CI =0.24 (0.12, 0.45)) and ≥ 80-year-old (OR 95 % CI = 0.19 (0.04, 0.86)) groups. Positive associations were observed between combined metals (Cr, Cu and As) and cognitive impairment, but Zn alleviated this tendency, especially in elderly individuals aged ≥80 years. Negative associations were observed between metabolites and cognitive impairment, especially in male, female and 60–70 years old groups. The mediation effects of metabolites on the association between metal exposure and cognitive impairment were observed, and the percentages of these effects were 15.60 % (Glu-Cr), 23.00 % (C5:1-Cu) and 16.36 % (Glu-Zn). Cr, Cu, and Zn could increase cognitive impairment risk through the “Malate−Aspartate Shuttle”, “Glucose−Alanine Cycle”, etc., pathways. Overall, we hypothesize that metabolites have mediation effects on the relationship between multi-metal exposure and cognitive impairment and that there are sex and age differences.

Abnormal functional connectivity of the occipital thalamus with the superior occipital gyrus is associated with mild cognitive impairment in elderly individuals with primary insomnia

AbstractStudy objectivesPrimary insomnia (PI) triggers a decline in cognitive function, and the thalamus plays an integral role in this process; however, the mechanisms are unclear. The purpose of this study was to investigate the altered functional connectivity (FC) of the thalamus in PI patients with mild cognitive impairment (MCI) and to explore the potential neural mechanisms of thalamic involvement in these patients.MethodsThis case–control study was conducted in older adults from various communities in Fuzhou, China with a PI diagnosis. These participants underwent neuropsychological assessment and were matched in a 1:2 ratio to the healthy control (HC) group and the PI group according to sex, age, and education level. Resting‐state functional magnetic resonance imaging was used to explore changes in thalamic FC in PI patients. To further compare changes in thalamic and whole‐brain FC, we further divided the PI group into cognitively normal patients and patients with MCI according to the diagnostic criteria for MCI. The relationship between abnormal FC and cognitive function was investigated.ResultsThe 28 HCs and 58 participants with PI showed significant differences in Montreal Cognitive Assessment (MoCA) scores (p = .044). In comparison to the HC group, the PI group showed enhanced FC of the occipital thalamus with the left inferior occipital gyrus, right lingual gyrus, left middle temporal gyrus, left superior marginal gyrus, left dorsolateral superior frontal gyrus, and right anterior central gyrus. The MoCA total score and the executive function, attention, and abstraction scores of PI patients with MCI (PI–MCI) were worse than those of PI patients without MCI. In comparison to the simple PI group, FC was enhanced in the PI–MCI group between the left occipital thalamus and the middle occipital gyrus, and between the right occipital thalamus and the right superior frontal gyrus, left middle frontal gyrus, right superior occipital gyrus, and orbital inferior frontal gyrus. There was a significant negative correlation between the MoCA total score and the enhanced FC between the right occipital thalamus and right superior occipital gyrus (r = −.419, p = .042).ConclusionThe early onset of cognitive impairment in patients with PI is associated with altered FC between the thalamus and the cortex. Enhanced FC between the thalamus and the visual cortex, that is, the superior occipital gyrus, which is involved in attentional processing, may play a role in the early onset of cognitive impairment in insomnia patients. Moreover, due to the fact that PI patients “overdraw” the compensatory capacity of these brain regions earlier, the PI–MCI may fall into the abyss of “decompensation” faster and face more severe cognitive impairments.

A screening method for mild cognitive impairment in elderly individuals combining bioimpedance and MMSE.

We investigated a screening method for mild cognitive impairment (MCI) that combined bioimpedance features and the Korean Mini-Mental State Examination (K-MMSE) score. Data were collected from 539 subjects aged 60 years or older at the Gwangju Alzheimer's & Related Dementias (GARD) Cohort Research Center, A total of 470 participants were used for the analysis, including 318 normal controls and 152 MCI participants. We measured bioimpedance, K-MMSE, and the Seoul Neuropsychological Screening Battery (SNSB-II). We developed a multiple linear regression model to predict MCI by combining bioimpedance variables and K-MMSE total score and compared the model's accuracy with SNSB-II domain scores by the area under the receiver operating characteristic curve (AUROC). We additionally compared the model performance with several machine learning models such as extreme gradient boosting, random forest, support vector machine, and elastic net. To test the model performances, the dataset was divided into a training set (70%) and a test set (30%). The AUROC values of SNSB-II scores were 0.803 in both sexes, 0.840 for males, and 0.770 for females. In the combined model, the AUROC values were 0.790 (0.773) for males (and females), which were significantly higher than those from the model including MMSE scores alone (0.723 for males and 0.622 for females) or bioimpedance variables alone (0.640 for males and 0.615 for females). Furthermore, the accuracies of the combined model were comparable to those of machine learning models. The bioimpedance-MMSE combined model effectively distinguished the MCI participants and suggests a technique for rapid and improved screening of the elderly population at risk of cognitive impairment.

Optimal cut-off MoCA score for screening for mild cognitive impairment in elderly individuals in China: A systematic review and meta-analysis.

To evaluate the optimal cut-off MoCA score for elderly individuals with MCI. A systematic review and meta-analysis. Articles were retrieved from PubMed, Ovid, Embase, The Cochrane Library, PsycINFO, CBM, CNKI, WanFang and CQVIP and were assessed by using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Figures of the assessment were made by using Review Manager 5.3, and a meta-analysis of the data was conducted by using Bivariate Random-effects Meta-Analysis (BRMA) via Stata 14.0. Seventeen articles were retrieved from the database, and when the cut-offs were 24/25 and 25/26, they represented the same diagnostic value; in addition, the AUC was 0.96, which demonstrated high predictive validity for mild cognitive impairment screening. However, the sensitivity was higher with 25/26 (se=0.95, sp=0.80), whereas the specificity was higher with 24/25 (se=0.92, sp=0.89).

Longitudinal real world correlation study of blood pressure and novel features of cerebral magnetic resonance angiography by artificial intelligence analysis on elderly cognitive impairment.

This study aims to investigate novel clinical risk factors for cognitive impairment (CI) in elderly. A total of 3221 patients (259 patients with CI and 2,962 subjects without CI) were recruited into this nested case-control study who underwent cerebral magnetic resonance angiography (MRA) from 2007 to 2021. All of the clinical data with MRA imaging were recorded followed by standardization processing blindly. The maximum stenosis score of the posterior circulatory artery, including the basilar artery, and bilateral posterior cerebral artery (PCA), was calculated by the cerebral MRA automatic quantitative analysis method. Logistic regression (LR) analysis was used to evaluate the relationship between risk factors and CI. Four machine learning approaches, including LR, decision tree (DT), random forest (RF), and support vector machine (SVM), employing 5-fold cross-validation were used to establish CI predictive models. After matching with age and gender, 208 CI patients and 208 control subjects were finalized the follow-up (3.46 ± 3.19 years) with mean age at 84.47 ± 6.50 years old. Pulse pressure (PP) in first tertile (<58 mmHg) (OR 0.588, 95% confidence interval (CI): 0.362-0.955) was associated with a decreased risk for CI, and ≥50% stenosis of the left PCA (OR 2.854, 95% CI: 1.387-5.872) was associated with an increased risk for CI after adjusting for body mass index, myocardial infarction, and stroke history. Based on the means of various blood pressure (BP) parameters, the performance of the LR, DT, RF and SVM models accurately predicted CI (AUC 0.740, 0.786, 0.762, and 0.753, respectively) after adding the stenosis score of posterior circulatory artery. Elderly with low pulse differential pressure may have lower risk for cognitive impairment. The hybrid model combined with the stenosis score of posterior circulatory artery, clinical indicators, and the means of various BP parameters can effectively predict the risk of CI in elderly individuals.

Measurement of Five Emotions Defined by Traditional Chinese Medicine With a Focus on Preventing Mild Cognitive Impairment.

Objectives: This study aimed to develop a novel Measurement of the Five Emotions (MFE) based on traditional Chinese medicine for assessing cognitive impairment in elderly individuals. Methods: Surveys were collected from 184 participants, over 65years of age, who were residents of Kyoto City, Japan. The surveys included the Measurement of the Five Emotions (MFE) and the Dementia Assessment Sheet for the Community-based Integrated Care System (DASC-21). Item-total reliability and internal consistency reliability were assessed using Spearman's correlation test and Cronbach's alpha coefficient analysis. Factor analysis was conducted to identify the main factors related to the theoretically constructed emotional reaction patterns. Criterion-related validity was examined by investigating the correlation between the scores of the 2 surveys (MFE and DASC-21). Results: The factor analysis revealed that the final version of MFE consisted of 5 factors, which accounted for a cumulative contribution rate of 57.71%. The Cronbach's alpha coefficient reached .71, indicating satisfactory internal consistency. There was a negative correlation between the MFE and DASC-21 scores with a correlation coefficient of -.3149. Furthermore, when comparing participants with lower cognitive function (DASC-21 score >26) to those with higher cognitive function, MFE subscale scores in the emotions of "Sorrow" and "Thought" were significantly lower, suggesting that these particular emotions are related to cognitive impairment. These findings confirmed the reliability and the construct validity of the MFE. Conclusion: The criterion reliability and validity tests provided evidence for the construct validity of the MFE. The negative correlation (coefficient = -.3149) between MFE scores and DASC-21 scores suggested that MFE can serve as a scale for detecting cognitive impairment.

Association between remnant cholesterol and verbal learning and memory function in the elderly in the US

BackgroundThe relationship between remnant cholesterol (RC) and atherosclerotic cardiovascular risk has been given increasing attention in recent years. However, its association with verbal learning and memory performance has not been reported.MethodsData were extracted from the National Health and Nutrition Examination Survey (NHANES) 2011–2014 database. Participants aged ≥60 years with available fasting lipid data were included. Verbal learning and memory performance were evaluated using the Consortium to Establish a Registry for Alzheimer’s Disease Word List Memory Task (CERAD-WL) subtest. The CERAD total score was calculated as the mean of three immediate recalls and a delayed recall. RC was calculated as total cholesterol (TC) minus the sum of low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). Multivariate ordinal logistic regression was performed to evaluate the association between RC, as well as its derived marker, the TC/RC ratio, and age-stratified quartiles of the CERAD total score.ResultsA total of 1377 participants were analysed. On a continuous scale, per 1 mmol/L increase in RC and per 1 unit increase in the TC/RC ratio were associated with multivariable adjusted odds ratios (95% CI) of 0.74 (0.58–0.94) and 1.45 (1.13–1.87), respectively, for having a CERAD total score in a higher quartile. On a categorical scale, higher RC quartiles were associated with a CERAD total score in a lower quartile; in contrast, the higher TC/RC quartile was associated with a CERAD total score in a higher quartile (all P for trend < 0.05).ConclusionsThe current study suggests that lower RC levels and a higher TC/RC ratio are associated with better verbal learning and memory function, which indicates that lowering RC levels could be beneficial for preventing cognitive impairment in elderly individuals. Further research is needed to validate the causal roles of RC and the TC/RC ratio in cognition.

Assessment of subjective and objective masticatory function among elderly individuals with mild cognitive impairment

BackgroundMasticatory function is known to be related to cognitive ability; therefore, factors for improving masticatory function should be identified.AimsThis study aimed to identify factors influencing masticatory function associated with mild cognitive impairment (MCI) in elderly individuals.MethodsA total of 123 elderly participants [mean age: 76.5 ± 6.5 years; 82 females (66.7%), 41 males (33.3%)] were included. Cognitive function was evaluated by the Korean version of the Mini-Mental State Examination (KMMSE). Questionnaires for subjective evaluation were administered, and dynamic objective masticatory function evaluations, including chewing tests and bite force measurements, were performed. Intergroup differences were evaluated by the Wilcoxon rank-sum and chi-square test, and correlations between cognitive ability and masticatory function were evaluated by multilinear logistic regression.ResultsThe number of teeth, number of posterior teeth, bite force, masticatory ability index (MAI) and posterior support status showed significant differences between the normal (KMMSE > 23) and MCI (KMMSE ≤ 23) groups. However, only the MAI, representing dynamic masticatory performance, was significantly associated with MCI regardless of age, sex and removable prostheses. The number of teeth and posterior teeth, bite force, subjective masticatory ability and posterior occlusal support showed no significant association with MCI.DiscussionThese results suggested the importance of chewing function for preventing the progression of cognitive impairment.ConclusionsConsidering that only the MAI was significantly associated with MCI, it is more important to improve chewing efficiency by harmonizing therapeutic prosthetics with the surrounding masticatory system than simply increasing the number of teeth to prevent or delay cognitive impairment in elderly individuals.

Fine or Gross Motor Index as a Simple Tool for Predicting Cognitive Impairment in Elderly People: Findings from The Irish Longitudinal Study on Ageing (TILDA).

Several kinds of motor dysfunction can predict future cognitive impairment in elderly individuals. However, the ability of the fine motor index (FINEA) and gross motor index (GROSSA) to predict the risk of cognitive impairment has not been assessed. We investigated the associations between FINEA/GROSSA and cognitive impairment. The data of 4,745 participants from The Irish Longitudinal Study on Ageing (TILDA) were analyzed. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). We first assessed the correlation between the FINEA/GROSSA and MMSE in a cross-sectional study. Then, we further investigated the predictive role of the incidence of cognitive impairment in a prospective cohort study. We found that both FINEA and GROSSA were negatively correlated with MMSE in both the unadjusted (FINEA: B = -1.00, 95%confidence intervals (CI): -1.17, -0.83, t = -11.53, p < 0.001; GROSSA: B = -0.85, 95%CI: -0.94, -0.76, t = -18.29, p < 0.001) and adjusted (FINEA: B = -0.63, 95%CI: -0.79, -0.47, t = -7.77, p < 0.001; GROSSA: B = -0.57, 95%CI: -0.66, -0.48, t = -12.61, p < 0.001) analyses in a cross-sectional study. In a prospective cohort study, both high FINEA and high GROSSA were associated with an increased incidence of cognitive function impairment (FINEA: adjusted odds ratios (OR) = 2.35, 95%CI: 1.05, 5.23, p = 0.036; GROSSA adjusted OR = 3.00, 95%CI: 1.49, 6.03, p = 0.002) after 2 years of follow-up. Higher FINEA and GROSSA scores were both associated with an increased incidence of cognitive impairment. FINEA or GROSSA might be a simple tool for identifying patients with cognitive impairment.

Relationship between peripheral neuropathy and cognitive performance in the elderly population.

There are only a few studies that have shown an association of peripheral neuropathy with cognitive impairment in elderly individuals. Therefore, we investigated the relationship between cognitive performance and peripheral neuropathy.From the database of the National Health and Nutrition Examination Survey (NHANES, 1999–2002), each participant completed a household interview, physical performance test, questionnaire regarding personal health, and Digit Symbol Substitution Test (DSST) to evaluate cognitive performance. The severity of peripheral neuropathy was assessed based on the number of insensate areas in both feet during monofilament examination. We used the multivariate linear regression to analyze the association of the DSST findings with insensate areas of the worse foot.There were 828 participants in our study from NHANES 1999 to 2002; their mean age was 69.96 ± 7.38 years, and 51.3% were male. The β coefficients of the number of insensate areas associated with the DSST findings were all negative values, and the absolute value increased as the number of insensate areas increased. After adjustment for pertinent variables, the correlations remained significantly negative (all P for trend <.001). In addition, subgroup analysis showed no gender differences in the negative association, but this association was not significant in obese participants (P > .05).Our study provides evidence that the severity of peripheral neuropathy is significantly negatively correlated with cognitive performance.

Obesity Is Less Frequently Associated with Cognitive Impairment in Elderly Individuals: A Cross-Sectional Study in Yogyakarta, Indonesia.

Obesity is one of the factors associated with cognitive impairment. However, obesity may differently affect cognitive function in different age groups, and scarce data are available from low- and middle-income countries. This cross-sectional study aimed to identify the association between obesity and cognitive impairment among 143 elderly individuals in Yogyakarta. We recorded the sociodemographic factors and some comorbidities, also measured the body mass index as a parameter of obesity, cognitive function using Montreal Cognitive Assessment—Indonesia, mood condition and depression status using geriatric depression scale-short form, as well as the daily life function using Activity of Daily Living and Instrumental Activity of Daily Living. After adjustment for the sociodemographic and comorbidities, we found that subjects with older age were more likely to have cognitive impairment (odds ratio [OR] 3.544, 95%CI: 1.36–9.22, p < 0.01) and compared with elderly individuals with normal weight, obese elderly individuals were 40% less likely to have cognitive impairment (OR 0.604, 95%CI: 0.39–0.95, p < 0.05). This study suggests that obesity in elderly individuals is less frequently associated with cognitive impairment. These findings support the reverse causation mechanism related to body mass index (BMI) and cognitive impairment in low/middle-income countries.

Association of β-Amyloid Burden With Sleep Dysfunction and Cognitive Impairment in Elderly Individuals With Cognitive Disorders

Evidence shows that sleep dysfunction and β-amyloid (Aβ) deposition work synergistically to impair brain function in individuals with normal cognition, increasing the risk of developing dementia later in life. However, whether Aβ continues to play an integral role in sleep dysfunction after the onset of cognitive decline in individuals with dementia is unclear. To determine whether Aβ deposition in the brain is associated with subjective measures of sleep quality and cognition in elderly individuals with cognitive disorders. A nested survey study was conducted at the Cognitive Disorders and Comprehensive Alzheimer Disease Center of Thomas Jefferson University Hospital in Philadelphia, Pennsylvania. Participants included patients aged 65 years and older with cognitive disorders verified by neuropsychological testing. Eligible participants were identified from a referral center-based sample of patients who underwent fluorine 18-labeled florbetaben positron emission tomography imaging at Thomas Jefferson University Hospital as part of the multicenter Imaging Dementia-Evidence for Amyloid Scanning study. Data collection and analysis occurred between November 2018 and March 2019. Sleep quality was measured via responses to sleep questionnaires, Aβ deposition was measured via fluorine 18-labeled florbetaben positron emission tomography, and cognition was measured via Mini-Mental State Examination (MMSE) performance. Of the 67 eligible participants, 52 (77.6%) gave informed consent to participate in the study. Of the 52 enrolled participants (mean [SD] age, 76.6 [7.4] years), 27 (51.9%) were women. Daytime sleepiness was associated with Aβ deposition in the brainstem (B = 0.0063; 95% CI, 0.001 to 0.012; P = .02), but not MMSE performance (B = -0.01; 95% CI, -0.39 to 0.37; P = .96). The number of nocturnal awakenings was associated with Aβ deposition in the precuneus (B = 0.11; 95% CI, 0.06 to 0.17; P < .001) and poor MMSE performance (B = -2.13; 95% CI, -3.13 to -1.13; P < .001). Mediation analysis demonstrated an indirect association between Aβ deposition and poor MMSE performance that relied on nocturnal awakenings as an intermediary (B = -3.99; 95% CI, -7.88 to -0.83; P = .01). Nighttime sleep disruption may mediate the association between Aβ and cognitive impairment, suggesting that there is an underlying sleep-dependent mechanism that links Aβ burden in the brain to cognitive decline. Further elucidation of this mechanism may improve understanding of disease processes associated with Aβ accumulation.

Relationship between normal weight obesity and mild cognitive impairment is reflected in cognitive-related genes in human peripheral blood mononuclear cells.

Obesity contributes to the development of mild cognitive impairment, but the potential role of normal weight obesity in this disease has not been explored in humans. The aim of the study was to reveal the relationship between normal weight obesity and mild cognitive impairment in elderly individuals. This study consisted of 360 patients with amnestic mild cognitive impairment and 360 cognitively normal controls. Normal weight obesity was defined as having metabolic syndrome but a normal weight. Metabolic health meant having no metabolic syndrome. Reverse transcription quantitative real-time polymerase chain reaction was adopted to measure the messenger RNA expression of four cognitive-related genes (amyloid precursor protein, cyclic adenosine monophosphate-responsive element-binding protein 1, sortilin-related receptor 1, and synapsin I) in peripheral blood mononuclear cells. Normal weight obesity was related to a higher risk of amnestic mild cognitive impairment (odds ratio = 3.14, 95% confidence interval: 2.13-4.60). In the patients, the expression of each gene in the peripheral blood mononuclear cells was linearly related to Mini-Mental State Examination and Montreal Cognitive Assessment scores (P < 0.05). The expression of these genes in the patients with metabolic health deviated from the normal levels found in the controls (P < 0.05), and the deviations were more significant in the patients with normal weight obesity (P < 0.05). Normal weight obesity may be a potential risk factor for amnestic mild cognitive impairment in elderly. This relationship was reflected in the abnormal expression of several cognitive-related genes in peripheral blood mononuclear cells.

Disrupted Topologic Efficiency of White Matter Structural Connectome in Individuals with Subjective Cognitive Decline.

Purpose To determine whether individuals with subjective cognitive decline (SCD), which is defined by memory complaints with normal performance at objective neuropsychologic examinations, exhibit disruptions of white matter (WM) connectivity and topologic alterations of the brain structural connectome. Materials and Methods Diffusion-tensor magnetic resonance imaging and graph theory approaches were used to investigate the topologic organization of the brain structural connectome in 36 participants with SCD (21 women: mean age, 62.0 years ± 8.6 [standard deviation]; age range, 42-76 years; 15 men: mean age, 65.5 years ± 8.9; age range, 51-80 years) and 51 age-, sex-, and years of education-matched healthy control participants (33 women: mean age, 63.7 years ± 8.8; age range, 46-83 years; 18 men: mean age, 59.4 years ± 9.3; age range, 43-75 years). Individual WM networks were constructed for each participant, and the network properties between two groups were compared with a linear regression model. Results Graph theory analyses revealed that the participants with SCD had less global efficiency (P = .001) and local efficiency (P = .008) compared with the healthy control participants. Lower regional efficiency was mainly distributed in the bilateral prefrontal regions and left thalamus (P < .05, corrected). Furthermore, a disrupted subnetwork was observed that consisted of widespread anatomic connections (P < .05, corrected), which has the potential to discriminate individuals with SCD from control participants. Moreover, similar hub distributions and less connection strength between the hub regions (P = .023) were found in SCD. Importantly, diminished strength of the rich-club and local connections was correlated with the impaired memory performance in patients with SCD (rich-club connection: r = 0.43, P = .011; local connection: r = 0.36, P = .037). Conclusion This study demonstrated disrupted topologic efficiency of the brain's structural connectome in participants with SCD and provided potential connectome-based biomarkers for the early detection of cognitive impairment in elderly individuals. © RSNA, 2017 Online supplemental material is available for this article.

Plasma metabolic profiling of mild cognitive impairment and Alzheimer's disease using liquid chromatography/mass spectrometry.

Alzheimer's disease (AD) is the main cause of gradual cognitive impairment in elderly individuals. This highlights the need of obtaining biomarkers to identify features that are different among mild cognitive impairment (MCI), AD and cognitively normal (CN) individuals. Ultra-performance liquid chromatography (UPLC)/mass spectrometry (MS) was employed to find the metabolic changes in plasma samples obtained from AD, MCI and CN individuals. Based on principal component analysis (PCA), the metabolic differences among AD, MCI and CN subjects were identified. The PCA of UPLC/MS spectra indicated metabolic differences among AD, MCI and CN subjects. The peak intensities of progesterone, lysophos- phatidylcholines (LPCs), tryptophan, L-phenylalanine, dihydrosphingosine and phytosphingosine in the plasma of the MCI and AD subjects were significantly different from the CN subjects. Furthermore, the peak intensities of tryptophan, LPCs, dihydrosphingosine in the plasma of the AD subjects were significantly lower compared to the MCI subjects. Our data provide a link between metabolite imbalance and AD, and suggest that metabolomics can be used to reveal the early disease mechanisms occurred in the progression from CN to MCI and AD.

Relationship between cognitive impairment and apparent diffusion coefficient values from magnetic resonance-diffusion weighted imaging&amp;nbsp;in elderly hypertensive patients

BackgroundThe purpose of this study was to determine a new method for the early diagnosis and assessment of mild cognitive impairment in elderly individuals with hypertension. Elderly hypertensive patients with cognitive impairment were assessed by the Montreal Cognitive Assessment (MoCA) and Clinical Dementia Rating Assessment (CDR). Cognitive results were compared to apparent diffusion coefficient (ADC) values from magnetic resonance-diffusion weighted imaging.MethodsA total of 191 patients were categorized into four groups: a control group (normal cognition and no hypertension; n=20); a normal group (hypertension and normal cognition; n=33); an mild cognitive impairment group (n=80); and a vascular dementia group (n=58). The MoCA and CDR tests were used to determine cognition. ADC values in eight brain regions were calculated with magnetic resonance-diffusion weighted imaging. Other characteristics were evaluated, eg, blood pressure, MoCA, and CDR scores, and the comparisons of the four groups were made.ResultsThe MoCA and CDR scores differed among the four groups (P<0.001). Systolic and diastolic blood pressure values increased as cognitive function declined (P<0.001). Cognitive function declined as ADC values increased, and they differed between elderly people with and without hypertension (P<0.001). Among elderly hypertensive participants, ADC values were significantly increased in the cortex and hippocampus.ConclusionThe MoCA and CDR tests were sufficiently sensitive to evaluate cognition. Blood pressure was closely related to cognition, as well as to functional and structural changes in the brain. These alterations were evidenced through changes in the ADC values and were most obvious in the cortex and hippocampus. Greater cognitive decline was observed in elderly participants with hypertension compared to those without. As hypertensive stage increased, greater ADC values were observed.

Protective effect of senegenin on splenectomy-induced postoperative cognitive dysfunction in elderly rats.

Postoperative cognitive dysfunction (POCD) is common in elderly patients. Senegenin, an active component of extracts from Polygala tenuifolia root, a traditional Chinese medicine, has neuroprotective and neuroregenerative effects. However, the mechanism underlying the effects of senegenin against postoperative cognitive impairment in elderly individuals has yet to be elucidated. The aim of this study was to investigate the protective effects of senegenin on the cognitive functions of elderly rats with splenectomy-induced POCD. Results from a Morris water maze test suggested that splenectomy induced a transient cognitive deficiency in the elderly rats; however, when the rats were treated with senegenin, the cognitive impairment was notably attenuated. Further experiments showed that senegenin significantly inhibited the mRNA and protein expression of several key pro-inflammatory cytokines, specifically, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6 and IL-8, in the hippocampal tissues of elderly rats following splenectomy. In order to investigate the molecular mechanism involved, the expression and activity of the Toll-like receptor 4 (TLR4) signaling pathway was assessed. On day 1 postoperatively, it was observed that senegenin markedly suppressed the mRNA and protein expression of TLR4, myeloid differentiation factor 88 (MyD88) and TIR domain-containing adaptor-inducing interferon-β (TRIF). Furthermore, the phosphorylation levels of nuclear factor-κB (NF-κB) p65 and inhibitor of NF-κB (IκBα) were also decreased following senegenin treatment on the first day subsequent to surgery. These results suggest that senegenin suppressed splenectomy-induced transient cognitive impairment in elderly rats, possibly by downregulating two signaling pathways involved in inflammation, TLR4/MyD88/NF-κB and TLR4/TRIF/NF-κB, to further inhibit the expression of key pro-inflammatory cytokines, specifically, TNF-α, IL-1β, IL-6 and IL-8, and ultimately the neuroinflammation in the hippocampal tissues. In conclusion, the present study revealed that senegenin exhibited neuroprotective effects against splenectomy-induced transient cognitive impairment in elderly rats, which indicated that senegenin may be a promising agent for the treatment of POCD.

Relationship of changes in cognitive and depressive symptoms during antidepressant treatment of individuals with geriatric depression and their relationship to the APOE epsilon 4 allele.

BackgroundCo-occurring cognitive impairment in geriatric depression may not improve with antidepressant treatment and it may progress to dementia.AimAssess the relationship between changes in cognitive and depressive symptoms among patients with geriatric depression and their association with the APOE epsilon 4 allele before and after antidepressant treatment.MethodsThe presence of the APOE epsilon 4 allele was assessed in 64 incident cases of geriatric depression and 31 elderly individuals without depression and the Geriatric Depression Scale (GDS), Mini-Mental State Examination (MMSE), digit span test, and Trail Making Tests A and B (TMT-A, TMT-B) were administered to these subjects at baseline and 12 months after baseline, during which time the depressed group received standardized treatment with selective serotonin reuptake inhibitors (SSRIs).ResultsPrior to treatment patients with geriatric depression had significantly worse cognitive functioning than control subjects and 31 (48%) met criteria for mild cognitive impairment (MCI). After treatment depressed patients with and without comorbid MCI both had significant improvements in their depressive and cognitive symptoms, but those with MCI had more residual symptoms. The severity of cognitive symptoms was not associated with the severity of depressive symptoms at baseline, but they were positively correlated at the 12-month follow-up. The APOE epsilon 4 allele was identified in 14% (9/64) of the patients and in 3% (1/31) of the controls (Fisher's Exact Test, p=0.158). Compared to depressed patients without the allele, depressed patients with the allele had more severe cognitive deficits both before and after treatment, though only some of these differences were statistically significant.ConclusionsThere is substantial cognitive impairment in elderly individuals with geriatric depression. Both the depressive and cognitive symptoms improve with standard SSRI treatment, but individuals with comorbid MCI have more residual depressive and cognitive symptoms after treatment. The APOE epsilon 4 allele is associated with greater cognitive impairment in geriatric depressed patients and may be associated with less responsiveness of cognitive symptoms to antidepressant treatment.