Degree Of Cognitive Decline Research Articles

The Post-Anaesthesia N-acetylcysteine Cognitive Evaluation (PANACEA) trial: study protocol for a randomised controlled trial.

BackgroundSome degree of cognitive decline after surgery occurs in as many as one quarter of elderly surgical patients, and this decline is associated with increased morbidity and mortality. Cognition may be affected across a range of domains, including memory, psychomotor skills, and executive function. Whilst the exact mechanisms of cognitive change after surgery are not precisely known, oxidative stress and subsequent neuroinflammation have been implicated. N-acetylcysteine (NAC) acts via multiple interrelated mechanisms to influence oxidative homeostasis, neuronal transmission, and inflammation. NAC has been shown to reduce oxidative stress and inflammation in both human and animal models. There is clinical evidence to suggest that NAC may be beneficial in preventing the cognitive decline associated with both acute physiological insults and dementia-related disorders. To date, no trials have examined perioperative NAC as a potential moderator of postoperative cognitive changes in the noncardiac surgery setting.Methods and designThis is a single-centre, randomised, double-blind, placebo-controlled clinical trial, with a between-group, repeated-measures, longitudinal design. The study will recruit 370 noncardiac surgical patients at the University Hospital Geelong, aged 60 years or older. Participants are randomly assigned to receive either NAC or placebo (1:1 ratio), and groups are stratified by age and surgery type. Participants undergo a series of neuropsychological tests prior to surgery, 7 days, 3 months, and 12 months post surgery. It is hypothesised that the perioperative administration of NAC will reduce the degree of postoperative cognitive changes at early and long-term follow-up, as measured by changes on individual measures of the neurocognitive battery, when compared with placebo. Serum samples are taken on the day of surgery and on day 2 post surgery to quantitate any changes in levels of biomarkers of inflammation and oxidative stress.DiscussionThe PANACEA trial aims to examine the potential efficacy of perioperative NAC to reduce the severity of postoperative cognitive dysfunction in an elderly, noncardiac surgery population. This is an entirely novel approach to the prevention of postoperative cognitive dysfunction and will have high impact and translatable outcomes if NAC is found to be beneficial.Trial registrationThe PANACEA trial has been registered with the Therapeutic Goods Administration, and the Australian New Zealand Clinical Trials Registry: ACTRN12614000411640; registered on 15 April 2014. Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-016-1529-4) contains supplementary material, which is available to authorized users.

CONGESTIVE HEART FAILURE, GENDER, AND RISK OF DEMENTIA IN A LARGE DIVERSE COHORT

Congestive heart failure (CHF) impacts 10% of individuals over age 65 and is the leading cause of hospitalization in the elderly population. 47% of patients hospitalized for CHF have some degree of cognitive decline. There is some evidence that CHF increases risk of dementia but this has not been well studied longitudinally in both men and women and in ethnoracial minority groups. We conducted a prospective cohort study of 499844 health plan members, who were aged > 60 years as of January 1st 2002 without any diagnoses of dementia. CHF was collected from the medical record between 1996-2001. Patients were followed for diagnoses of Alzheimer disease, vascular dementia and general dementia between 2002-2014. The association between CHF and risk of dementia was evaluated with Cox proportional hazards models overall and stratified by gender with censoring for death and health plan membership coverage. Multivariable adjusted models include age, race, stroke and diabetes. The cohort had a mean age of 71 years at baseline, 54.7% female, 68.0% White, 5.5% Black, 6.5% Hispanic and 9.0% Asian, and 36,506 (7.3%) had CHF. 59,127 individuals (11.8 %) were diagnosed with dementia during an average follow-up time of 8.2 years. Overall, CHF was associated with a more than 100% increase in dementia risk; unadjusted hazard ratio (HR) =2.24, 95% confidence intervals (CI) 2.1,2.3, Males: HR=2.21; 95 % CI 2.2, 2.3; Females: HR=2.3, 95% CI 2.3,2.4. After multivariable adjustment for age, race, and diabetes the risk of dementia is 20% increased (HR=1.2 with 95% CI:1.17,1.24), for females only an 18% increased risk of dementia (HR:1.18, 95% CI:1.13,1.22), males only a 25% increased risk of dementia (HR 1.25, 95% CI:1.20,1.31). This study shows an elevated longitudinal risk of dementia associated with CHF in a large diverse sample. CHF increased risk of dementia slightly more for women than men but this changed to a higher risk for men after adjustment of diabetes and stroke. Further research is warranted whether this gender difference is due to selective survival and/or competing risk with gender differences in cardiovascular mortality.

Progression of Dementia Assessed by Temporal Correlations of Physical Activity: Results From a 3.5-Year, Longitudinal Randomized Controlled Trial.

Cross-sectional studies show that activity fluctuations in healthy young adults possess robust temporal correlations that become altered with aging, and in dementia and depression. This study was designed to test whether or not within-subject changes of activity correlations (i) track the clinical progression of dementia, (ii) reflect the alterations of depression symptoms in patients with dementia, and (iii) can be manipulated by clinical interventions aimed at stabilizing circadian rhythmicity and improving sleep in dementia, namely timed bright light therapy and melatonin supplementation. We examined 144 patients with dementia (70–96 years old) who were assigned to daily treatment with bright light, bedtime melatonin, both or placebos only in a 3.5-year double-blinded randomized clinical trial. We found that activity correlations at temporal scales <~2 hours significantly decreased over time and that light treatment attenuated the decrease by ~73%. Moreover, the decrease of temporal activity correlations positively correlated with the degrees of cognitive decline and worsening of mood though the associations were relatively weak. These results suggest a mechanistic link between multiscale activity regulation and circadian/sleep function in dementia patients. Whether temporal activity patterns allow unobtrusive, long-term monitoring of dementia progression and mood changes is worth further investigation.

Nutritional status of elderly and its association with the degree of cognitive decline

s / Clinical Nutrition ESPEN 13 (2016) e55ee74 e64 Materials and methods: In 699 healthy adults (436 women, 273 men) of 18 to 75 years old weight, height, body circumferences and body skinfolds measurements were obtained. Five simple noninvasive models estimating %TBF were examined, based on the mentioned measurements. Dual Xenergy Absorptiometry (DXA) was the reference method. The validity and reliability of each method was determined with Bland Altman Test and Intraclass Correlation Coefficient. Results: Mean %BFDXA was 35.2% and 22.9% for women and men respectively. Waist circumference was found to correlate with %BFDXA more than any other anthropometric measurement, both for women (r1⁄40.794, p<0.01) and men (r1⁄40.826, p<0.01). Regarding the evaluated models, % BFDEURENBERG was found to have a relative low bias (0.04%, p1⁄40.831 and limits of agreement1⁄4± 10.78) and high reliability (ІCC1⁄40.919). Conclusions: Among the five simple noninvasive models, only the one of Deurenberg et al, was found to be valid and reliable in estimating %BF. Development of noninvasive and low cost models estimating body composition customized for Greek population is considered to be necessary. Furthermore, the results of this study suggest the use of waist circumference in such models. NUTRITIONAL STATUS OF ELDERLY AND ITS ASSOCIATION WITH THE DEGREE OF COGNITIVE DECLINE Angeliki Morari , Constantinos Stevis , Charalambos Neocleous , Constantinos Giaginis . Department of Food Science and Nutrition, School of Environment, University of Aegean, Lemnos, Greece; Nursing Department, School of Health Sciences, Cyprus University of

Cortical phosphorylated α-Synuclein levels correlate with brain wave spectra in Parkinson's disease.

Quantitative EEG features have been identified as surrogates and predictors of cognitive decline/dementia, a common feature of progressive PD. The biochemical correlates for altered quantitative EEG features are unknown. Our primary objective was to test the hypothesis that quantitative EEG measures correlate with cortical levels of phosphorylated α-synuclein, a modified form of the synaptic protein α-synuclein, in PD cases, in contrast to other pathology-associated proteins. A secondary objective was to explore the same correlations among cellular fractions of these proteins. We used posterior cingulate cortex autopsy tissue from 44 PD subjects with various degrees of cognitive decline, who had undergone EEG. In this brain region, which is a major hub of the default mode network, biochemical measurements for levels of phosphorylated α-synuclein, unmodified α-synuclein, amyloid beta peptide, phosphorylated tau, and key synaptic proteins were analyzed and data correlated with spectral EEG measures. Findings revealed significant correlations between background rhythm peak frequency and all bandpower values (highest in delta bandpower) with total phosphorylated α-synuclein, but not any correlation with total α-synuclein, phosphorylated tau protein, amyloid beta peptide, or synaptic proteins. Certain fractions of synaptosomal-associated protein 25 showed correlation with some quantitative EEG measures. These data show an association between increased phosphorylation of α-synuclein and the abnormal EEG signatures of cognitive decline. Results suggest that quantitative EEG may provide an in vivo approximation of phosphorylated α-synuclein in PD cortex. This adds to previous evidence that quantitative EEG measures can be considered valid biomarkers of PD cognitive decline. © 2016 International Parkinson and Movement Disorder Society.

Depression and mild cognitive impairment – Comorbidity and/or continuum?

IntroductionDepression and mild cognitive impairment are common among the elderly. Half the patients with late-life depression also present some degree of cognitive decline, making the distinction between these conditions difficult.ObjectivesTo conduct a database review in order to understand the relationship between these entities, and treatment approaches.AimsTo create and implement clinical guidelines at our institution, to evaluate and treat elderly patients presenting with depression and mild cognitive impairment.MethodsA PubMed database search using as keywords “late life depression”, “depression”; “cognitive impairment”; “mild cognitive impairment” and “dementia” between the year 2008 and 2015.ResultsLate-life depression and cognitive impairment are frequent among the elderly (10–20%). Depression is also common in the early stages of dementia decreasing as the cognitive decline progresses. The causal relationship between these entities is not well understood and some authors advocate a multifactorial model (genetic risk factors; neuroendocrine changes; vascular risk factors) and the cognitive impairment of said changes is dependent on the individual's cognitive reserve. Regarding treatment of depression in patients with cognitive impairment, most authors advocate a stepped approach with watchful waiting and then, if symptoms persist, the introduction of pharmacotherapy and psychosocial intervention.ConclusionsThe relationship between cognitive impairment and depression is still not clear and probably multifactorial. The diagnosis of depressive symptoms in patients with severe cognitive impairment can be difficult and most forms of pharmacological treatment in this population are not beneficial, making it important to carefully evaluate the benefits of introducing new medication.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Abstract WP428: Changes of Microstructural White Matter in Vascular Cognitive Disorder and Amnestic Mild Cognitive Impairment: a Diffusion Tensor Imaging Study

Background: White matter (WM) damage could be observed in both vascular cognitive disorder predementia (VCD-P) and amnestic mild cognitive impairment (aMCI). In the period of VCD-P, the degree of cognitive decline was similar to aMCI, but they are different in the specific cognitive domains. However whether the differences in cognitive domains are related to the pattern of WM impairment hasn’t been illustrated. Hypothesized: The region or degree of WM impairment differs from VCD-P to aMCI. Methods: All subjects include 28 patients with VCD-P, 34 aMCI and 39 normal controls (NC) underwent a comprehensive neuropsychological assessment and DTI. We compared fractional anisotropy (FA), mean diffusivity (MD) and axial diffusivity (AxD) of whole brain WM regions. Then the diffusion tensor was reconstructed, analyzed by tract-based spatial statistics. Results: Patient groups exhibited significant differences in FA, MD and AxD, the VCD-P group has a lower FA, higher MD and AxD. The different FA and MD region between VCD-P and aMCI was in left anterior limb of internal capsule, bilateral corona radiata, corpus callosum, cerebral peduncle, external capsule, posterior limb of internal capsule, fornix, inferior longitidinal fasciculus, inferior and superior fronto-occipital fasciculus, whereas in AxD it was showed in bilateral corona radiata, internal capsule, external capsule, corpus callosum, posterior thalamic radiation and superior longitudinal fasciculus. Conclusion: Our findings suggest that VCD-P and aMCI have divergent topography of WM microstructural changes in the degree and the region, the WM integrity was impaired more severe in VCD-P. The differences in regions may illustrate the clinical and neuropsychological features characterized by executive or memory deficit. These findings provide insights into the biological mechanism of cognitive disorders and highlight the potential of DTI as the imaging biomarker for diagnosis. All authors report no conflicts of interest. This work was supported by the National Natural Science Funds of China (Grant No. 81301188).

Microstructural white matter changes mediate age-related cognitive decline on the Montreal Cognitive Assessment (MoCA).

Although the relationship between aging and cognitive decline is well established, there is substantial individual variability in the degree of cognitive decline in older adults. The present study investigates whether variability in cognitive performance in community-dwelling older adults is related to the presence of whole brain or tract-specific changes in white matter microstructure. Specifically, we examine whether age-related decline in performance on the Montreal Cognitive Assessment (MoCA), a cognitive screening tool, is mediated by the white matter microstructural decline. We also examine if this relationship is driven by the presence of cardiovascular risk factors or variability in cerebral arterial pulsatility, an index of cardiovascular risk. Sixty-nine participants (aged 43-87) completed behavioral and MRI testing including T1 structural, T2-weighted FLAIR, and diffusion-weighted imaging (DWI) sequences. Measures of white matter microstructure were calculated using diffusion tensor imaging analyses on the DWI sequence. Multiple linear regression revealed that MoCA scores were predicted by radial diffusivity (RaD) of white matter beyond age or other cerebral measures. While increasing age and arterial pulsatility were associated with increasing RaD, these factors did not mediate the relationship between total white matter RaD and MoCA. Further, the relationship between MoCA and RaD was specific to participants who reported at least one cardiovascular risk factor. These findings highlight the importance of cardiovascular risk factors in the presentation of cognitive decline in old age. Further work is needed to establish whether medical or lifestyle management of these risk factors can prevent or reverse cognitive decline in old age.

CSF tau correlates with CJD disease severity and cognitive decline

Creutzfeldt-Jakob disease (CJD) is the most common prion disease in humans. The clinical diagnosis of CJD is supported by a combination of electroencephalogram, MRI, and the presence in the CSF of biomarkers. CSF tau is a marker for neuronal damage and tangle pathology, and is correlated with cognitive status in Alzheimer's disease (AD). The aim of this study was to test whether tau levels in the CSF also correlate with the degree of the neurological deficit and cognitive decline in patients with CJD as reflected by various clinical scales that assess disease severity and cognitive performance. Consecutive patients with familial CJD (fCJD) were examined by a neurologist who performed several tests including minimental status examination (MMSE), frontal assessment battery (FAB), NIH stroke scale (NIHSS), CJD neurological scale (CJD-NS), and the expanded disability status scale (EDSS). CSF tau was tested as part of the workout, and the correlation was tested using Pearson correlation. Fifty-two patients with fCJD were recruited to the study (35 males, mean age 59.4±5.7, range 48-75years). A significant negative correlation was found between CSF tau levels and the cognitive performance of the patients as reflected by their MMSE and FAB scores. In addition, a significant positive correlation was found between tau levels and the clinical disease severity scales of CJD-NS, NIHSS, and EDSS. The correlation between tau levels and the disease severity and degree of cognitive decline in patients with fCJD suggests that tau can be a biomarker reflecting the extent of neuronal damage.

Validity and reliability of the "Trail Making Peg" test as a performance measurement for evaluating the cognitive function

To investigate the validity and reliability of a novel performance test, called the "Trail Making Peg" (TMP) test, for evaluating the cognitive function. We recruited 632 community-dwelling older adults (mean age: 73.3±5.2 years) as subjects for the assessment of the validity of the test and 319 adults (mean age: 73.1±5.2 years) as subjects for the assessment of reliability. Five cognitive tests (5-Cog) were used to evaluate the cognitive function, and the degree of cognitive decline was delineated for subjects scoring below 1 SD from the mean 5-Cog score. A receiver operating characteristic analysis was employed to calculate the cut-off point. There were no sex differences in the TMP scores (P=0.951), and the TMP and 5-Cog scores were found to correlate significantly (r=-0.63) with each other. The Trail Making Peg test demonstrated an area under the curve of 0.855 for discriminating between non-cognitive decline and cognitive decline. At this cutoff point, the sensitivity was 85% and the specificity was 69%. The intraclass correlation coefficient of the TMP was 0.746. The TMP exhibits sufficient validity and reliability. Our results suggest that TMP is a useful screening test for detecting cognitive decline.

Arterial Stiffness Predicts Cognitive Decline in Japanese Community-dwelling Elderly Subjects: A One-year Follow-up Study.

The purpose of this study was to determine whether arterial stiffness can be used to predict one-year changes in the cognitive function in Japanese community-dwelling elderly subjects. A total of 103 Japanese community-dwelling elderly patients joined this study. Information regarding the age, height, weight, gender and past medical history of each participant was obtained. Additionally, arterial stiffness was determined according to the cardio-ankle vascular index (CAVI), and the cognitive function was assessed with the Mini-Mental State Examination (MMSE). One year later, we performed the MMSE in the same subjects. After dividing the cohort according to the 80th percentile of the CAVI (normal and arterial stiffness [AS] groups), we examined whether the degree of cognitive decline, as determined using the pre- and post-MMSE, was significantly different based on the severity of arterial stiffness, adjusted for age, BMI, gender and the pre-MMSE scores. Of the 103 subjects who participated in the pre-data collection, 74 (38 men and 36 women, 73.4±4.0 years) joined the post-data collection. We found a significant difference in the change in the post-MMSE scores between the normal and AS groups (pre-MMSE: normal group [27.4±2.1] and AS group [26.9±2.4] and post-MMSE: normal group [27.2±2.1] and AS group [25.5±2.3], F=5.95, p=0.02). For each domain of the MMSE, the changes in MMSE-attention-and-calculation (F=5.11, p=0.03) and MMSE-language (F=4.32, p=0.04) were significantly different according to an ANCOVA. We found that arterial stiffness predicts cognitive decline in Japanese community-dwelling elderly subjects regardless of the initial level of the global cognitive function. This finding indicates the potential use of the degree of arterial stiffness as an indicator for preventing or delaying the onset of dementia in the elderly.

Failure of perivascular drainage of β-amyloid in cerebral amyloid angiopathy.

In Alzheimer's disease, amyloid-β (Aβ) accumulates as insoluble plaques in the brain and deposits in blood vessel walls as cerebral amyloid angiopathy (CAA). The severity of CAA correlates with the degree of cognitive decline in dementia. The distribution of Aβ in the walls of capillaries and arteries in CAA suggests that Aβ is deposited in the perivascular pathways by which interstitial fluid drains from the brain. Soluble Aβ from the extracellular spaces of gray matter enters the basement membranes of capillaries and drains along the arterial basement membranes that surround smooth muscle cells toward the leptomeningeal arteries. The motive force for perivascular drainage is derived from arterial pulsations combined with the valve effect of proteins present in the arterial basement membranes. Physical and biochemical changes associated with arteriosclerosis, aging and possession of apolipoprotein E4 genotype lead to a failure of perivascular drainage of soluble proteins, including Aβ. Perivascular cells associated with arteries and the lymphocytes recruited in the perivenous spaces contribute to the clearance of Aβ. The failure of perivascular clearance of Aβ may be a major factor in the accumulation of Aβ in CAA and may have significant implications for the design of therapeutics for the treatment of Alzheimer's disease.

Identification of p.Gln858* in ATP13A2 in two EOPD patients and presentation of their clinical features

We present results of homozygosity mapping in two siblings affected with early onset Parkinson's disease (EOPD) and mutation screening of ATP13A2 in these and other Iranian EOPD patients. Genome-wide SNP homozygosity analysis revealed linkage to a locus that included ATP13A2, and sequencing of the gene revealed a novel p.Gln858*-causing mutation in the homozygous state in the siblings. Sequencing of the gene in seven other unrelated EOPD patients previously shown not to have mutations in PRKN, DJ-1, PINK1, and LRRK2 identified the same homozygous p. Gln858*-causing mutation in another patient. Haplotype analysis revealed that two alleles harboring the mutation were not identical by decent. The variation identified represents the13th known disease causing mutation in ATP13A2. The clinical features of the patients who harbored the mutation are compared to those of previously reported patients with mutations in ATP13A2. Bradykinesia and rigidity, but not tremor, were reported in nearly all the patients. l-dopa administration, though initially effective, usually caused dyskinesia upon prolonged usage. Eye movement abnormalities including saccades and supranuclear gaze palsy, were almost always observed. Dystonia and bulbar anomalies were common but more variable manifestations. Although a degree of cognitive decline was found in most of the patients, the decline was often mild and absent in one patient. Age at onset of symptoms was usually in the second decade of life, and sometimes in the third decade.

Non-high-density lipoprotein cholesterol and other risk factors of mild cognitive impairment among Chinese type 2 diabetic patients

ObjectiveTo identify some risk factors of MCI among patients with type 2 diabetes(T2DM) and to find if there is any correlation between these factors and the degree of cognitive decline. MethodsA total of 155 patients with T2DM referred to the Department of Endocrinology at First Hospital of Qinhuangdao were enrolled. To assess MCI the Montreal Cognitive Assessment (MoCA) scoring system was used. There were 66 patients with MCI and 89 patients without MCI (control). HbAlc, blood lipid, liver and renal functions were measured in all subjects. ResultsCompared with the control group, type 2 diabetic patients with MCI had a longer duration of diabetes; higher non-high-density lipoprotein cholesterol (non-HDL-C), triglycerides, total cholesterol, HbA1c, and BMI; and lower high-density lipoprotein cholesterol (HDL-C) (P<0.05). The rates of patients with a history of habitual light-to-moderate alcohol consumption, a high proportion of Mediterranean-type diet, and regular physical activity were lower; and the rate of current smoking was higher in type 2 diabetic patients with MCI than the control group (P<0.05). Among patients with MCI, the results indicated that MoCA score was negatively correlated with non-HDL-C (r=−0.761 P<0.001). ConclusionsOur results suggest that non-HDL-C can act as a readily available method for estimating risk of MCI in Chinese type 2 diabetic patient in routine clinical practice. Good lifestyle likely reduces MCI risk in diabetic patients.

Fixing Hearts and Protecting Minds

Ischemic heart disease is a significant cause of mortality and morbidity in Western populations. Consistent with this, coronary artery bypass graft (CABG) surgery remains one of the most frequently performed major surgeries. Improved survival rates mean that our research focus now extends beyond surgical technique to include quality of postoperative outcome. Postoperative cognitive dysfunction (POCD) has emerged as one of the most challenging and hotly debated issues, with increasing impetus to answer the unresolved question: does fixing the heart come at a cost to the brain? CABG surgery is associated with neurological events including stroke in 1.6%1 and delirium in 5.8%2 of patients. Beyond these severe and marked alterations to neurological function, there has been a widely held belief that CABG surgery is associated with POCD, which may presage a decline toward dementia. Research has been influenced by the 1995 Consensus Statement3 into the study of POCD in patients undergoing CABG surgery. Although the methods of investigation set forth by the Consensus Statement achieved widespread acknowledgment, its specific recommendations have not always been followed.4 Despite significant methodological issues, it seems that the balance of interpretation has historically been in favor of CABG surgery as a cause of significant POCD. More recently, however, a review of a series of publications from a well-controlled longitudinal cohort study conducted at Johns Hopkins5 and a meta-analysis6 suggested that cognition is in fact stable or may even show some improvement after CABG surgery in the majority of patients, at least within the first year (Figures 1 and 2). There is little doubt that POCD affects some patients in the short term, but the pathophysiological mechanisms underlying this and the influence on longer-term cognitive function remain uncertain. For research to progress, we require a paradigmatic shift in our focus from …

Multielectrode array analysis of cerebrospinal fluid in Alzheimer’s disease versus mild cognitive impairment: A potential diagnostic and treatment biomarker

Pathological cerebrospinal fluid (CSF) alterations like changes in amyloid-β1–42 and tau protein concentration are typical in Alzheimer’s disease (AD). However, it remains unclear, if the composition of known or unknown pathological factors in native CSF has a functional significance in AD. In this pilot study, we used multielectrode array (MEA) neurochips to determine whether CSF of individuals with AD (AD-CSF) may have distinct neurofunctional properties that may distinguish it from that of individuals with mild cognitive impairment (MCI) – a differential diagnosis of high clinical importance. MEAs are neuronal cultures coupled to a multisite electrical recording system with the ability to reflect pharmacological or toxicological alterations on the functional level of whole neuronal networks. Collective rhythmical electrical activity was substantially enhanced after exposure to CSF of cognitively healthy subjects (controls) and of MCI individuals (MCI-CSF) alike. However, this activity increment was significantly reduced when MEAs were exposed to AD-CSF compared to MCI-CSF. Moreover, following AD-CSF exposure, networks showed significantly enhanced burst durations and less synchronous bursting, respectively. Thus, AD-CSF and MCI-CSF could be distinguished by characteristic changes of the network firing pattern on MEAs. When data of MCI individuals and AD patients were pooled, the network suppression correlated significantly with the degree of cognitive decline. The findings of this pilot study may set the stage for a unique and straightforward diagnostic bioassay of AD with particular value in the differential diagnosis to MCI and as a much needed biomarker for clinical trials.

Cerebroprotective Effect of Preoperative Dual Antiplatelet Therapy in Patients Undergoing Coronary Bypass Surgery

Reduction of cognitive function is a possible side effect after coronary artery surgery using cardiopulmonary bypass (CPB). We investigated the effect of single versus dual antiplatelet therapy on cognitive performance in patients undergoing coronary artery bypass grafting (CABG) with CPB. 50 consecutive CABG patients with preoperative intake of aspirin were compared to 49 consecutive patients with aspirin and clopidogrel. Six neuropsychological subtests from the Syndrom Kurz Test and the Alzheimer's Disease Assessment Scale were performed preoperatively and on the third postoperative day. To assess the overall cognitive function and the degree of cognitive decline across all tests after surgery we combined the six test-scores by principal component analysis. Patients had a mean age of 66.1 ± 9.3 years, received a mean of 2.8 ± 1.0 bypasses within an average of 87 ± 31 minutes on cardiopulmonary bypass. These parameters as well as the preoperative combined neurocognitive score were not significantly different between the groups. After the operation there was a significant deterioration of the combined neuropsychological score in both groups (single: preop -0.2 ± 1.5 vs. postop -1.8 ± 1.7, p = 0.000 and dual: preop 0.2 ± 1.5 vs. postop -0.5 ± 2.1, p = 0.004). However, the patients operated under dual antiplatelet therapy showed a significant less decline of overall cognitive function compared to the single antiplatelet therapy patients (dual: 0.7 ± 1.5 vs single: 1.6 ± 1.6, p = 0.004). Dual antiplatelet therapy has a cerebroprotective effect in patients undergoing coronary artery bypass surgery. Compared to single antiplatelet therapy it reduces an early postoperative substantial decline of neuropsychological abilities.

Correlation of cognitive decline and behavioral changes in patients with presenile and senile onset Alzheimer’s disease

Alzheimer?s disease (AD), the most prevalent dementia, is characterized not only by cognitive but also behavioral changes that pose the heaviest burden to caregivers. Differences in the clinical picture depending on the time of disease onset have been observed. We correlated cognitive and behavioral deficits in patients with presenile- and senile-onset AD to explore the differences. We tested 60 AD patients, 19 male and 41 female, mean age 65.2 years with the Dementia Behavior Disturbance Scale (DBD) and a standard neuropsychological battery. The patients were divided according to their DBD score into two groups: group I - score 0-2 (n=24; 40%), group II - score 3? (n=36; 60%), comparable in disease duration and neurological findings. The cognitive scores were significantly higher in the group with less behavioral changes than in the group with more behavioral changes: Mini Mental State Examination score (p=0.0015), serial subtraction (p=0.0009), block design (p=0.0049), copy of complex figure (p=0.0125), complex visual organization (p=0.0099), divided attention, visual memory and speech comprehension. A significantly higher frequency of behavioral disturbances was registered in patients with senile onset than in the presenile-onset group (p&lt;0.005). There were no sex differences. Our data show a correlation between cognitive decline and behavioral changes in late onset AD patients, indicating that more behavioral disturbances were associated with a more severe degree of cognitive decline, especially in non-verbal functions and attention deficits, compared to early onset patients.

Effect of Different Pump Heads for CPB on Early Cognitive Outcome after Coronary Artery Bypass Surgery

Reduction of cognitive function is a possible side effect after coronary artery surgery using cardiopulmonary bypass (CPB). We investigated the effect of roller versus centrifugal pumps for CPB on cognitive performance in patients undergoing coronary artery bypass grafting (CABG). 50 consecutive CABG patients operated with centrifugal pump were compared to 50 roller pump patients matched for age and duration of CPB. Six neuropsychological subtests from the Syndrom Kurz Test and the Alzheimer's Disease Assessment Scale were performed preoperatively and on the third postoperative day in a double blind fashion. To assess the overall cognitive function and the degree of cognitive decline across all tests after surgery we combined the six test-scores by principal component analysis. Patients with a mean age of 63.9±8.4 years received a mean of 3.0±0.9 bypasses within an average of 80.6±20.7 mins on CPB. These parameters as well as the preoperative combined neurocognitive score were not significantly different between the groups. After the operation there was a significant deterioration of the combined neuropsychological score in both groups (centrifugal: preop 0.41±2.49 vs.postop -2.86±2.70, p <0.0005 and roller: preop -0.41±2.35 vs. postop -2.73±3.16, p <0.0005). However, the patients operated with a centrifugal pump had a significantly greater decline of overall cognitive function compared to the roller pump patients(3.3±1.7 vs. 2.3±2.7, p = 0.04). Roller pumps have a less cerebro-damaging effect than centrifugal pumps since they lead to a smaller postoperative decline of neuropsychological abilities in coronary bypass patients.

Spreading of Neurodegenerative Pathology via Neuron-to-Neuron Transmission of -Amyloid

Alzheimer's disease (AD) is the major cause of dementia. During the development of AD, neurofibrillary tangles progress in a fixed pattern, starting in the transentorhinal cortex followed by the hippocampus and cortical areas. In contrast, the deposition of β-amyloid (Aβ) plaques, which are the other histological hallmark of AD, does not follow the same strict spatiotemporal pattern, and it correlates poorly with cognitive decline. Instead, soluble Aβ oligomers have received increasing attention as probable inducers of pathogenesis. In this study, we use microinjections into electrophysiologically defined primary hippocampal rat neurons to demonstrate the direct neuron-to-neuron transfer of soluble oligomeric Aβ. Additional studies conducted in a human donor-acceptor cell model show that this Aβ transfer depends on direct cellular connections. As the transferred oligomers accumulate, acceptor cells gradually show beading of tubulin, a sign of neurite damage, and gradual endosomal leakage, a sign of cytotoxicity. These observations support that intracellular Aβ oligomers play a role in neurodegeneration, and they explain the manner in which Aβ can drive disease progression, even if the extracellular plaque load is poorly correlated with the degree of cognitive decline. Understanding this phenomenon sheds light on the pathophysiological mechanism of AD progression. Additional elucidation will help uncover the detailed mechanisms responsible for the manner in which AD progresses via anatomical connections and will facilitate the development of new strategies for stopping the progression of this incapacitating disease.