Graph analysis of verbal fluency test discriminate between patients with Alzheimer’s disease, Mild Cognitive Impairment and normal elderly controls

Verbal fluency is the ability to produce a satisfying sequence of spoken words during a given time interval. The core of verbal fluency lies in the capacity to manage the executive aspects of language. The standard scores of the semantic verbal fluency test are broadly used in the neuropsychological assessment of the elderly, and different analytical methods are likely to extract even more information from the data generated in this test. Graph theory, a mathematical approach to analyze relations between items, represents a promising tool to understand a variety of neuropsychological states. This study reports a graph analysis of data generated by the semantic verbal fluency test by cognitively healthy elderly (NC), patients with Mild Cognitive Impairment – subtypes amnestic(aMCI) and amnestic multiple domain (a+mdMCI) - and patients with Alzheimer’s disease (AD). Sequences of words were represented as a speech graph in which every word corresponded to a node and temporal links between words were represented by directed edges. To characterize the structure of the data we calculated 13 speech graph attributes (SGAs). The individuals were compared when divided in three (NC – MCI – AD) and four (NC – aMCI – a+mdMCI – AD) groups. When the three groups were compared, significant differences were found in the standard measure of correct words produced, and three SGA: diameter, average shortest path, and network density. SGA sorted the elderly groups with good specificity and sensitivity. When the four groups were compared, the groups differed significantly in network density, except between the two MCI subtypes and NC and aMCI. The diameter of the network and the average shortest path were significantly different between the NC and AD, and between aMCI and AD. SGA sorted the elderly in their groups with good specificity and sensitivity, performing better than the standard score of the task. These findings provide support for a new methodological frame to assess the strength of semantic memory through the verbal fluency task, with potential to amplify the predictive power of this test. Graph analysis is likely to become clinically relevant in neurology and psychiatry, and may be particularly useful for the differential diagnosis of the elderly.

Caregivers' experiences and coping strategies relating to patient's subjective treatment-related cognitive impairment following Haematopoietic Stem Cell Transplant (HSCT)

The treatments involved in cancers of the blood and bone marrow can be physically and psychologically challenging and be associated with adverse secondary effects, including cognitive impairment. The incidence and severity of treatment-related cognitive impairment varies widely, however it can significantly impact quality of life by interfering with patients’ activities of daily living, relationships and future plans. It can also pose challenges for the patients’ caregivers, an area which has received comparatively less research attention. The aim of this study was to investigate caregivers’ experiences of treatment-related cognitive impairment in patients who have undergone Haematopoietic Stem Cell Transplant (HSCT); how they coped, both practically and emotionally, and what supports they believe could help them. Participants were caregivers to individuals who had undergone HSCT within the past 20 years and who had reported cognitive changes at the HSCT Late Effects Clinic, Beatson West of Scotland Cancer Centre. Five participants completed a single semi-structured interview. The data was then analysed using Interpretative Phenomenological Analysis (IPA). Results of this analysis illustrated four super-ordinate themes: noticing change; managing expectations, managing personal feelings and commitment. Findings from the current study highlighted the importance of caregiver education regarding post HSCT cognitive and behavioural changes and providing caregiver emotional support. Future research should explore the mutual needs of both care recipient and caregiver.

Time perception in mild cognitive impairment: Interval length and subjective passage of time

Objectives: Patients with mild cognitive impairment (MCI) may have difficulties in time perception, which in turn might contribute to some of their symptoms, especially memory deficits. The aim of this study was to evaluate perception of interval length and subjective passage of time in MCI patients as compared to healthy controls. Methods: Fifty-five MCI patients and 57 healthy controls underwent an experimental protocol for time perception on interval length, a questionnaire for the subjective passage of time and a neuropsychological evaluation. Results: MCI patients presented no changes in the perception of interval length. However, for MCI patients, time seemed to pass more slowly than it did for controls. This experience was significantly correlated with memory deficits but not with performance in executive tests, nor with complaints of depression or anxiety. Conclusions: Memory deficits do not affect the perception of interval length, but are associated with alterations in the subjective passage of time.

Delay discounting in mild cognitive impairment

Introduction : Patients with mild cognitive impairme nt (MCI) may make suboptimal decisions particularly in complex situations, and thi s could be due to temporal discounting, the tendency to prefer immediate rewards over delayed but larger rewards. The present study proposes to evaluate intertemporal prefere nces in MCI patients as compared to healthy controls. Method : Fifty-five patients with MCI and 57 h ealthy controls underwent neuropsy- chological evaluation and a delay discounting questionnaire, which evaluates three para- meters: hyperbolic discounting ( k ), the percentage of choices for delayed and later rewards (%LL), and response consistency (Acc). Results : No significant differences were found in the delay discounting questionnaire between MC I patients and controls for the three reward sizes considered, small, medium, and large, using both k and %LL parameters. There were also no differences in the response consistency, Acc, between the two groups. Conclusions : Patients with MCI perform similarly to healthy controls in a delay discounting task. Memory deficits do not notably affect intertemporal preferences.

Mild cognitive impairment

Abstract Mild Cognitive Impairment (MCI) is a disease between normal cognitive ageing and dementia. In recent years the term MCI has been recognized as a pre-dementia state, raising an important subject for investigation in the prevention of dementia. There are various terms related to pre-dementia MCI, such as isolated memory complaint and pre-Alzheimer’s disease; most of them do not comprise all the areas related to MCI. A central cholinergic deficit is present in amnestic MCI with neuronal loss in the Meynert basal nucleus. It is estimated that the rate of progression to dementia is about 10% every year. The prevalence of MCI is 10%-11% and the risk of progression to dementia is about 5%-16%. The continual development of pharmacologic approaches to modify and delay the natural history of progression of the disease motivates a great interest in an earlier diagnosis.

Spoken Language in Hearing Impairment Children with Digital Hearing-Aid or Cochlear Implant: Grammatical Strenghts and Weaknesses

In this study, semi spontaneous samples of spoken language are analysed. Participants are 30 children with severe or profound deafness who employ digital hearing-aid or cochlear implant. The main goal is to find out the strengths and weaknesses of their grammatical skills in order to employ that information in dessigning speech therapy programs.

The Influence of Neurocognitive Impairment, Alcohol and other Drug (AOD) Use, and Psychosocial Factors on Antiretroviral Treatment Adherence, Service Utilization and Viral Load Among HIV-Seropositive Adults

Among people living with HIV (PLWH), adherence to antiretroviral therapy (ART) can be affected by problems of neurocognitive (NC) impairment, stress, alcohol and other drug (AOD) abuse, and other barriers. The aims of this research were to: (1) examine factors associated with NC impairment, (2) explore relationships between psychosocial variables with ART adherence and viral load (VL), and (3) evaluate the efficacy of an evidence-based intervention in improving ART adherence, increasing service utilization, and decreasing VL. The first study (n=370) was cross sectional and used structural equation modeling to test whether AOD use, years living with HIV, and time from HIV diagnosis to seeking care were associated with poorer NC functioning. The second study (n=246) used similar methods to test the hypothesis that stress, barriers to adherence, NC impairment, poor social support, and AOD use were related to lower VL mediated by ART adherence. The third study (n=243) evaluated an evidence-based, eight-session program to improve ART adherence, reduce VL, and increase service utilization in a randomized controlled trial. Study participants were PLWH living in South Florida, 18 to 60 years old, with a history of alcohol abuse enrolled from January 2009 through November 2012. Secondary analysis of available data showed: (1) scores on interference with executive functioning increased by 0.32 for each day of marijuana use and 1.18 for each year living with HIV, but no association was found between alcohol use and NC functioning; (2) each barrier to adherence was associated with a 10% decrease in adherence to ART and a 0.42 unit increase in VL (log10) and the relationship between barriers and VL was partially mediated by ART adherence; (3) participants in the evidence-based program were more likely than the comparison group to report an undetectable VL (OR=2.25, p Psychosocial factors affect VL, but ART adherence is essential in achieving an undetectable VL in PLWH.

Targeting microRNAs involved in the BDNF signaling impairment in neurodegenerative diseases

Neurodegenerative diseases are becoming an ever-increasing problem in aging populations. Low levels of brain-derived neurotrophic factor (BDNF) have previously been associated with the pathogenesis of numerous neurodegenerative diseases. Recently, microRNAs (miRNAs) have been proposed as potential novel therapeutic targets for treating various diseases of the central nervous system (CNS), and interestingly, few studies have reported several miRNAs that downregulate the expression levels of BDNF. However, substantial challenges exist when attempting to translate these findings into practical anti-miRNA therapeutics, especially when the targets remain inside the CNS. Thus, in this review, we summarize the specific molecular mechanisms by which several miRNAs negatively modulate the expressions of BDNF, address the potential clinical difficulties that can be faced during the development of anti-miRNA-based therapeutics and propose strategies to overcome these challenges.

Peripheral brain-derived neurotrophic factor levels in alzheimer's disease and mild cognitive impairment: A comprehensive systematic review and meta-analysis

Alzheimer's disease (AD) is becoming a growing global problem, and there is an urgent need to identify reliable blood biomarkers of the risk and progression of this condition. A potential candidate is the brain-derived neurotrophic factor (BDNF), which modulates major trophic effects in the brain. However, findings are apparently inconsistent regarding peripheral blood BDNF levels in AD patients vs. healthy people. We thus performed a systematic review and meta-analysis of the studies that have examined peripheral BDNF levels in patients with AD or mild cognitive impairment (MCI) and healthy controls. We searched articles through PubMed, EMBASE, and hand searching. Over a total pool of 2061 potential articles, 26 met all inclusion criteria (including a total of 1584 AD patients, 556 MCI patients, and 1294 controls). A meta-analysis of BDNF levels between early AD and controls showed statistically significantly higher levels (SMD [95 % CI]: 0.72 [0.31, 1.13]) with no heterogeneity. AD patients with a low (<20) mini-mental state examination (MMSE) score had lower peripheral BDNF levels compared with controls (SMD [95 % CI]: -0.33 [-0.60, -0.05]). However, we found no statistically significant difference in blood (serum/plasma) BDNF levels between all AD patients and controls (standard mean difference, SMD [95 % CI]: -0.16 [-0.4, 0.07]), and there was heterogeneity among studies (P < 0.0001, I 2 = 85.8 %). There were no differences in blood BDNF levels among AD or MCI patients vs. controls by subgroup analyses according to age, sex, and drug use. In conclusion, this meta-analysis shows that peripheral blood BDNF levels seem to be increased in early AD and decreased in AD patients with low MMSE scores respectively compared with their age- and sex-matched healthy referents. At present, however, this could not be concluded from individual studies.

A qualitative impairment in face perception in Alzheimer’s disease : evidence from a reduced face inversion effect

Prevalent face recognition difficulties in Alzheimer’s disease (AD) have typically been attributed to the underlying episodic and semantic memory impairment. The aim of the current study was to determine if AD patients are also impaired at the perceptual level for faces, more specifically at extracting a visual representation of an individual face. To address this question, we investigated the matching of simultaneously presented individual faces and of other nonface familiar shapes (cars), at both upright and inverted orientation, in a group of mild AD patients and in a group of healthy older controls matched for age and education. AD patients showed a reduced inversion effect (i.e., larger performance for upright than inverted stimuli) for faces, but not for cars, both in terms of error rates and response times. While healthy participants showed a much larger decrease in performance for faces than for cars with inversion, the inversion effect did not differ significantly for faces and cars in AD. This abnormal inversion effect for faces was observed in a large subset of individual patients with AD. These results suggest that AD patients have deficits in higher-level visual processes, more specifically at perceiving individual faces, a function that relies on holistic representations specific to upright face stimuli. These deficits, combined with their memory impairment, may contribute to the difficulties in recognizing familiar people that are often reported in patients suffering from the disease and by their caregivers.

Memory for public events in mild cognitive impairment and Alzheimer’s disease : the importance of rehearsal

Ribot’s law refers to the better preservation of remote memories compared with recent ones that presumably characterizes retrograde amnesia. Even if Ribot-type temporal gradient has been extensively studied in retrograde amnesia, particularly in Alzheimer’s disease (AD), this pattern has not been consistently found. One explanation for these results may be that rehearsal frequency rather than remoteness accounts for the better preservation of these memories. Thus, the aim of present study was to address this question by studying retrograde semantic memory in subjects with amnestic mild cognitive impairment (aMCI) (n = 20), mild AD (n = 20) and in healthy older controls (HC; n = 19). In order to evaluate the impact of repetition as well as the impact of remoteness, we used a test assessing memory for enduring and transient public events that occurred in the recent and remote past. Results show no clear temporal gradient across time periods (1960–1975; 1976–1990; 1991–2005; 2006–2011), but a better performance was observed in all three groups for enduring compared with transient events. Moreover, although deficits were globally found in both patients groups compared with HC, more specific analyses revealed that aMCI patients were only impaired on transient events while AD patients were impaired on both transient and enduring events. Exploratory analyses also revealed a tendency suggesting preservation of remote transient events in aMCI. These findings are discussed with regards to memory consolidation models.

An investigation into the utility of the Mini Addenbrooke's Cognitive Examination (M-ACE) for the early detection of dementia and mild cognitive impairment in people aged 75 and over

Background/Aims: The Mini Addenbrooke’s Cognitive Examination (M-ACE) is the abbreviated version of the widely-used Addenbrooke’s Cognitive Examination (ACE-III), a cognitive screening tool that is used internationally in the assessment of mild cognitive impairment (MCI) and dementia. The objectives of this study were to investigate the diagnostic accuracy of the M-ACE with individuals aged 75 and over to distinguish between those who do and do not have a dementia or MCI, and also to establish whether the cut-off scores recommended by Hsieh et al. (2014) [9] in the original validation study for the M-ACE are optimal for this age group. Methods: The M-ACE was administered to 58 participants (24 with a diagnosis of dementia, 17 with a diagnosis of MCI and 17 healthy controls). The extent to which scores distinguished between groups (dementia, MCI or no diagnosis) was explored using receiver operating characteristic curve analysis. Results: The optimal cut-off for detecting dementia was ≤ 21/30 (score ≤ 21/30 indicating dementia with a sensitivity of 0.95, a specificity of 1 and a positive predictive value of 1) compared to the original higher published cut-off of ≤ 25/30 (sensitivity of 0.95, specificity of 0.70 and a positive predictive value of 0.82 in this sample). Conclusions: The M-ACE has excellent diagnostic accuracy for the detection of dementia in a UK clinical sample. It may be necessary to consider lower cut-offs than those given in the original validation study.

Cognitive impairment in heart failure

The clinical syndrome of heart failure is one of the leading causes of hospitalisation and mortality in older adults. Due to ageing of the general population and improved survival from cardiac disease the prevalence of heart failure is rising. Despite the fact that the majority of patients with heart failure are aged over 65 years old, many with multiple co-morbidities, the association between cognitive impairment and heart failure has received relatively little research interest compared to other aspects of cardiac disease. The presence of concomitant cognitive impairment has implications for the management of patients with heart failure in the community. There are many evidence based pharmacological therapies used in heart failure management which obviously rely on patient education regarding compliance. Also central to the treatment of heart failure is patient self-monitoring for signs indicative of clinical deterioration which may prompt them to seek medical assistance or initiate a therapeutic intervention e.g. taking additional diuretic. Adherence and self-management may be jeopardised by cognitive impairment. Formal diagnosis of cognitive impairment requires evidence of abnormalities on neuropsychological testing (typically a result ≥1.5 standard deviation below the age-standardised mean) in at least one cognitive domain. Cognitive impairment is associated with an increased risk of dementia and people with mild cognitive impairment develop dementia at a rate of 10-15% per year, compared with a rate of 1-2% per year in healthy controls.1 Cognitive impairment has been reported in a variety of cardiovascular disorders. It is well documented among patients with hypertension, atrial fibrillation and coronary artery disease, especially after coronary artery bypass grafting. This background is relevant to the study of patients with heart failure as many, if not most, have a history of one or more of these co-morbidities. A systematic review of the literature to date has shown a wide variation in the reported prevalence of cognitive impairment in heart failure. This range in variation probably reflects small study sample sizes, differences in the heart failure populations studied (inpatients versus outpatients), neuropsychological tests employed and threshold values used to define cognitive impairment. The main aim of this study was to identify the prevalence of cognitive impairment in a representative sample of heart failure patients and to examine whether this association was due to heart failure per se rather than the common cardiovascular co-morbidities that often accompany it such as atherosclerosis and atrial fibrillation. Of the 817 potential participants screened, 344 were included in this study. The study cohort included 196 patients with HF, 61 patients with ischaemic heart disease and no HF and 87 healthy control participants. The HF cohort consisted of 70 patients with HF and coronary artery disease in sinus rhythm, 51 patients with no coronary artery disease in sinus rhythm and 75 patients with HF and atrial fibrillation. All patients with HF had evidence of HF-REF with a LVEF <45% on transthoracic echocardiography. The majority of the cohort was male and elderly. HF patients with AF were more likely to have multiple co-morbidities. Patients recruited from cardiac rehabilitation clinics had proven coronary artery disease, no clinical HF and a LVEF >55%. The ischaemic heart disease group were relatively well matched to healthy controls who had no previous diagnosis of any chronic illness, prescribed no regular medication and also had a LVEF >55%. All participants underwent the same baseline investigations and there were no obvious differences in baseline demographics between each of the cohorts. All 344 participants attended for 2 study visits. Baseline investigations including physiological measurements, electrocardiography, echocardiography and laboratory testing were all completed at the initial screening visit. Participants were then invited to attend their second study visit within 10 days of the screening visit. 342 participants completed all neuropsychological assessments (2 participants failed to complete 1 questionnaire). A full comprehensive battery of neuropsychological assessment tools were administered in the 90 minute study visit. These included three global cognitive screening assessment tools (mini mental state examination, Montreal cognitive assessment tool and the repeatable battery for the assessment of neuropsychological status) and additional measures of executive function (an area we believe has been understudied to date). In total there were 9 cognitive tests performed. These were generally well tolerated. Data were also collected using quality of life questionnaires and health status measures. In addition to this, carers of the study participant were asked to complete a measure of caregiver strain and an informant questionnaire on cognitive decline. The prevalence of cognitive impairment varied significantly depending on the neuropsychological assessment tool used and cut-off value used to define cognitive impairment. Despite this, all assessment tools showed the same pattern of results with those patients with heart failure and atrial fibrillation having poorer cognitive performance than those with heart failure in sinus rhythm. Cognitive impairment was also more common in patients with cardiac disease (either coronary artery disease or heart failure) than age-, sex- and education-matched healthy controls, even after adjustment for common vascular risk factors.

Feminist Disability Theory: Domestic Violence Against Women with a Disability

Women with a disability continue to experience social oppression and domestic violence as a consequence of gender and disability dimensions. Current explanations of domestic violence and disability inadequately explain several features that lead women who have a disability to experience violent situations. This article incorporates both disability and material feminist theory as an alternative explanation to the dominant approaches (psychological and sociological traditions) of conceptualising domestic violence. This paper is informed by a study which was concerned with examining the nature and perceptions of violence against women with a physical impairment. The emerging analytical framework integrating material feminist interpretations and disability theory provided a basis for exploring gender and disability dimensions. Insight was also provided by the women who identified as having a disability in the study and who explained domestic violence in terms of a gendered and disabling experience. The article argues that material feminist interpretations and disability theory, with their emphasis on gender relations, disablism and poverty, should be used as an alternative tool for exploring the nature and consequences of violence against women with a disability.