ResearchPad - cognitive-impairment https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Psychometric testing of the Fall Risks for Older People in the Community screening tool (FROP-Com screen) for community-dwelling people with stroke]]> https://www.researchpad.co/article/elastic_article_14472 The Falls Risk for Older People in the Community assessment (FROP-Com) was originally developed using 13 risk factors to identify the fall risks of community-dwelling older people. To suit the practical use in busy clinical settings, a brief version adopting 3 most fall predictive risk factors from the original FROP-Com, including the number of falls in the past 12 months, assistance required to perform domestic activities of daily living and observation of balance, was developed for screening purpose (FROP-Com screen). The objectives of this study were to investigate the inter-rater and test-retest reliability, concurrent and convergent validity, and minimum detectable change of the FROP-Com screen in community-dwelling people with stroke.ParticipantsCommunity-dwelling people with stroke (n = 48) were recruited from a local self-help group, and community-dwelling older people (n = 40) were recruited as control subjects.ResultsThe FROP-Com screen exhibited moderate inter-rater (Intraclass correlation coefficient [ICC]2,1 = 0.79, 95% confidence interval [CI]: 0.65–0.87) and test-retest reliability (ICC3,1 = 0.70, 95% CI: 0.46–0.83) and weak associations with two balance measures, the Berg Balance Scale (BBS) (rho = -0.38, p = 0.008) and the Timed “Up & Go” (TUG) test (rho = 0.35, p = 0.016). The screen also exhibited a moderate association with the Chinese version of the Activities-specific Balance Confidence Scale (ABC-C) (ABC-C; rho = -0.65, p<0.001), a measure of subjective balance confidence.ConclusionsThe FROP-Com screen is a reliable clinical tool with convergent validity paralleled with subjective balance confidence measure that can be used in fall risk screening of community-dwelling people with stroke. However, one individual item, the observation of balance, will require additional refinement to improve the potential measurement error. ]]> <![CDATA[The effects of age and sex on cognitive impairment in schizophrenia: Findings from the Consortium on the Genetics of Schizophrenia (COGS) study]]> https://www.researchpad.co/article/elastic_article_13860 Recently emerging evidence indicates accelerated age-related changes in the structure and function of the brain in schizophrenia, raising a question about its potential consequences on cognitive function. Using a large sample of schizophrenia patients and controls and a battery of tasks across multiple cognitive domains, we examined whether patients show accelerated age-related decline in cognition and whether an age-related effect differ between females and males. We utilized data of 1,415 schizophrenia patients and 1,062 healthy community collected by the second phase of the Consortium on the Genetics of Schizophrenia (COGS-2). A battery of cognitive tasks included the Letter-Number Span Task, two forms of the Continuous Performance Test, the California Verbal Learning Test, Second Edition, the Penn Emotion Identification Test and the Penn Facial Memory Test. The effect of age and gender on cognitive performance was examined with a general linear model. We observed age-related changes on most cognitive measures, which was similar between males and females. Compared to controls, patients showed greater deterioration in performance on attention/vigilance and greater slowness of processing social information with increasing age. However, controls showed greater age-related changes in working memory and verbal memory compared to patients. Age-related changes (η2p of 0.001 to .008) were much smaller than between-group differences (η2p of 0.005 to .037). This study found that patients showed continued decline of cognition on some domains but stable impairment or even less decline on other domains with increasing age. These findings indicate that age-related changes in cognition in schizophrenia are subtle and not uniform across multiple cognitive domains.

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<![CDATA[Functional magnetic resonance imaging of the trail-making test in older adults]]> https://www.researchpad.co/article/elastic_article_13819 The trail-making test (TMT) is a popular neuropsychological test, which is used extensively to measure cognitive impairment associated with neurodegenerative disorders in older adults. Behavioural performance on the TMT has been investigated in older populations, but there is limited research on task-related brain activity in older adults. The current study administered a naturalistic version of the TMT to a healthy older-aged population in an MRI environment using a novel, MRI-compatible tablet. Functional MRI was conducted during task completion, allowing characterization of the brain activity associated with the TMT. Performance on the TMT was evaluated using number of errors and seconds per completion of each link. Results are reported for 36 cognitively healthy older adults between the ages of 52 and 85. Task-related activation was observed in extensive regions of the bilateral frontal, parietal, temporal and occipital lobes as well as key motor areas. Increased age was associated with reduced brain activity and worse task performance. Specifically, older age was correlated with decreased task-related activity in the bilateral occipital, temporal and parietal lobes. These results suggest that healthy older aging significantly affects brain function during the TMT, which consequently may result in performance decrements. The current study reveals the brain activation patterns underlying TMT performance in a healthy older aging population, which functions as an important, clinically-relevant control to compare to pathological aging in future investigations.

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<![CDATA[Participant and informant memory-specific cognitive complaints predict future decline and incident dementia: Findings from the Sydney Memory and Ageing Study]]> https://www.researchpad.co/article/elastic_article_7842 Subjective Cognitive Complaints (SCCs) may represent one of the earliest stages of preclinical dementia. The objective of the present study was to extend previous work by our group to examine the relationship between participant-reported and informant-reported memory and non-memory SCCs, cognitive decline and incident dementia, over a six-year period. Participants were 873 community dwelling older adults (Mage = 78.65, SD = 4.79) without dementia and 843 informants (close friends or family) from the Sydney Memory and Ageing Study. Comprehensive neuropsychological testing and diagnostic assessments were carried out at baseline and biennially for six years. Linear mixed models and Cox proportional hazard models were performed to determine the association of SCCs, rate of cognitive decline and risk of incident dementia, controlling demographics and covariates of mood and personality. Participant and informant memory-specific SCCs were associated with rate of global cognitive decline; for individual cognitive domains, participant memory SCCs predicted decline for language, while informant memory SCCs predicted decline for executive function and memory. Odds of incident dementia were associated with baseline participant memory SCCs and informant memory and non-memory SCCs in partially adjusted models. In fully adjusted models, only informant SCCs were associated with increased risk of incident dementia. Self-reported memory-specific cognitive complaints are associated with decline in global cognition over 6-years and may be predictive of incident dementia, particularly if the individual is depressed or anxious and has increased neuroticism or decreased openness. Further, if and where possible, informants should be sought and asked to report on their perceptions of the individual’s memory ability and any memory-specific changes that they have noticed as these increase the index of diagnostic suspicion.

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<![CDATA[Pooling individual participant data from randomized controlled trials: Exploring potential loss of information]]> https://www.researchpad.co/article/elastic_article_7838 Pooling individual participant data to enable pooled analyses is often complicated by diversity in variables across available datasets. Therefore, recoding original variables is often necessary to build a pooled dataset. We aimed to quantify how much information is lost in this process and to what extent this jeopardizes validity of analyses results.MethodsData were derived from a platform that was developed to pool data from three randomized controlled trials on the effect of treatment of cardiovascular risk factors on cognitive decline or dementia. We quantified loss of information using the R-squared of linear regression models with pooled variables as a function of their original variable(s). In case the R-squared was below 0.8, we additionally explored the potential impact of loss of information for future analyses. We did this second step by comparing whether the Beta coefficient of the predictor differed more than 10% when adding original or recoded variables as a confounder in a linear regression model. In a simulation we randomly sampled numbers, recoded those < = 1000 to 0 and those >1000 to 1 and varied the range of the continuous variable, the ratio of recoded zeroes to recoded ones, or both, and again extracted the R-squared from linear models to quantify information loss.ResultsThe R-squared was below 0.8 for 8 out of 91 recoded variables. In 4 cases this had a substantial impact on the regression models, particularly when a continuous variable was recoded into a discrete variable. Our simulation showed that the least information is lost when the ratio of recoded zeroes to ones is 1:1.ConclusionsLarge, pooled datasets provide great opportunities, justifying the efforts for data harmonization. Still, caution is warranted when using recoded variables which variance is explained limitedly by their original variables as this may jeopardize the validity of study results. ]]> <![CDATA[FEASIBILITY AND ACCEPTABILITY OF DETECTING COGNITIVE IMPAIRMENT AND DEMENTIA IN PRIMARY CARE PRACTICES]]> https://www.researchpad.co/article/Nd3705a81-4c76-4aed-873e-143b9060a401

Abstract

As the age of the US population increases, so does cognitive impairment (CI); therefore early detection of CI is critical for ensuring its appropriate management. As part of a NINDS Consortium to detect CI and dementia in primary care (DetectCID), we are implementing and evaluating a brief 2-step CI detection paradigm (MyCog), that can be delivered in clinics with diverse populations via the electronic health record (step 1) and iPad (step 2). We conducted focus groups with 25 clinicians and administrative leaders from academic and community primary care practices to 1) understand how CI is being assessed, and 2) evaluate the feasibility of implementing the MyCog paradigm into existing primary care workflows. Several key themes emerged from the discussions. No proactive detection strategy for CI was regularly used outside of the Medicare Annual Wellness Visits (AWV); variable assessments including the Minicog, MoCA, or MMSE were used to fulfill the AWV requirement. Regarding the feasibility of our MyCog Paradigm, our 2-step process was positively received, with the brief case-finding step 1 satisfying AWV requirements and replacing the longer assessments currently being used. Clinicians preferred that step 2 be self-administered due to limited clinician time for wellness visits, and highlighted logistical challenges such as room availability and storage and maintenance of the iPad. Overall, clinicians felt that the identification of CI was valuable and supported standardization, but indicated regular case finding was unlikely without clear guidance on clinical decision-making.

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<![CDATA[Clinical impact of melatonin on breast cancer patients undergoing chemotherapy; effects on cognition, sleep and depressive symptoms: A randomized, double-blind, placebo-controlled trial]]> https://www.researchpad.co/article/Nf52b3d22-02a5-4e7e-bb1d-9e73ca6c7e6b

This randomized, double-blinded, placebo-controlled trial tested the hypothesis that 20mg of melatonin before and during the first cycle of adjuvant chemotherapy for breast cancer (ACBC) reduced the side effects associated with cognitive impairment. We evaluated the effects of melatonin on cognition, depressive symptoms and sleep quality, and whether these effects were related to serum levels of Brain Derived Neurotrophic Factor (BDNF) and its receptor, tropomyosin kinase B (TrkB). Thirty-six women were randomly assigned to receive melatonin or placebo for 10 days. To evaluate cognitive performance, we used the Trail-Making-Test Parts A and B (A-B), Rey Auditory-Verbal Learning Test (RAVLT), Controlled Oral Word Association Test (COWAT) and an inhibitory task type Go / No-Go. Our results revealed that melatonin improved executive function on TMT scores, enhanced episodic memory (immediate and delayed) and recognition on RAVLT, and increased verbal fluency in the orthographic COWAT. The TMT-A-B(A-B) were negatively correlated with baseline levels of TrkB and BDNF, respectively. At the end of treatment, changes in TrkB and BDNF were inversely associated with depressive symptoms and sleep quality, but not with the TMT scores. These results suggest a neuroprotective effect of melatonin to counteract the adverse effects of ACBC on cognitive function, sleep quality and depressive symptoms.

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<![CDATA[A smartphone-based test for the assessment of attention deficits in delirium: A case-control diagnostic test accuracy study in older hospitalised patients]]> https://www.researchpad.co/article/N8fecd5fe-2073-4d74-805a-6132ddca5eea

Background

Delirium is a common and serious acute neuropsychiatric syndrome which is often missed in routine clinical care. Inattention is the core cognitive feature. Diagnostic test accuracy (including cut-points) of a smartphone Delirium App (DelApp) for assessing attention deficits was assessed in older hospital inpatients.

Methods

This was a case-control study of hospitalised patients aged ≥65 years with delirium (with or without pre-existing cognitive impairment), who were compared to patients with dementia without delirium, and patients without cognitive impairment. Reference standard delirium assessment, which included a neuropsychological test battery, was based on Diagnostic and Statistical Manual of Mental Disorders-5 criteria. A separate blinded assessor administered the DelApp arousal assessment (score 0–4) and attention task (0–6) yielding an overall score of 0 to 10 (lower scores indicate poorer performance). Analyses included receiver operating characteristic curves and sensitivity and specificity. Optimal cut-points for delirium detection were determined using Youden’s index.

Results

A total of 187 patients were recruited, mean age 83.8 (range 67–98) years, 152 (81%) women; n = 61 with delirium; n = 61 with dementia without delirium; and n = 65 without cognitive impairment. Patients with delirium performed poorly on the DelApp (median score = 4/10; inter-quartile range 3.0, 5.5) compared to patients with dementia (9.0; 5.5, 10.0) and those without cognitive impairment (10.0; 10.0, 10.0). Area under the curve for detecting delirium was 0.89 (95% Confidence Interval 0.84, 0.94). At an optimal cut-point of ≤8, sensitivity was 91.7% (84.7%, 98.7%) and specificity 74.2% (66.5%, 81.9%) for discriminating delirium from the other groups. Specificity was 68.3% (56.6%, 80.1%) for discriminating delirium from dementia (cut-point ≤6).

Conclusion

Patients with delirium (with or without pre-existing cognitive impairment) perform poorly on the DelApp compared to patients with dementia and those without cognitive impairment. A cut-point of ≤8/10 is suggested as having optimal sensitivity and specificity. The DelApp is a promising tool for assessment of attention deficits associated with delirium in older hospitalised adults, many of whom have prior cognitive impairment, and should be further validated in representative patient cohorts.

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<![CDATA[Mixed evidence for the relationship between periodontitis and Alzheimer’s disease: A bidirectional Mendelian randomization study]]> https://www.researchpad.co/article/N89b89fe7-2f39-423b-9f5f-6e2e7b2736b5

Recent experimental studies indicated that a periodontitis-causing bacterium might be a causal factor for Alzheimer’s disease (AD). We applied a two-sample Mendelian randomization (MR) approach to examine the potential causal relationship between chronic periodontitis and AD bidirectionally in the population of European ancestry. We used publicly available data of genome-wide association studies (GWAS) on periodontitis and AD. Five single-nucleotide polymorphisms (SNPs) were used as instrumental variables for periodontitis. For the MR analysis of periodontitis on risk of AD, the causal odds ratio (OR) and 95% confidence interval (CI) were derived from the GWAS of periodontitis (4,924 cases vs. 7,301 controls) and from the GWAS of AD (21,982 cases vs. 41,944 controls). Seven non-overlapping SNPs from another latest GWAS of periodontitis was used to validate the above association. Twenty SNPs were used as instrumental variables for AD. For the MR analysis of liability to AD on risk of periodontitis, the causal OR was derived from the GWAS of AD including 30,344 cases and 52,427 controls and from the GWAS of periodontitis consisted of 12,289 cases and 22,326 controls. We employed multiple methods of MR. Using the five SNPs as instruments of periodontitis, there was suggestive evidence of genetically predicted periodontitis being associated with a higher risk of AD (OR 1.10, 95% CI 1.02 to 1.19, P = 0.02). However, this association was not verified using the seven independent SNPs (OR 0.97, 95% CI 0.87 to 1.08, P = 0.59). There was no association of genetically predicted AD with the risk of periodontitis (OR 1.00, 95% CI 0.96 to 1.04, P = 0.85). In summary, we did not find convincing evidence to support periodontitis being a causal factor for the development of AD. There was also limited evidence to suggest genetic liability to AD being associated with the risk of periodontitis.

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<![CDATA[Executive task-based brain function in children with type 1 diabetes: An observational study]]> https://www.researchpad.co/article/Nd7290b0a-e9f9-4731-9f28-e7228fa093e0

Background

Optimal glycemic control is particularly difficult to achieve in children and adolescents with type 1 diabetes (T1D), yet the influence of dysglycemia on the developing brain remains poorly understood.

Methods and findings

Using a large multi-site study framework, we investigated activation patterns using functional magnetic resonance imaging (fMRI) in 93 children with T1D (mean age 11.5 ± 1.8 years; 45.2% female) and 57 non-diabetic (control) children (mean age 11.8 ± 1.5 years; 50.9% female) as they performed an executive function paradigm, the go/no-go task. Children underwent scanning and cognitive and clinical assessment at 1 of 5 different sites. Group differences in activation occurring during the contrast of “no-go > go” were examined while controlling for age, sex, and scan site. Results indicated that, despite equivalent task performance between the 2 groups, children with T1D exhibited increased activation in executive control regions (e.g., dorsolateral prefrontal and supramarginal gyri; p = 0.010) and reduced suppression of activation in the posterior node of the default mode network (DMN; p = 0.006). Secondary analyses indicated associations between activation patterns and behavior and clinical disease course. Greater hyperactivation in executive control regions in the T1D group was correlated with improved task performance (as indexed by shorter response times to correct “go” trials; r = −0.36, 95% CI −0.53 to −0.16, p < 0.001) and with better parent-reported measures of executive functioning (r values < −0.29, 95% CIs −0.47 to −0.08, p-values < 0.007). Increased deficits in deactivation of the posterior DMN in the T1D group were correlated with an earlier age of T1D onset (r = −0.22, 95% CI −0.41 to −0.02, p = 0.033). Finally, exploratory analyses indicated that among children with T1D (but not control children), more severe impairments in deactivation of the DMN were associated with greater increases in hyperactivation of executive control regions (T1D: r = 0.284, 95% CI 0.08 to 0.46, p = 0.006; control: r = 0.108, 95% CI −0.16 to 0.36, p = 0.423). A limitation to this study involves glycemic effects on brain function; because blood glucose was not clamped prior to or during scanning, future studies are needed to assess the influence of acute versus chronic dysglycemia on our reported findings. In addition, the mechanisms underlying T1D-associated alterations in activation are unknown.

Conclusions

These data indicate that increased recruitment of executive control areas in pediatric T1D may act to offset diabetes-related impairments in the DMN, ultimately facilitating cognitive and behavioral performance levels that are equivalent to that of non-diabetic controls. Future studies that examine whether these patterns change as a function of improved glycemic control are warranted.

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<![CDATA[BRIDGING THE GAP BETWEEN COGNITIVE HEALTH AND FINANCIAL CAPACITY IN OLDER ADULTS: A SCOPING REVIEW]]> https://www.researchpad.co/article/N2fc66949-0c12-40ac-b3fb-875b6199d0eb

Abstract

Significant declines in everyday functioning are often indicators of cognitive impairment. Although researchers agree that a diminished ability to carry out a variety of instrumental activities of daily living (IADL) tasks is a harbinger of cognitive impairment (CI), studies have repeatedly found that a compromised ability to successfully complete financial management tasks may be one of the initial IADLs affected by prodromal CI. Due to the combination of compromised financial functioning and the increased prevalence of CI, older adults as group are, therefore, put at a greater risk for financial abuse and exploitation. The aims of this scoping review were two-fold: 1) to synthesize current literature on CI as it relates to financial decision-making (FDM) and 2) to analyze the measures and instruments used to assess FDM in older adults. In a review of four databases, 39 studies were identified that met inclusion criteria. These studies used 22 different instruments to measure and assess financial functioning. Across the 39 studies, consistent themes emerged relevant to factors that impacted cognitive impairment and financial functioning. These themes included participants’ education levels, premorbid financial literacy, and age. White participants were overrepresented in research samples from these studies. Future research should investigate how FDM and early signs of CI may interact in people of color. Additionally, research should be focused on how to make instrumentation more accessible and feasible for the general public to administer without extensive training. This would enable the lay population to more easily identify early signs of cognitive impairment.

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<![CDATA[Effects of frontal-executive dysfunction on self-perceived hearing handicap in the elderly with mild cognitive impairment]]> https://www.researchpad.co/article/5c897757d5eed0c4847d2a69

It is increasingly agreed upon that cognitive and audiological factors are associated with self-perceived hearing handicap in old adults. This study aimed to compare self-perceived hearing handicap among mild cognitive impairment (MCI) subgroups and a cognitively normal elderly (CNE) group and determine which factors (i.e., demographic, audiometric, or neuropsychological factors) are correlated with self-perceived hearing handicap in each group. A total of 46 MCI patients and 39 hearing threshold-matched CNE subjects participated in this study, and their age ranged from 55 to 80 years. The MCI patients were reclassified into two groups: 16 with frontal-executive dysfunction (FED) and 30 without FED. All subjects underwent audiometric, neuropsychological, and self-perceived hearing handicap assessments. The Korean version of the Hearing Handicap Inventory for the Elderly (K-HHIE) was administered to obtain the hearing handicap scores for each subject. After controlling for age, years of education, and depression levels, we found no significant differences in the K-HHIE scores between the MCI and the CNE groups. However, after we classified the MCI patients into the MCI with FED and MCI without FED groups, the MCI with FED group scored significantly higher than did both the MCI without FED and the CNE groups. In addition, after controlling for depression levels, significant partial correlations of hearing handicap scores with frontal-executive function scores and speech-in-noise perception performance were found in the MCI groups. In the CNE group, the hearing handicap scores were related to peripheral hearing sensitivity and years of education. In summary, MCI patients with FED are more likely to experience everyday hearing handicap than those without FED and cognitively normal old adults. Although educational level and peripheral hearing function are related to self-perceived hearing handicap in cognitively normal old adults, speech-in-noise perception and frontal-executive function are mainly associated with hearing handicap in patients with MCI.

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<![CDATA[Association of metformin, sulfonylurea and insulin use with brain structure and function and risk of dementia and Alzheimer’s disease: Pooled analysis from 5 cohorts]]> https://www.researchpad.co/article/5c70673cd5eed0c4847c6c7d

Objective

To determine whether classes of diabetes medications are associated with cognitive health and dementia risk, above and beyond their glycemic control properties.

Research design and methods

Findings were pooled from 5 population-based cohorts: the Framingham Heart Study, the Rotterdam Study, the Atherosclerosis Risk in Communities (ARIC) Study, the Aging Gene-Environment Susceptibility-Reykjavik Study (AGES) and the Sacramento Area Latino Study on Aging (SALSA). Differences between users and non-users of insulin, metformin and sulfonylurea were assessed in each cohort for cognitive and brain MRI measures using linear regression models, and cognitive decline and dementia/AD risk using mixed effect models and Cox regression analyses, respectively. Findings were then pooled using meta-analytic techniques, including 3,590 individuals with diabetes for the prospective analysis.

Results

After adjusting for potential confounders including indices of glycemic control, insulin use was associated with increased risk of new-onset dementia (pooled HR (95% CI) = 1.58 (1.18, 2.12);p = 0.002) and with a greater decline in global cognitive function (β = -0.014±0.007;p = 0.045). The associations with incident dementia remained similar after further adjustment for renal function and excluding persons with diabetes whose treatment was life-style change only. Insulin use was not related to cognitive function nor to brain MRI measures. No significant associations were found between metformin or sulfonylurea use and outcomes of brain function and structure. There was no evidence of significant between-study heterogeneity.

Conclusions

Despite its advantages in controlling glycemic dysregulation and preventing complications, insulin treatment may be associated with increased adverse cognitive outcomes possibly due to a greater risk of hypoglycemia.

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<![CDATA[Impulsivity across reactive, proactive and cognitive domains in Parkinson's disease on dopaminergic medication: Evidence for multiple domain impairment]]> https://www.researchpad.co/article/5c6dc9fad5eed0c48452a639

Impulse control disorders (ICD) may occur in Parkinson’s disease (PD) although it remains to be understood if such deficits may occur even in the absence of a formal ICD diagnosis. Moreover, studies addressing simultaneously distinct neurobehavioral domains, such as cognitive, proactive and reactive motor impulsivity, are still lacking. Here, we aimed to investigate if reactive, proactive and cognitive impulsivity involving risk taking are concomitantly affected in medicated PD patients, and whether deficits were dependent on response strategies, such as speed accuracy tradeoffs, or the proportion of omission vs. commission errors. We assessed three different impulsivity domains in a sample of 21 PD patients and 13 matched controls. We found impaired impulsivity in both reactive (p = 0.042) and cognitive domains (p = 0.015) for the PD patients, irrespective of response strategy. For the latter, effect sizes were larger for the actions related with reward processing (p = 0.017, dCohen = 0.9). In the proactive impulsivity task, PD patients showed significantly increased number of omissions (p = 0.041), a response strategy which was associated with preserved number of commission errors. Moreover, the number of premature and proactive response errors were correlated with disease stage. Our findings suggest that PD ON medication is characterized compared to healthy controls by impairment across several impulsivity domains, which is moderated in the proactive domain by the response strategy.

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<![CDATA[Inhibitory control during selective retrieval may hinder subsequent analogical thinking]]> https://www.researchpad.co/article/5c6c7579d5eed0c4843cfdec

Analogical reasoning is a complex cognitive activity that involves access and retrieval of pre-existing knowledge in order to find a suitable solution. Prior work has shown that analogical transfer and reasoning can be influenced by unconscious activation of relevant information. Based on this idea, we report two experiments that examine whether reduced access to relevant information in memory may further disrupt analogical reasoning unwittingly. In both experiments, we use an adaptation of the retrieval practice paradigm [1] to modulate memory accessibility of potential solutions to a subsequent set of analogy problems of the type ‘A is to B as C is to ?’. Experiment 1 showed a retrieval-induced impairment in analogical problem solving. Experiment 2 replicated this finding and demonstrated that it cannot be due to the deliberative episodic retrieval of the solutions to the analogies. These findings, predictable from an inhibitory framework of memory control, provide a new focus for theories of analogical transfer and highlight the importance of unconscious memory processes that may modulate problem solving.

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<![CDATA[Association of small fiber neuropathy and post treatment Lyme disease syndrome]]> https://www.researchpad.co/article/5c6c75a6d5eed0c4843cff72

Objectives

To examine whether post-treatment Lyme disease syndrome (PTLDS) defined by fatigue, cognitive complaints and widespread pain following the treatment of Lyme disease is associated with small fiber neuropathy (SFN) manifesting as autonomic and sensory dysfunction.

Methods

This single center, retrospective study evaluated subjects with PTLDS. Skin biopsies for assessment of epidermal nerve fiber density (ENFD), sweat gland nerve fiber density (SGNFD) and functional autonomic testing (deep breathing, Valsalva maneuver and tilt test) were performed to assess SFN, severity of dysautonomia and cerebral blood flow abnormalities. Heart rate, end tidal CO2, blood pressure, and cerebral blood flow velocity (CBFv) from middle cerebral artery using transcranial Doppler were monitored.

Results

10 participants, 5/5 women/men, age 51.3 ± 14.7 years, BMI 27.6 ± 7.3 were analyzed. All participants were positive for Lyme infection by CDC criteria. At least one skin biopsy was abnormal in all ten participants. Abnormal ENFD was found in 9 participants, abnormal SGNFD in 5 participants, and both abnormal ENFD and SGNFD were detected in 4 participants. Parasympathetic failure was found in 7 participants and mild or moderate sympathetic adrenergic failure in all participants. Abnormal total CBFv score was found in all ten participants. Low orthostatic CBFv was found in 7 participants, three additional participants had abnormally reduced supine CBFv.

Conclusions

SFN appears to be associated with PTLDS and may be responsible for certain sensory symptoms. In addition, dysautonomia related to SFN and abnormal CBFv also seem to be linked to PTLDS. Reduced orthostatic CBFv can be associated with cerebral hypoperfusion and may lead to cognitive dysfunction. Autonomic failure detected in PTLDS is mild to moderate. SFN evaluation may be useful in PTLDS.

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<![CDATA[Impact of moderate to severe obstructive sleep apnea on the cognition in idiopathic pulmonary fibrosis]]> https://www.researchpad.co/article/5c5df31bd5eed0c484580d2d

Introduction

Idiopathic pulmonary fibrosis (IPF) is a relentlessly progressive lung disease with a fatal prognosis to whose rapid evolution multiple comorbidities may contribute, one of the most common being obstructive sleep apnea (OSA). There are several potential factors and conditions for the emergence of a cognitive deficit in relation to IPF or associated morbidities.

Objectives

The goals of this study were to assess cognition in patients with IPF in stable phase and to identify clinical cognition modifiers.

Methods

In a cross-sectional study, 23 patients with IPF were evaluated using Montreal Cognitive Assessment (MoCA), an instrument for detecting mild cognitive impairments and were screened for OSA through overnight cardiorespiratory polygraphy and for anxiety and depression with three specific scale (Generalized Anxiety Disorder 7-item scale: GAD-7; the Patient Health Questionnaire: PHQ-9; Hospital Anxiety and Depression Scale: HADS).

Results

MoCA score was lower in patients with IPF when compared to controls subjects (24 [21,26] vs. 27 [26,28], p = 0.003) but not as significantly as in COPD patients (21 [18.8,23.3], p<0.0001). OSA was diagnosed in 19 (82.6%) IPF patients, 12 patients showed the presence of moderate-severe forms (63.15%). IPF patients with cognitive impairment (MoCA<23) exhibit a higher severity of OSA (apneea hypopnea index–AHI: 33.0±19.1 vs. 12.44±8.2, p = 0.018), and a higher Epworth score (7.1±3.3 vs. 4.3±1.8, p = 0.013). Anxiety and depression scores were not correlated with MoCA results.

Conclusions

Impaired cognition in patients with IPF is mild and affect the areas of visuospatial abilities, language and working memory. OSA could be a possible predictor of IPF cognition deficit. Given the high prevalence of multiple types of sleep disorders in IPF patients, these should be investigated at least by cardiorespiratory polygraphy.

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<![CDATA[Imprinting methylation in SNRPN and MEST1 in adult blood predicts cognitive ability]]> https://www.researchpad.co/article/5c5df30fd5eed0c484580c36

Genomic imprinting is important for normal brain development and aberrant imprinting has been associated with impaired cognition. We studied the imprinting status in selected imprints (H19, IGF2, SNRPN, PEG3, MEST1, NESPAS, KvDMR, IG-DMR and ZAC1) by pyrosequencing in blood samples from longitudinal cohorts born in 1936 (n = 485) and 1921 (n = 223), and anterior hippocampus, posterior hippocampus, periventricular white matter, and thalamus from brains donated to the Aberdeen Brain Bank (n = 4). MEST1 imprint methylation was related to childhood cognitive ability score (-0.416 95% CI -0.792,-0.041; p = 0.030), with the strongest effect evident in males (-0.929 95% CI -1.531,-0.326; p = 0.003). SNRPN imprint methylation was also related to childhood cognitive ability (+0.335 95%CI 0.008,0.663; p = 0.045). A significant association was also observed for SNRPN methylation and adult crystallised cognitive ability (+0.262 95%CI 0.007,0.517; p = 0.044). Further testing of significant findings in a second cohort from the same region, but born in 1921, resulted in similar effect sizes and greater significance when the cohorts were combined (MEST1; -0.371 95% CI -0.677,-0.065; p = 0.017; SNRPN; +0.361 95% CI 0.079,0.643; p = 0.012). For SNRPN and MEST1 and four other imprints the methylation levels in blood and in the five brain regions were similar. Methylation of the paternally expressed, maternally methylated genes SNRPN and MEST1 in adult blood was associated with cognitive ability in childhood. This is consistent with the known importance of the SNRPN containing 15q11-q13 and the MEST1 containing 7q31-34 regions in cognitive function. These findings, and their sex specific nature in MEST1, point to new mechanisms through which complex phenotypes such as cognitive ability may be inherited. These mechanisms are potentially relevant to both the heritable and non-heritable components of cognitive ability. The process of epigenetic imprinting—within SNRPN and MEST1 in particular—and the factors that influence it, are worthy of further study in relation to the determinants of cognitive ability.

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<![CDATA[Mutation screening in non-syndromic hearing loss patients with cochlear implantation by massive parallel sequencing in Taiwan]]> https://www.researchpad.co/article/5c79b005d5eed0c4841e3c60

Objectives

To explore the molecular epidemiology of rare deafness genes in Taiwanese sensorineural hearing impairment (SNHI) patients with cochlear implantation (CI) by performing massive parallel sequencing (MPS) and correlating genetic factors and CI outcomes.

Methods

We enrolled 41 Taiwanese non-syndromic deafness patients with CI that lacked known mutations in common deafness genes. All probands were screened by a targeted exon amplification method that used massively parallel sequencing to screen a customized panel that included 40 relatively rare non-syndromic deafness genes.

Results

Thirteen candidate variants in nine relatively rare deafness genes (MYO15A, TMC1, MYH14, MYO3A, ACTG1, COL11A2, DSPP, GRHL2, and WFS1) were identified in 24.4% (10/41) of the non-syndromic deafness probands with CI. According to the ACMG Standards and Guidelines, five variants in MYO15A and ACTG1 were classified as likely pathogenic variants. Two of three multi-generational pedigrees exhibiting deafness were analyzed for the segregation of the disorder with the possible disease-causing variants. Patients with variants detected in most of the identified variant-bearing genes showed relatively good CI outcomes.

Conclusions

We successfully identified candidate variants in partially deaf Taiwanese probands who lacked the known mutations in common deafness genes. Comparing the progress of hearing rehabilitation in CI patients with their apparent causative variants and the expression profiles of their altered genes allowed us to speculate on how alterations in specific gene sets may influence outcomes in hearing rehabilitation after CI.

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<![CDATA[Health-related quality of life loss associated with first-time stroke]]> https://www.researchpad.co/article/5c58d61cd5eed0c484031668

Objectives

This study aimed to quantify health-related quality of life (HRQoL) loss associated with first episode of stroke by comparing patient-reported HRQoL before and after stroke onset. The impact of stroke in local population was also evaluated by comparing the pre- and post-stroke HRQoL with that of the general population.

Methods

The HRQoL of stroke survivors was assessed with the EQ-5D-3L index score at recruitment, for recalled pre-stroke HRQoL, and at 3 and 12 month post-stroke. Change in HRQoL from pre-stroke to 3 and 12 month was self-reported by 285 and 238 patients, respectively. Mean EQ index score at each time point (baseline: 464 patients; 3 month post-stroke: 306 patients; 12 month post-stroke: 258 patients) was compared with published population norms for EQ-5D-3L.

Results

There was a significant decrease in HRQoL at 3 (0.25) and 12 month (0.09) post-stroke when compared to the retrospectively recalled patients’ mean pre-stroke HRQoL level (0.87). The reduction at 3 month was associated with the reduction in all EQ-5D-3L health dimensions; reductions remaining at 12 month were limited to dimensions of mobility, self-care, usual activities, and anxiety/depression. Stroke patients had a lower mean EQ index than the general population by 0.07 points pre-stroke (0.87 vs. 0.94), 0.33 points at 3 month (0.61 vs. 0.94) and 0.18 points at 12 month (0.76 vs. 0.94) post-stroke.

Conclusions

Stroke has a substantial impact on HRQoL in Singapore, especially in the first three months post-stroke. Compared to the general population, stroke survivors have lower HRQoL even before stroke onset. This pre-stroke deficit in HRQoL should be taken into account when quantifying health burden of stroke or setting goals for stroke rehabilitation.

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