Addenbrooke's Cognitive Examination Research Articles

#1806 Cycling is safe – effect of intradialytic cycle ergometry on cerebral oxygenation and cognitive function – a pilot study

Abstract Background and Aims Patients on chronic hemodialysis benefit from intradialytic exercise with improvements in endurance, muscle strength and health-related quality of life. It is not known whether the increased oxygen demand during intradialytic exercise negatively affects cerebral oxygenation and cerebral function. The aim of the study was to assess the risk of cerebral undersupply by measuring cerebral oxygenation, perfusion and cognitive function during and after intradialytic ergometer training. Method Twelve patience on maintenance hemodialysis (HD) trice weekly were included in the study. In an initial ramp test, using bed cycle ergometer, we first determined the maximum physical strength (Pmax) at the level of exhaustion (HD A). Then, one hour after start of a second HD (HD B), patients performed 40%, 50% and 60% of Pmax for 6 min. Pulmonary function tests, blood volume (BVM), cardiac output (by electrical cardiometry), regional cerebral oxygen saturation (rSO2) (by near-infrared spectroscopy) and cerebral blood flow (CBF, by Doppler sonography) were measured. The relative changes in rSO2, CBF and hematocrit were used to calculate cerebral oxygen supply (DO2). Cognitive tests (Stroop, Trail Making and Mini Addenbrookes Cognitive Examination Test) were performed before and after HD sessions with and, as controls, without ergometry (HD-C). Results Median age was 68 (42-85) years, 9/12 were male, complete data set was obtained in 10 patients. During step test exercise (HD B), at the highest exercise level (according to Borg (1-10) 6.75 ± 2.9), rSO2 increased (+6 ± 9%, p=0.034) without a significant change in CBF. In the meantime, relative blood volume decreased during ergometry (-5.8 ± 2.73%; p=0.002), causing a temporary increase of hematocrit. Despite a small decrease in CBF in 3 patients, the mean change of rSO2, CBF and hematocrit always had a positive trend in all patients, as a surrogate of stable cerebral oxygen supply (Table 1). In comparative cognitive tests (B vs. C), we observed no significant changes in cognitive functions. Conclusion In this pilot study, intradialytic bed-cycle ergometry during the first hour of HD for <20 min at 40-60% of patients’ individual maximum intensity had no negative effects on cerebral oxygenation and function. Specific studies testing the safety intradialytic exercise with different conditions, such as increasing intensity or duration, are needed.

Associations Between Midlife Anticholinergic Medication Use and Subsequent Cognitive Decline: A British Birth Cohort Study.

Anticholinergic medication use is associated with cognitive decline and incident dementia. Our study, a prospective birthcohortanalysis, aimed to determine if repeated exposure to anticholinergic medicationswas associated with greater decline, and whether decline was reversed with medication reduction. From the Medical Research Council (MRC) National Survey of Health and Development, a British birth cohort with all participants born in a single week of March 1946, we quantified anticholinergic exposure between ages 53 and 69 years using the Anticholinergic Cognitive Burden Scale (ACBS). We used multinomial regression to estimate associations with global cognition, quantified bythe Addenbrooke's Cognitive Examination, 3rd Edition (ACE-III). Longitudinal associations between ACBS and cognitive test results (Verbal memory quantifiedby theWord Learning Test [WLT], and processing speed quantified by theTimed Letter Search Task [TLST]) at three time points (age 53, 60-64 and 69) were assessed using mixed and fixed effects linear regression models. Analyses were adjusted for sex, childhood cognition, education, chronic disease count and severity, and mental health symptoms. Anticholinergic exposure was associated cross-sectionally with lower ACE-III scores at age 69, with the greatest effects in those with high exposure at ages 60-64 (mean difference - 2.34, 95% confidence interval [CI] - 3.51 to - 1.17). Longitudinally, both mild-moderate and high ACBS scores were linked to lower WLT scores, again with high exposure showing larger effects (mean difference with contemporaneous exposure - 0.90, 95% CI - 1.63 to - 0.17; mean difference with lagged exposure - 1.53, 95% CI - 2.43 to - 0.64). Associations remained in fixed effects models (mean difference with contemporaneous exposure -1.78, 95% CI -2.85 to - 0.71; mean difference with lagged exposure - 2.23, 95% CI - 3.33 to - 1.13). Associations with TLST were noted only in isolated contemporaneous exposure (mean difference - 13.14, 95% CI - 19.04 to - 7.23; p<0.01). Anticholinergic exposure throughout mid and later life was associated with lower cognitive function. Reduced processing speed was associated only with contemporaneous anticholinergic medication use, and not historical use. Associations with lower verbal recall were evident with both historical and contemporaneous use of anticholinergic medication, and associations with historical use persisted in individuals even when their anticholinergic medication use decreased over the course of the study.

Differential Synaptic Loss in β-Amyloid Positive Versus β-Amyloid Negative Corticobasal Syndrome.

The corticobasal syndrome (CBS) is a complex asymmetric movement disorder, with cognitive impairment. Although commonly associated with the primary 4-repeat-tauopathy of corticobasal degeneration, clinicopathological correlation is poor, and a significant proportion is due to Alzheimer's disease (AD). Synaptic loss is a pathological feature of many clinical and preclinical tauopathies. We therefore measured the degree of synaptic loss in patients with CBS and tested whether synaptic loss differed according to β-amyloid status. Twenty-five people with CBS, and 32 age-/sex-/education-matched healthy controls participated. Regional synaptic density was estimated by [11C]UCB-J non-displaceable binding potential (BPND), AD-tau pathology by [18F]AV-1451 BPND, and gray matter volume by T1-weighted magnetic resonance imaging. Participants with CBS had β-amyloid imaging with 11C-labeled Pittsburgh Compound-B ([11C]PiB) positron emission tomography. Symptom severity was assessed with the progressive supranuclear palsy-rating-scale, the cortical basal ganglia functional scale, and the revised Addenbrooke's Cognitive Examination. Regional differences in BPND and gray matter volume between groups were assessed by ANOVA. Compared to controls, patients with CBS had higher [18F]AV-1451 uptake, gray matter volume loss, and reduced synaptic density. Synaptic loss was more severe and widespread in the β-amyloid negative group. Asymmetry of synaptic loss was in line with the clinically most affected side. Distinct patterns of [11C]UCB-J and [18F]AV-1451 binding and gray matter volume loss, indicate differences in the pathogenic mechanisms of CBS according to whether it is associated with the presence of Alzheimer's disease or not. This highlights the potential for different therapeutic strategies in CBSs. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

PSYCHIATRIC COMORBIDITIES IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Objective: COPD often exists with comorbidities that may have a significant impact on prognosis. Patients with COPD are predisposed to both cognitive and psychiatric disorders. Anxiety and depression are common and important comorbidities in patients with chronic obstructive pulmonary disease (COPD). Regarding this, there is a lack of data from state of Himachal Pradesh.&#x0D; Methods: Our study was a cross-sectional study wherein 100 patients who attended the Pulmonary Medicine outpatient clinic of IGMC, Shimla were recruited. Patients were evaluated using tools International Classification of Disease, 10threvision, MINI 6.0, Addenbrooke's Cognitive Examination, Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale.&#x0D; Results: About two-third (62%) of the patients were found to have psychiatric co-morbidities. The most common psychiatric co-morbidity was found to be mixed anxiety and depression in 20% of the patients followed by unspecified anxiety disorder in 12% of the patients,9% of the patients were diagnosed with dementia while 6% were found to have a major depressive disorder. As per our observation, the severity of anxiety and depressive symptoms as per the HARS scale and HAMD scales, respectively, increased as the severity of the disease increased.&#x0D; Conclusion: The present study shows that about two third (62%) of the patients were found to have psychiatric co-morbidities. Psychiatric comorbidities have a significant impact on quality of life, exacerbation frequency and survival. Another multicentre large observational study can be planned in the future to overcome the above problems.

The testamentary capacity in acute stroke. A cross-sectional study.

Succession law, which governs the creation and validity of wills, is closely tied to testamentary capacity (TC), the cognitive competence required for a valid will. This study explores TC in acute stroke patients and its connections to demographic and clinical characteristics. The research included first-time stroke patients admitted within 24 hours of symptom onset, meeting specific criteria. Data were collected, and assessment tools like the Addenbrooke's Cognitive Examination III (ACE-III) and Testamentary Capacity Assessment Tool (TCAT) were used. The study found that TCAT scores were not significantly affected by age or gender but positively correlated with education, the Barthel Index and ACE-III scores. They were negatively associated with National Institutes of Health Stroke Scale (NIHSS) and Modified Rankin Scale (mRS) scores. Specific cognitive domains, particularly memory and attention, were independent determinants of TCAT scores. This research introduces TCAT as a valuable tool for evaluating testamentary capacity in stroke patients and highlights the multifaceted nature of TC, emphasizing the need for a nuanced approach. As the population ages and complex medical conditions become more prevalent, understanding the interplay between cognitive functioning and testamentary capacity becomes increasingly crucial for both legal and medical professionals.

Hippocampal subfields volume changes and its correlation with memory functions in patients with mild cognitive impairment

BackgroundThis study examined hippocampal subfields volumes in patients with mild cognitive impairment (MCI) as potential non-invasive predictive neuroimaging markers of cognitive decline. MethodsT1-weighted images and Addenbrooke's cognitive examination III (ACE-III) data were obtained from 36 healthy controls and 27 MCI patients. The hippocampal subfields volumes were extracted using Freesurfer software, and group differences and correlation were assessed using general linear model (GLM) with age, sex, and total intracranial volume (TIV) as covariates. ResultsMCI participants exhibited significant decrease in memory scores and notable volumetric changes in hippocampal subfields, including the bilateral hippocampal tail, subiculum, CA1, CA3, molecular layer, as well as the left presubiculum, parasubiculum, CA4, GC-ML-DG, and HATA. Moreover, the left presubiculum, left parasubiculum, and left GC-ML-DG showed significant positive correlations with ACE memory scores in MCI patients. ConclusionsThe alterations in hippocampal subfields in MCI patients may indicate underlying neurodegenerative processes associated with Alzheimer's disease (AD) pathology.

Remote digital cognitive assessment reveals cognitive deficits related to hippocampal atrophy in autoimmune limbic encephalitis: a cross-sectional validation study

Autoimmune limbic encephalitis (ALE) is a neurological disease characterised by inflammation of the limbic regions of the brain, mediated by pathogenic autoantibodies. Because cognitive deficits persist following acute treatment of ALE, the accurate assessment of long-term cognitive outcomes is important for clinical assessments and trials. However, evaluating cognition is costly and an unmet need exists for validated digital methods. In this cross-sectional validation study, we investigated whether a remote digital platform could identify previously characterised cognitive impairments in patients with chronic ALE and whether digital metrics would correlate with standard neuropsychological assessment and hippocampal volume. Patients with ALE who had a chronic and stable presentation and received a clinical diagnosis of ALE were recruited for this study. The cognitive performance of 21 patients with ALE and 54 age-matched healthy controls - enrolled via the University of Oxford (UK) Cognitive Neurology Lab testing programme - was assessed with a battery of 12 cognitive tasks from the Cognitron online platform. The platform was optimised with National Institute for Health and Care Research (NIHR) support to be deliverable remotely to elderly and patient groups. The primary outcome measure was behavioural performance and corresponding neuroimaging and neuropsychological assessment metrics. Between February 15, 2021, and April 21, 2022, 21 patients with ALE (mean age 63.01 years, 14 males) and 54 healthy controls (mean age 65.56 years, 23 males) completed the digital cognitive assessment. Patients with ALE performed significantly worse in memory, visuospatial abilities, executive function, and language. No impairments in digit & spatial span, target detection (attention) and emotion discrimination were observed. The global score on the online cognitive tasks correlated significantly with the established Addenbrooke's Cognitive Examination III (ACE) pen-and-paper test. Deficits in visuospatial processing and language were identified in ALE compared to controls using remote digital testing but not using the ACE, highlighting higher sensitivity of computerised testing to residual cognitive impairment. Finally, the hippocampal volumes of patients with ALE and healthy controls correlated with online cognitive scores. These findings demonstrate that subtle cognitive deficits in patients with chronic ALE, who often show full recovery in measures of disability and dependence on daily activities, are detectable using a remote online platform, which also relates to hippocampal atrophy. Such methods may facilitate the characterisation of cognitive profiles in complex neurological diseases. Future longitudinal studies designed to assess the utility of such digital methods for further clinical characterisation are needed. The Wellcome Trust, Medical Research Council, National Institute for Health Research, Rhodes Scholarship, and the Berrow Foundation Scholarship.

Shorter Reperfusion Time in Stroke is Associated with Better Cognition.

Cognitive changes that result from cerebrovascular disease contribute to a poor functional outcome with reduced quality of life. Among patients undergoing endovascular therapy (EVT), we aim to assess cognitive function and evaluate the impact of reperfusion time in cognitive performance. Patients with acute right anterior circulation strokes that underwent EVT between January 2018 and August 2020 at Centro Hospitalar de Vila Nova de Gaia/Espinho, participated in the study. Modified treatment in cerebral infarction (mTICI) assessed the level of recanalization. Cognitive evaluation was assessed with Addenbrooke's Cognitive Examination revised (ACE-R). Multiple linear regression analyses were used to determine the association between time for recanalization and ACE-R. The level of significance adopted was 0.05. The mean age of participants was 71.5 (interquartile range [IQR] 62.0-78.2) years, and 50% (22) were women. The median time after stroke was 28.6 months (IQR 18.94-31.55). All patients in our sample had a successful level of recanalization with EVT (mTICI ≥ 2b). Time for recanalization showed an inverse association with the ACE-R (b = -0.0207, P = 0.0203). Also the mRS at 3 months had an inverse association with cognition (b = -5.2803, p = 0.0095). Level of education had a strong and direct relationship with ACE-R results (b = 3.0869, p < 0.0001). Longer time between stroke symptoms and recanalization with EVT in patients with right hemisphere ischemic stroke lead to lower ACE-R scores. Measures to improve door-to-recanalization time are also important for cognitive performance after ischemic stroke.

Relationship between occupation and cognitive performance in patients with cognitive impairment. Preliminary study

AbstractBackgroundPrevious studies showed the protective effect of cognitive reserve for the development of cognitive impairment and dementia symptoms. Some factors have been postulated that may influence cognitive reserve, including education, participation in cognitively stimulating activities, and occupation. It has been observed that certain occupations have better cognitive performance and different professions may generate better functioning in certain cognitive domains than others. The aim of this study is to assess whether there is greater strength in certain cognitive domains related to the occupations of patients with subjective memory complaints or mild cognitive impairment diagnosis.MethodRetrospective observational study with patients under follow‐up in a memory clinic in Buenos Aires, Argentina. Patients with &gt;17 education years, &gt; 50 years with a diagnosis of subjective memory complaint and/or mild cognitive impairment of any origin were included. Subjects with dementia were excluded. The occupations were classified according to the ISCO‐88 (2008 International Labor Organization) utilizing professionals’ subcategory. A complete cognitive evaluation was performed in all the patients, including memory, attention, language, executive functions, and visuospatial domains. For the statistical analysis, the z scores of the results of the different cognitive tests were used and parametric student`s‐t tests were performed using the Graphpad software,ResultA total of 57 patients from our center were included to date. The mean age was 71 (55‐85), years of education 19 (17‐25) and a total of 35 (61%) women. The mean of Addenbrooke’s Cognitive Examination (ACE) was 91.3 (82‐99). The predominant occupation was in the health category with a total of 24 (42%) patients. No statistically significant differences were obtained in the values of the different cognitive tests of each occupational category and the value of the total population.ConclusionThe study has not shown significant differences between specific cognitive variables and occupation in patients with cognitive impairment. However, a larger number of subjects would be needed to support this statement. It is important to note that extra‐work activities of patients that can also influence their cognitive performance have not been taken into account.

Plasma glucose does not influence performance on standard cognitive screening tests in a mixed memory clinic cohort

AbstractBackgroundIt has been shown under experimental conditions that cognitive performance, especially working memory, is impaired in type I and type II diabetes during hyperglycemic and hypoglycemic conditions, perhaps due to altered cerebral glucose metabolism. It is not known if patients with neurodegenerative diseases, who also exhibit pathological cerebral glucose metabolism, are affected in a similar manner by their intrinsic plasma glucose levels. We aimed to test if performance on two standard cognitive screening tests is influenced by intrinsic plasma glucose levels in a memory clinic cohort.MethodIn this retrospective study, we included patients from the Copenhagen Memory Clinic Cohort (CMCC) with an available Mini Mental‐State Examination (MMSE) test score and a plasma glucose measurement performed in conjunction with cognitive testing. Patients were included from the inception of the cohort in 2008 till September 2021. We built linear regression models with MMSE and Addenbrooke’s Cognitive Examination (ACE) test scores as the outcome and plasma glucose as the explaining variable and adjusted models for age, sex and diabetes (plasma glucose measurement &gt; 11.1 mmol/L). We explored non‐linear relationships by adding squared terms to the models and by fitting cubic spline regression models.ResultIn total, 2714 patients had an available MMSE score and a plasma glucose measurement. Patients had a mean age of 71.6 years [range 19‐99] and a baseline plasma glucose level of 5.8 mmol/L [range 2.7‐28.1]. A total of 581 of patients had a plasma glucose level outside normal range (&lt;4.2 or &gt;6.3 mmol/L). A total of 31.2% of the cohort studied had a diagnosis of Alzheimer’s disease (AD). MMSE and ACE total scores were not influenced by plasma glucose in a linear nor in a non‐linear fashion, when we adjusted for age, sex and diabetes. Sub‐group analyses in patients with AD and in patients with cerebrovascular disease showed similar results.ConclusionPlasma glucose levels inside normal range were not shown to influence performance on routinely applied cognitive tests and do not need be taken into consideration when interpreting test results from memory clinic patients.

FDG-PET-based neural correlates of Addenbrooke's cognitive examination III scores in Alzheimer's disease and frontotemporal degeneration.

The Addenbrooke's Cognitive Examination III (ACE-III) is a brief test useful for neuropsychological assessment. Several studies have validated the test for the diagnosis of Alzheimer's disease (AD) and frontotemporal dementia (FTD). In this study, we aimed to examine the metabolic correlates associated with the performance of ACE-III in AD and behavioral variant FTD. We enrolled 300 participants in a cross-sectional study, including 180 patients with AD, 60 with behavioral FTD (bvFTD), and 60 controls. An 18F-Fluorodeoxyglucose positron emission tomography study was performed in all cases. Correlation between the ACE-III and its domains (attention, memory, fluency, language, and visuospatial) with the brain metabolism was estimated. The ACE-III showed distinct neural correlates in bvFTD and AD, effectively capturing the most relevant regions involved in these disorders. Neural correlates differed for each domain, especially in the case of bvFTD. Lower ACE-III scores were associated with more advanced stages in both disorders. The ACE-III exhibited high discrimination between bvFTD vs. HC, and between AD vs. HC. Additionally, it was sensitive to detect hypometabolism in brain regions associated with bvFTD and AD. Our study contributes to the knowledge of the brain regions associated with ACE-III, thereby facilitating its interpretation, and highlighting its suitability for screening and monitoring. This study provides further validation of ACE-III in the context of AD and FTD.

1 Adaptation of the Addenbrooke’s Cognitive Examination III for the Bengali speaking population in India: A systematic approach to reducing cultural and linguistic bias

Objective:A systematic approach is vital for adapting neuropsychological tests developed and validated in western monocultural, educated and English-speaking populations. However, rigorous and uniform methods are often not implemented during adaptation of neuropsychological tests and cognitive screening tools across different languages and cultures. This has serious clinical implications. Our group has adapted the Addenbrooke’s Cognitive Examination (ACE) III for the Bengali speaking population in India. We have taken a 'culture-specific’ approach to adaptation and illustrate this by describing the process of adapting the ACE III naming sub-test, with a focus on the process of selecting culturally appropriate and psychometrically reliable itemsParticipants and Methods:Two studies were conducted in seven phases for adapting the ACE III naming test. Twenty-three items from the naming test in the English and the different Indian ACE-R versions were administered to healthy Bengali speaking literate adults to determine image agreement, naming and familiarity of the items. Eleven items were identified as outliers. We then included 16 culturally appropriate items that were semantically similar to the items in the selected ACE-R versions of which 3 were identified as outliers. The final corpus consisting of 24 items was administered to 30 patients with mild cognitive Impairment, Alzheimer’s disease and vascular dementia, and 60 healthy controls matched for age and education to determine which items in the corpus best discriminated patients and the controls, and to examine their difficulty levels.Results:The ACE III Bengali naming test with an internal consistency of .76 included 12 psychometrically reliable, culturally relevant high naming-high familiarity and high naming-low familiarity living and non-living items. Item difficulty ranged from .47 to .88 and had discrimination indices &gt;.44.Conclusions:A key question for test development/adaptation is whether to aim for culture-broad or culture-specific tests. Either way, a systematic approach to test adaption will increase the likelihood that a test is appropriate for the linguistic/cultural context in which it is intended to be used. Adaptation of neuropsychological tests based on a familiarity driven approach helps to reduce cultural bias at the content level. This coupled with appropriate item selection statistics helps to improve the validity of the adapted tests and ensure cross-cultural comparability of test scores both across and within nations.

GLIOMA-16 EARLY NEUROCOGNITIVE OUTCOME POST RESECTION OF ADULT SUPRATENTORIAL GLIOMAS AT THE KENYATTA NATIONAL HOSPITAL

Abstract Gliomas are the commonest brain tumors in our setting. Traditionally; Overall Survival, progression free survival and Extent of resection are used to define oncologic outcome in gliomas. These measures don’t reflect the complete patient status and hence the need for functional outcome determination. Cognitive outcome, is a key functional measure in gliomas. This was a prospective Cohort Study whose objective was to determine the Early Neurocognitive outcome post-resection of adult supratentorial gliomas at the Kenyatta National Hospital. Our study population was adult patients with supratentorial gliomas. We examined twenty patients who met the inclusion criteria. Data collection was by an interviewer-based questionnaire incorporating the ACE III (Addenbrooke Cognitive Examination III) tool administered at three instances as follows: - Within two weeks Preoperatively (T0), at one week postoperatively (T1) and at four weeks postoperatively (T2). The pre and post operative cognitive scores were then analyzed to determine the cognitive outcome. Statistical significance was considered where the p-value was &amp;lt;0.05. Ninety five percent of patients had cognitive impairment at baseline. Mean age of presentation was 34.3 years for Low grade glioma (LGG) and 43.8 years for High Grade Glioma (HGG). 55% of patients had LGG while 45% had HGG. Overall, there was transient decline in cognition from T0-T1 and a gradual improvement beyond the baseline from T1-T2. This improvement was across all domains but was significant in the total ACE score, memory and fluency. LGG showed the greatest improvement in cognition especially in the fluency domain. Sixty percent of the tumors were subtotally resected and showed significant cognitive change in the domains of Attention, fluency and Visuospatial association. Glioma surgery in our setting results in a transient decline in cognition one week postoperatively after which improvement in cognition beyond baseline is noted one month post operatively.

Prevalence, correlates and explanatory models of cognitive deficits in patients with schizophrenia-A cross sectional study.

Schizophrenia may cause significant impairment in social and economic aspects of a patient's life. Current evidence suggests that cognitive deficits may affect the functioning of a person with schizophrenia more than positive or negative symptoms. There is a lack of literature on explanatory models of cognitive deficits in schizophrenia that can influence help-seeking behavior. This study aimed to estimate the prevalence of cognitive deficits and assess their relationship with socio-demographic and clinical characteristics among patients with schizophrenia. We also planned to explore the explanatory models of cognitive deficits in these patients. Consecutive outpatients with schizophrenia who met eligibility criteria were recruited after obtaining informed consent. The Addenbrooke's Cognitive Examination Tamil version (ACE III) and Observable Social Cognition - A Rating Scale (OSCARS) and Positive and Negative Symptom Scale (PANSS) were used to assess cognitive functioning and symptom profile, respectively. Beliefs about illness were recorded using the modified Short Explanatory Model Interview (SEMI). Socio-demographic and treatment-related details were collected with a structured proforma. Statistical analysis was done using SPSS for Windows (version 16.0.1). One hundred and forty patients participated in the study. The prevalence of cognitive deficits was 75.7% using ACE-III scores, 19.3% on OSCARS, and 40% based on subjective reports. Though the majority (81.4%) of patients reported a medical explanatory model for cognitive impairment, a significant number of them (70.7%) also held non-medical models simultaneously. Cognitive deficits are prevalent in the majority of patients with schizophrenia. Poor test performance on cognitive testing was observed in those with a significant family history. Multiple contradictory explanatory models for the causation of cognitive deficits were reported.

Cognitive and gait in Wilson's disease: a cognitive and motor dual-task study.

Cognitive and motor dual-tasks play important roles in daily life. Dual-task interference impacting gait performance has been observed not only in healthy subjects but also in subjects with neurological disorders. Approximately 44-75% of Wilson's disease (WD) patients have gait disturbance. According to our earlier research, 59.7% of WD patients have cognitive impairment. However, there are few studies on how cognition affects the gait in WD. Therefore, this study aims to explore the influence of cognitive impairment on gait and its neural mechanism in WD patients and to provide evidence for the clinical intervention of gait disturbance. We recruited 63 patients who were divided into two groups based on their scores on the Addenbrooke's cognitive examination III (ACE-III) scale: a non-cognitive impairment group and a cognitive impairment group. In addition to performing the timed up and go (TUG) single task and the cognitive and motor dual-task digital calculation and animal naming tests, the Tinetti Balance and Gait Assessment (POMA), Berg Balance Scale (BBS), and brain MRI severity scale of WD (bMRIsc-WD) were evaluated. The dual-task cost (DTC) was also computed. Between the two groups, the results of the enhanced POMA, BBS, and bMRIsc-WD scales, as well as gait performance measures such as TUG step size, pace speed, pace frequency, and DTC value, were compared. (1) Among the 63 patients with WD, 30 (47.6%) patients had gait disturbance, and the single task TUG time was more than 10 s. A total of 43 patients had cognitive impairment, the incidence rate is 44.4%. Furthermore, 28 (44.4%) patients had cognitive impairment, 39 (61.9%) patients had abnormal brain MRI. (2) The Tinetti gait balance scale and Berg balance scale scores of patients with cognitive impairment were lower than those of patients without cognitive impairment (p < 0.05), and the pace, step size, and pace frequency in the single task TUG were slower than those of patients without cognitive impairment (p < 0.05). There was no change in the pace frequency between the dual-task TUG and the non-cognitive impairment group, but the pace speed and step size in the dual-task TUG were smaller than non-cognitive impairment group (p < 0.05). There was no difference in DTC values between cognitive impairment group and non-cognitive impairment group when performing dt-TUG number calculation and animal naming respectively (p > 0.05). However, regardless of cognitive impairment or not, the DTC2 values of number calculation tasks is higher than DTC1 of animal naming tasks in dt-TUG (p < 0.05). (3) Pace speed and step size were related to the total cognitive score, memory, language fluency, language understanding, and visual space factor score of the ACE-III (p < 0.05), and step frequency was correlated with memory and language comprehension factors (p < 0.05). There was no correlation between the attention factor scores of the ACE-III and TUG gait parameters of different tasks (p > 0.05). Brain atrophy, the thalamus, caudate nucleus, and cerebellum were correlated with cognitive impairment (p < 0.05), the lenticular nucleus was related to the step size, brain atrophy was related to the pace speed, and the thalamus, caudate nucleus, and midbrain were involved in step frequency in WD patients (p < 0.05). WD patients had a high incidence of cognitive impairment and gait disorder, the pace speed and step size can reflect the cognitive impairment of WD patients, cognitive impairment affects the gait disorder of WD patients, and the different cognitive and motor dual-tasks were involved in affecting gait parameters. The joint participation of cognitive impairment and lesion brain area may be the principal neural mechanism of gait abnormality in WD patients.

Potential modifications on verbal-language/orientation-memory ratio from Addenbrooke's cognitive examination III to predict mild cognitive impairment from healthy controls.

Potential modifications on verbal-language/orientation-memory ratio from Addenbrooke's cognitive examination III to predict mild cognitive impairment from healthy controls.

Association of periodontitis with cognitive decline and its progression: Contribution of blood-based biomarkers of Alzheimer's disease to this relationship.

To assess whether periodontitis is associated with cognitive decline and its progression as well as with certain blood-based markers of Alzheimer's disease. Data from a 2-year follow-up prospective cohort study (n = 101) was analysed. Participants with a previous history of hypertension and aged ≥60 years were included in the analysis. All of them received a full-mouth periodontal examination and cognitive function assessments (Addenbrooke's Cognitive Examination (ACE) and Mini-Mental State Examination [MMSE]). Plasma levels of amyloid beta (Aβ)1-40 , Aβ1-42 , phosphorylated and total Tau (p-Tau and t-Tau) were determined at baseline, 12 and 24 months. Periodontitis was associated with poor cognitive performance (MMSE: β = -1.5 [0.6]) and progression of cognitive impairment (hazard ratio [HR] = 1.8; 95% confidence interval: 1.0-3.1). Subjects with periodontitis showed greater baseline levels of p-Tau (1.6 [0.7] vs. 1.2 [0.2] pg/mL, p < .001) and Aβ1-40 (242.1 [77.3] vs. 208.2 [73.8] pg/mL, p = .036) compared with those without periodontitis. Concentrations of the latter protein also increased over time only in the periodontitis group (p = .005). Periodontitis is associated with cognitive decline and its progression in elderly patients with a previous history of hypertension. Overexpression of p-Tau and Aβ1-40 may play a role in this association.

Resting EEG power spectra across middle to late life: associations with age, cognition, APOE-ɛ4 carriage, and cardiometabolic burden

We investigated how resting electroencephalography (EEG) measures are associated with risk factors for late-life cognitive impairment and dementia, including age, apolipoprotein E ɛ4 (APOE-ɛ4) carriage, and cardiometabolic burden. Resting EEG was recorded from 86 adults (50–80 years of age). Participants additionally completed the Addenbrooke’s Cognitive Examination (ACE) III and had blood drawn to assess APOE-ɛ4 carriage status and cardiometabolic burden. EEG power spectra were decomposed into sources of periodic and aperiodic activity to derive measures of aperiodic component slope and alpha (7–14 Hz) and beta (15–30 Hz) peak power and peak frequency. Alpha and beta peak power measures were corrected for aperiodic activity. The aperiodic component slope was correlated with ACE-III scores but not age. Alpha peak frequency decreased with age. Individuals with higher cardiometabolic burden had lower alpha peak frequencies and lower beta peak power. APOE-ɛ4 carriers had lower beta peak frequencies. Our findings suggest that the slope of the aperiodic component of resting EEG power spectra is more closely associated with measures of cognitive performance rather than chronological age in older adults.

Evaluation of a comprehensive multicomponent support program for people with dementia and their carers: Study protocol for pilot trial

AbstractBackgroundA growing body of evidence demonstrates the importance of comprehensive multicomponent, person‐centred interventions, including education and support for people living with dementia and their carers following a diagnosis of dementia. However, in Australia, people with dementia and carers frequently face challenges accessing appropriate information, care and support services to support living in the community with different stages of dementia.MethodThe Sustainable Personalised Interventions for Cognition, Care, and Engagement (SPICE) program consists of evidence‐based therapeutic activities for people with dementia and carers. The project aims to recruit 24 dyads (24 people with dementia and 24 carers; four groups of six) to participate in a twelve‐week, twice per week support program using a randomised waiting‐list study design. The SPICE program intervention is delivered by allied health professionals and includes physical activity, cognitive stimulation therapy, and nutrition assessment for the person with dementia. Carers will receive support aimed to promote capacity building and self‐care, including practical strategies to manage behavioural changes. The dyad will also receive the Care of People with Dementia in their Environments (COPE) program which focuses on problem solving and goal setting in the home.ResultThe primary outcome for the intervention is quality of life of the person with dementia using the health‐related quality of life (DEMQOL) questionnaire. Secondary outcomes will assess cognition (Addenbrookes Cognitive Examination (ACE‐III)), neuropsychiatric symptoms (NPI), health and functional ability (WHODAS 2.0), physical function assessments, carer quality of life (C‐DEMQOL), and program satisfaction of the dyad. Categorical data will be summarised using frequency statistics and visualisation. Continuous and other numerical data will be visually explored and summarised using sample descriptive statistics, selected as appropriate based on apparent distributions.ConclusionThe SPICE program has the potential to promote quality of life of people with dementia and potentially delay cognitive decline while also providing a toolkit for carers to reduce carer burden. If successful, the outcomes of the study have the potential to improve post‐diagnostic care and clinical practice for people with dementia and their carers in Australia and inform services worldwide.

The Effect of Anaesthesia Management with Different Fresh Gas Flows on Cognitive Functions of Geriatric Patients: A Randomized Double-blind Study.

The present study aimed to compare the effects of two different fresh gas flows (FGFs) (0.5 L min-1 and 2 L min-1) applied during maintenance of anaesthesia on recovery from anaesthesia and early cognitive functions in geriatric patients. In this prospective, randomised, double-blind study, sixty patients were divided into two groups according to the amount of FGF. Minimal-flow anaesthesia (0.5 L min-1 FGF) was applied to group I and medium-flow anaesthesia (2 L min-1 FGF) was applied to group II during maintenance of anaesthesia. Following the termination of inhalation anaesthesia, recovery times were recorded. The evaluation of cognitive functions was performed using the Addenbrooke's Cognitive Examination (ACE-R). There was no significant difference between the two groups in terms of demographic characteristics and recovery (P > 0.05). There was no significant difference between the two groups in terms of the preoperative day, the first postoperative day, and the third postoperative day; ACE-R scores (P > 0.05). In group II, on the third postoperative day ACE-R scores were found to be significantly lower than the preoperative ACE-R scores (P=0.04). In group II, third postoperative day ACE-R memory sub-scores (14.53 ± 3.34) were found to be significantly lower than preoperative ACE-R memory sub-scores (15.03 ± 3.57) (P=0.04). In geriatric patients, minimal-flow anaesthesia was not superior to medium-flow anaesthesia in terms of recovery properties and cognitive functions. Keeping in mind that hypoxaemia and changes in anaesthesia levels may occur with the reduction of FGF, both minimal- and medium-flow anaesthesia can be applied with appropriate monitoring without adverse effects on recovery and cognitive functions.