Cognitive Neuropsychological Tests Research Articles

Unilateral Magnetic Resonance-Guided Focused Ultrasound Lesion of the Subthalamic Nucleus in Parkinson's Disease: A Prospective Study.

Unilateral subthalamic nucleus (STN) ablation using magnetic resonance-guided focused ultrasound (MRgFUS) is being explored as a new treatment for asymmetric Parkinson's disease (PD). The aims were to study the efficacy and safety of this treatment in asymmetric PD patients and to characterize the lesions. This prospective, single-center, open-label study evaluated asymmetric PD patients at 6 (n = 20) and 12 months (n = 12) after MRgFUS lesion of the STN. The primary outcome was the change in the Movement Disorders Society-Unified Parkinson's Disease Rating Scale, Part III (MDS-UPDRS III), score in off medication on the treated side and the adverse events (AEs) at 6-month follow-up. We also evaluated cognitive-neuropsychological changes, self-assessment of clinical improvement, and the correlation of the lesion volume with the motor outcomes. On the treated side, the MDS-UPDRS III score (mean difference = 13.8) and the scores in rigidity, bradykinesia, and tremor improved (P < 0.001) throughout the follow-up compared to baseline (at 6 months: rigidity mean difference = 2.8, improvement: 83.5%; bradykinesia mean difference = 6.0, improvement: 69.4%; tremor mean difference = 4.7, improvement: 91.5%). One patient had severe weakness in the treated hemibody, 1 had moderate dyskinesia, and 1 was in moderate confusional state that became mild (weakness) or completely resolved (dyskinesia and confusional state) at 6 months. The rest of the AEs were mild. We observed no clinically relevant changes in cognitive-neuropsychological tests. The percentage of ablation of the STN correlated with the improvement in the total MDS-UPDRS III and contralateral tremor scores (P < 0.05). Unilateral MRgFUS lesion of the STN resulted in a significant motor improvement. We observed no persistent severe AEs, although mild, mostly transient AEs were frequent. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

NEIGHBORHOOD DISADVANTAGE, IMAGING BIOMARKERS OF ALZHEIMER’S DISEASE, AND COGNITION IN DIVERSE OLDER ADULTS

Abstract Neuroimaging biomarkers of Alzheimer’s disease (AD) are well-validated in White populations. However, it remains unclear how these biomarkers are associated with cognition in non-White populations disproportionately affected by systemic socioeconomic discrimination. We investigated whether neighborhood disadvantage modifies associations of neuroimaging biomarkers with cognition in a diverse cohort of 198 adults ≥50 years, 50% of whom are Black. Outcomes included cognitive impairment and neuropsychological test scores. Predictors were indices of neurodegeneration, vascular damage, and brain amyloid burden, quantified using MR-based measures of cortical thickness and white matter hyperintensities (WMH) and [11C]PiB PET, respectively. We measured neighborhood disadvantage using area deprivation index (ADI), a composite measurement of socioeconomic conditions in a census tract. In linear models, higher ADI, neurodegeneration, and WMH were separately associated with worse cognition. We found an ADI*neurodegeneration interaction on delayed recall memory (p=0.08). Neurodegeneration-positive participants had worse story delayed recall compared to neurodegeneration-negative regardless of ADI (β=-1.57, p=0.01). In neurodegeneration-negative participants, higher ADI is associated with worse delayed recall (β=-0.04, p=0.004): those with a high ADI exhibited low delayed recall, comparable to neurodegeneration-positive participants. ADI was not associated with cognition in neurodegeneration-positive participants. WMH and ADI interacted in models of impairment, visual memory, and visual copy (interaction p’s&amp;lt; 0.10). In those with high ADI, greater WMH was associated with worse cognition (β=-0.30, p=0.02) while participants with low ADI scored well regardless of WMH volume. Taken together, the relationship between neuroimaging biomarkers and cognition differs by neighborhood socioeconomic conditions, highlighting the need for clinical strategies that acknowledge structural disadvantage.

Detection of behavioral, depressive, and anxious symptoms in patients with Subjective Cognitive Complaints

AbstractBackgroundSubjective Cognitive Complaints (SCC) are frequent in Neurology. They may be defined as the self‐perception of cognitive decline without objective deficits in Neuropsychological tests. SCC have been associated with poorer cognitive performance, a higher risk of developing Cognitive Impairment or Dementia as well as neuropsychiatric symptoms such as depression and anxiety.Depression and anxiety are frequent mental health issues, with a remarkable impact on cognitive function. An increase in prevalence in both of them is estimated during the COVID‐19 pandemic. Also, behavioral symptoms have a negative impact on quality of life. Nevertheless, they may remain unnoticed if not investigated or without a family report.The objective is to report the frequency of depression, anxiety, and behavioral symptoms in a population with SCC.MethodWe selected patients with cognitive complaints and normal neuropsychological test performance. Demographic data, and behavioral, depressive, and anxious symptoms were collected. Anxious symptoms were assessed with the Beck Anxiety Inventory‐(BAI) and depressive symptoms with the Beck Depression Inventory‐(BDI‐II) and the Geriatric Depression Scale‐(GDS‐15). Neuropsychiatric Symptoms Inventory‐(NPI) was also investigated when an accompanist was available.Result166 patients were included. The mean age was 63.13 (SD 12.2) years, Mean Education was 11.25 (SD 3.62) years. In this sample the frequency of anxiety symptoms was 44.57% (n = 74) according to BAI; 48,64% (n = 36) were mild, 32.43% (n = 24) moderate and 18.93% (n = 14) severe. BDI‐II and GDS‐15 detected depression symptoms in 33.13% (n = 55) of the patients; 58.18% (n = 32) were mild, 32.72% (n = 18) moderate and 9.09% (n = 5) severe. In 59 cases we administer the NPI; 76.27% (n = 45) reported a symptom.ConclusionOur study showed a significant frequency of anxiety and depression symptoms as well as behavioral symptoms in patients with SCC. This reminds us how valuable it is to assess behavioral, depressive, and anxious symptoms in standard Neuropsychological Testing to take a comprehensive approach to the patients. Future studies will help to determine dementia‐developing predictors.

Long-term psychological outcomes following stroke: the OX-CHRONIC study

BackgroundStroke survivors rate longer-term (> 2 years) psychological recovery as their top priority, but data on how frequently psychological consequences occur is lacking. Prevalence of cognitive impairment, depression/anxiety, fatigue, apathy and related psychological outcomes, and whether rates are stable in long-term stroke, is unknown.MethodsN = 105 long-term stroke survivors (M [SD] age = 72.92 [13.01]; M [SD] acute NIH Stroke Severity Score = 7.39 [6.25]; 59.0% Male; M [SD] years post-stroke = 4.57 [2.12]) were recruited (potential N = 208). Participants completed 3 remote assessments, including a comprehensive set of standardized cognitive neuropsychological tests comprising domains of memory, attention, language, and executive function, and questionnaires on emotional distress, fatigue, apathy and other psychological outcomes. Ninety participants were re-assessed one year later. Stability of outcomes was assessed by Cohen’s d effect size estimates and percent Minimal Clinically Important Difference changes between time points.ResultsOn the Montreal Cognitive Assessment 65.3% scored < 26. On the Oxford Cognitive Screen 45.9% had at least one cognitive impairment. Attention (27.1%) and executive function (40%) were most frequently impaired. 23.5% and 22.5% had elevated depression/anxiety respectively. Fatigue (51.4%) and apathy (40.5%) rates remained high, comparable to estimates in the first-year post-stroke. Attention (d = -0.12; 85.8% stable) and depression (d = 0.09, 77.1% stable) were the most stable outcomes. Following alpha-adjustments, only perceptuomotor abilities (d = 0.69; 40.4% decline) and fatigue (d = -0.33; 45.3% decline) worsened over one year. Cognitive impairment, depression/anxiety, fatigue and apathy all correlated with worse quality of life.ConclusionNearly half of participants > 2 years post-event exhibited psychological difficulties including domains of cognition, mood, and fatigue, which impact long-term quality of life. Stroke is a chronic condition with highly prevalent psychological needs, which require monitoring and intervention development.

Clinical Features of Subjective Cognitive Decline in The Early Stages of Alzheimer’s Disease

Subclinical stage of the disease precedes the clinical stage of moderate cognitive decline in Alzheimer's disease (AD). Subjective cognitive decline (SCD) — a condition in which the level of cognitive function habitual for the subject gradually begins to decrease. In 2021, researchers from the National Institute on Aging and the Alzheimer's Association (NIA-AA) clinical criteria for the diagnosis of SCD have been proposed, as well as features that increase the probability of preclinical stage AD in patients with moderate cognitive impairment have been identified. Patients should be offered a complex of examinations — questionnaires regarding the impact of memory impairment on current cognitive activity (forgetfulness, searching for things, difficulty finding words, etc.), testable self-report of cognitive dynamics, neuropsychological testing and diagnosis of pathopsychological changes such as depression and anxiety. It would appear that counselling in the form of interviews and/or testing of persons able to provide relevant information about the patient should be included in the examination of patients with complaints of memory disorders, regardless of their degree of severity. It may be necessary to conduct a survey on the patient’s daily activity, ability to self-service (score, orientation, planning, control and so on), as well as to obtain information about any memory-related changes that have become visible to others, because it is the data from the partner/relative that increase the predictive value of the diagnostic. The modern approach to the study of cognitive functions in elderly people without dementia in the long-term is certainly able to help identify people with a high risk of developing AD.

Cross-sectional and longitudinal evaluation of plasma glial fibrillary acidic protein to detect and predict clinical syndromes of Alzheimer's disease.

This study examined plasma glial fibrillary acidic protein (GFAP) as a biomarker of cognitive impairment due to Alzheimer's disease (AD) with and against plasma neurofilament light chain (NfL), and phosphorylated tau (p-tau)181+231. Plasma samples were analyzed using Simoa platform for 567 participants spanning the AD continuum. Cognitive diagnosis, neuropsychological testing, and dementia severity were examined for cross-sectional and longitudinal outcomes. Plasma GFAP discriminated AD dementia from normal cognition (adjusted mean difference=0.90 standard deviation [SD]) and mild cognitive impairment (adjusted mean difference=0.72 SD), and demonstrated superior discrimination compared to alternative plasma biomarkers. Higher GFAP was associated with worse dementia severity and worse performance on 11 of 12 neuropsychological tests. Longitudinally, GFAP predicted decline in memory, but did not predict conversion to mild cognitive impairment or dementia. Plasma GFAP was associated with clinical outcomes related to suspected AD and could be of assistance in a plasma biomarker panel to detect in vivo AD.

Understanding the impact of radical changes in diet and the gut microbiota on brain function and structure: rationale and design of the EMBRACE study.

Bariatric surgery leads to profound changes in gut microbiota and dietary patterns, both of which may interact to impact gut-brain communication. Though cognitive function improves postsurgery, there is a large variability in outcomes. How bariatric surgery-induced modifications in the gut microbiota and dietary patterns influence the variability in cognitive function is still unclear. To elucidate the associations between bariatric surgery-induced changes in dietary and gut microbiota patterns with cognition and brain structure. University hospital. A total of 120 adult patients (≥30 years) scheduled to undergo a primary bariatric surgery along with 60 age-, sex-, and body mass index-matched patients on the surgery waitlist will undergo assessments 3-months presurgery and 6- and 12-month postsurgery (or an equivalent time for the waitlist group). Additionally, 60 age-and sex-matched nonbariatric surgery eligible individuals will complete the presurgical assessments only. Evaluations will include sociodemographic and health behavior questionnaires, physiological assessments (anthropometrics, blood-, urine-, and fecal-based measures), neuropsychological cognitive tests, and structural magnetic resonance imaging. Cluster analyses of the dietary and gut microbiota changes will define the various dietary patterns and microbiota profiles, then using repeated measures mixed models, their associations with global cognitive and structural brain alterations will be explored. The coordinating study site (Centre intégré universitaire de santé et de services sociaux du Nord-de-l'Île-de-Montréal, QC, Canada), provided the primary ethical approval (Research Ethics Board#: MP-32-2022-2412). The insights generated from this study can be used to develop individually-targeted neurodegenerative disease prevention strategies, as well as providing critical mechanistic information.

Long-term neurological complications in COVID-19 survivors: study protocol of a prospective cohort study (NeurodegCoV-19)

BackgroundEvidence suggests an association between SARS-CoV-2 infection and worse performance on cognitive tests, and a higher risk of Parkinson’s disease (PD) and dementia up to 6 and 12 months after...

Gender differences in cognitive function and its associated factors among older adults with type 2 diabetes

Diabetes is widely prevalent among older people and can influence accelerated cognitive decline. Gender-based disparities may contribute to variations in cognitive decline. This study examined gender differences in cognitive function and associated factors among older adults with diabetes. A cross-sectional study was conducted involving 318 Taiwanese older adults with type 2 diabetes. Demographic, health, and diabetes-related data were collected, and cognitive neuropsychological tests were evaluated. Compared to men, women with diabetes showed significantly poorer performance in global cognitive function and executive function. Age, years of education, sleep quality, and HbA1c were correlated with domains of cognitive function in men, whereas age, years of education, depressive symptoms, HbA1c, and duration of diabetes were associated with domains of cognitive function among women. Nurses should recognize gender differences in factors associated with cognitive function in older adults with diabetes and should develop individualized interventions to improve patients’ cognitive function.

Pausing before verb production is associated with mild cognitive impairment in Parkinson's disease.

Cognitive dysfunction and communication impairment are common and disabling symptoms in Parkinson's Disease (PD). Action verb deficits occur in PD, but it remains unclear if these impairments are related to motor system dysfunction and/or cognitive decline. The objective of our study was to evaluate relative contributions of cognitive and motor dysfunction to action verb production in naturalistic speech of patients with PD. We proposed that pausing before action-related language is associated with cognitive dysfunction and may serve as a marker of mild cognitive impairment in PD. Participants with PD (n = 92) were asked to describe the Cookie Theft picture. Speech files were transcribed, segmented into utterances, and verbs classified as action or non-action (auxiliary). We measured silent pauses before verbs and before utterances containing verbs of different classes. Cognitive assessment included Montreal Cognitive Assessment (MoCA) and neuropsychological tests to categorize PD participants as normal cognition (PD-NC) or mild cognitive impairment (PD-MCI) based on Movement Disorders Society (MDS) Task Force Tier II criteria. Motor symptoms were assessed using MDS-UPDRS. We performed Wilcoxon rank sum tests to identify differences in pausing between PD-NC and PD-MCI. Logistic regression models using PD-MCI as dependent variables were used to evaluate the association between pause variables and cognitive status. Participants with PD-MCI demonstrated more pausing before and within utterances compared to PD-NC, and the duration of these pauses were correlated with MoCA but not motor severity (MDS-UPDRS). Logistic regression models demonstrated that pauses before action utterances were associated with PD-MCI status, whereas pauses before non-action utterances were not significantly associated with cognitive diagnosis. We characterized pausing patterns in spontaneous speech in PD-MCI, including analysis of pause location with respect to verb class. We identified associations between cognitive status and pausing before utterances containing action verbs. Evaluation of verb-related pauses may be developed into a potentially powerful speech marker tool to detect early cognitive decline in PD and better understand linguistic dysfunction in PD.

Instruments Assessing Cognitive Impairment in Survivors of Critical Illness and Reporting of Race Norms: A Systematic Review.

A comprehensive search was conducted in PubMed (National Center for Biotechnology Information), Excerpta Medica dataBASE (Ovid), Psychological Information Database (ProQuest), and Web of Science (Clarivate) for English language studies published since 2002. Studies were eligible if the population included adult ICU survivors assessed for postdischarge cognitive outcomes. Two independent reviewers screened abstracts, examined full text, and extracted data from all eligible articles. A total of 98 articles (55 unique cohorts: 22 general ICU, 14 Acute respiratory distress syndrome/Acute respiratory failure/Sepsis, 19 COVID-19 and other subpopulations) were eligible for data extraction and synthesis. Among general ICU survivors, the majority of studies (n = 15, 68%) assessed cognition using multiple instruments, of which the most common was the Mini-Mental State Examination. Only nine of the 22 studies (41%) explicitly reported using patient demographic norms for scoring neuropsychological cognitive tests. Of the nine, all reported using age as a norming characteristic, education was reported in eight (89%), sex/gender was reported in five (55%), and race/ethnicity was reported in three (33%). Among Acute respiratory distress syndrome/Acute respiratory failure/Sepsis survivors, norming characteristics were reported in only four (28%) of the 14 studies, of which all reported using age and none reported using race/ethnicity. Less than half of the studies measuring cognitive outcomes in ICU survivors reported the use of norming characteristics. There is substantial heterogeneity in how studies reported the use of cognitive instruments, and hence, the prevalence of the use of patient norms may be underestimated. These findings are important in the development of appropriate standards for use and reporting of neuropsychological tests among ICU survivors.

P.002 Saccade parameters reveal cognitive impairment and differentially associate with cognitive domains across neurodegenerative diseases

Background: Eye movements reveal neurodegenerative disease processes due to overlap between oculomotor circuitry and disease-affected areas. Characterizing oculomotor behaviour in context of cognitive function may enhance disease diagnosis and monitoring. We therefore aimed to quantify cognitive impairment in neurodegenerative disease using saccade behaviour and neuropsychology. Methods: The Ontario Neurodegenerative Disease Research Initiative recruited individuals with neurodegenerative disease: one of Alzheimer’s disease, mild cognitive impairment, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, or cerebrovascular disease. Patients (n=450, age 40-87) and healthy controls (n=149, age 42-87) completed a randomly interleaved pro- and anti-saccade task (IPAST) while their eyes were tracked. We explored the relationships of saccade parameters (e.g. task errors, reaction times) to one another and to cognitive domain-specific neuropsychological test scores (e.g. executive function, memory). Results: Task performance worsened with cognitive impairment across multiple diseases. Subsets of saccade parameters were interrelated and also differentially related to neuropsychology-based cognitive domain scores (e.g. antisaccade errors and reaction time associated with executive function). Conclusions: IPAST detects global cognitive impairment across neurodegenerative diseases. Subsets of parameters associate with one another, suggesting disparate underlying circuitry, and with different cognitive domains. This may have implications for use of IPAST as a cognitive screening tool in neurodegenerative disease.

Prevalence of cognitive impairment following chemotherapy treatment for breast cancer: a systematic review and meta-analysis

Breast cancer survival rates have markedly improved. Consequently, survivorship issues have received increased attention. One common sequel of treatment is chemotherapy-induced cognitive impairment (CICI). CICI causes a range of impairments that can have a significant negative impact on quality of life. Knowledge of the prevalence of this condition is required to inform survivorship plans, and ensure adequate resource allocation and support is available for sufferers, hence a systematic review of prevalence data was performed. Medline, Scopus, CINAHL and PSYCHInfo were searched for eligible studies which included prevalence data on CICI, as ascertained though the use of self-report, or neuropsychological tests. Methodological quality of included studies was assessed. Findings were synthesised narratively, with meta-analyses being used to calculate pooled prevalence when impairment was assessed by neuropsychological tests. The review included 52 studies. Time-points considered ranged from the chemotherapy treatment period to greater than 10 years after treatment cessation. Summary prevalence figures (across time-points) using self-report, short cognitive screening tools and neuropsychological test batteries were 44%, 16% and 21–34% respectively (very low GRADE evidence). Synthesised findings demonstrate that 1 in 3 breast cancer survivors may have clinically significant cognitive impairment. Prevalence is higher when self-report based on patient experience is considered. This review highlights a number of study design issues that may have contributed to the low certainty rating of the evidence. Future studies should take a more consistent approach to the criteria used to assess impairment. Larger studies are urgently needed.

Characteristics of Dysregulated Proinflammatory Cytokines and Cognitive Dysfunction in Late-Life Depression and Amnestic Mild Cognitive Impairment.

BackgroundLate-life depression (LLD) and amnestic mild cognitive impairment (aMCI) are two different diseases associated with a high risk of developing Alzheimer’s disease (AD). Both diseases are accompanied by dysregulation of inflammation. However, the differences and similarities of peripheral inflammatory parameters in these two diseases are not well understood.MethodsWe used Luminex assays to measure 29 cytokines simultaneously in the plasma of two large cohorts of subjects at high risk for AD (23 LLD and 23 aMCI) and 23 normal controls (NCs) in the community. Demographics and lifestyle factors were also collected. Cognitive function was evaluated with the Chinese versions of the Montreal Cognitive Assessment (C-MoCA) and neuropsychological test battery (NTB).ResultsWe observed a remarkably increased level of IL-6 in the plasma and reduced levels of chemokines (CXCL11 and CCL13) in the LLD group compared with the aMCI group. The LLD group also showed lower levels of CXCL16 than the NC group. Furthermore, altered cytokine levels were associated with abnormal results in neuropsychological testing and Geriatric Depression Scale scores in both the LLD and aMCI groups. Notably, combinations of cytokines (IL-6 and CCL13) and two subitems of C-MoCA (orientation and short-term memory) generated the best area under the receiver operating characteristic curve (AUROC = 0.974).ConclusionA novel model based on proinflammatory cytokines and brief screening tests performs with fair accuracy in the discrimination between LLD and aMCI. These findings will give clues to provide new therapeutic targets for interventions or markers for two diseases with similar predementia syndromes.

Olive polyphenols and bioavailable glutathione: Promising results in patients diagnosed with mild Alzheimer's disease.

IntroductionRecent studies highlighted the role of olive polyphenols in disrupting the ordered structure of highly cytotoxic amyloid beta protofibrils and the efficacy of a derivatized form of glutathione to counteract neuronal oxidative stress affecting specific brain regions at early stages of Alzheimer's disease (AD) pathogenesis. We performed a randomized cross‐over clinical trial to evaluate their potential benefits in mild AD.MethodsOleuropein and S‐acetyl glutathione were administered as dietary supplement for 6 months to 18 patients diagnosed for probable mild AD according to International Working Group 2 criteria. Patients underwent an extensive cognitive and behavioral neuropsychological test battery at the beginning and end of the study to evaluate cognitive deterioration, memory, visuospatial abilities, attention, language, executive functions, and behavioral disorders. We compared patients receiving treatment to patients receiving no treatment.ResultsAll the measured neurocognitive parameters stabilized or improved after the treatment in all patients.DiscussionDietary supplement with olive polyphenols and bioavailable glutathione could be useful for patients diagnosed with mild AD.

Brain amyloid load and cognitive trajectories in older individuals at risk for dementia

AbstractBackgroundMost studies have so far investigated the cognitive performances and amyloid status on brain PET scans in cognitively normal, cognitively impaired, or individuals with dementia. In this study associations between brain amyloid status and changes in cognitive performance over time in an at‐risk older general population without dementia or substantial cognitive impairment were evaluated.MethodForty‐eight individuals from the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) main study participated in the 11C‐Pittsburgh compound B (PiB)‐positron emission tomography (PET) exploratory sub‐study. Participants were categorized as amyloid+ or amyloid– after baseline PET scans were assessed visually by two experienced readers. A comprehensive cognitive Neuropsychological Test Battery (NTB) was used to assess cognitive performance at baseline, 12‐ and 24‐month follow‐up. The Prospective and Retrospective Memory Questionnaire was used to measure subjective cognitive complaints (SCCs) during the study. Changes in cognitive functions during the 2‐year study were compared across baseline amyloid groups using mixed effects regression models with maximum likelihood estimation.ResultThe mean age for all participants (n=48) was 71.4 years, and 22 participants (45%) were female. At baseline, 20 participants (42%) had amyloid+ PET scans and amyloid positivity was associated with lower NTB executive function (estimate = ‐0.38, 95% CI= ‐0.70 – ‐0.05, p=0.03). Interaction terms between baseline amyloid+ status and time were significant for NTB total score (estimate=‐0.10, 95% CI= ‐0.20 – ‐0.01, p=0.04) and NTB memory score (estimate = ‐0.18, 95% CI= ‐0.34 – ‐0.03, p=0.02). No significant associations were observed between amyloid positivity and change in NTB executive function score or NTB processing speed score. Furthermore, amyloid status was not significantly related to SCCs.ConclusionResults from this study suggest that positive amyloid status is likely to reduce cognitive abilities over time. Interestingly, in this very early at‐risk stage before the onset of substantial impairment or dementia, amyloid status was related to poorer trajectories in global cognition and memory over time, but not to subjective cognitive complaints. However, future studies with larger sample sizes and longer follow up period will be needed to further investigate the impact of amyloid accumulation.

Effects of Combined Cognitive and Exercise Interventions on Poststroke Cognitive Function: A Systematic Review and Meta-Analysis.

Objective We investigated combined cognitive and exercise interventions in the literature and summarized their effectiveness in improving poststroke cognitive impairment (PSCI). Data Sources. Electronic databases and trial registries were searched from their inception until July 2020. Study Selection. Trials were collected with the following study inclusion criteria: (1) patients over 18 years of age who were diagnosed with PSCI; (2) combined cognitive-exercise interventions, regardless of the order of the two types of interventions or whether they were administered simultaneously; (3) any control group studied at the same time that was deemed acceptable, including no intervention/routine care, delayed intervention, sham intervention, and passive training; (4) the use of any validated cognitive neuropsychological test to evaluate cognitive function; and (5) clinically administered random trials with controls. Data Extraction. Five randomized controlled trials met the inclusion criteria. Two reviewers independently assessed the eligibility of the full texts and methodological quality of the included studies using the Cochrane risk of bias tool. Inconsistent results were resolved by additional discussion or decided by a third examiner, if necessary. Data Analysis. Meta-analysis demonstrated that the combined interventions had a significant effect on executive function and working memory [Stroop test (time), standardized mean difference (SMD) = 0.42, 95% confidence interval (CI): 0.80–0.04, p = 0.02; Trail Making Test, SMD = 0.49, 95% CI: 0.82–0.16, p = 0.004; Forward Digit Span Test, SMD = 0.91, 95% CI: 0.54–1.29, p ≤ 0.001]. While it was impossible to conduct a meta-analysis of global cognitive function and other cognitive domains, individual experiments demonstrated that the combined interventions played a significant role in global cognition, reasoning ability, logical thinking, and visual-spatial memory function. Conclusions Our analyses demonstrated that the combined interventions had a significant effect on the improvement of PSCI, particularly in terms of executive function. However, the moderate risk of bias in the included trials and the small number of relevant studies indicated a need for more uniform diagnostic and evaluation criteria, and larger trials would provide stronger evidence to better understand the effectiveness of the combined interventions. This trial is registered with trial registration number INPLASY202160090.

Cognitive Profile of Adults with Sickle Cell Disease - Cluster Analysis

Background: Published literature on cognitive functioning in adults with sickle cell disease (SCD) is sparse when compared to children. A few reports describe deficits in processing speed and executive functioning. Some studies suggest that these deficits are more severe in patients with silent cerebral infarcts (SCI). Even in the absence of radiological evidence of ischemic injury, some cognitive deficits have been depicted in adults . We hypothesize that in SCD adults, the cognitive profile varies with the presence of ischemic injury (SCI or overt stroke). The aims of this study were 1) to describe the neuropsychological profiles of SCD adults, and 2) to characterize clusters of patients with similar cognitive profiles.Methods: We conducted a retrospective analysis of all consecutive SCD adults who underwent comprehensive neuropsychological assessment during routine care at the UMGGR clinic at Henri Mondor Hospital, Créteil (France), between January 2017 and April 2021. The Montreal Cognitive Assessment (MoCA) and Hospital Anxiety and Depression Scale (HADS) were used for cognitive disorder, anxiety and depression screening, respectively. The cognitive battery combined standardized neuropsychological tests with established clinical utility and validity. Educational attainment was scored based on the number of years of schooling for the highest completed diploma. Principal component analysis was performed. ANOVA was used to compare patients' characteristics between clusters.Results: 80 patients, median age 36.5 [range 19-63] years were included. 40 (50.0%) were male. Genotype distribution was 62 patients (77.5%) with SS/Sbeta 0, 12 (15.0%) with SC and 6 (7.5%) with Sbeta +. On Principal Component Analysis, a 5-factor model presented the best fit (Bartlett's sphericity test (χ²(171)=1174; p<0.001)), explaining 71.8% of the variance in neuropsychological scores. The first factor encompassed tests specifically assessing visual attention/visual organization (right hemisphere). The second included tests for mental/cognitive control (frontal lobe), the third tests of selective inhibition/attention (fronto-parietal), the fourth tests for language/memory (left temporal lobe) and the last referred to shifting skill (sub-cortical loop). On hierarchical classification, 3 different clusters emerged: 32 patients in cluster 1, 32 in cluster 2 and 16 in cluster 3. Cluster 1 had a lower mean educational level (F(2,77) = 15,65; p<0,001). Cluster 1 showed the lowest mean MoCA score (20.0/30.0), relative to cluster 2 and 3 (24.6 and 26.4; p<0.001 and p<0.001, respectively). Cluster 1 patients presented deficits on all five factors. Cluster 2 patients compared to cluster 3 were altered in 4 factors (factors 1-4), but to a lesser extent than cluster 1. Processing speed was slower and some frontal-executive deficits were present in cluster 2 compared to cluster 3. There was no statistical difference between clusters in terms of ethnic origins. There was a trend for the presence of more cerebral vasculopathy in cluster 1 (chi2; p=0.06). Regarding stroke, 70% occurred during childhood in cluster 1, whereas 70% during adulthood in cluster 2, and 100% during adulthood in cluster 3.Conclusions: Overall, these results suggest at least three different cognitive profiles in adults with SCD: 1) few or no cognitive deficits (cluster 3), 2) some cognitive impairment with a sub-cortical cognitive profile (cluster 2) and 3) more global cognitive impairment with cortical/sub-cortical profile and specific deficits of memory, language and constructional praxis, depending on the location of prior overt neurological events (cluster 1). To reduce the long-term cognitive morbidity of SCD, patients can be identified by their distinct cognitive profiles and neurorehabilitation tailored to their unique profile should be applied. The large proportion of childhood stroke in patients with global cognitive impairment in contrast with majority of those with milder to no cognitive impairment having had their stroke in adulthood emphasize the crucial importance of preventing early childhood stroke and implementing early neurorehabilitation. DisclosuresForté: Canadian Hematology Society: Research Funding; Pfizer: Research Funding; Novartis: Honoraria. Kuo: Pfizer: Consultancy, Research Funding; Bluebird Bio: Consultancy; Novartis: Consultancy, Honoraria; Apellis: Consultancy; Alexion: Consultancy, Honoraria; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy; Bioverativ: Membership on an entity's Board of Directors or advisory committees. Bartolucci: Jazz Pharma: Other: Lecture fees; AGIOS: Consultancy; Emmaus: Consultancy; GBT: Consultancy; F. Hoffmann-La Roche Ltd: Consultancy; Hemanext: Consultancy; INNOVHEM: Other: Co-founder; Bluebird: Consultancy, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Lecture fees, Steering committee, Research Funding; Fabre Foundation: Research Funding; Addmedica: Consultancy, Other: Lecture fees, Research Funding.

Application of neuropsychology and imaging to brain injury and use of the integrative cognitive rehabilitation psychotherapy model.

An early approach to cognitive rehabilitation therapy (CRT) was developed based on A. R. Luria's theory of brain function. Expanding upon this approach, the Integrative Cognitive Rehabilitation Psychotherapy model (ICRP) was advanced. To describe the ICRP approach to treatment of clients post brain injury and provide a comprehensive list of evaluation tools to determine the client's abilities and needs. Finally, to provide a link between CRT and functional imaging studies designed to improve rehabilitation efforts. History of cognitive rehabilitation and neuropsychological testing is reviewed and description of cognitive, academic, psychiatric, and substance abuse tools are provided. Cognitive and emotional treatment techniques are fully described. Additionally, a method of determining the client's stage of recovery and pertinent functional imaging studies is detailed. Authors have been able to provide a set of tools and techniques to use in comprehensive treatment of clients with brain injury. Inclusive treatment which is outlined in the ICRP model is optimal for the client's recovery and return to a full and satisfying life post brain injury. The model provides a framework for neuropsychologists to integrate issues that tend to co-occur in clients living with brain injury into a unified treatment plan.

Invited Perspective: Air Pollution and Dementia: Challenges and Opportunities.

Invited Perspective: Air Pollution and Dementia: Challenges and Opportunities.