Impairment In Cognitive Domains Research Articles

Relationships between Serum Lipid, Uric Acid Levels and Mild Cognitive Impairment in Parkinson's Disease and Multiple System Atrophy.

Mild cognitive impairment is one of the non-motor symptoms in Parkinson's disease (PD) and multiple system atrophy (MSA). Few studies have previously been conducted on the correlation between serum uric acid (SUA) and lipid levels and mild cognitive impairment in PD and MSA. Participants included 149 patients with PD and 99 patients with MSA. The Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to evaluate cognitive function. Evaluations were conducted on SUA and lipid levels, which included triglyceride, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and total cholesterol (TC). Patients with PD and MSA diagnosed with mild cognitive impairment demonstrated multiple cognitive domain impairment when compared with patients with normal cognition. Attentional impairment was more pronounced in patients with MSA when compared with PD (p = 0.001). In PD, the risk of mild cognitive impairment was lower in the highest quartiles and secondary quartile of SUA than in the lowest quartiles (odds ratio [OR] = 0.281, 95% confidence intervals [CI]: 0.097-0.810, p = 0.019; and OR = 0.317, 95% CI: 0.110-0.911, p = 0.033). In MSA, the risk of mild cognitive impairment was lower in the third and highest quartile of SUA than in the lowest quartile (OR = 0.233, 95% CI: 0.063-0.868, p = 0.030; and OR = 0.218, 95% CI: 0.058-0.816, p = 0.024). In patients with PD, the MoCA scores were negatively correlated with TC levels (r = -0.226, p = 0.006) and positively correlated with SUA levels (r = 0.206, p = 0.012). In MSA, the MoCA scores were positively correlated with SUA levels (r = 0.353, p = 0.001). Lower SUA levels and higher TC levels are a possible risk factor for the risk and severity of mild cognitive impairment in PD. Lower SUA levels are a possible risk factor for the risk and severity of mild cognitive impairment in MSA.

Elevated cerebral perfusion in neonatal encephalopathy is associated with neurodevelopmental impairments.

Neonatal encephalopathy (NE) represents a primary cause of neonatal death and neurodevelopmental impairments. In newborns with NE, cerebral hyperperfusion is related to an increased risk of severe adverse outcomes, but less is known about the link between perfusion and mild to moderate developmental impairments or developmental delay. Using arterial spin labelling perfusion MRI, we investigated the link between perfusion in 36 newborns with NE and developmental outcome at 2 years. 53% of the infants demonstrated a normal outcome at 24 months, while two had cerebral palsy with impairments in cognitive, motor, and language domains, and three infants died. The remaining infants showed mild or moderate delays in development in one or two domains. Hyperperfusion across the whole brain was associated with more adverse outcome, including an increased risk of death or severe disability such as cerebral palsy. Among the surviving infants, higher perfusion in the bilateral basal ganglia, thalamus, hippocampus and cerebellum during the neonatal period was related to a poorer cognitive outcome at 2 years. Hyperperfusion in infants with NE was associated with a more adverse outcome and lower cognitive outcome scores. In addition to severe adverse outcomes, altered perfusion is also related to mild to moderate impairment following HIE. Neonates with neonatal encephalopathy (NE) show increased cerebral perfusion globally, which is linked to a more adverse outcome. Higher perfusion in the bilateral basal ganglia, thalamus, hippocampus and cerebellum during the neonatal period was related to a poorer cognitive outcome at 2 years. In addition to severe adverse outcomes altered perfusion is related to mild to moderate impairment following NE. To improve neurodevelopmental outcomes, it is important to improve our understanding of the factors influencing cerebral perfusion in infants with NE.

Visuospatial Skills Explain Differences in the Ability to Use Propulsion Biofeedback Post-stroke.

Visual biofeedback can be used to help people post-stroke reduce biomechanical gait impairments. Using visual biofeedback engages an explicit, cognitively demanding motor learning process. Participants with better overall cognitive function are better able to use visual biofeedback to promote locomotor learning; however, which specific cognitive domains are responsible for this effect are unknown. We aimed to understand which cognitive domains were associated with performance during acquisition and immediate retention when using visual biofeedback to increase paretic propulsion in individuals post-stroke. Participants post-stroke completed cognitive testing, which provided scores for different cognitive domains, including executive function, immediate memory, visuospatial/constructional skills, language, attention, and delayed memory. Next, participants completed a single session of paretic propulsion biofeedback training, where we collected treadmill-walking data for 20min with biofeedback and 2min without biofeedback. We fit separate regression models to determine if cognitive domain scores, motor impairment (measured with the lower-extremity Fugl-Meyer), and gait speed could explain propulsion error and variability during biofeedback use and recall error during immediate retention. Visuospatial/constructional skills and motor impairment best-explained propulsion error during biofeedback use (adjusted R 2 =0.56, P =0.0008), and attention best-explained performance variability (adjusted R 2 =0.17, P =0.048). Language skills best-explained recall error during immediate retention (adjusted R 2 =0.37, P =0.02). These results demonstrate that specific cognitive domain impairments explain variability in locomotor learning outcomes in individuals with chronic stroke. This suggests that with further investigation, specific cognitive impairment information may be useful to predict responsiveness to interventions and personalize training parameters to facilitate locomotor learning.

Prevalence and Prognostic Impact of Multiple Frailty Domain in Japanese Older Adults

ObjectivesIn this observational study, we aimed to evaluate the independent and overlapping effects of multiple frailty domains on long-term care insurance (LTCI) use. DesignPopulation-based cohort design. Setting and ParticipantsIn total, 9804 community-dwelling older adults were recruited from the National Center for Geriatrics and Gerontology-Study of Geriatric Syndromes. MethodsThe physical domain of frailty was assessed using the revised Japanese version of the Cardiovascular Health Study criteria. The cognitive domain of frailty was identified as impairment of memory, attention, executive function, or processing speed using standardized thresholds established for each domain in population-based cohorts. The social domain was operationalized using the National Center for Geriatrics and Gerontology-Social Frailty Scale. The use of LTCI was prospectively determined over 60 months using data extracted from the Japanese long-term care insurance system. ResultsThe data from 7745 participants were analyzed, of whom 793 (10.2%) required LTCI certification within 60 months (interquartile range: 60–60 months). The Kaplan–Meier curve analysis demonstrated that a high number of frailty domains was associated with incident LTCI use. The proportions of incident LTCI use were 6.0%, 12.4%, 30.1%, and 43.9% for non-frail participants and those with impairments in 1, 2, and 3 frailty domains, respectively. In the multivariate Cox regression model, physical, cognitive, and social domain impairments independently increased the risk of incident LTCI use [physical domain impairment, hazard ratio (HR), 1.67; 95% CI, 1.39–2.01; cognitive domain impairment, HR, 1.59; 95% CI, 1.37–1.84; social domain impairment, HR, 1.26; 95% CI, 1.05–1.50]. Conclusions and ImplicationsOverlapping frailty domains were strongly associated with incident LTCI use among community-dwelling older adults. These findings emphasize the importance of assessing multiple frailty domains and tailoring interventions according to the unique circumstances of older adults to prevent functional disabilities.

Symptom Dimensions and Cognitive Impairments in Individuals at Clinical High Risk for Psychosis

BackgroundUnderstanding the intricate relationships between symptom dimensions, clusters, and cognitive impairments is crucial for early detection and intervention in individuals at clinical high risk for psychosis. This study delves into this complex interplay in a clinical high risk sample with the aim of predicting the conversion to psychosis. MethodsA comprehensive cognitive assessment was performed in 744 clinical high risk individuals. The study included a 3-year follow-up period to allow assessment of conversion to psychosis. Symptom profiles were determined using the Structured Interview for Prodromal Syndromes. By applying factor analysis, symptom dimensions were categorized as dominant negative symptoms (NSs), positive symptoms-stressful, and positive symptoms-odd. The factor scores were used to define 3 dominant symptom groups. Latent class analysis (LCA) and factor mixture model (FMM) were employed to identify discrete clusters based on symptom patterns. The 3-class solution was chosen for the LCA and FMM analysis. ResultsIndividuals in the dominant NS group exhibited significantly higher conversion rates to psychosis than those in the other groups. Specific cognitive variables, including performance on the Brief Visuospatial Memory Test–Revised (odds ratio = 0.702, p = .001) and Neuropsychological Assessment Battery Mazes Test (odds ratio = 0.776, p = .024), significantly predicted conversion to psychosis. Notably, cognitive impairments associated with NSs and positive symptoms-stressful affected different cognitive domains. LCA and FMM cluster 1, which was characterized by severe NSs and positive symptoms-odd, exhibited more impairments in cognitive domains than other clusters. No significant difference in the conversion rate was observed among the LCA and FMM clusters. ConclusionsThese findings highlight the importance of NSs in the development of psychosis and suggest specific cognitive domains that are affected by symptom dimensions.

Sleep, cognitive functions, behavioral, and emotional disturbance in self-limited focal childhood epilepsies

BackgroundSelf-limited focal epilepsies of childhood, including self-limited epilepsy with centrotemporal spikes (SeLECTS), idiopathic childhood occipital epilepsy of Gastaut (ICOE-G), and self-limited epilepsy with autonomic seizures (SeLEAS), were considered benign conditions. However, recent research assumed potential adverse impacts on sleep, cognition, behavior, and emotional well-being. Our aim was to investigate the effects of self-limited focal epilepsies on sleep architecture, cognitive functions, behavior, and emotional disturbances in drug naive children. A cross-sectional study was conducted on 46 newly diagnosed children (ages 6–12) with SeLECTS (n = 22), ICOE-G (n = 12), SeLEAS (n = 12), and 20 healthy controls. Overnight polysomnography was performed. Cognitive assessments included intelligence scales, executive function tests, verbal fluency, visuospatial abilities, and memory. Behavioral and emotional problems were evaluated using standardized questionnaires and psychiatric interviews.ResultsChildren with epilepsy exhibited significant disturbances in sleep architecture, impairments in cognitive domains (executive functions, verbal fluency, visuospatial skills, and memory), and higher rates of internalizing/externalizing problems, social issues, attention deficit hyperactive disorder, depression, and anxiety compared to controls. No significant differences were found among the three epilepsy subtypes.ConclusionSelf-limited focal epilepsies in childhood are associated with sleep disruption, cognitive deficits, behavioral issues, and psychiatric comorbidities, challenging their traditional "benign" perception. Comprehensive management approaches addressing these multidimensional impacts are warranted.

Chronic pain is specifically associated with updating working memory: a longitudinal twin study.

Worse executive function (EF) is associated with chronic pain and could mechanistically contribute to pain chronification. It is unclear whether there is overall impairment in EFs or whether there are impairments in specific cognitive domains. Furthermore, the possible genetic risk underlying these associations has not been tested. Participants were from the Colorado Longitudinal Twin study; 786 same-sex twins completed a battery of EF tasks at ages 23 and/or 28 and 634 of these twins self-reported chronic pain at mean age = 28.1; prevalence = 27.76% using the Brief Pain History Questionnaire. The EF tasks were used to define a Common EF factor and 2 factors specific to updating working memory and shifting mental set. We estimated the phenotypic and genetic associations of stable EF variance across ages 23 and 28, as well as EF variance unique to age 28, with pain. With respect to stable EF variance, pain phenotypically correlated with the Updating-specific factor (r = -0.21, P = 0.008) but did not significantly correlate with the Common EF factor (r = -0.06, P = 0.350) nor with the Shifting-specific factor (r = -0.03, P = 0.709). There were no significant phenotypic correlations between pain and EF variance unique to age 28. A twin model indicated that pain and Updating-specific variance share genetic risk (rA = -0.46, P = 0.005) but not environmental risk (rE = 0.05, P = 0.844). Updating working memory shares a phenotypic and genetic relationship with pain in young adults. Impairments in gating or monitoring pain signals may play a mechanistic role in pain development.

Neurocognitive and social cognitive correlates of social exclusion in psychotic disorders: a 20-year follow-up cohort study.

Little is known about the relationship between social exclusion and cognitive impairment in psychosis. We conducted a long-term cohort study of first-episode psychosis to examine the association between comprehensive measures of cognitive impairment and social exclusion assessed at follow-up. A total of 173 subjects with first-episode psychosis were assessed after a 20-year follow-up for 7 cognitive domains and 12 social exclusion indicators. Associations between sets of variables were modeled using multivariate regression, where social exclusion indicators were the dependent variables, cognitive domains were the independent variables, and age, gender, and duration of follow-up were covariates. The total scores on the measures of cognition and social exclusion were strongly associated (β = - .469, ∆R2 = 0.215). Participants with high social exclusion were 4.24 times more likely to have cognitive impairment than those with low social exclusion. Verbal learning was the cognitive function most related to social exclusion domains, and legal capacity was the exclusion domain that showed the strongest relationships with individual cognitive tests. Neurocognition uniquely contributed to housing, work activity, income, and educational attainment, whereas social cognition uniquely contributed to neighborhood deprivation, family and social contacts, and discrimination/stigma. Neurocognition explained more unique variance (11.5%) in social exclusion than social cognition (5.5%). The domains of cognitive impairment were strongly and differentially related to those of social exclusion. Given that such an association pattern is likely bidirectional, a combined approach, both social and cognitive, is of paramount relevance in addressing the social exclusion experienced by individuals with psychotic disorders.

Brain Network Localization of Gray Matter Atrophy and Neurocognitive and Social Cognitive Dysfunction in Schizophrenia

BackgroundNumerous studies have established the presence of gray matter atrophy and brain activation abnormalities during neurocognitive and social cognitive tasks in schizophrenia. Despite a growing consensus that diseases localize better to distributed brain networks than individual anatomical regions, relatively few studies have examined brain network localization of gray matter atrophy and neurocognitive and social cognitive dysfunction in schizophrenia. MethodsTo address this gap, we initially identified brain locations of structural and functional abnormalities in schizophrenia from 301 published neuroimaging studies with 8712 individuals with schizophrenia and 9275 healthy control participants. By applying novel functional connectivity network mapping to large-scale resting-state functional magnetic resonance imaging datasets, we mapped these affected brain locations to 3 brain abnormality networks of schizophrenia. ResultsThe gray matter atrophy network of schizophrenia comprised a broadly distributed set of brain areas predominantly implicating the ventral attention, somatomotor, and default networks. The neurocognitive dysfunction network was also composed of widespread brain areas primarily involving the frontoparietal and default networks. By contrast, the social cognitive dysfunction network consisted of circumscribed brain regions mainly implicating the default, subcortical, and visual networks. ConclusionsOur findings suggest shared and unique brain network substrates of gray matter atrophy and neurocognitive and social cognitive dysfunction in schizophrenia, which may not only refine the understanding of disease neuropathology from a network perspective but may also contribute to more targeted and effective treatments for impairments in different cognitive domains in schizophrenia.

A study of the correlation between gray matter atrophy in multiple sclerosis and impairment of cognitive function domains

Objective: To quantify cerebral cortical and deep gray matter atrophy in patients with multiple sclerosis (MS) and explore its correlation with impairment in domains of cognitive function. Methods: Twenty patients with MS and 16 healthy controls (HC) matched for age, sex, and education level were included. Using FreeSurfer software, based on 3D-MRI technology, the differences in cortical thickness and deep gray matter volume between the two groups were comparatively analyzed. A neuropsychological scale that included six domains of cognitive function was scored on both study groups to analyze the correlation between cortical thickness and volume of deep gray matter in MS patients with impairment in cognitive function domains. Results: Impairment in domains of cognitive function: cognitive impairment was present in 60% MS patients in this study, mainly manifesting as impairment of verbal memory, verbal fluency, visuospatial memory, and information processing speed function (all P<0.05). Of these, the majority had impaired visuospatial memory function (55.0%), and the least number of patients had impaired information processing speed (15.0%). Changes in cortical thickness: compared with the HC group, the MS group showed that cortical atrophy was mainly concentrated in the frontoparietal region, including significant thinning of cortical thickness in the left inferior parietal gyrus, right superior frontal gyrus, and the right superior parietal gyrus (all P<0.05). Among them, atrophy of the left inferior parietal gyrus was significantly positively correlated with the impairment of verbal memory, verbal fluency, and information processing speed (all P<0.05). There was a significant positive correlation between the right superior frontal gyrus atrophy and verbal memory, verbal fluency, and visuospatial memory impairment (all P<0.05). Changes in deep gray matter volume: compared with the HC group, deep gray matter volume in the MS group decreased significantly in the bilateral thalamus, bilateral putamen, bilateral pallidum (all P<0.01), and right nucleus accumbens (P<0.05). Among them, left thalamus atrophy was significantly positively correlated with visuospatial memory impairment (r=0.45, P=0.046), and left putamen atrophy was both significantly positively correlated with visuospatial memory (r=0.45, P=0.047) and information processing speed impairment (r=0.50, P=0.026). Conclusions: Early structural brain changes in MS are dominated by gray matter atrophy. Deep gray matter is more prominent than cortical atrophy.

Cognitive impairment in children and adults with cerebrotendinous xanthomatosis: A French cohort study.

Cerebrotendinous xanthomatosis is a rare and treatable metabolic disorder related to the accumulation of cholestanol. This disorder is primarily associated with motor and cognitive impairments, although the latter has not been extensively characterized. The objectives of this work were to define the cognitive profile found in cerebrotendinous xanthomatosis patients, investigate the progression of cognitive impairment over time, and search for radio-clinical correlations. Through a multicentric chart review study, we collected cognitive and radiological data from nine children and eighteen adults with genetically proven cerebrotendinous xanthomatosis. We performed a volumetric and morphological analysis of the brain magnetic resonance imaging. In our cohort, 44% (4/9) of children and 78% (14/18) of adults exhibited cognitive impairment that can be severe. The study revealed a significant impairment in various cognitive domains, specifically executive, attentional, language, and visuo-spatial. Among adults, 16% (3/18) developed dementia after age 50. These three patients had delayed chenodeoxycholic acid treatment and important cerebral atrophy. Besides these three cases of late-onset cognitive decline, Mini-Mental State Evaluation was generally stable, suggesting cognitive impairment due to a neurodevelopmental disorder and persisting in adulthood. Cognitive impairment was less common in children, possibly related to early chenodeoxycholic acid treatment in our cohort. The severity of magnetic resonance imaging abnormalities did not predict cognitive impairment in patients. Overall, in cerebrotendinous xanthomatosis, cognitive impairment can be severe and mainly neurodevelopmental. Early chenodeoxycholic acid treatment might be associated with a reduced risk of cognitive decline.

The risk of Alzheimer's disease and cognitive impairment characteristics in eight mental disorders: A UK Biobank observational study and Mendelian randomization analysis.

The cognitive impairment patterns and the association with Alzheimer's disease (AD) in mental disorders remain poorly understood. We analyzed data from 486,297 UK Biobank participants, categorizing them by mental disorder history to identify the risk of AD and the cognitive impairment characteristics. Causation was further assessed using Mendelian randomization (MR). AD risk was higher in individuals with bipolar disorder (BD; hazard ratio [HR]=2.37, P<0.01) and major depressive disorder (MDD; HR=1.63, P<0.001). MR confirmed a causal link between BD and AD (ORIVW=1.098), as well as obsessive-compulsive disorder (OCD) and AD (ORIVW=1.050). Cognitive impairments varied, with BD and schizophrenia showing widespread deficits, and OCD affecting complex task performance. Observational study and MR provide consistent evidence that mental disorders are independent risk factors for AD. Mental disorders exhibit distinct cognitive impairment prior to dementia, indicating the potential different mechanisms in AD pathogenesis. Early detection of these impairments in mental disorders is crucial for AD prevention. This is the most comprehensive study that investigates the risk and causal relationships between a history of mental disorders and the development of Alzheimer's disease (AD), alongside exploring the cognitive impairment characteristics associated with different mental disorders. Individuals with bipolar disorder (BD) exhibited the highest risk of developing AD (hazard ratio [HR]=2.37, P<0.01), followed by those with major depressive disorder (MDD; HR=1.63, P<0.001). Individuals with schizophrenia (SCZ) showed a borderline higher risk of AD (HR=2.36, P=0.056). Two-sample Mendelian randomization (MR) confirmed a causal association between BD and AD (ORIVW=1.098, P<0.05), as well as AD family history (proxy-AD, ORIVW=1.098, P<0.001), and kept significant after false discovery rate correction. MR also identified a nominal significant causal relationship between the obsessive-compulsive disorder (OCD) spectrum and AD (ORIVW=1.050, P<0.05). Individuals with SCZ, BD, and MDD exhibited impairments in multiple cognitive domains with distinct patterns, whereas those with OCD showed only slight declines in complex tasks.

Cognitive impairment in schizophrenia is associated with prefrontal-striatal functional hypoconnectivity and striatal dopaminergic abnormalities.

A better understanding of the mechanisms underlying cognitive impairment in schizophrenia is imperative, as it causes poor functional outcomes and a lack of effective treatments. This study aimed to investigate the relationships of two proposed main pathophysiology of schizophrenia, altered prefrontal-striatal connectivity and the dopamine system, with cognitive impairment and their interactions. Thirty-three patients with schizophrenia and 27 healthy controls (HCs) who are right-handed and matched for age and sex were recruited. We evaluated their cognition, functional connectivity (FC) between the dorsolateral prefrontal cortex (DLPFC)/middle frontal gyrus (MiFG) and striatum, and the availability of striatal dopamine transporter (DAT) using a cognitive battery investigating attention, memory, and executive function, resting-state functional magnetic resonance imaging with group independent component analysis and single-photon emission computed tomography with 99mTc-TRODAT. Patients with schizophrenia exhibited poorer cognitive performance, reduced FC between DLPFC/MiFG and the caudate nucleus (CN) or putamen, decreased DAT availability in the left CN, and decreased right-left DAT asymmetry in the CN compared to HCs. In patients with schizophrenia, altered imaging markers are associated with cognitive impairments, especially the relationship between DLPFC/MiFG-putamen FC and attention and between DAT asymmetry in the CN and executive function. This study is the first to demonstrate how prefrontal-striatal hypoconnectivity and altered striatal DAT markers are associated with different domains of cognitive impairment in schizophrenia. More research is needed to evaluate their complex relationships and potential therapeutic implications.

Long-term neurological and neurocognitive impairments after tick-borne encephalitis in Lithuania - a prospective study

Background The aim of this study was to characterise long-term neurological and neurocognitive sequelae after tick-borne encephalitis (TBE) in adults. Methods 98 prospective consecutive TBE patients, classified by disease severity, were included. Immediate outcomes were evaluated with Glasgow Outcome Scale (GOS) and Rankin Scale (RS). After 6 and 18 months, long-term disability was evaluated using Modified Rankin Scale (MRS) and neurocognitive assessment was performed with Matrics Consensus Cognitive Battery (MCCB), measuring processing speed, attention/vigilance, working memory, verbal learning, visual learning, reasoning/problem solving and social cognition. The MCCB results were compared to healthy age, gender and education-matched controls. Results Mild, moderate, and severe TBE was diagnosed in 53.1%, 38.8%, and 8.2% of cases, respectively. At discharge, 25.5% of the patients had major or moderate impairments (GOS) and various levels of disability in 34.7% (RS). Up to 18 months from the onset of TBE, over 20% remained with slight to moderate disability (MRS). GOS, RS and MRS scores correlated with disease severity. At 6 months after the onset, TBE patients scored significantly lower than controls in processing speed, verbal, and visual learning. Two latter domains were significantly more impaired in patients with mild TBE. Patients aged 18-39 performed significantly worse in attention/vigilance and working memory, whereas aged 60+ in verbal learning. A year later, significant improvement was observed in six of seven cognitive domains. Conclusions Long-term neurological sequelae persist in a substantial proportion of TBE patients with significant impairment in several cognitive domains, especially in younger patients and even after mild TBE.

Predictors of post stroke cognitive impairment: VITATOPS cognition substudy

IntroductionPost stroke cognitive impairment (PSCI) is a common complication of ischemic stroke. PSCI can involve different depending on clinical and stroke related characteristics. The aim of this study is to determine the factors associated with impairments in specific cognitive domains. MethodsThe Vitamins to Prevent Stroke (VITATOPS) trial is a large, multinational randomised controlled trial. In this substudy, consecutive patients admitted for ischaemic stroke or transient ischaemic attack (TIA) at a tertiary hospital in Singapore were included. PSCI was defined as impairment of any of the six cognitive subgroups – visuoconstruction, attention, verbal memory, language, visual memory and visuomotor function – that were assessed annually for up to five years. Univariate and multivariate Cox proportional hazard models were used to determine factors associated with impairments in each of these cognitive domains. ResultsA total of 736 patients were included in this study, of which 173 (23.5 %) developed cognitive impairment. Out of the six cognitive domains, the greatest proportion of patients had an impairment in visuoconstruction (26.4 %) followed by attention (19.8 %), verbal memory (18.3 %), language (17.5 %), visual memory (17.3 %) and visuomotor function (14.8 %). Patients with posterior circulation cerebral infarction (POCI) as the index stroke subtype had higher rates of cognitive impairment. Further subgroup analyses show that Indian race and advanced age were predictive of language impairment, whilst fewer years of education and POCI were predictive of verbal memory impairment. POCI was predictive of visual memory impairment, and advanced age and POCI were predictive of visuomotor function impairment. ConclusionWe identified visuoconstruction and attention domains to be the most affected in our Asian cohort of PSCI. Advanced age, lower levels of education, posterior circulation strokes and concomitant comorbidities such as peripheral artery disease are independent predictors of PSCI.

Abstract P337: Clonal Hematopoiesis of Indeterminate Potential and Cognitive Decline in Chronic Kidney Disease Patients

Introduction: Patients with chronic kidney disease (CKD) are at substantially increased risk of dementia. Clonal hematopoiesis of indeterminate potential (CHIP), caused by clonal expansion of blood cells with somatic mutations in certain driver genes, is an established risk factor for cardiovascular diseases, including cerebral vascular disease. In contrast, CHIP was recently shown to be associated with a decreased risk of Alzheimer’s disease. Given emerging evidence of a key role of vascular compared to neurodegenerative mechanisms in CKD-related dementia, the relation of CHIP with cognitive decline in CKD patients needs clarity. We investigated the prospective associations of CHIP with cognitive impairment in a cohort of patients with CKD. Methods: Our study included 1989 participants aged 65 years or older from the Chronic Renal Insufficiency Cohort. Participants underwent high-depth targeted gene sequencing to ascertain CHIP status. Cognitive function was assessed by four cognitive tests (see Table ). For each test, incident cognitive impairment was defined as a test score one standard deviation worse than the baseline group mean. Sequential Cox proportional hazards models tested associations between CHIP and cognitive impairment after adjusting for demographics (model 1), clinical measures (model 2), and APOE genotype in a subset with available data (model 3). Results: CHIP carriers were significantly less likely to experience impairment in attention (Trails A) and executive function (Trails B) in our fully adjusted models ( Table ). There were no significant associations between CHIP and impairment in global cognition (3MS) or verbal memory (Buschke). There were no differences in the associations of CHIP with cognitive impairment across sex or race groups (data not shown). Conclusions: In patients with CKD, we observed markedly reduced risks of impairment in cognitive domains of attention and executive function. Further studies are needed to confirm our findings and evaluate mechanisms of these relations.

Sex-specific neuropsychological correlates of apathy and depression across neurodegenerative disorders.

Apathy and depression are common neuropsychiatric symptoms across neurodegenerative disorders and are associated with impairment in several cognitive domains, yet little is known about the influence of sex on these relationships. We examined the relationship between these symptoms with neuropsychological performance across a combined cohort with mild or major neurodegenerative disorders, then evaluated the impact of sex. We conducted a cohort analysis of participants in the COMPASS-ND study with mild cognitive impairment (MCI), vascular MCI, Alzheimer's disease, mixed dementia, Parkinson's disease, frontotemporal dementia, and cognitively unimpaired (CU) controls. Participants with neurodegenerative disease and CU controls were stratified by the presence (severity ≥1 on Neuropsychiatric Inventory Questionnaire) of either depressive symptoms alone, apathy symptoms alone, both symptoms, or neither. A neuropsychological battery evaluated executive function, verbal fluency, verbal learning, working memory, and visuospatial reasoning. Analysis of covariance was used to assess group differences with age, sex, and education as covariates. Groups included depressive symptoms only (n=70), apathy symptoms only (n=52), both (n=68), or neither (n=262). The apathy and depression+apathy groups performed worse than the neither group on tests of working memory (t(312) =-2.4, p=0.02 and t(328) =-3.8, p=0.001, respectively) and visuospatial reasoning (t(301) =-2.3, p=0.02 and t(321) =-2.6, p=0.01, respectively). The depression, apathy, and depression+apathy groups demonstrated a similar degree of impairment on tests of executive function, processing speed, verbal fluency, and verbal learning when compared to participants without apathy or depression. Sex-stratified analyses revealed that compared to the male neither group, the male apathy and depression+apathy groups were impaired broadly across all cognitive domains except for working memory. Females with depression alone showed deficits on tests of executive function (t(166) =2.4, p=0.01) and verbal learning (t(167) =-4.3, p=0.001) compared to the female neither group. This study demonstrated that in neurodegenerative diseases, apathy with or without depression in males was associated with broad cognitive impairments. In females, depression was associated with deficits in executive function and verbal learning. These findings highlight the importance of effectively treating apathy and depression across the spectrum of neurodegenerative disorders with the goal of optimizing neuropsychological outcomes.

Entorhinal-based path integration selectively predicts midlife risk of Alzheimer's disease.

Entorhinal cortex (EC) is the first cortical region to exhibit neurodegeneration in Alzheimer's disease (AD), associated with EC grid cell dysfunction. Given the role of grid cells in path integration (PI)-based spatial behaviors, we predicted that PI impairment would represent the first behavioral change in adults at risk of AD. We compared immersive virtual reality (VR) PI ability to other cognitive domains in 100 asymptomatic midlife adults stratified by hereditary and physiological AD risk factors. In some participants, behavioral data were compared to 7T magnetic resonance imaging (MRI) measures of brain structure and function. Midlife PI impairments predicted both hereditary and physiological AD risk, with no corresponding multi-risk impairment in episodic memory or other spatial behaviors. Impairments associated with altered functional MRI signal in the posterior-medial EC. Altered PI may represent the transition point from at-risk state to disease manifestation in AD, prior to impairment in other cognitive domains.

Atypical clinical variants of Alzheimer's disease: are they really atypical?

Alzheimer's disease (AD) is a neuropathological disorder defined by the deposition of the proteins, tau and β-amyloid. Alzheimer's disease is commonly thought of as a disease of the elderly that is associated with episodic memory loss. However, the very first patient described with AD was in her 50's with impairments in multiple cognitive domains. It is now clear that AD can present with multiple different non-amnestic clinical variants which have been labeled as atypical variants of AD. Instead of these variants of AD being considered "atypical," I propose that they provide an excellent disease model of AD and reflect the true clinical heterogeneity of AD. The atypical variants of AD usually have a relatively young age at onset, and they show striking cortical tau deposition on molecular PET imaging which relates strongly with patterns of neurodegeneration and clinical outcomes. In contrast, elderly patients with AD show less tau deposition on PET, and neuroimaging and clinical outcomes are confounded by other age-related pathologies, including TDP-43 and vascular pathology. There is also considerable clinical and anatomical heterogeneity across atypical and young-onset amnestic variants of AD which reflects the fact that AD is a disease that causes impairments in multiple cognitive domains. Future studies should focus on careful characterization of cognitive impairment in AD and consider the full clinical spectrum of AD, including atypical AD, in the design of research studies investigating disease mechanisms in AD and clinical treatment trials, particularly with therapeutics targeting tau.

Longitudinal trajectory effects of different MCI subtypes on general cognitive and daily functions in a population-based cohort of older adults

ObjectivesTo identify different mild cognitive impairment (MCI) phenotypes based on substantial relative impairment in specific cognitive domains and then characterize the complex process of general cognitive and daily functions over time in older adults with these MCI subtypes. MethodsA total of 1020 participants with MCI at baseline from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were recruited. MCI subtypes were obtained based on neuropsychological tests in five cognitive domains: memory (M), visuospatial function (V), language (L), processing speed (P), and executive function (E). General cognitive function and daily function were measured by the Mini-Mental State Examination (MMSE) and the Functional Assessment Questionnaire (FAQ), respectively. Linear mixed models were fitted to curve their trajectories across different MCI subtypes. ResultsConsidering visuospatial function, subtypes were MO (memory impaired only), M&V (memory and visuospatial function impaired) and M&nV (memory impaired and visuospatial function non-impaired). Similar subtypes and naming rules were obtained based on language, executive function, and processing speed. Further, depending on the number of relative impaired cognitive domains M&S and M&M were obtained. Participants with MO had the highest prevalence in the sample (53.4 %), followed by M&nV (31.1 %). Participants with M&V had the highest mean age (74.69 years) at baseline and the greatest dementia conversion rate (53.2 %). The MMSE and FAQ score trajectories changed most slowly in participants with MO while fastest in those with M&V. Obvious different trajectories of both MMSE and FAQ scores were observed across different subtypes based on visuospatial function and executive function. ConclusionCompared to MO, individuals with multi-dimensional cognitive impairment have worse general cognitive and daily functions, especially for those with M&V.