Persistent Cognitive Impairment Research Articles

Resting state EEG relates to short- and long-term cognitive functioning after cardiac arrest

BackgroundApproximately half of cardiac arrest survivors have persistent cognitive impairment. Guidelines recommend early screening to identify patients at risk for cognitive impairment, but there is no consensus on the best screening method. We aimed to identify quantitative EEG measures relating with short- and long-term cognitive function after cardiac arrest for potential to cognitive outcome prediction. MethodsWe analyzed data from a prospective longitudinal multicenter cohort study designed to develop a prediction model for cognitive outcome after cardiac arrest. For the current analysis, we used twenty-minute EEG registrations from 80 patients around one week after cardiac arrest. We calculated power spectral density, normalized alpha-to-theta ratio (nATR), peak frequency, and center of gravity (CoG) of this peak frequency. We related these with global cognitive functioning (scores on the Montreal Cognitive Assessment (MoCA)) at one week, three and twelve months follow-up with multivariate mixed effect models, and with performance on standard neuropsychological examination at twelve months using Pearson correlation coefficients. ResultsEach individual EEG parameter related to MoCA at one week (βnATR=7.36; P<0.01; βpeak frequency=1.73, P<0.01; βCoG=-9.88, P <0.01). The nATR also related with the MoCA at three months ((βnATR=2.49; P 0.01). No EEG metrics significantly related to the MoCA score at twelve months. nATR and peak frequency related with memory performance at twelve months. Results were consistent in sensitivity analyses. ConclusionEarly resting-state EEG parameters relate with short-term global cognitive functioning and with memory function at one year after cardiac arrest. Additional predictive values in multimodal prediction models need further study.

Cognitive and everyday functioning after bacterial brain abscess: a prospective study of functional recovery from 8 weeks to 1 year post-treatment

ABSTRACT Objective A bacterial brain abscess may damage surrounding brain tissue by mass effect, inflammatory processes, and bacterial toxins. The aim of this study was to examine cognitive and functional outcomes at 8 weeks and 1 year following acute treatment. Methods Prospective study of 20 patients with bacterial brain abscess (aged 17–73 years; 45% females) with neuropsychological assessment at 8 weeks and 1 year post-treatment. Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) and Patient Competence Rating Scale (PCRS) were used to assess everyday functioning and administered to patients and informants. Results Cognitive impairment was found in 30% of patients at 8 weeks and 22% at 1 year. Significant improvements were seen on tests of perceptual reasoning, attention, verbal fluency, and motor abilities (p < 0.05). At 1 year, 45% had returned to full-time employment. Nevertheless, patients and their informants obtained scores within the normal range on measures of everyday functioning (PCRS and BRIEF-A) at 8 weeks and 1 year. No significant improvements on these measures emerged over time. Conclusion Residual long-term cognitive impairment and diminished work ability affected 22% and 45% of patients one year after BA. Persistent cognitive impairment emphasizes the importance of prompt acute treatment and cognitive rehabilitation.

Exertional heat stroke-induced changes in gut microbiota cause cognitive impairment in mice

BackgroundThe incidence of exertional heat stroke (EHS) escalates during periods of elevated temperatures, potentially leading to persistent cognitive impairment postrecovery. Currently, effective prophylactic or therapeutic measures against EHS are nonexistent.MethodsThe selection of days 14 and 23 postinduction for detailed examination was guided by TEM of neuronal cells and HE staining of intestinal villi and the hippocampal regions. Fecal specimens from the ileum and cecum at these designated times were analyzed for changes in gut microbiota and metabolic products. Bioinformatic analyses facilitated the identification of pivotal microbial species and metabolites. The influence of supplementing these identified microorganisms on behavioral outcomes and the expression of functional proteins within the hippocampus was subsequently assessed.ResultsTEM analyses of neurons, coupled with HE staining of intestinal villi and the hippocampal region, indicated substantial recovery in intestinal morphology and neuronal injury on Day 14, indicating this time point for subsequent microbial and metabolomic analyses. Notably, a reduction in the Lactobacillaceae family, particularly Lactobacillus murinus, was observed. Functional annotation of 16S rDNA sequences suggested diminished lipid metabolism and glycan biosynthesis and metabolism in EHS models. Mice receiving this intervention (EHS + probiotics group) exhibited markedly reduced cognitive impairment and increased expression of BDNF/TrKB pathway molecules in the hippocampus during behavioral assessment on Day 28.ConclusionProbiotic supplementation, specifically with Lactobacillus spp., appears to mitigate EHS-induced cognitive impairment, potentially through the modulation of the BDNF/TrKB signaling pathway within the hippocampus, illustrating the therapeutic potential of targeting the gut-brain axis.

Implementing cognitive screenings for outpatients with bipolar disorder following optimized treatment in a specialized mood disorder clinic

Bipolar disorder (BD) is often accompanied by persistent cognitive impairment. However, screening for cognitive impairment in the clinic is challenged by a lack of consensus on screening procedures. This study assesses cognitive impairment prevalence and screening feasibility in alignment with the International Society for Bipolar Disorder Targeting Cognition Task Force recommendations. Between January 2022 and May 2023, 136 newly diagnosed BD outpatients were assessed with the Screen for Cognitive Impairment in Psychiatry after 15-20 months of specialized care at the Copenhagen Affective Disorder Clinic. Cognitive impairment patterns and associations with cognitive complaints, perceived stress, and functioning were examined. Most screened patients (73%) achieved full or partial remission, with 51% being cognitively normal, 38% showing global impairments, and 11% displaying selective impairments. Among remitted patients, 56% were cognitively normal, while 31% and 13% exhibited global or selective impairments, respectively. Both objectively impaired patient groups reported more subjective cognitive difficulties than those who were cognitively normal. The globally impaired group also demonstrated poorer functioning, more depressive symptoms and lower quality of life than cognitively normal patients. Across all patients, lower cognitive performance correlated with more cognitive complaints, lower functioning, lower quality of life, and more depressive symptoms. Cognitive screenings were relatively easily implementable, involving only a 1.5-hour session including mood ratings, feedback and cognitive strategy discussion. The study highlights the clinical relevance and feasibility of cognitive screenings in BD patients, emphasizing the need for tailored interventions given frequent cognitive impairment in clinically stable individuals.

Anxiety-, and depression-like behavior following short-term finasteride administration is associated with impaired synaptic plasticity and cognitive behavior in male rats

Finasteride, a 5α-Reductase inhibitor, is used to treat male pattern baldness and benign prostatic hyperplasia. Several clinical studies show that chronic finasteride treatment induces persistent depression, suicidal thoughts and cognitive impairment and these symptoms are persistent even after its withdrawal. Previous results from our lab showed that repeated administration of finasteride for six days induces depression-like behavior. However, whether short-term finasteride administration induces anxiety-like behavior and memory impairment and alters synaptic plasticity are not known, which formed the basis of this study. Finasteride was administered to 2–2.5 months old male Wistar rats for six days and subjected to behavioral evaluation, biochemical estimation and synaptic plasticity assessment. Anxiety-like behavior was evaluated in the elevated plus maze (EPM), open field test (OFT), light/dark test (LDT), and novelty suppressed feeding test (NSFT), and learning and memory using novel object recognition test (NORT) and novel object location test (NOLT) and depression-like behavior in the sucrose preference test (SPT). Synaptic plasticity in the hippocampal Schaffer collateral-CA1 was evaluated using slice field potential recordings. Plasma corticosterone levels were estimated using ELISA. Finasteride administration induced anxiety-like behavior in the EPM, OFT, LDT and NSFT, and depression-like behavior in the SPT. Further, finasteride induced hippocampal dependent spatial learning and memory impairment in the NOLT. In addition, finasteride decreased basal synaptic plasticity and long-term potentiation (LTP) in the hippocampus. A trend of increased plasma corticosterone levels was observed following repeated finasteride administration. These results indicate the potential role of corticosterone and synaptic plasticity in finasteride-induced effects and further studies will pave way for the development of novel neurosteroid-based therapeutics in neuropsychiatric diseases.

One-Year Recovery Among Survivors of Prolonged Severe COVID-19: A National Multicenter Cohort.

Understanding the long-term effects of severe COVID-19 illness on survivors is essential for effective pandemic recovery planning. Therefore, we investigated impairments among hospitalized adults discharged to long-term acute care hospitals (LTACHs) for prolonged severe COVID-19 illness who survived 1 year. The Recovery After Transfer to an LTACH for COVID-19 (RAFT COVID) study was a national, multicenter, prospective longitudinal cohort study. We included hospitalized English-speaking adults transferred to one of nine LTACHs in the United States between March 2020 and February 2021 and completed a survey. None. Validated instruments for impairments and free response questions about recovering. Among 282 potentially eligible participants who provided permission to be contacted, 156 (55.3%) participated (median age, 65; 38.5% female; 61.3% in good prior health; median length of stay of 57 d; 77% mechanically ventilated for a median of 26 d; 42% had a tracheostomy). Approximately two-thirds (64%) had a persistent impairment, including physical (57%), respiratory (49%; 19% on supplemental oxygen), psychiatric (24%), and cognitive impairments (15%). Nearly half (47%) had two or more impairment types. Participants also experienced persistent debility from hospital-acquired complications, including mononeuropathies and pressure ulcers. Participants described protracted recovery, attributing improvements to exercise/rehabilitation, support, and time. While considered life-altering with 78.7% not returning to their usual health, participants expressed gratitude for recovering; 99% returned home and 60% of previously employed individuals returned to work. Nearly two-thirds of survivors of among the most prolonged severe COVID-19 illness had persistent impairments at 1 year that resembled post-intensive care syndrome after critical illness plus debility from hospital-acquired complications.

Lower cognitive reserve is related to worse working memory performance in older adults after mTBI. An ERP study

ABSTRACT Objective Older adults (OA) after mild traumatic brain injury (mTBI) have a high risk of developing persistent post-injury cognitive impairments. Lower pre-morbid cognitive reserve (CR) is increasingly investigated as a risk factor for cognitive dysfunction in OA. However, how CR protects against effects of mTBI at the brain level remains largely understudied. Methods We examined 22 OA who sustained mTBI (mean 67.69 years, SD 5.11) in the sub-acute phase and 15 age- and CR-matched healthy OA (mean 68 years, SD 5.55) performing a three-level visual N-back task using electroencephalography. We calculated inverse efficiency scores of performance from accuracy and reaction times. Event-related potentials served as neurocognitive correlates of attentional (P2) and working memory (P3) processing. Results Overall, mTBI OA performed worse than healthy OA (p = 0.031). Lower CR generally decreased performance (p < 0.001). Furthermore, with increasing task difficulty, task performance was more affected by CR (p = 0.004). At the brain level, P2 amplitude was lower in mTBI OA than in healthy OA (p = 0.05). There was no clear effect of CR on P2 or P3 measures. Conclusion As mTBI OA with lower CR performed worse on a working-memory task, lower CR may be a risk factor for worse recovery after mTBI in this group.

Iron/ROS/Itga3 mediated accelerated depletion of hippocampal neural stem cell pool contributes to cognitive impairment after hemorrhagic stroke

Hemorrhagic stroke, specifically intracerebral hemorrhage (ICH), has been implicated in the development of persistent cognitive impairment, significantly compromising the quality of life for affected individuals. Nevertheless, the precise underlying mechanism remains elusive. Here, we report for the first time that the accumulation of iron within the hippocampus, distal to the site of ICH in the striatum, is causally linked to the observed cognitive impairment with both clinical patient data and animal model. Both susceptibility-weighted imaging (SWI) and quantitative susceptibility mapping (QSM) demonstrated significant iron accumulation in the hippocampus of ICH patients, which is far from the actual hematoma. Logistical regression analysis and multiple linear regression analysis identified iron level as an independent risk factor with a negative correlation with post-ICH cognitive impairment. Using a mouse model of ICH, we demonstrated that iron accumulation triggers an excessive activation of neural stem cells (NSCs). This overactivation subsequently leads to the depletion of the NSC pool, diminished neurogenesis, and the onset of progressive cognitive dysfunction. Mechanistically, iron accumulation elevated the levels of reactive oxygen species (ROS), which downregulated the expression of Itga3. Notably, pharmacological chelation of iron accumulation or scavenger of aberrant ROS levels, as well as conditionally overexpressed Itga3 in NSCs, remarkably attenuated the exhaustion of NSC pool, abnormal neurogenesis and cognitive decline in the mouse model of ICH. Together, these results provide molecular insights into ICH-induced cognitive impairment, shedding light on the value of maintaining NSC pool in preventing cognitive dysfunction in patients with hemorrhagic stroke or related conditions.

Microstructural brain abnormalities, fatigue, and cognitive dysfunction after mild COVID-19

Although some studies have shown neuroimaging and neuropsychological alterations in post-COVID-19 patients, fewer combined neuroimaging and neuropsychology evaluations of individuals who presented a mild acute infection. Here we investigated cognitive dysfunction and brain changes in a group of mildly infected individuals. We conducted a cross-sectional study of 97 consecutive subjects (median age of 41 years) without current or history of psychiatric symptoms (including anxiety and depression) after a mild infection, with a median of 79 days (and mean of 97 days) after diagnosis of COVID-19. We performed semi-structured interviews, neurological examinations, 3T-MRI scans, and neuropsychological assessments. For MRI analyses, we included a group of non-infected 77 controls. The MRI study included white matter (WM) investigation with diffusion tensor images (DTI) and functional connectivity with resting-state functional MRI (RS-fMRI). The patients reported memory loss (36%), fatigue (31%) and headache (29%). The quantitative analyses confirmed symptoms of fatigue (83% of participants), excessive somnolence (35%), impaired phonemic verbal fluency (21%), impaired verbal categorical fluency (13%) and impaired logical memory immediate recall (16%). The WM analyses with DTI revealed higher axial diffusivity values in post-infected patients compared to controls. Compared to controls, there were no significant differences in the functional connectivity of the posterior cingulum cortex. There were no significant correlations between neuropsychological scores and neuroimaging features (including DTI and RS-fMRI). Our results suggest persistent cognitive impairment and subtle white matter abnormalities in individuals mildly infected without anxiety or depression symptoms. The longitudinal analyses will clarify whether these alterations are temporary or permanent.

Early childhood malnutrition impairs adult resting brain function using near-infrared spectroscopy.

Early childhood malnutrition affects 200+ million children under 5 years of age worldwide and is associated with persistent cognitive, behavioral and psychiatric impairments in adulthood. However, very few studies have investigated the long-term effects of childhood protein-energy malnutrition (PEM) on brain function using a functional hemodynamic brain imaging technique. This study aims to investigate functional brain network alterations using near infrared spectroscopy (NIRS) in adults, aged 45-51 years, from the Barbados Nutrition Study (BNS) who suffered from a single episode of malnutrition restricted to their first year of life (n = 26) and controls (n = 29). A total of 55 individuals from the BNS cohort underwent NIRS recording at rest. Using functional connectivity and permutation analysis, we found patterns of increased Pearson's correlation with a specific vulnerability of the frontal cortex in the PEM group (ps < 0.05). Using a graph theoretical approach, mixed ANCOVAs showed increased segregation (ps = 0.0303 and 0.0441) and decreased integration (p = 0.0498) in previously malnourished participants compared to healthy controls. These results can be interpreted as a compensatory mechanism to preserve cognitive functions, that could also be related to premature or pathological brain aging. To our knowledge, this study is the first NIRS neuroimaging study revealing brain function alterations in middle adulthood following early childhood malnutrition limited to the first year of life.

An exploratory study of longitudinal trajectory of language, swallowing and cognition post endovascular clot retrieval.

Endovascular clot retrieval (ECR) is known to reduce global disability at 3 months post stroke however limited research exists regarding the trajectory of specific clinical impairments including language, swallowing and cognitive deficits between onset and 3 months. To assess language, swallowing, and cognitive performance following ECR and explore whether impairment severity is correlated with modified Thrombolysis in Cerebral Infarction score (mTICI), stroke severity or quality of life (QoL). Assessment was completed within 7 days (T1), 1 month (T2) and 3 months (T3) post-stroke. Performance was measured with the Functional Oral Intake Scale (FOIS), Repeatable Battery for Assessment of Neuropsychological Status (RBANS), Trail Making Test (TMT A and B) and Brixton Spatial Awareness Test. The Western Aphasia Battery (WAB) was used for left hemisphere stroke. QoL was measured with the Stroke and Aphasia Quality of Life Scale. Twenty-five participants (median 72 years; 64% male) were prospectively recruited following ECR. High reperfusion success (68% mTICI 3) and low stroke severity post ECR (median 24h NIHSS = 3, IQR 7-18) were noted. At T1, 10 participants presented with aphasia, eight required a modified diet and 20 had impaired cognition. At T3 all had recovered to a normal oral diet, 39% had persistent cognitive impairment and 45% of patients with left hemisphere stroke remained aphasic. Performance on the WAB, FOIS, RBANS and TMT changed significantly over time (all p<0.05). The severity score at T1 for all measures, excluding TMT B and Brixton, was significantly correlated with 24h NIHSS. WAB scores at T3 were correlated with QoL (r = 0.618; p = 0.043). This exploratory study found the longitudinal performance of language, swallowing and cognition significantly improved over time and severity in the first-week post-ECR was correlated with 24h NIHSS rather than the degree of reperfusion. What is already known on the subject Randomised control trials have demonstrated the benefit of ECR in patients with ischemic stroke using global measures of disability and function. Limited research exists regarding the trajectory of specific clinical impairments including language, swallowing and cognitive deficits. There is also a reliance on screening assessments and a lack of consideration of the influence of co-occurring impairments. What this paper adds to existing knowledge This prospective study is amongst the first to explore the longitudinal trajectory of language, swallowing and cognitive impairment using a standardised assessment battery. Twenty-four-hour NIHSS was significantly correlated with language, swallowing, global cognition and some measures of executive function. Language performance post ECR was correlated with domain-specific cognitive assessment of attention, immediate memory and delayed memory, which differed from swallowing performance post ECR that correlated with measures of executive function. What are the potential or actual clinical implications of this work? It is important for speech-language pathologists and the wider medical team to monitor language, swallowing and cognitive performance post ECR regardless of treatment success. Stroke severity at 24h post-ECR influences the severity of language, swallowing and cognitive impairments.

Profiles of Cognitive Functioning at 6 Months After Traumatic Brain Injury Among Patients in Level I Trauma Centers

Cognitive dysfunction is common after traumatic brain injury (TBI), with a well-established dose-response relationship between TBI severity and likelihood or magnitude of persistent cognitive impairment. However, patterns of cognitive dysfunction in the long-term (eg, 6-month) recovery period are less well known. To characterize the prevalence of cognitive dysfunction within and across cognitive domains (processing speed, memory, and executive functioning) 6 months after injury in patients with TBI seen at level I trauma centers. This prospective longitudinal cohort study used data from Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) and included patients aged 17 years or older presenting at 18 US level I trauma center emergency departments or inpatient units within 24 hours of head injury, control individuals with orthopedic injury recruited from the same centers, and uninjured friend and family controls. Participants were enrolled between March 2, 2014, and July 27, 2018. Data were analyzed from March 5, 2020, through October 3, 2023. Traumatic brain injury (Glasgow Coma Scale score of 3-15) or orthopedic injury. Performance on standard neuropsychological tests, including premorbid cognitive ability (National Institutes of Health Toolbox Picture Vocabulary Test), verbal memory (Rey Auditory Verbal Learning Test), processing speed (Wechsler Adult Intelligence Scale [4th edition] Processing Speed Index), and executive functioning (Trail Making Test). The sample included 1057 persons with TBI (mean [SD] age, 39.3 [16.4] years; 705 [67%] male) and 327 controls without TBI (mean [SD] age, 38.4 [15.1] years; 222 [68%] male). Most persons with TBI demonstrated performance within 1.5 SDs or better of the control group (49.3% [95% CI, 39.5%-59.2%] to 67.5% [95% CI, 63.7%-71.2%] showed no evidence of impairment). Similarly, 64.4% (95% CI, 54.5%-73.4%) to 78.8% (95% CI, 75.4%-81.9%) of participants demonstrated no evidence of cognitive decline (defined as performance within 1.5 SDs of estimated premorbid ability). For individuals with evidence of either cognitive impairment or decline, diverse profiles of impairment across memory, speed, and executive functioning domains were observed (ie, the prevalence was >0 in each of the 7 combinations of impairment across these 3 cognitive domains for most TBI subgroups). In this cohort study of patients seen at level I trauma centers 6 months after TBI, many patients with TBI demonstrated no cognitive impairment. Impairment was more prevalent in persons with more severe TBI and manifested in variable ways across individuals. The findings may guide future research and treatment recommendations.

Neuroprotective Profile of Triazole Grandisin Analogue against Amyloid-Beta Oligomer-Induced Cognitive Impairment.

Alzheimer's disease (AD) is a neurodegenerative disorder caused by accumulation of amyloid-β oligomers (AβO) in the brain, neuroinflammation, oxidative stress, and cognitive decline. Grandisin, a tetrahydrofuran neolignan, exhibits relevant anti-inflammatory and antioxidant properties. Interestingly, grandisin-based compounds were shown to prevent AβO-induced neuronal death in vitro. However, no study has assessed the effect of these compounds on the AD animal model. This study focuses on a triazole grandisin analogue (TGA) synthesized using simplification and bioisosteric drug design, which resulted in improved potency and solubility compared with the parent compound. This study aimed to investigate the possible in vivo effects of TGA against AβO-induced AD. Male C57/Bl6 mice underwent stereotaxic intracerebroventricular AβO (90 μM) or vehicle injections. 24 h after surgery, animals received intraperitoneal treatment with TGA (1 mg/kg) or vehicle, administered on a 14 day schedule. One day after treatment completion, a novel object recognition task (NORT) was performed. Memantine (10 mg/kg) was administered as a positive control. NORT retention sessions were performed on days 8 and 16 after AβO injection. Immediately after retention sessions, animals were euthanized for cortex and hippocampus collection. Specimens were subjected to oxidative stress and cytokine analyses. TGA reduced the level of cortex/hippocampus lipoperoxidation and prevented cognitive impairment in AβO-injected mice. Additionally, TGA reduced tumor necrosis factor (TNF) and interferon-γ (IFN-γ) levels in the hippocampus. By contrast, memantine failed to prevent cortex/hippocampus lipid peroxidation, recognition memory decline, and AβO-induced increases in TNF and IFN-γ levels in the hippocampus. Thus, memantine was unable to avoid the AβO-induced persistent cognitive impairment. The results showed that TGA may prevent memory impairment by exerting antioxidant and anti-inflammatory effects in AβO-injected mice. Moreover, TGA exhibited a persistent neuroprotective effect compared to memantine, reflecting an innovative profile of this promising agent against neurodegenerative diseases, such as AD.

Long term high‐fat feeding induces cognitive impairment, alterations in microglial morphology, and spatial transcriptomic changes

AbstractBackgroundObesity and metabolic dysfunction (Metabolic Syndrome, prediabetes, and diabetes) increase the risk of later life cognitive impairment, including dementias such as Alzheimer’s Disease1‐3. One common etiology that might underly this increased risk is immune system dysregulation and inflammation4, 5. Specifically, microglial dependent mechanisms are thought to play an important role in pathology6‐8. However, the precise immune and inflammatory mechanisms promoting cognitive decline secondary to obesity and metabolic dysfunction are unclear.MethodBL6 male mice were fed 60% HFD (high fat diet) or 10% SD (standard diet) for 1 year. Body weight and glucose tolerance were assessed longitudinally. Cognition was repeatedly evaluated using Morris water maze, social recognition, and puzzle box. At study termination, mice were given either an intraperitoneal injection of lipopolysaccharide as an immune challenge or saline as a control. Activation of hippocampal microglia was assessed via immunohistochemistry (IHC) and analysis of microglial morphology. Changes in brain gene expression were measured via spatial transcriptomics using the 10X Visium platform.ResultHFD feeding caused increased weight, impaired glucose tolerance, and cognitive deficits which persisted throughout the study period. Body weight in particular was predictive of cognitive changes, especially for later time points. In response to immune challenge, hippocampal microglia in SD mice had a normal morphological response indicative of activation. However, microglia of HFD mice had no change in their morphology in response to lipopolysaccharide injection. Additionally, changes in morphology significantly correlated with cognition and indicated that a higher percentage of activated hippocampal microglia is associated with a worse cognitive phenotype. Spatial transcriptomics analysis showed changes in gene expression in multiple brain regions of HFD mice, including the hippocampus, many of which were related to neurodegenerative and inflammatory pathways.ConclusionThese data support that HFD feeding causes an early and persistent cognitive impairment, which is associated with obesity. Our data also confirm a role for microglia in HFD‐induced cognitive impairment. Indeed, microglial and transcriptomic data strongly indicate a role for inflammation and inflammatory pathways in HFD‐induced cognitive impairment.

Age determines the profile of cognitive impairment after COVID‐19. Results of an international, multi‐cohort, pooled analysis and meta‐analysis

AbstractBackgroundEvidence‐based data are still lacking to define de characteristics of cognitive impairment after COVI‐19. Previous findings suggest that Covid‐19 sequelae may resemble early Alzheimer’s disease (AD). In this abstract, our team present data from Argentina, Canada, Russia, Greece, and the UK including 1919 patients and 1031 controls.MethodParticipants were 18 to 97 years old. Neuropsychological evaluation included Montreal Cognitive Assessment – MoCA, Toronto Cognitive Assessment‐ TORCA, and/or batteries specially built for the evaluation of cognitive dimensions. Some cohorts included the anosmia. Participants were evaluated at a maximum of 6 months after discharge. A factorial analysis was performed on each country identifying 3 factors that could be compared between countries: one accounting for memory and language, the second is an attentional factor, and the last is a working memory factor. Between countries that have young population, there was a fourth factor accounting for executive functioning (planning and inhibition). We carried out meta‐analysis of common factors and co‐variates.ResultAverage duration of formal learning is 11.06 ± 5.11 years, and the mean age is 52.61 ± 15.87 years. Meta‐analysis revealed an impairment in language (verbal fluency) for all patients vs controls. Factorial scores revealed that all the participants were impaired in attentional tasks but those over 60 years old were impaired also in working memory and the youngest participants in executive functioning. Significant differences between cases and controls in attentional, memory, and language tasks identified 4 different groups: normal cognition (71%); one dimension impaired (20.5%); two dimensions impaired (6.5%); and three dimensions impaired (2%). In older adults, these proportions rise to 28% for the impairment in one dimension; 11.5% for two dimensions, and 3.5% for three dimensions and is significantly associated with the infection diagnoses (p = 0.013) and with presence and severity of anosmia (p = 0,000).ConclusionOlder adults are at greater risk of suffering persistent cognitive impairment after recovery from SARS‐CoV‐2 infection and cognitive impairment is correlated with the presence and severity of anosmia.

Volumetric and cognitive findings in transient global amnesia: results of the FORGOT cohort

AbstractBackgroundTransient global amnesia (TGA) is a sudden onset syndrome of episodic amnesia with unclear pathophysiology. Although expected to last less than 24 hours, different studies described persistent cognitive impairment primarily in memory and executive functions. We aim to analyze the cognitive performance and cortical volume of patients after a TGA as contributing factors to its pathophysiology.MethodCase‐control study of matched TGA subjects (n = 50) and normal controls (NC) (n = 50). All were studied with brain MRI with volumetric T1 sequences (in TGA subjects performed 1.4 months after the episode (SD±3.4)). Voxel‐based morphometry (VBM), region‐based morphometry (RBM) and surface‐based morphometry (SBM) steps were performed using an extension of the software package SPM12. All subjects were evaluated with a modified UDS3 neuropsychological battery. TGA patients were assesed 3 months after the event to avoid confusors. A deficit in each cognitive domain was diagnosed when individuals scored below ‐1.5 SD for normal values for age, sex and education. Anxiety, depression and cognitive complaints were also assessed. For VBM and RBM, a two‐sample independent t‐test was modeled and estimated with TIV, sex, and age as covariates. For SBM, a two‐sample independent t‐test without covariates was modeled and estimated. We applied the FDR method for multiple comparison corrections and defined a p&lt;.05 threshold for statistical significance.ResultAmong 50 patients with TGA, 54% were female. Mean age was 66 (±9). No significant differences were found in VBM analysis. In the RBM test, we observed reduced volume in the left accumbens nucleus (figure 1) and in SBM, reduced cortical thickness on the right temporal pole and ventromedial visual area 2 (figure 2). No differences were found among cognitive performance between TGA and control patients (table 1).ConclusionThe absence of abnormalities in cortical volume and cognitive failure beyond three months of the event affirms the transient nature of the episode and dispells the association with a neurodegenerative disease as a predisposing factor. SBM abnormalities in distant regions may suggest a network disruption beyond the hippocampus.

Effect of oxygen therapy duration on cognitive impairment 12 months after hospitalization for SARS-COV-2 infection.

To identify predictors of persistent cognitive impairment at 12 months after hospitalization due to COVID-19 (SARS-CoV-2) infection. Retrospective, single-centre study. All consecutive patients assessed in physical and rehabilitation medicine consultations at 3 months with a neuropsychiatric testing (NPT) at 6 months. A Mini Mental State Examination (MMSE) was performed at 3 months and NPT at 6 and 12 months, exploring global cognitive efficiency, attention and processing speed, short-term memory and executive function. Logistic regression and receiver operating characteristic curves were used to identify predictors of persistent cognitive impairment. Among 56 patients, 64.3% and 53.6% had 1 or more impaired cognitive functions at 6 and 12 months, respectively, attention and processing speed being the most represented (41.1% at 12 month). Duration of oxygen therapy (odds ratio 0.926 [0.871-0.985], p = 0.015) and MMSE score at 3 months (odds ratio 0.464 [0.276-0.783], p = 0.004) were associated with cognitive impairment at 12 months by multivariable analysis (R² 0.372-0.497). Half of patients have cognitive impairment 12 months after acute SARS-CoV-2 infection requiring hospitalization. The duration of oxygen therapy in acute care could be a protective parameter. Systematic evaluation with the MMSE at 3 months after infection might be an effective tool to detect risk.

"Is My Brain Ever Going to Work Fully Again?": Challenges and Needs of Cancer Survivors with Persistent Cancer-Related Cognitive Impairment.

Many cancer survivors experience cognitive impairments that impact memory, concentration, speed of information processing, and decision making. These impairments, collectively known as cancer-related cognitive impairments (CRCIs), are a key domain of unmet needs and can significantly impact a cancer survivor's identity and quality of life. However, there are no purpose-built, multi-domain, needs assessment tools specifically for CRCI. The development of such tools requires an in-depth understanding of cancer survivors' CRCI-specific challenges and associated needs. This study explored the challenges and associated needs of cancer survivors with persistent CRCI. An in-depth qualitative design using semi-structured interviews with (a) cancer survivors with perceived CRCI (n = 32) and (b) oncology health professionals (n = 19) was utilised. A reflexive thematic analysis of the interviews resulted in five overarching themes: (1) executing regular activities, (2) relational difficulties, (3) occupational functioning, (4) psychological distress, and (5) social functioning, as well as an additional informational needs domain. Ultimately, CRCI was found to directly produce a range of challenges that negatively, and persistently, impact cancer survivors' quality of life. Cancer survivors were also found to have a range of needs associated with these challenges. This research should be used to inform future challenges and needs assessment tools as well as treatment and supportive care priority areas directly relating to CRCI.

44 A Case Study of Non-Alcoholic Wernicke’s Encephalopathy in a Young Man with Intractable Vomiting

Objective:Wernicke’s encephalopathy (WE) is an acute neurological condition caused by thiamine deficiency. The typical presentation is characterized by a triad of oculomotor abnormalities, gait ataxia, and altered mental status, though patients rarely present with all three symptoms. WE is a serious medical condition that is associated with high rates of morbidity and mortality if left untreated. It is most commonly seen in patients with severe alcohol use disorder; however, it has also been found in patients with thiamine deficiency due to other causes of malnutrition such as prolonged starvation, hyperemesis, dialysis, cancer, and geriatric surgery. Despite growing research demonstrating WE in non-alcoholic populations, it is frequently misdiagnosed in patients without an extensive alcohol-use history, particularly when they do not present with the typical clinical triad of symptoms. Thus, more knowledge about non-alcoholic WE is needed to improve diagnostic accuracy.Participants and Methods:We present a case of a 26-year-old male with an unremarkable alcohol use history, who was diagnosed with WE following a 6-week period of excessive nausea and vomiting of unclear etiology. He presented to the ED three times prior to his diagnosis, and was treated with intravenous hydration, Zofran, and Pepcid. He presented to the ED for the fourth time with altered mental status and gait ataxia and was diagnosed with WE based on MRI findings. He was admitted and treated with high doses of IV thiamine and folate. His clinical course was tracked over time via outpatient neurology examinations, and his cognitive functioning was assessed with an outpatient neuropsychological evaluation approximately six months post-discharge. Record review, including clinical notes, lab tests, and imaging results supplement his outpatient neuropsychological evaluation performance.Results:Data from a comprehensive outpatient neuropsychological evaluation approximately six months after WE diagnosis is presented. His cognitive profile was characterized by impaired performance on measures of verbal fluency and memory, including encoding and retention of verbal and visual information (with minimal benefit from cueing). Given these impairments and continued functional declines related to cognitive deficits, he met criteria for a Major Neurocognitive Disorder. These results demonstrate persistent cognitive deficits beyond the acute WE period.Conclusions:WE is a serious neurological condition that can have lasting cognitive effects if left untreated. This case demonstrates persistent cognitive impairments six months after WE diagnosis in a young patient with an unremarkable alcohol history. These findings highlight the necessity of increased diagnostic efficiency of WE in non-alcoholic patients, as immediate thiamine treatment is essential to the recovery process. Neuropsychological functioning at a longer interval will be useful in further elucidating cognitive prognosis as well as providing quality of life recommendations.

Regional white matter hyperintensity volume predicts persistent cognitive impairment in acute lacunar infarct patients.

White matter hyperintensity (WMH) is often described in acute lacunar stroke (ALS) patients. However, the specific relationship between regional WMH volume and persistent cognitive impairment remains unclear. We enrolled patients with ALS who were hospitalized at the First Affiliated Hospital of Soochow University between January 2020 and November 2022. All patients were assessed for global cognitive function using the Montreal Cognitive Assessment (MoCA) scale at 14 ± 2 days and 6 months after the onset of ALS. Manifestations of chronic cerebral small vessel disease (CSVD) were assessed via MRI scan. The distributions of regional WMH were segmented, and their relationship with cognitive impairment was evaluated. A total of 129 patients were enrolled. Baseline frontal WMH volume (OR = 1.18, P = 0.04) was an independent risk factor for long-term cognitive impairment after ALS. Furthermore, the presence of WMH at the genu of the corpus callosum (GCC) at baseline (OR = 3.1, P = 0.033) was strongly associated with persistent cognitive decline. Multivariable logistic regression analysis showed that depression (OR = 6.252, P = 0.029), NIHSS score (OR = 1.24, P = 0.011), and albumin at admission (OR = 0.841, P = 0.032) were also important determinants of long-term cognitive impairment after ALS. Our study found that WMH, especially frontal WMH volume and the presence of WMH at the GCC at baseline, independently contributed to long-term cognitive decline in ALS patients. This study provides new evidence of the clinical relationship between regional WMH volume and cognitive impairment in ALS patients.