Formal Neuropsychological Testing Research Articles

Frequency, Characteristics, and Correlates of Cognitive Complaints in a Cohort of Individuals with Post-Acute Sequelae of COVID-19.

Cognitive complaints are among the most frequent symptoms of post-acute sequelae of COVID-19 (PASC). This study aimed to investigate the frequency, characteristics, and clinical correlates of cognitive complaints (CC) in PASC, particularly in relation to objective neuropsychological (NP) performance. Seventy-four participants underwent psychiatric, medical, and NP testing approximately 7 months after acute COVID-19. The Patient Assessment of Own Functioning Inventory (PAOFI) was used to characterize the frequency and severity of CC in domains of memory, language, and cognitive/executive function. The associations of CC with sociodemographic, medical, psychiatric, and NP variables were assessed utilizing correlational analysis, logistic regression, and pairwise comparisons of those categorized as having CC vs. not having CC. Taken together, approximately one-third of the study participants had clinically significant CC. Memory difficulty was the most frequent CC, although all categories were frequently endorsed. Memory and cognitive/executive complaints correlated with NP tests in these and multiple other NP domains. CC were more likely to be under-reported in those with diminished NP performance than over-reported in those without diminished performance. Acute COVID-19 symptom severity, elevated depressive symptoms, and NP tests of diminished attention and psychomotor processing speed were independent predictors of CC in logistic regression. Cognitive complaints after acute COVID-19 should be taken seriously, as they are likely to reflect diminished NP performance, as well as medical, psychiatric, and functional burdens. However, patients with PASC may not accurately identify or characterize objective cognitive difficulties, so programs offering comprehensive care for patients with PASC should offer formal neuropsychological testing.

Relationship Between Memory and Brain Metabolism is Markedly Disordered in non‐Demented Patients Who Have Worsening Sleep Over Time

AbstractBackgroundDisturbances in circadian rhythm often emerge during disease progression in patients with dementia. We recently reported that subjects with worsening sleep experienced significantly faster cerebral decline compared to subjects with improved sleep over comparable timeframes. Here we describe relationships between brain metabolism and memory as a function of changing sleep status.MethodA consecutive series of 2,005 cognitively normal and mildly impaired subjects from more than 50 North American sites participating in the first three phases of the Alzheimer’s Disease Neuroimaging Initiative was studied. Changes in cognition assessed through formal neuropsychological testing, and in regional cerebral metabolism assessed through brain PET using the radiotracer [F‐18]fluorodeoxyglucose (FDG), were examined. Activities in 47 standardized volumes of interest (sVOI’s), as normalized to each subject’s whole brain activity, were longitudinally measured, and significance of changes in memory were evaluated using a Pearson correlational analysis and two‐sided one‐sample t tests.ResultIn this consecutive series of 2005 subjects, 211 were documented to have had a change in insomnia status during their participation: 83 who were documented to have insomnia at baseline that was subsequently alleviated (“improving sleep”), and 128 who were documented to have no insomnia at baseline but developed it during the study period (“worsening sleep”); among them, 62 (29%) underwent FDG‐PET scans during both baseline insomnia and subsequent insomnia‐free status, or both baseline normal sleep and subsequent insomnia status periods. In subjects with improving sleep, baseline metabolism of posterior cingulate cortex, the brain region with metabolism that declines most significantly in the earliest stages of Alzheimer’s disease, was strongly associated with memory domain performance (r = 0.65, p = 0.00003). In marked contrast, this relationship was severely degraded in subjects who had worsening sleep (r = 0.20, p = 0.18). Similar relative relationships, though somewhat less statistically dramatic, were also observed with respect to global cognition, as assessed by both ADAS‐COG and MMSE scores in both groups of subjects.ConclusionSubjects with worsening sleep over time showed a highly disordered relationship between their baseline regional brain metabolism and cognitive function, and this effect was most dramatic with respect to their memory domain performance.

A - 125 Posttraumatic Stress Disorder Symptom Severity and its Relationship to Performance on the Test of Memory Malingering in a Veteran Sample.

To examine relationships between Posttraumatic Stress Disorder (PTSD) symptom severity and performance on the Test of Memory Malingering (TOMM) trials in veterans without a diagnosis of neurocognitive disorder. A sample of 47 clinically-referred veterans (80.9% male; Mage = 57.47, SD = 14.83; Medu = 13.91, SD = 2.5) who did not meet criteria for a neurocognitive disorder completed the PTSD Checklist for DSM-5 (PCL-5) and the TOMM. Primary diagnoses included PTSD (48.9%), no diagnosis (23.4%), and depression (19.1%). A cutoff of 45 was used for each trial; 47 completed Trial 1 (TOMM-T1), 17 completed Trial 2 (TOMM-T2), and 10 completed Retention Trial (TOMM-Ret). Nine participants (19.1%) failed the TOMM. Analyses included Pearson correlation, Spearman correlation, and independent-samples t-tests. Age was negatively correlated with PCL-5 and positively correlated with TOMM-T1; therefore, relevant partial correlations were conducted. TOMM-T1 demonstrated a moderate, negative correlation with PCL-5, rs(45) = -0.469, p < 0.001, 95%CI(-0.688,-0.248). A moderate non-significant correlation was found between TOMM-T2 and PCL-5, rs(15) = -0.405, p = 0.053, 95%CI(-0.775,0.014). PCL-5 and TOMM-Ret were not correlated. Controlling for age, the correlation between PCL-5 and TOMM-T1 remained significant (rs[44] = -0.426, p = 0.002). Those who passed TOMM (M = 38.45, SD = 16.48) had significantly lower PCL-5 scores compared to those who failed (M = 57.67, SD = 13.83), t(45) = -3.231, p = 0.001, Cohen's D = 16.04. Among veterans, PTSD symptom severity was related to TOMM scores and/or failure. Findings highlight a need to consider the role PTSD symptoms may play in neuropsychological assessment. Findings further support recommendations for trauma-focused treatment before formal neuropsychological testing, as psychiatric symptoms may interfere with obtaining a valid assessment of cognition.

Association of a ≥2 point decrease of MoCA 1 year after noncardiac surgery with patient-important outcomes: a secondary analysis of the NeuroVISION cohort study (P2-12.001)

<h3>Objective:</h3> To evaluate whether, among ≥65 years old people, a ≥2 point decline in the Montreal Cognitive Assessment (MoCA) 1 year after noncardiac surgery is associated with patient-important outcomes. <h3>Background:</h3> NeuroVISION was an international prospective cohort study of 1114 patients, ≥65 years old, undergoing elective noncardiac surgery. In NeuroVISION, 30.3% of patients had a ≥2 point decrease in MoCA from baseline to 1 year after surgery. A ≥2 point MoCA decrease has been associated with cognitive decline based on formal neuropsychological testing. However, there is paucity of data on its association with patient-important outcomes. <h3>Design/Methods:</h3> NeuroVISION participants had MoCA, Lawton iADL, and EQ-5D questionnaires administered at baseline and 1 year after surgery. The iADL score was defined as the number of instrumental activities in which patients were independent (range 0–8). At 1 year participants also reported whether they had had any fall in the previous year. We performed multivariable regression analyses adjusting for age, sex, and baseline scores. <h3>Results:</h3> At baseline, the median iADL score of NeuroVISION participants was 8 (interquartile range 7–8). At 1-year, patients with ≥2 point MoCA decline reported a greater decline in iADL (adjusted beta coefficient −0.20, 95% CI −0.36 to −0.05; p=0.010) and in EQ-5D VAS scores (adjusted beta-coefficient −2.90, 95% CI −5.08 to −0.73; p=0.009) than patients without. 22.2% of the patents with <i>versus</i> 12.1% of patients without a ≥2 point MoCA decline lost independence in ≥1 iADL (adjusted odds ratio 1.93, 95% CI 1.35–2.76, p&lt;0.001). At 1 year, patients with a ≥2 point MoCA decline reported more frequently ≥1 fall (14.9% versus 10.2%), and a higher number of falls (adjusted incident risk ratio 1.76, 95% CI 1.28 – 2.40). <h3>Conclusions:</h3> In the large NeuroVISION cohort, a ≥2 point MoCA decline 1 year after noncardiac surgery was not only frequent but also associated with functional decline. <b>Disclosure:</b> Dr. Marcucci has nothing to disclose. The institution of Dr. Thirumala has received research support from University of Pittsburgh. Dr. Mrkobrada has nothing to disclose. The institution of Dr. Devereaux has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Trimedic. The institution of Dr. Devereaux has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bayer. The institution of Dr. Devereaux has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Quidel. The institution of Dr. Devereaux has received research support from Abbott Diagnostics. The institution of Dr. Devereaux has received research support from CloudDX. The institution of Dr. Devereaux has received research support from Philips Healthcare. The institution of Dr. Devereaux has received research support from Roche Diagnostics. The institution of Dr. Devereaux has received research support from Siemens.

"Look straight ahead"-A new test to diagnose spatial neglect by computed tomography.

Spatial neglect is the dominant behavioral disorder after right hemisphere brain lesions. Reliabel diagnosis by formal neuropsychological testing is often achieved only later during hospitalization, leading to delays in targeted therapies. We propose a way to diagnose spatial neglect right at admission. We measured the conjugated eye deviation (CED) on the initial computed tomography (CT) scans, in combination with the verbal instruction "Please look straight ahead" during the scan. The command was implemented in the scanner program and automatically played before a cranial CT started. This prospective study included a total 46 consecutive subjects (16 patients with first ever right brain damage and no spatial neglect, 12 patients with first ever right brain damage and spatial neglect, and 18 healthy controls). The right brain damaged groups were submitted to paper pencil tests to access the diagnosis of a spatial neglect after radiological confirmation of the brain damage during the initial phase of their hospitalisation. This procedure allowed us to define a cut-off value of 14.1 degrees of CED to the ipsilesional side to differentiate right hemispheric stroke patients with versus without spatial neglect with a confidence interval of 99%. This simple addition to a radiological routine procedure provides a new tool to help diagnose spatial neglect at the earliest stage possible and thus offers the possibility of providing patients with optimized rehabilitative therapy from a very early stage on.

Formal Neuropsychological Testing: Test Batteries, Interpretation, and Added Value in Practice.

Neuropsychologists evaluate patients for cognitive decline and dementia, using validated psychometric tests, along with behavioral observation, record review, clinical interview, and information about psychological functioning, to evaluate brain-behavior relationships and aid in differential diagnosis and treatment planning. Also considered are premorbid functioning, education, sex, socioeconomic status, primary language, culture, and race-related health disparities when selecting tests, interpreting performance, and providing a diagnostic impression. Neuropsychologists provide diagnostic clarity, explain symptoms and likely disease course to patients and family members, and assist the family with future planning, behavioral management strategies, and ways to mitigate caregiver burden.

Arterial spin labelling reveals multi-regional cerebral hypoperfusion in patients with transient ischemic attack that are unrelated to ischemia location: A proof-of-concept study

Patients with transient ischemic attack (TIA) have a substantially increased risk of early dementia. In this exploratory study, we aim to determine whether patients with TIA have 1) measurable regional cerebral hypoperfusion unrelated to the location of ischemia, and 2) determine the relationship of regional cerebral blood flow (rCBF) with their cognitive profiles. Patients with TIA (N=49) and seventy-nine (N=79) age and sex matched controls underwent formal neuropsychological testing and MRI. Quantitative arterial spin labelling rCBF maps (mL/min/100g) were registered to the corresponding high resolution T1-weighted image. Linear regression was used to determine the association between demographic, clinical and cognitive variables and rCBF. Patients with TIA had significantly (p<0.05) lower cognitive scores in the MMSE, MOCA, ACE-R, WAIS-IV DS Coding and Trail Making Tests A and B compared to controls. TIA patients had significantly lower rCBF in the left entorhinal cortex (p=0.03), right posterior cingulate (p=0.04), and right precuneus (p=0.05), after adjusting for age and sex, that were unrelated to the regional anatomical volume and DWI positivity. Regional hypoperfusion in the right posterior cingulate and right precuneus was associated with impaired visual memory (BVMT total, p=0.05 for both regions) and slower processing speed (TMT A, p=0.04 and p=0.01), respectively after adjusting for age and sex. TIA patients have patterns of regional hypoperfusion in multiple cortical regions unrelated to the parcellated regional anatomical volume or the presence of a DWI lesion. Regional hypoperfusion in patients with TIA may be an early marker conferring risk of future cognitive decline that needs to be confirmed by future studies.

Neuropsychological effects of a six‐month online cognitive health program with a weekly telehealth lifestyle support group and personalized precision medicine recommendations for health optimization in older adults with subjective cognitive impairment

AbstractBackgroundMaintaining healthy lifestyle behaviors and optimizing health may slow cognitive decline through risk reduction in older adults with cognitive impairments. Curriculum‐based health coaching, weekly psychosocial support, and use of biomarkers to guide health optimization may aid in establishing effective behavior change centered around multiple reversible dementia risk factors.MethodWe piloted combined use of a six‐month online Cognitive Health Program (www.amosinstitute.com) with a telehealth lifestyle support group in six patients with subjective cognitive complaints receiving ongoing outpatient memory care. These patients were given lab‐guided personalized health recommendations for dementia risk reduction throughout the pilot intervention during monthly individual appointments with the study physician overseeing the group. A registered dietician was invited to lead the weekly telehealth lifestyle support group, which was delivered in partnership with the Center’s memory clinicians and health coaches. Highlights of the online Cognitive Health Program were reviewed by the dietician each week followed by group discussion on topics including diet, exercise, sleep, stress, and cognitive training. Cognition was assessed at baseline and post‐intervention using a computerized battery (www.cambridgebrainsciences.com). The significance of cognitive changes was estimated with nonparametric tests and effect sizes (Cohen’s d). The participants were also queried qualitatively on adherence and satisfaction.ResultCompared to baseline, the participants improved significantly in the global cognition score (p&lt;.02, d = 1.6), and had significant improvements in spatial planning (p&lt;.01, d = 2.3) and visuospatial processing (p&lt;.05, d = 1.1). There was a borderline improvement in verbal reasoning (p&lt;.06, d = 1.0). Subjective reports indicated that participants were able to successfully adhere to multiple lifestyle habits in the areas of sleep, nutrition, and exercise. Participants reported high levels of satisfaction with the virtual group format, the online curriculum, and access to the additional online resources.ConclusionA virtually administered, six‐month, weekly health coaching group that addresses multiple lifestyle factors associated with brain health, supplemented by self‐paced online health education and lab‐based health optimization by a physician, is feasible and potentially efficacious for improving cognition in participants with subjective cognitive impairment. This format may facilitate behavior change to slow cognitive decline. Future studies will include neuroimaging, formal neuropsychological testing, controls, and larger sample sizes.

Pre- and postoperative self-reported and objectively assessed neurocognitive functioning in lower grade glioma patients

Due to the tumor itself or its therapy glioma patients may complain on cognitive impairment, while validated neuropsychological testing (NPT) capturing specific neuropsychological domains does not indicate “objective” dysfunction. Little is known on the relevance of this disturbance for patients’ everyday life. We aimed to address whether glioma patients treated with state-of-the-art neurosurgical techniques complain on neuropsychological impairment and whether these subjective complaints are disclosed in formal NPT. We assessed both, “objective” and “subjective” neurocognitive functioning in 13 patients with newly diagnosed WHO grade 2 and 3 gliomas, operated between 06/2018 and 12/2020. All underwent both, preoperative and follow-up NPT as well as a semi-structured interview on subjective complaints and specific questionnaires (post-therapeutic) on attention, memory and executive functioning. On group level, no significant changes between preoperative and post-therapeutic NPT occurred. On the individual level, in 3/13 patients new post-therapeutic deficits in objective NPT were detected in specific domains (verbal memory, non-verbal memory, verbal fluency). By contrast, 8/13 patients reported on “subjective” memory impairments post-therapeutically. Furthermore, on specific questionnaires cognitive and emotional executive dysfunction and increased fatigue occurred in patients relative to normative data. Although the findings have to be replicated in larger populations, a discrepancy between “subjective” and “objective” measures was evident. While subjective neurocognitive impairment may simply not represent a true dysfunction, an alternative explanation might be that established standardized NPT is not suitable to detect subtle dysfunction in this population. “Subjective” and “objective” neurocognitive functioning might represent distinct constructs, which should complement each other in patient-centered Neuro-Oncology.

Montreal cognitive assessment as a screening instrument for cognitive impairment in systemic lupus erythematosus patients without overt neuropsychiatric manifestations.

The Montreal Cognitive Assessment (MoCA) is an increasingly used screening tool for cognitive impairment. The aim of this study was to examine how MoCA performed in identifying cognitive impairment (CI) domains in SLE patients compared with formal standardized neuropsychological testing (NPT). Factors related to SLE disease, immunologic and psychological state associated with CI were also explored. This cross-sectional study recruited 50 SLE patients without overt neuropsychiatric manifestations from April 2017 to May 2018. The patients were evaluated with MoCA, formal NPT and the Depression, Anxiety, and Stress Scales (DASS) 42-item self-report questionnaire. Values of sensitivity and specificity were computed for different cut-offs of MoCA within each cognitive domain of NPT and descriptive analysis was used to identify the factors affecting cognitive function. The median score for MoCA was 27.5 (range 22-30). Using a MoCA cutoff of <26, 18 (36%) were identified to have CI using NPT compared to 8 (16%) using MoCA. The most frequently affected cognitive domain was executive functioning with 15 affected patients. Sensitivities and specificities of the MoCA range from 50% to 100% and 5.7% to 16.7%, respectively, across cognitive domains. A lower MoCA cutoff of <25 improve sensitivity of identifying impairment in executive functioning from 60% to 80%. In univariate analysis, DASS scores, disease activity, presence of antiphospholipid antibodies, presence of concurrent autoimmune disease, current, and cumulative corticosteroid therapy did not predict cognitive performance. MoCA may be a useful screening tool to identify the most frequently affected cognitive domain which is executive functioning using a lower cutoff of <25 in SLE patients without overt neuropsychiatric manifestations.

Role of autoantibodies and blood–brain barrier leakage in cognitive impairment in systemic lupus erythematosus

ObjectiveCognitive impairment is common in patients with SLE but the cause is unknown. The current cross-sectional study examined the association between select SLE-related autoantibodies, other serological biomarkers and extensive blood–brain...

Tuberous sclerosis complex is a novel, amyloid-independent tauopathy associated with elevated phosphorylated 3R/4R tau aggregation

Tuberous sclerosis complex (TSC) is a neurodevelopmental disorder caused by mutations in the TSC1 and TSC2 genes and autosomal dominantly inherited. These mutations cause hyperactivation of the mammalian Target of Rapamycin (mTOR) pathway, leading to the development of nonmalignant masses involving various organ systems. Patients with TSC also experience neuropsychiatric symptoms collectively termed Tuberous Sclerosis Complex Associated Neuropsychiatric Disorder (TAND). Due to research advancements in TSC, patients now live well beyond the age of 50. Many experience objective impairment of memory and executive function, supported by formal neuropsychological testing, beginning in their late 40s. Biomarker analysis has described elevated levels of phosphorylated tau-181 in the cerebrospinal fluid of patients with TAND. Tau-PET imaging has also shown focal accumulation of the radiotracer flortaucipir (AV1451), suggesting that TSC may be a neurodegenerative disorder arising from accumulation of phosphorylated tau. However, the flortaucipir tracer has been reported to have significant off-target binding, preventing definitive conclusions from being drawn about the molecular etiology of neurodegeneration in TSC. Therefore, we initiated the Colocalization of AV1451 and Phosphorylated Tau in Adult brain tissue (CAPA) study. This study aimed to determine if flortaucipir is bound to phosphorylated tau in brains of patients with TSC and further sought to determine the specific tau isoform seen in TSC. Our results show that flortaucipir labels the 3R/4R isoform of phosphorylated tau, commonly seen in Alzheimer’s disease. However, amyloid staining was negative in brains of adult patients with TSC. Therefore, we conclude that TAND symptoms are due to the accumulation of the phosphorylated tau isoform seen in Alzheimer’s disease. This study suggests that hyperactivation of the mammalian Target of Rapamycin pathway may play a role in the amyloid-independent development of 3R/4R tau aggregation. Our findings could lead to a new era of anti-tau therapies used to treat both disorders.

"My sympathetic clinician": perception of sympathy by patients with Alzheimer's disease increases when asked to provide autobiographical memories.

Autobiographical memory serves to recall past personal experiences and share them with others, promoting social bonding and communication. In this study, we investigated whether encouraging patients with Alzheimer's disease (AD) to share autobiographical memories during formal neuropsychological testing may boost the patient-clinician relationship, and more specifically, the neuropsychologist's level of sympathy as perceived by patients. We invited patients with mild AD to perform neuropsychological testing in two conditions. In one condition, we invited patients to retrieve and share two autobiographical memories after testing, while in a control condition, the testing session ended without asking patients to retrieve and share any autobiographical memories. After the two conditions, patients were invited to rate the neuropsychologist's level of sympathy towards them. Analysis demonstrated that patients perceived a higher level of sympathy when their neuropsychologist invited them to retrieve and share past personal experiences. By inviting patients with AD to retrieve past personal experiences, clinicians can promote a sense of sharing, create a social bond and, consequently, enhance the therapeutic relationship. In other words, by inviting patients with AD to share autobiographical memories, clinicians can promote a "social glue" with their patients, boosting mutual sympathy and patients' well-being.

Recurrent missense variant in the nuclear export signal of FMR1 associated with FXS-like phenotype including intellectual disability, ASD, facial abnormalities

Fragile X syndrome (FXS; MIM 300624) is an X-linked genetic disorder characterized by physical abnormalities associated with intellectual disability and a wide spectrum of neurological and psychiatric impairments. FXS occurs more frequently in males, 1 in 5000 males and 1 in 8000 females accounting for 1–2% of overall intellectual disability (ID). In more than 99% of patients, FXS results from expansions of a CGG triplet repeat (>200 in male) of the FMR1 gene. In the last years an increasing number, albeit still limited, of FXS subjects carrying FMR1 mutations including deletions, splicing errors, missense, and nonsense variants was reported. Nevertheless, the studies concerning the functional consequences of mutations in the FMR1 gene are rare so far and, therefore, we do not have sufficient knowledge regarding the genotype/phenotype correlation. We report a child carrying a hemizygous missense FMR1 (NM_002024.5:c.1325G > A p.Arg442Gln) variant, maternally inherited, associated with facial abnormalities, developmental delay, and social and communication deficits assessed with formal neuropsychological tests. The study contributes to highlighting the clinical differences between the CGG triplet repeat dependent phenotype and FMR1variant dependent phenotype and it also confirms the pathogenicity of the variant being reported for the second time in the literature.

Long-Term Cognitive Dysfunction in Cancer Survivors.

Cancer-related cognitive impairment (CRCI) is a frequent side effect experienced by an increasing number of cancer survivors with a significant impact on their quality of life. Different definitions and means of evaluation have been used in available literature; hence the exact incidence of CRCI remains unknown. CRCI can be described as cognitive symptoms reported by cancer patients in self-reported questionnaires or as cognitive changes evaluated by formal neuropsychological tests. Nevertheless, association between cognitive symptoms and objectively assessed cognitive changes is relatively weak or absent. Studies have focused especially on breast cancer patients, but CRCI has been reported in multiple types of cancer, including colorectal, lung, ovarian, prostate, testicular cancer and hematological malignancies. While CRCI has been associated with various treatment modalities, including radiotherapy, chemotherapy, hormone therapy and novel systemic therapies, it has been also detected prior to cancer treatment. Therefore, the effects of cancer itself with or without the psychological distress may be involved in the pathogenesis of CRCI as a result of altered coping mechanisms after cancer diagnosis. The development of CRCI is probably multifactorial and the exact mechanisms are currently not completely understood. Possible risk factors include administered treatment, genetic predisposition, age and psychological factors such as anxiety, depression or fatigue. Multiple mechanisms are suggested to be responsible for CRCI, including direct neurotoxic injury of systemic treatment and radiation while other indirect contributing mechanisms are hypothesized. Chronic neuroinflammation mediated by active innate immune system, DNA-damage or endothelial dysfunction is hypothesized to be a central mechanism of CRCI pathogenesis. There is increasing evidence of potential plasma (e.g., damage associated molecular patterns, inflammatory components, circulating microRNAs, exosomes, short-chain fatty acids, and others), cerebrospinal fluid and radiological biomarkers of cognitive dysfunction in cancer patients. Discovery of biomarkers of cognitive impairment is crucial for early identification of cancer patients at increased risk for the development of CRCI or development of treatment strategies to lower the burden of CRCI on long-term quality of life. This review summarizes current literature on CRCI with a focus on long-term effects of different cancer treatments, possible risk factors, mechanisms and promising biomarkers.

The risk of cognitive impairment in spouses of patients with cognitive impairment

AbstractBackgroundWe aimed to investigate demographics, neuropsychological performance, and amyloid pathology in spouses of people with cognitive impairment.MethodA total of 30 patients and 30 spouse controls were enrolled in a prospective cohort for Alzheimer’s disease between June 2018 and December 2020. All subjects had a comprehensive interview, laboratory findings, formal neuropsychological test battery, brain computed tomography or magnetic resonance imaging, and 18F‐ Florbetaben positron emission tomography (FBB PET).ResultThere were no differences in age, sex, education level, family history of dementia, and vascular risk factors between the patient group and spouse group. APOE e4 carriers were more common in the patient group (40.0%) than in the spouse group (10.0%). Although none of the spouses complained of impaired cognition, 40.0% of them were shown to have mild cognitive impairment. Visual analysis of FBB PET showed that 24.1 % of spouses showed amyloid deposition.ConclusionForty percent of spouses of people with cognitive impairment showed mild cognitive impairment and about 24% of them had amyloid pathology. This finding implicates high risk of cognitive impairment in spouses of people with cognitive impairment, which may be associated with shared environmental factors and psychosocial burden as a caregiver. Early diagnosis and intervention for spouses of people with cognitive impairment may be necessary for both patients and spouses. In the future, further investigations in a larger cohort is warranted to confirm findings from this study.

Klinefelter Syndrome and Turner Syndrome.

1. Carole Samango-Sprouse, EdD*,†,‡ 2. Sophia Q. Song, BA‡ 3. Angela E. Lin, MD§ 4. Cynthia M. Powell, MD¶ 5. Andrea L. Gropman, MD*,** 1. *George Washington University, Washington, DC 2. †Florida International University, Miami, FL 3. ‡Department of Research, The Focus Foundation, Davidsonville, MD 4. §Massachusetts General Hospital for Children, Boston, MA 5. ¶University of North Carolina at Chapel Hill, Chapel Hill, NC 6. **Children’s National Medical Center, Washington, DC Sex chromosome aneuploidy (SCA) syndromes refer to disorders with an abnormality of sex chromosome number. The most common are Klinefelter syndrome (KS), resulting from the gain of an X chromosome in males, and Turner syndrome (TS), reflecting the loss of an X chromosome or the presence of a structurally different X chromosome in females. Whereas most patients with KS have nonmosaic 47,XXY, only 40% of women with TS have 45,X; the remainder have a variety of mosaicisms. The syndromes also contrast in that males with KS are characteristically tall, whereas females with TS are typically short unless they receive hormonal treatment. Despite efforts to increase awareness, KS and TS are often underdiagnosed, leading to delayed care. Only 25% of men with KS are ever diagnosed, with fewer than 10% detected prenatally, and with a median age of 27 years for those identified later in life. For TS, the median age at diagnosis is 6.6 years. Although not exclusively, optimal neurocognitive outcomes depend on the timing of diagnosis and access to early targeted treatment, so fortunately the recent development of noninvasive prenatal screening is increasing the early identification of these disorders dramatically. Pediatricians should be aware of signs that allow for early detection, and the importance of prompt referral for testing and therapy. KS occurs in 1 in 660 live births, representing the most common SCA. Affected males have androgen deficiency, which affects endocrine, central nervous system, and neurodevelopmental function. Characteristics include increased height, clinodactyly of the fifth finger, pes planus, and hypogonadism manifesting as …

Long-term cognitive and psychiatric outcomes of acute respiratory distress syndrome managed with Extracorporeal Membrane Oxygenation

BackgroundCognitive dysfunction is often reported in patients who have experienced acute respiratory distress syndrome (ARDS). Extra Corporeal Membrane Oxygenation (ECMO) therapy is increasingly used to manage ARDS patients in ICU, transforming survival rates. However, few studies have examined cognitive outcomes. MethodsWe examined self-reported cognitive complaints, psychiatric outcomes and neuropsychological test performance in survivors of severe hypoxaemia managed with VV-ECMO, at 18–24 month follow-up, compared with a group of healthy controls. ResultsOver 70% of ECMO-treated patients (N = 46) complained of difficulty in at least one aspect of cognition on self-report measures (study 1). However, a much lower frequency of cognitive impairment was found on formal neuropsychological testing (study 2). Mean neuropsychological test scores of the ECMO group (N = 24) did not significantly differ from healthy controls (N = 23) after controlling for depression. Less than 30% of ECMO-treated patients showed impairments in anterograde memory, and deficits on general IQ or executive function were seen in <17% of patients. However, we observed high levels of self-reported anxiety and depression in the ECMO-treated patients. ConclusionsCognitive outcomes in ECMO-treated patients were generally good, with preserved neuropsychological function in the majority of patients, despite severe hypoxaemia and high rates of self-reported difficulties. However, we saw high levels of mental health symptoms in these patients, highlighting a need for psychological support.

Neurocognitive deficits in severe COVID-19 infection: Case series and proposed model

Objective: To date, very few studies investigating neurocognitive deficits in COVID-19 have been published. This case series addresses cognition in post-COVID-19 patient by describing three patients in acute rehabilitation to inform a model of cognitive sequelae of COVID-19. Methods: Three English-speaking inpatients with severe symptoms and long-term intensive care unit (ICU) treatment are described. All patients had a premorbid history of hypertension and hyperlipidemia and experienced delirium and hypoxemia when hospitalized. Patient 1 is a 62-year-old male with 15 years of education with additional history of obstructive sleep apnea and type 2 diabetes. Patient 2 is a 73-year-old female with 12 years of education with a premorbid medical history of alcohol use disorder and Guillain-Barre syndrome. Patient 3 is a 75-year-old male with 14 years of education. No patients had premorbid psychiatric histories. Results: The three patients demonstrated deficits on formal neuropsychological testing, particularly with encoding and verbal fluency. Memory measures improved with a more structured story memory task compared to a less-structured verbal list-learning task, suggesting executive dysfunction impacted learning. None of the patients demonstrated rapid forgetting of information. Two patients endorsed new depressive and/or anxiety symptoms. Conclusions: The results suggest evidence for neurocognitive deficits after severe COVID-19 infection, particularly in encoding and verbal fluency. These results were interpreted with caution given the limited number of patients and the telephone-based battery. The specific mechanism that caused these cognitive deficits in these individuals remains unclear. A proposed three-stage model of cognitive dysfunction is described to help guide future research.

The Italian Version of the Test Your Memory (TYM-I): A Tool to Detect Mild Cognitive Impairment in the Clinical Setting.

The Test Your Memory (TYM) is a brief self-administered, cognitive screening test, currently used in several settings. It requires minimal administrator supervision and the computation of the final test score takes approximately 2 min. We assessed the discrimination ability of the Italian version of the TYM (TYM-I) in detecting Mild Cognitive Impairment (MCI) in clinical setting. TYM-I was administered to 94 MCI patients and 134 healthy controls. The clinical diagnosis of MCI was considered as the gold standard. An extended formal neuropsychological test battery was used to define MCI subtypes. Receiver Operating Characteristic (ROC) analyses were conducted to find the optimal cut-off and measure discrimination ability of TYM-I in detecting MCI. TYM-I had a similar area under the curve (AUC = 0.85) point estimate as Mini Mental State Examination (MMSE) (AUC = 0.83). A TYM-I score lower or equal to 36 was found to be optimal cut off to detect MCI. The TYM-I showed the highest discrimination ability among individuals aged more than 70 and high educational level (AUC = 0.89). The amnestic MCI subtype patients, compared to non-amnestic MCI patients, had worse performance in recall, orientation and visuospatial abilities TYM-I subscores. The TYM-I is a valid screening test in detecting cognitive dysfunction, easily carried out in clinical practice. The TYM-I subscores may allow to identify amnestic and non-amnestic MCI subtypes.