Severity Of Neurocognitive Impairment Research Articles

Does neurocognition functioning impact driving habits in older adults with HIV?

Nearly 30%–50% of people living with HIV (PLWH) have HIV-Associated Neurocognitive Disorder. With half of PLWH being 50 and older, concerns mount that the prevalence and severity of neurocognitive impairment will increase with age. Yet, neurocognitive functioning can impact driving safety in older adults, but may also impact driving in older PLWH. Impairment in the neurocognitive domains utilized in driving may put PLWH at risk for decreased mobility that impacts their treatment adherence and quality of life. This study is the first to examine the driving habits of PLWH 40+ years and determine whether impairment in particular neurocognitive domains are predictive of driving habits.

Neurocognitive course at 2-year follow-up in a Swiss cohort of people with well-treated HIV

Objective:The aim of this study was to examine neurocognitive course over time among people with well treated HIV.Design:The Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study is an ongoing, prospective, longitudinal, multicenter and multilingual study within the Swiss HIV Cohort Study (SHCS). Participants undergo neuropsychological assessment at baseline and two-yearly follow-up.Setting:Seven SHCS centres.Participants:Patients aged at least 45 years enrolled in the SHCS with fluency in the local language (French, German or Italian) and agreeing to participate in the NAMACO study: 981 participants at baseline, 720 at 2-year follow-up of whom 644 had complete data sets.Intervention:Standardized neuropsychological assessment at baseline and 2-year follow-up.Main outcome measure:Neurocognitive performance using Frascati criteria and mean z-scores.Results:Four participants (of 644, 0.6%) had plasma HIV-1 RNA more than 50 copies/ml; median CD4+ cell count was 660 cells/μl. According to Frascati criteria, 204 participants (31.7%) had neurocognitive impairment (NCI) at baseline. NCI severity in these participants changed little over 2 years and comprehensive models based on Frascati criteria were not feasible. Examining mean z-scores, however, we observed neurocognitive stability or improvement over two years in five of seven neurocognitive domains assessed. Age at least 65 years (P = 0.02) and cognitive complaints (P = 0.004) were associated with neurocognitive decline, while black race (P = 0.01) and dolutegravir treatment (P = 0.002) were associated with improvement.Conclusion:Frascati criteria were less sensitive in measuring NCI change and therefore unsuitable for following neurocognitive course in our cohort of people with well treated HIV. Examining neurocognitive course by mean z-score change, we observed stability or improvement.

Neurocognitive impairment in Asian childhood cancer survivors: a systematic review.

Childhood cancer survivors are at higher risk of developing neurocognitive deficits due to the intensive treatment they received at an early age. Most studies on childhood cancer survivorship have so far focused on the Western populations. Due to the ethnic, genetic, environmental, and cultural differences, clinical data of the Western populations may not be representative of Asian countries. This scoping review systematically summarized the existing clinical evidence of the neurocognitive impairment of Asian childhood cancer survivors. We searched the Embase and Medline databases for studies assessing the neurocognitive functions of survivors in Asia, who were diagnosed with cancer before the age of 19 and completed active treatment. The literature search identified 13 studies involving 2212 participants from five Asian countries: South Korea (n = 4, 30.8%), Taiwan (n = 3, 23.1%), Japan (n = 3, 23.1%), Hong Kong (n = 2, 15.4%), and Thailand (n = 1, 7.7%). The included studies focused on CNS tumors (n = 10, 76.9%), hematological malignancies (n = 7, 53.8%), or heterogeneous cancer diagnoses (n = 3, 23.1%). Collectively, mild-to-moderate impairment in intelligence was observed in 10.0 to 42.8% of survivors, which seemed higher than the reported rate in Western survivors. We speculate that the ethnic and genetic variations in drug responses and susceptibility to adverse chronic toxicities may have contributed to the differences in the prevalence and severity of neurocognitive impairment between these two populations. To better understand the effects of culturally relevant and region-specific environmental risk factors on the post-treatment neurocognitive development in cancer survivors, a holistic approach that addresses the complex interactions between biological, physical, and psychosocial factors is needed. This will aid the development of effective intervention strategies to improve the functional and psychosocial outcomes of cancer survivors in Asian societies.

When Epilepsy Grows Up….

Neurocognition in Childhood Epilepsy: Impact on Mortality and Complete Seizure Remission 50 Years Later Sillanpää M, Saarinen MM, Karrasch M, Schmidt D, Hermann BP. Epilepsia. 2019;60(1):131-138. doi:10.1111/epi.14606. Epub 2018 Nov 22.Objective:To study associations of the severity of impairment in childhood neurocognition (NC) with long-term mortality and complete seizure remission.Methods:A population-based cohort of 245 subjects with childhood-onset epilepsy was followed up for 50 years (median = 45, range = 2-50). Childhood NC before age 18 years was assessed as a combination of formal intelligence quotient scores and functional criteria (school achievement, working history, and psychoneurological development). Impaired NC was categorized with respect to definitions of intellectual functioning in International Classification of Diseases, Tenth Revision (R41.83, F70-F73). The outcome variables, defined as all-cause mortality and 10-year terminal remission with the 5 past years off medication (10YTR), were analyzed with Cox regression models.Results:Of the 245 subjects, 119 (49%) had normal childhood NC, whereas 126 (51%) had various degrees of neurocognitive impairment. During the 50-year observation period, 71 (29%) of the subjects died, 13% of those with normal and 44% of those with impaired NC. The hazard of death increased gradually in line with more impaired cognition, reaching significance in moderate, severe, and profound impairment versus normal NC (hazard ratio [Bonferroni corrected 95% confidence interval] = 3.3 [1.2-9.2], 4.2 [1.2-14.2], and 5.5 [2.4-12.3], respectively). The chance for 10YTR was highest among subjects with normal NC (61%), whereas none of those with profound impairment reached 10YTR. In the intermediate categories, the chance was, however, not directly related to the increasing severity of impairment.Significance:The severity of neurocognitive impairment during childhood shows a parallel increase in the risk of death. In comparison with normal NC, subjects with lower childhood NC are less likely to enter seizure remission. However, normal NC does not guarantee complete remission or prevent premature death in some individuals with childhood-onset epilepsy.

Severity of neurocognitive impairment in women who have experienced intimate partner violence in Spain

ABSTRACTThis study examines neuropsychological impairment in women who have experienced intimate partner violence using DSM 5 criteria for mild and severe cognitive impairment. A total of 108 females in Spain were included in one of three groups: psychological abuse (n = 24), physical and psychological abuse (n = 45), and no-abuse (n = 39). There were differences between the control and IPV groups in attention and executive functioning. Furthermore, approximately 25% of women experiencing IPV suffer mild neuropsychological alterations and 5% severe, mostly in memory and executive function domains. This evidence supports the growth in research that suggests psychological violence on its own to be as strongly related to poor health outcomes as physical violence in intimate partner relationships.

Neurocognition in childhood epilepsy: Impact on mortality and complete seizure remission 50 years later.

To study associations of the severity of impairment in childhood neurocognition (NC) with long-term mortality and complete seizure remission. A population-based cohort of 245 subjects with childhood onset epilepsy was followed up for 50 years (median = 45, range = 2-50). Childhood NC before age 18 years was assessed as a combination of formal intelligence quotient scores and functional criteria (school achievement, working history, and psychoneurological development). Impaired NC was categorized with respect to definitions of intellectual functioning in International Classification of Diseases, 10th revision (R41.83, F70-F73). The outcome variables, defined as all-cause mortality and 10-year terminal remission with the 5 past years off medication (10YTR), were analyzed with Cox regression models. Of the 245 subjects, 119 (49%) had normal childhood NC, whereas 126 (51%) had various degrees of neurocognitive impairment. During the 50-year observation period, 71 (29%) of the subjects died, 13% of those with normal and 44% of those with impaired NC. The hazard of death increased gradually in line with more impaired cognition, reaching significance in moderate, severe, and profound impairment versus normal NC (hazard ratio [Bonferroni corrected 95% confidence interval] = 3.3 [1.2-9.2], 4.2 [1.2-14.2], and 5.5 [2.4-12.3], respectively). The chance for 10YTR was highest among subjects with normal NC (61%), whereas none of those with profound impairment reached 10YTR. In the intermediate categories, the chance was, however, not directly related to the increasing severity of impairment. The severity of neurocognitive impairment during childhood shows a parallel increase in the risk of death. In comparison with normal NC, subjects with lower childhood NC are less likely to enter seizure remission. However, normal NC does not guarantee complete remission or prevent premature death in some individuals with childhood onset epilepsy.

Spatial Memory Performance of Socially Mature Wistar Rats is Impaired after Exposure to Low (5 cGy) Doses of 1 GeV/n 48Ti Particles.

Prolonged deep space missions to planets and asteroids will expose astronauts to galactic cosmic radiation (GCR), a mixture of low-LET ionizing radiations, high-energy protons and high-Z and energy (HZE) particles. Ground-based experiments are used to determine whether this radiation environment will have an effect on the long-term health of astronauts and their ability to complete various tasks during their mission. Emerging data suggest that mission-relevant HZE doses impair several hippocampus-dependent neurocognitive processes in rodents, but that there is substantial interindividual variation in the severity of neurocognitive impairment, ranging from no observable effects to severe impairment. While the majority of studies have established the effect that the most abundant HZE species (56Fe) has on neurocognition, some studies suggest that the lighter 48Ti HZE particles may be equally, if not more, potent at impairing neurocognition. In this study, we assessed the effect that exposure to 5-20 cGy 1 GeV/n 48Ti had on the spatial memory performance of socially mature male Wistar rats. Acute exposures to mission-relevant doses (≤5 cGy) of 1 GeV/n 48Ti significantly (P < 0.05) reduced the mean spatial memory performance of the rats at three months after exposure, and significantly (P < 0.015) increased the percentage of rats that have severe (Z score ≥ 2) impairment, i.e., poor performers. Collectively, these data further support the notion that the LET dependency of neurocognitive impairment may differ from that of cell killing.

Long-Term Neurocognitive Functioning and Social Attainment in Adult Survivors of Pediatric CNS Tumors: Results From the St Jude Lifetime Cohort Study.

To assess the prevalence and severity of neurocognitive impairment in adult survivors of pediatric CNS tumors and to examine associated treatment exposures. Participants included 224 survivors of CNS tumors who were treated at St Jude Children's Research Hospital (current median age [range], 26 years [19 to 53 years]; time from diagnosis, 18 years [11 to 42 years]) and completed neurocognitive testing. Information on cranial radiation therapy (CRT) doses and parameters of delivery were abstracted from medical records. The prevalence of severe impairment (ie, at least two standard deviations below normative mean) was compared across radiation treatment groups (no CRT, focal irradiation, craniospinal irradiation) using the χ(2) test. Log-binomial models were used to estimate risk ratios (RRs) and corresponding 95% CIs for severe impairment. In multivariable models, craniospinal irradiation was associated with a 1.5- to threefold increased risk of severe impairment compared with no CRT (eg, intelligence: RR = 2.70; 95% CI, 1.37 to 5.34; memory: RR = 2.93; 95% CI, 1.69 to 5.08; executive function: RR = 1.74; 95% CI, 1.24 to 2.45). Seizures were associated with impaired academic performance (RR = 1.48; 95% CI, 1.02 to 2.14), attention (RR = 1.54; 95% CI, 1.12 to 2.13), and memory (RR = 1.44; 95% CI, 1.04 to 1.99). Hydrocephalus with shunt placement was associated with impaired intelligence (RR = 1.78; 95% CI, 1.12 to 2.82) and memory (RR = 1.42; 95% CI, 1.03 to 1.95). Differential follow-up time contributed to variability in prevalence estimates between survivors treated with older nonconformal and those treated with more contemporary conformal radiation therapy methods. Neurocognitive impairment was significantly associated with lower educational attainment, unemployment, and nonindependent living. Survivors of pediatric CNS tumors are at risk of severe neurocognitive impairment in adulthood. The prevalence of severe impairment is greater than expected in the general population, even in the absence of CRT, and is associated with disrupted attainment of adult social milestones.

Diabetes and cognitive decline in a French cohort of patients infected with HIV-1.

We investigated the relationship of diabetes and prediabetes with cognitive performances, assessed through raw test and z scores and according to neurocognitive impairment (NCI) classification in a cohort of individuals infected with HIV. The ANRS CO3 Aquitaine cohort is a prospective hospital-based cohort of HIV-1-infected patients under routine clinical management in 6 public hospitals in southwestern France. Between 2007 and 2009, an ancillary study consisted of a neuropsychological battery of 10 tests at baseline and 2-year follow-up. The severity of NCI (normal, asymptomatic, mild, HIV dementia) was assessed according to international guidelines. At baseline (400 patients, 33 with prediabetes, 39 with diabetes), in cross-sectional multivariable analyses, patients with diabetes performed significantly worse on 9 neuropsychological tests that assessed memory, executive functions, attention, psychomotor speed, language, and manual dexterity. Participants with prediabetes had worse performances compared with those who had normal glycemia in 5 tests. The longitudinal analysis of the association between glycemia status at baseline and change in cognitive performances over 2-year follow-up (n = 283) suggested that patients with diabetes also showed a slightly higher decline on 5 of the 10 tests, those involving executive functions and memory functioning. Glycemia status at baseline was not significantly associated with NCI severity in cross-sectional (p = 0.44) and longitudinal (p = 0.64) analyses. In this hospital-based cohort of people living with HIV, diabetes, but not the other cardiovascular risk factors, is associated with worse cognitive performances in several cognitive domains and with larger decline in fewer domains over the short term.

Cerebrospinal fluid (CSF) CD8+ T-cells that express interferon-gamma contribute to HIV associated neurocognitive disorders (HAND).

BackgroundHIV associated neurocognitive disorders (HAND) continue to affect cognition and everyday functioning despite anti-retroviral treatment (ART). Previous studies focused on mechanisms related to monocyte/macrophage mediated inflammation. However, in the ART era, there is increasing evidence for the involvement of CD8+ T-cells in CNS pathogenesis.MethodsTo investigate the relationship between T-cell responses and neurocognitive impairment (NCI), cerebrospinal fluid (CSF) and peripheral blood CD4+ and CD8+ T-cell intracellular cytokine (IFNγ, IL-2, TNFα) and lytic marker (CD107a) expression were assessed in HIV infected subjects who underwent comprehensive neurocognitive (NC) evaluation and either initiated or changed ART.ResultsData were collected from 31 participants at 70 visits. The frequency of cytokine expressing T-cells in CSF was significantly higher than in peripheral blood for CD4+T-cells: TNFα, IL-2, IFNγ and CD8+T-cells: IL-2 and IFNγ. Analysis of T-cell activity and NCI as a function of CSF HIV RNA levels suggested a general association between NCI, high CSF CD8+ (but not CD4+T-cell) cytokine expression and CSF HIV RNA <103 copies/ml (p<0.0001). Specifically, CSF CD8+ T-cell IFNγ expression correlated with severity of NCI (r = 0.57, p = 0.004). Multivariable analyses indicated that CSF CD8+T-cell IFNγ and myeloid activation (CD163) contributed equally and independently to cognitive status and a composite variable produced the strongest correlation with NCI (r = 0.83, p = 0.0001). In contrast, CD8+ cytolytic activity (CD107a expression) was negatively correlated with NCI (p = 0.05) but was dependent on CD4 levels >400/μl and low CSF HIV RNA levels (<103 copies/ml). In our longitudinal analysis of 16 subjects, higher CSF CD8+IFNγ expression at baseline predicted NC decline at follow-up (p = 0.02). Severity of NCI at follow-up correlated with level of residual HIV RNA in CSF.ConclusionsPresence of IFNγ expressing CD8+ T-cells, absence of cytolytic CD8+ T-cells, high myeloid activation, and failure of ART to suppress HIV replication in CSF contribute to increased risk of HAND.

A-104 Gender and Neurocognitive Impairment among HIV Infected Individuals in Nigeria

Background: Neurocognitive impairment (NCI) in HIV infection occurs as a frequent complication of HIV infection and, among HIV infected individuals in Nigeria, can be detected during the early stages of infection. The presence and severity of NCI can correlate with elevation of plasma levels of monocyte activation markers. In this study was examined the potential role of gender in the occurrence of NCI and associations between NCI and levels markers of HIV disease activity. Methods: One hundred thirty-three antiretroviral-naive seropositive (SP; 94 women and 59 men) and 56 seronegative (SN; 38 women and 18 men) participants received neuropsychological testing in 7 ability domains with calculation of demographically adjusted domain scores and a global deficit score (GDS). Also measured were plasma HIV RNA levels and plasma levels of the monocyte activation markers soluble CD163 and soluble CD14. Results: SP women in the study were younger than SP men, and SP women and men were less educated than their SN counterparts. CD4+ T cell counts, which were lower SP than for SN individuals, were higher for SN woman and SP women than for their male counterparts. Within the various ability domains, SP women scored worse than SN women with respect to verbal fluency and motor function and had higher overall mean GDS scores. In addition, SP women scored worse than SP men with respect to learning and memory. Mean log HIV viral load was higher and the frequency of non-detectable virus was lower for SP women than for SP men. Among SP women there was a borderline statistically significant correlation between sCD163 levels and GDS, and sCD14 levels were higher for impaired SP women than for non-impaired SP women. Viral load was higher for impaired SP men than non-impaired men and did not differ for impaired versus non-impaired SP women. Conclusions: Gender can have a significant impact on the occurrence of NCI among HIV infected individuals in Nigeria. This association appears to be linked to specific immune and viral factors, which require further study.

Neurocognitive functioning in a Romanian cohort of young adults with parenterally-acquired HIV-infection during childhood.

The Romanian cohort can provide valuable information about the effect of chronic HIV-infection and exposure to combined antiretroviral therapy (cART) on the developing brain, based on its unique characteristics: young adults infected parenterally with HIV clade F in the late 1980s and exposed to cART for a decade. We conducted a prospective study using a neuropsychological test battery validated in other international HIV cohorts, in order to evaluate the rate and severity of neurocognitive impairment in a group of young Romanian adults. The 49 HIV-infected (HIV+) participants and the 20 HIV negative (HIV-) controls were similar for age and gender, although the HIV- group tended to be more educated. We found higher cognitive impairment prevalence in the HIV+ group (59.1 %) versus the HIV- group (10 %), and the impairment rate remained significantly higher even when the groups were matched based on the educational level (38.7 % for the HIV+ group vs. 10.0 % for the HIV- controls; p = 0.025). The nadir CD4 count was <200 in 71.4 % of patients, but at the time of neurocognitive assessment, 89.5 % of patients had normal immunological status and 81.8 % undetectable HIV load. Among the HIV-impaired group, 26 % of the participants had syndromic impairment while the other 74 % had asymptomatic neurocognitive impairment. We found a high prevalence of neurocognitive dysfunction in the Romanian young adults growing-up with HIV. The greatest HIV-related cognitive deficits were in the domains of executive and motor functioning, consistent with a frontosubcortical pattern.

Long-Term Neurodevelopmental Outcomes After Intrauterine and Neonatal Insults

A large proportion of mortality in children younger than 5 years occurs during the neonatal period, especially in resource-poor countries. The long-term effects of intrauterine and neonatal insults among surviving infants on the frequency and severity of neurocognitive impairment and other sequelae is unknown. Most neonatal interventions in neonates exposed to intrauterine and neonatal insults have largely focused on survival. This systematic review was designed to estimate the long-term effects of intrauterine and neonatal insults on neurocognitive and other sequelae, especially in low- and middle-income countries. The authors conducted a search of several databases (Medline, Cumulative Index to Nursing and Allied Health Literature, the Cochrane Library, and Embase) to identify studies published between 1966 and 2011 that reported neurodevelopmental sequelae after preterm or neonatal insult. A search of Dissertation Abstracts International and the World Health Organization library was performed for unpublished studies and gray literature. Studies reviewed reported data for long-term outcomes after identifiable and well-defined neonatal insults. The overall risk of each insult for at least 1 long-term impairment was summarized by calculating medians and interquartile range (IQR). Impairments were graded as severe, moderate, or mild. Of the 28,212 studies identified in the search, 153 met criteria for inclusion. The overall median risk of one or more impairment in any one domain was 39.4% (IQR, 20.0–54.8). The overall risk for at least 1 severe, moderate, or mild impairment was as follows: 18.5% (95% confidence interval [CI], 7.7–33.3) with a risk of severe impairment, 5.0% (95% CI, 0.0%–13.3%) with a risk of moderate impairment, and 10.0% (95% CI, 1.4%–17.9%) with risk of mild impairment. The pooled risk estimate of at least 1 impairment (weighted mean) for one or more insults (excluding human immunodeficiency virus) was 37.0% (95% CI, 27.0%–48.0%). No significant effect on risk was found for any of the 4 covariables tested: World Health Organization region, period of data collection, duration of follow-up, or study design. The most common impairments were learning difficulties, cognition, or developmental delay (59%); cerebral palsy (21%); hearing impairment (20%); and visual impairment (18%). Data for multidomain impairments were included in only 40 (26%) of the studies. Among the 2815 individuals included in the studies, 37% (n = 1048) had impairments and 32% (n = 334) had multiple impairments. These findings show a high risk of substantial long-term neurological morbidity among survivors of intrauterine and neonatal insults. The least data are available for resource-poor countries, which account for 98% of neonatal morbidity.

Abstract 2706: Neurocognitive Deficits Associated with Advanced Heart Failure

The measures of general cognition which have previously been used to demonstrate cognitive impairment in patients with congestive heart failure (CHF) provide only broad indications of what cognitive function(s) in particular are impaired. The objectives of this study are: quantify the severity of neurocognitive impairment; use specific neurocognitive subtests to identify what functions are impaired; use fMRI to identify brain regions putatively involved in neurocognitive impairments of patients with advanced CHF. Hypoperfusion associated with CHF has been thought to be the primary cause of neuropathology in this population. We tested the hypothesis, suggested by our own preliminary data, that Verbal Fluency is impaired relative to Picture Naming and pathology of frontal lobe function is involved. Veterans with NYHA class III or IV CHF from our Advanced Heart Failure Clinic were given several cognitive tests, including the Addenbrooke Cognitive Exam (ACE). The ACE is a validated indicator of dementia comprised of four indices: Verbal Fluency, Language (Naming), Orientation, and Immediate Memory. Follow-up fMRI while performing Verbal Fluency and Picture Naming tasks was conducted to localize abnormalities of brain activation. Results showed that 64.5% of the group (n = 31, age = 62.3 (11.4) years) met the ACE cut-off score criterion of probable dementia (Total Score less than or equal to 88). Significantly lower scores on Verbal Fluency (p = .01), Language (p = .02), and Immediate Memory (p = .00), but not Orientation, were found in the probable dementia subgroup compared to the cognitively intact subgroup. After partialling out dementia status, ACE Total Score significantly correlated (r(31) = .31, p = .05) with cardiac output (measured with bioimpedance plethysmograhy). The fMRI procedure was administered on 7 patients. Activation patterns revealed absence of frontal activation (Brodmann Area 46) on Verbal Fluency relative to Picture Naming. In conclusion, many advanced heart failure patients appear to be undergoing a dementing process, and neurocognitive and neuroimaging results are consistent in suggesting impairment of explicit word generation and retrieval, but not semantic knowledge, with associated frontal lobe dysfunction.