Neurometabolite Alterations Associated with Cognitive Performance in Perinatally HIV-Infected Children

Despite treatment with combination antiretroviral therapy (cART), cognitive impairment is still observed in perinatally HIV-infected children. We aimed to evaluate potential underlying cerebral injury by comparing neurometabolite levels between perinatally HIV-infected children and healthy controls. 

This cross-sectional study evaluated neurometabolites, as measured by Magnetic Resonance Spectroscopy (MRS), in perinatally HIV-infected children stable on cART (n = 26) and healthy controls (n = 36).Participants were included from a cohort of perinatally HIV-infected children and healthy controls, matched group-wise for age, gender, ethnicity, and socio-economic status. N-acetylaspartate (NAA), glutamate (Glu), myo-inositol (mI), and choline (Cho) levels were studied as ratios over creatine (Cre). Group differences and associations with HIV-related parameters, cognitive functioning, and neuronal damage markers (neurofilament and total Tau proteins) were determined using age-adjusted linear regression analyses.HIV-infected children had increased Cho:Cre in white matter (HIV-infected = 0.29 ± 0.03; controls = 0.27 ± 0.03; P value = 0.045). Lower nadir CD4+ T-cell Z-scores were associated with reduced neuronal integrity markers NAA:Cre and Glu:Cre. A Centers for Disease Control and Prevention (CDC) stage C diagnosis was associated with higher glial markers Cho:Cre and mI:Cre. Poorer cognitive performance was mainly associated with higher Cho:Cre in HIV-infected children, and with lower NAA:Cre and Glu:Cre in healthy controls. 

There were no associations between neurometabolites and neuronal damage markers in blood or CSF.Compared to controls, perinatally HIV-infected children had increased Cho:Cre in white matter, suggestive of ongoing glial proliferation. Levels of several neurometabolites were associated with cognitive performance, suggesting that MRS may be a useful method to assess cerebral changes potentially linked to cognitive outcomes.

Below:  Exemplar planning of chemical shift imaging (CSI), superimposed on a 3D-T1-weighted image. Based on the 3D-T1-weighted scan (A), gray matter (GM), and white matter (WM) segmentation was performed within the CSI field-of-view (B). Estimated metabolite levels (C) were averaged within all GM and WM voxels to obtain mean GM and WM values (D). CSI = chemical shift imaging, GM = gray matter, WM = white matter.

Full article at:   http://goo.gl/cfpC6B

By:  Van Dalen YW1, Blokhuis C, Cohen S, Ter Stege JA, Teunissen CE, Kuhle J, Kootstra NA, Scherpbier HJ, Kuijpers TW, Reiss P, Majoie CB, Caan MW, Pajkrt D.

• 1From the Department of Pediatric Hematology, Immunology and Infectious Diseases, (YWVD, CB, SC, JATS, HJS, TWK, DP); Psychosocial Department (JATS), Emma Children's Hospital/Academic Medical Center; Neurochemistry Laboratory and Biobank (CET), Department of Clinical Chemistry, VU University Medical Center and Neurocampus Amsterdam, the Netherlands; Neurology (JK), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, Basel, Switzerland; Department of Experimental Immunology (NAK); Department of Global Health and Amsterdam Institute of Global Health and Development (PR), Academic Medical Center; HIV Monitoring Foundation (PR); Department of Internal Medicine (PR), Division of Infectious Diseases, Center for Infection and Immunity Amsterdam (CINIMA); and Department of Radiology (CBLMM, MWAC), Academic Medical Center, Amsterdam, the Netherlands. 
• Medicine (Baltimore). 2016 Mar;95(12):e3093. doi: 10.1097/MD.0000000000003093.

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Neuropsychological Impairment and Its Association with Violence Risk in Japanese Forensic Psychiatric Patients

Background

In Japan, the legislation directing treatment of offenders with psychiatric disorders was enacted in 2005. Neuropsychological impairment is highly related to functional outcomes in patients with psychiatric disorders, and several studies have suggested an association between neuropsychological impairment and violent behaviors. However, there have been no studies of neuropsychological impairment in forensic patients covered by the Japanese legislation. This study is designed to examine the neuropsychological characteristics of forensic patients in comparison to healthy controls and to assess the relationship between neuropsychological impairment and violence risk.

Methods

Seventy-one forensic patients with psychiatric disorders and 54 healthy controls (matched by age, gender, and education) were enrolled. The CogState Battery (CSB) consisting of eight cognitive domains, the Iowa Gambling Task (IGT) to test emotion-based decision making, and psychological measures of violence risk including psychopathy were used.

Results

Forensic patients exhibited poorer performances on all CSB subtests and the IGT than controls. For each group, partial correlational analyses indicated that poor IGT performance was related to psychopathy, especially antisocial behavior. In forensic patients, the CSB composite score was associated with risk factors for future violent behavior, including stress and noncompliance with remediation attempts.

Conclusion

Forensic patients with psychiatric disorders exhibit a wide range of neuropsychological impairments, and these findings suggest that neuropsychological impairment may increase the risk of violent behavior. Therefore, the treatment of neuropsychological impairment in forensic patients with psychiatric disorders is necessary to improve functional outcomes as well as to prevent violence.

Below:  Magnitude of impairment in forensic patients relative to healthy controls on each CSB measure

Below:  The IGT net scores for the 5 blocks for forensic patients and healthy controls

Full article at:   http://goo.gl/TpZu9X

By:  

Hirofumi Nishinaka, Kenji Hashimoto

Division of Clinical Neuroscience, Center for Forensic Mental Health, Chiba University, Chiba, Japan

Jun Nakane

National Hospital Organization Shimofusa Psychiatric Medical Center, Chiba, Japan

Takako Nagata, Mayu Omori, Naotsugu Hirabayashi

Department of Psychiatry, National Center of Neurology and Psychiatry, Tokyo, Japan

Atsushi Imai, Noriomi Kuroki, Noriko Sakikawa, Osamu Kuroda

Department of Psychiatry, Tokyo Metropolitan Matsuzawa Hospital, Tokyo, Japan

Yoshito Igarashi

Division of Law and Psychiatry, Center for Forensic Mental Health, Chiba University, Chiba, Japan

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Cognitive Impairment in Manic Bipolar Patients: Important, Understated, Significant Aspects

BACKGROUND:

Bipolar disorder is a chronic mood disorder with episodic progress and high relapse rate. Growing evidence suggests that individuals with bipolar disorder display cognitive impairment which persists even throughout periods of symptom's remission.

METHOD:

137 bipolar patients met the inclusion criteria (depressive episode: DSM-IV-TR criteria for major depressive episode, HAMD score ≥17; manic/hypomanic episode: DSM-IV-TR criteria for manic/hypomanic episode, YMRS score ≥12, euthymic: 6 months of remission, HAMD score ≤8, YMRS score ≤6; and mixed: DSM-IV-TR criteria for mixed episode, HAMD score >8 and YMRS score >6) and were therefore enrolled in the study. Patients were free of psychotic symptoms (hallucinations/delusions) at the moment of testing. Control group consisted of 62 healthy subjects without history of neurological and/or psychiatric disorder. Cognitive battery has been applied in order to assess verbal memory, working memory, psychomotor speed, verbal fluency, attention and speed of information processing, and executive function. Following data were collected: demographics, psychiatric history, age of illness onset; current and previous treatment (including hospitalizations). Cognitive deficits were assessed in bipolar patients experiencing manic, depressive, mixed episodes or who were euthymic in mood. Results were compared between the subgroups and with healthy individuals. The association of impaired cognition with illness course was analyzed.

RESULTS:

Bipolar patients showed cognitive deficits in all evaluated domains when compared to controls. The lowest scores were obtained for the verbal fluency test. After adjusting for current episode, manic subgroup showed greater cognitive impairment in verbal and working memory, executive function/reasoning and problem solving, compared to depressive, mixed, and euthymic subgroup. Low-neurocognitive performance was directly associated with a predominance of manic episodes and severe course of bipolar illness. An increased number of past manic episodes was the strongest correlated event with the poorest outcomes in verbal memory testing. Other factors correlated with poor verbal memory scores in manic subgroup were age at illness onset (positive correlation), illness length, and hospitalizations (negative correlations).

CONCLUSIONS:

Bipolar patients showed cognitive deficits regardless of the phase of illness. Subjects experiencing a manic episode displayed higher deficits in verbal and working memory, executive function/reasoning, and problem solving. Severe course of illness also showed significant contribution in terms of cognitive impairment.

Full article at:  http://goo.gl/VEQEWB

By:  Vrabie M1, Marinescu V2, Talaşman A3, Tăutu O4, Drima E5, Micluţia I6.

• 1University of Medicine and Pharmacy "Iuliu Hatieganu" Cluj-Napoca, Cluj-Napoca, Romania ; 7th Ward, Clinical Hospital of Psychiatry "Al. Obregia" Bucharest, Bucharest, Romania.
• 27th Ward, Clinical Hospital of Psychiatry "Al. Obregia" Bucharest, Bucharest, Romania ; University of Medicine and Pharmacy "Carol Davila" Bucharest, Bucharest, Romania.
• 3University of Medicine and Pharmacy "Carol Davila" Bucharest, Bucharest, Romania ; 9th Ward, Clinical Hospital of Psychiatry "Al. Obregia" Bucharest, Bucharest, Romania.
• 4University of Medicine and Pharmacy "Carol Davila" Bucharest, Bucharest, Romania ; Department of Cardiology, Clinical Emergency Hospital Bucharest, Bucharest, Romania.
• 5Faculty of Medicine and Pharmacy, "Danubius" University, Galati, Romania ; Clinical Hospital of Psychiatry "Elisabeta Doamna" Galati, Galati, Romania.
• 6University of Medicine and Pharmacy "Iuliu Hatieganu" Cluj-Napoca, Cluj-Napoca, Romania ; Second Psychiatric Clinic, Emergency County Hospital Cluj-Napoca, Cluj-Napoca, Romania. 

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Neuropsychological Impairment in Acute HIV and the Effect of Immediate Antiretroviral Therapy

To investigate neuropsychological performance (NP) during acute HIV infection (AHI) before and after combination antiretroviraltherapy (cART).

Prospective study of Thai AHI participants examined at 3 and 6 months after initiation of cART.

Thirty-six AHI participants were evaluated pre-cART at median 19 days since HIV exposure and 3 and 6 months after cART with the Grooved Pegboard test, Color Trails 1 & 2 (CT1, CT2), and Trail Making Test A. Raw scores were standardized to 251 age- and education-matchedHIV-uninfected Thais. To account for learning effects, change in NP performance was compared with that of controls at 6 months. Analyses included multivariable regression, nonparametric repeated measures analysis of variance, and Mann-Whitney U test.

Baseline NP scores for the AHI group were within normal range (z-scores range: -0.26 to -0.13). NP performance improved on CT1, CT2, and Trail Making Test A in the initial 3 months (P < 0.01) with no significant change during the last 3 months. Only improvement in CT1 was greater than that seen in controls at 6 months (P = 0.018). Participants who performed >1 SD below normative means on ≥2 tests (n = 8) exhibited higher baseline cerebrospinal fluid HIV RNA (P = 0.047) and had no improvement after cART.

Most AHI individuals had normal NP performance, and early cART slightly improved their psychomotor function. However, approximately 25% had impaired NP performance, which correlated with higher cerebrospinal fluid HIV RNA, and these abnormalities were not reversed by early cART possibly indicating limited reversibility of cognitive impairment in a subset of AHI individuals.

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By:  Kore I1, Ananworanich J, Valcour V, Fletcher JL, Chalermchai T, Paul R, Reynolds J, Tipsuk S, Ubolyam S, Rattanamanee S, Jagodzinski L, Kim J, Spudich S.

• 1*Yale University School of Medicine, New Haven, CT; †SEARCH, The Thai Red Cross AIDS Research Center, Bangkok, Thailand; ‡US Military HIVResearch Program, Walter Reed Army Institute of Research, Silver Spring, MD; §Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD; ‖University of California, San Francisco, CA; ¶Missouri Institute of Mental Health, University of Missouri, St. Louis, MO; #Yale Center for Analytical Sciences, New Haven, CT; and **HIV-NAT, The Thai Red Cross AIDS Research Center, Bangkok, Thailand. 

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Does the Informal Caregiver Notice HIV Associated Mild Cognitive Impairment in People Living with HIV?

HIV associated minor neurocognitive disorder (MND) may be difficult to identify as key signs and symptoms (S & S) may be due to other clinical conditions. Using a self-assessment booklet "HIV and associated MND" we recruited 123 people living with HIV (PLHIV) from three sites: two hospital HIV clinics and a sexual health clinic in Sydney, Australia. Patients may down play S & S. Caregivers may notice subtle changes. By including caregivers, we aimed to find whether the caregivers noticed S & S undetected by the PLHIV. This is a sub-study of a prospective observational multi-site study aimed to validate the usefulness of a patient self-assessment tool (HIV-associated MND booklet). 

Using the booklet, participants and their caregivers subsequently identified S & S of MND. Sixty-four per cent (79) did not nominate a caregiver to be contacted. Participants from 2 sites 44 (36%) nominated caregivers to be contacted. Twenty-five caregivers identified more than four S & S of MND. S & S reported most by caregivers related to participants being more tired at the end of the day (76%). Participants agreed (77%). Participants also reported that they found it more difficult to remember things such as taking medications or attending medical appointments (67%). The most agreed on symptom was the requirement for increased concentration to get the same things done (Kappa P 0.599 <0.001 and McNemar 0.289). For each question at least one caregiver identified a symptom when the PLHIV did not. 

Caregivers were more likely than participants to report irritability and communication difficulties. It is important to include caregivers when investigating PLHIV for MND, as caregivers may validate the experience of the patient, and may also be uniquely placed to identify S & S not otherwise identified.

Purchase full article at: http://goo.gl/IE0aHr

By: Murray KJ1, Cummins D2, Batterham M3, Trotter G4, Healey L5, O'Connor CC5,6,7.

• 1 HIV & Related Programs Unit, South Eastern Sydney Local Health District , NSW , Australia.
• 2 Sydney District Nursing, Sydney Local Health District , NSW , Australia.
• 3 Statistical Consulting Centre , University of Wollongong , NSW , Australia.
• 4 Royal Prince Alfred Hospital , NSW , Australia.
• 5 R P A Sexual Health, Sydney Local Health District , NSW , Australia.
• 6 Kirby Institute, UNSW , Kensington , NSW , Australia.
• 7 Central Clinical School , University of Sydney , Sydney , NSW , Australia.

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Self-Reported Care Needs of Dutch Homeless People with & without a Suspected Intellectual Disability: A 1.5-Year Follow-Up Study

Cognitive impairment is a prevalent problem among the homeless and seems related to more psychosocial problems. However, little is known about the care needs of the subgroup of homeless people with an intellectual disability compared to those without an intellectual disability and how their care needs develop over time. This study explores self-reported care needs within a broad range of life domains among Dutch homeless people with and without a suspected intellectual disability to gain insight into the transition of self-reported care needs from baseline to follow-up in both subgroups. 

This longitudinal study is part of a cohort study among homeless people who had been accepted for an individual programme plan in four major Dutch cities. The initial cohort consisted of 513 participants who were interviewed in 2011. At 1.5-year follow-up, 336 participants (65.5%) were also interviewed and screened for intellectual disability. Of these participants, 31% had a suspected intellectual disability. For both groups, between baseline and follow-up, the number of 'unmet care needs' decreased significantly and the number of 'no care needs' increased significantly, while at follow-up, participants with a suspected intellectual disability reported 'no care needs' on significantly fewer life domains than those without a suspected intellectual disability (mean numbers 16.4 vs. 17.5). Between baseline and follow-up, 'met care needs' decreased significantly on housing for both groups, and increased on finances and dental care for participants with a suspected intellectual disability. At follow-up, participants with a suspected intellectual disability more often preferred housing support available by appointment than those without a suspected intellectual disability. 

These findings suggest that homeless people who had been accepted for an individual programme plan with a suspected intellectual disability have care needs for a longer period of time than those without a suspected intellectual disability. Providing care to homelesspeople with a suspected intellectual disability might require ongoing care and support, also after exiting homelessness. Support services should take this into account when considering their care provision and planning of services.

Purchase full article at: http://goo.gl/xiUGN6

By: Van Straaten B1,2, Rodenburg G1,2, Van der Laan J3,4, Boersma SN3, Wolf JR3, Van de Mheen D1,2,5.

• 1Erasmus Medical Centre, Rotterdam, the Netherlands.
• 2IVO Addiction Research Institute, Rotterdam, the Netherlands.
• 3Impuls - Netherlands Center for Social Care Research, Department of Primary and Community Care, Radboud university medical center, Nijmegen, the Netherlands.
• 4Amsterdam University of Applied Sciences, Amsterdam, the Netherlands.
• 5Department of Health Promotion, Maastricht University, Maastricht, the Netherlands.  

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Homelessness and Cognitive Impairment: An Exploratory Study in Tokyo, Japan

Homelessness has frequently been associated with neuropsychological impairment. This has been observed using general screening tests for dementia as well as tests of more focal abilities, particularly executive function. Most studies have been of homeless individuals from North America with none reported from Japan.

In this exploratory study we interviewed a sample of 16 homeless adults from Tokyo, Japan, and performed tests of cognitive function, assessed head injury, addictive behaviours (drug use, gambling, alcohol abuse), and recorded details of homelessness history. The cognitive examination involved the Japanese Adult Reading Test to estimate premorbid intelligence quotient, the Wisconsin Card Sorting Test to measure frontal lobe-related cognitive function, and the Mini-Mental State Examination to measure global cognitive impairment associated with dementia.

Among the 16 homeless individuals, 7 (44%) displayed global cognitive impairment. In addition, executive function tended to be poor. In contrast, estimated premorbid intelligence quotient was within the normal range. Substance abuse in general was not at a level to cause clinical concern, although a high level of pathological gambling was observed. There were no associations between cognitive function and clinical and addictive behaviour variables, although associations were noted between cognitive scores and time spent homeless.

The results suggest high levels of neuropsychological impairment in this sample of homeless adults in Japan. Furthermore, cognitive impairment is acquired rather than developmental in origin, and is proportional to the length of time spent homeless.

Full article at: http://goo.gl/O4Mi3z

By: Pluck G1, Nakakarumai M2, Sato Y2.

• 1Quito Brain and Behavior Laboratory, Universidad San Francisco de Quito, Ecuador; Faculty of Policy Studies, Chuo University, Tokyo, Japan.
• 2Faculty of Policy Studies, Chuo University, Tokyo, Japan.

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HIV-Related Cognitive Impairment of Orphans in Myanmar with Vertically Transmitted HIV Taking Antiretroviral Therapy

We determined the effect of perinatally acquired HIV on neurocognition in Myanmar children treated with antiretroviral therapy by comparison to demographically matched seronegative children.

Myanmar has one of the highest HIV-1 prevalence rates in Southeast Asia. Studies from other resource-poor countries have shown that HIV-infected children differ in socioeconomic, nutritional and caregiver status compared to normal controls. Some vertically infected orphans in Myanmar reside separately from HIV-uninfected children in separate orphanages, thus the demographic variables of interest are naturally controlled. This study provides a unique evaluation of the neurocognitive effects of HIV in children, with control over key demographic variables. We hypothesized that HIV-infected orphans would perform significantly worse on cognitive indices compared with HIV-negative orphans.

A battery of cognitive tests sensitive to HIV-associated impairments in children was administered to 28 perinatally acquired HIV-positive children and 31 HIV-negative children from two orphanages in Myanmar; 21 children from each cohort underwent testing at baseline and again after 12 months.

Baseline comparison of the two groups indicated that the HIV-infected children performed poorly across all tests, with significant group differences in executive function, visuospatial reasoning, fine motor dexterity, and visual motor integration. On subsequent testing, both cohorts of children showed improvements across multiple domains, with no significant effect of age at treatment initiation.

Our results demonstrate a strong effect of HIV infection on specific neurocognitive deficits in vertically infected children. Understanding viral and host determinants and timing and choice of antiretroviral therapy on cognition will be critical to preventing cognitive impairment of children with HIV.

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By: Linn K1, Fay A2, Meddles K3, Isbell S4, Lin PN1, Thair C1, Heaps J5, Paul R6, Mar SS3.

• 1Pediatric Neurology Unit, Yangon Children's Hospital, Yangon, Myanmar.
• 2Department of Pediatric Neurology, Washington University, St. Louis, Missouri
• 3Department of Pediatric Neurology, Washington University, St. Louis, Missouri.
• 4Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, St. Louis, Missouri.
• 5Department of Psychology and Behavioral Neuroscience, University of Missouri, St. Louis, Missouri.
• 6Missouri Institute of Mental Health, University of Missouri, St. Louis, Missouri.