Anatomy and Neuroscience - Research Publications

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    Apolipoprotein E gene polymorphism, trauma burden, and posttraumatic stress symptoms in US military veterans: Results from the National Health and Resilience in Veterans Study
    Mota, NP ; Han, S ; Harpaz-Rotem, I ; Maruff, P ; Krystal, JH ; Southwick, SM ; Gelernter, J ; Pietrzak, RH (WILEY, 2018-02-01)
    BACKGROUND: Previous research examining the association between apolipoprotein E (APOE) gene polymorphism and risk for posttraumatic stress disorder (PTSD) has been inconsistent due to the use of small and select samples. This study examined the relation between APOE genotype and PTSD symptoms in two nationally representative samples of U.S. military veterans. The potential effect of cumulative trauma burden and social support in moderating this association was also evaluated. METHODS: The main sample consisted of 1,386 trauma-exposed European American (EA) veterans (mean age: 62-63 years) who participated in the National Health and Resilience in Veterans Study (NHRVS) in 2011. The independent replication sample consisted of 509 trauma-exposed EA veterans from the 2013 NHRVS. RESULTS: APOE ε4 allele carriers reported significantly greater severity of PTSD symptoms than noncarriers in the main, but not the replication, sample. In both samples, the interaction of APOE ε4 carrier status and cumulative trauma burden was associated with greater severity of PTSD symptoms (F range = 2.53-8.09, all P's < .01), particularly re-experiencing/intrusion symptoms (F range = 3.59-4.24, P's < .001). Greater social support was associated with lower severity of PTSD symptoms among APOE ε4 allele carriers with greater cumulative trauma burden (β range -.27 to -.60, P's < .05). CONCLUSION: U.S. military veterans who are APOE ε4 allele carriers and exposed to a high number of traumas may be at increased risk for developing PTSD symptoms than ε4 noncarriers. Greater social support may moderate this association, thereby highlighting the potential importance of social support promoting interventions in mitigating the effect of ε4 × cumulative trauma burden on PTSD risk.
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    Trajectories of depressive and anxiety symptoms in older adults: a 6-year prospective cohort study
    Holmes, SE ; Esterlis, I ; Mazure, CM ; Lim, YY ; Ames, D ; Rainey-Smith, S ; Fowler, C ; Ellis, K ; Martins, RN ; Salvado, O ; Dore, V ; Villemagne, VL ; Rowe, CC ; Laws, SM ; Masters, CL ; Pietrzak, RH ; Maruff, P (WILEY, 2018-02-01)
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    Cerebrovascular disease, Alzheimer's disease biomarkers and longitudinal cognitive decline
    Yates, PA ; Villemagne, VL ; Ames, D ; Masters, CL ; Martins, RN ; Desmond, P ; Burnham, S ; Maruff, P ; Ellis, KA ; Rowe, CC (WILEY-BLACKWELL, 2016-06-01)
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    Amyloid burden and incident depressive symptoms in cognitively normal older adults
    Harrington, KD ; Gould, E ; Lim, YY ; Ames, D ; Pietrzak, RH ; Rembach, A ; Rainey-Smith, S ; Martins, RN ; Salvado, O ; Villemagne, VL ; Rowe, CC ; Masters, CL ; Maruff, P (WILEY, 2017-04-01)
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    A Placebo-Controlled Trial of AQW051 in Patients With Moderate to Severe Levodopa-Induced Dyskinesia
    Trenkwalder, C ; Berg, D ; Rascol, O ; Eggert, K ; Ceballos-Baumann, A ; Corvol, J-C ; Storch, A ; Zhang, L ; Azulay, J-P ; Broussolle, E ; Defebvre, L ; Geny, C ; Gostkowski, M ; Stocchi, F ; Tranchant, C ; Derkinderen, P ; Durif, F ; Espay, AJ ; Feigin, A ; Houeto, J-L ; Schwarz, J ; Di Paolo, T ; Feuerbach, D ; Hockey, H-U ; Jaeger, J ; Jakab, A ; Johns, D ; Linazasoro, G ; Maruff, P ; Rozenberg, I ; Sovago, J ; Weiss, M ; Gomez-Mancilla, B (WILEY, 2016-07-01)
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    Recommendations for the nomenclature of cognitive change associated with anaesthesia and surgery-2018
    Evered, L ; Silbert, B ; Knopman, DS ; Scott, DA ; DeKosky, ST ; Rasmussen, LS ; Oh, ES ; Crosby, G ; Berger, M ; Eckenhoff, RG (WILEY, 2018-11-01)
    Cognitive change affecting patients after anaesthesia and surgery has been recognised for more than 100 yr. Research into cognitive change after anaesthesia and surgery accelerated in the 1980s when multiple studies utilised detailed neuropsychological testing for assessment of cognitive change after cardiac surgery. This body of work consistently documented decline in cognitive function in elderly patients after anaesthesia and surgery, and cognitive changes have been identified up to 7.5 yr afterwards. Importantly, other studies have identified that the incidence of cognitive change is similar after non-cardiac surgery. Other than the inclusion of non-surgical control groups to calculate postoperative cognitive dysfunction, research into these cognitive changes in the perioperative period has been undertaken in isolation from cognitive studies in the general population. The aim of this work is to develop similar terminology to that used in cognitive classifications of the general population for use in investigations of cognitive changes after anaesthesia and surgery. A multispecialty working group followed a modified Delphi procedure with no prespecified number of rounds comprised of three face-to-face meetings followed by online editing of draft versions. Two major classification guidelines [Diagnostic and Statistical Manual for Mental Disorders, fifth edition (DSM-5) and National Institute for Aging and the Alzheimer Association (NIA-AA)] are used outside of anaesthesia and surgery, and may be useful for inclusion of biomarkers in research. For clinical purposes, it is recommended to use the DSM-5 nomenclature. The working group recommends that 'perioperative neurocognitive disorders' be used as an overarching term for cognitive impairment identified in the preoperative or postoperative period. This includes cognitive decline diagnosed before operation (described as neurocognitive disorder); any form of acute event (postoperative delirium) and cognitive decline diagnosed up to 30 days after the procedure (delayed neurocognitive recovery) and up to 12 months (postoperative neurocognitive disorder).
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    Effect of BDNFVal66Met on disease markers in dominantly inherited Alzheimer's disease
    Lim, YY ; Hassenstab, J ; Goate, A ; Fagan, AM ; Benzinger, TLS ; Cruchaga, C ; McDade, E ; Chhatwal, J ; Levin, J ; Farlow, MR ; Graff-Radford, NR ; Laske, C ; Masters, CL ; Salloway, S ; Schofield, P ; Morris, JC ; Maruff, P ; Bateman, RJ (WILEY, 2018-09-01)
    OBJECTIVE: Previous studies suggest that the brain-derived neurotrophic factor (BDNF) Val66Met (rs6265) polymorphism may influence symptom onset in Alzheimer's disease (AD). Our recent cross-sectional findings suggest that Met66 may influence clinical expression in dominantly inherited AD (DIAD) through its effects on tau. However, it remains unclear whether carriage of Met66 in DIAD results in faster increases in cerebrospinal fluid (CSF) tau and ptau181 , and whether these increases are associated with accelerated brain volume loss and memory decline. METHODS: A total of 211 subjects (101 mutation noncarriers, 110 mutation carriers), who were cognitively normal, as defined by a Clinical Dementia Rating global score of 0, completed assessments of cognitive function, neuroimaging, and CSF sampling over 3.5 years as part of the Dominantly Inherited Alzheimer's Network. RESULTS: In mutation carriers, Met66 carriers showed faster memory decline (4×), hippocampal volume loss (16×), and CSF tau and ptau181 increases (6×) than Val66 homozygotes. BDNF did not influence rates of cortical β-amyloid accumulation or change in CSF Aβ42 levels in mutation carriers. In mutation noncarriers, BDNF genotype had no effect on change in cognition, brain volume, cortical β-amyloid accumulation, or change in any CSF measures of tau, ptau181 , and CSF Aβ42 . INTERPRETATION: As in sporadic AD, the deleterious effects of β-amyloid on cognitive function, brain volume loss, and CSF tau in DIAD mutation carriers are less in Val66 homozygotes. The BDNF Val66Met polymorphism should be considered as a potential moderator of clinical trial outcomes in current treatment and prevention trials in DIAD and sporadic AD. Ann Neurol 2018;84:424-435.
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    Similar neurocognitive outcomes after 48 weeks in HIV-1-infected participants randomized to continue tenofovir/emtricitabine plus atazanavir/ritonavir or simplify to abacavir/lamivudine plus atazanavir
    Robertson, K ; Maruff, P ; Ross, LL ; Wohl, D ; Small, CB ; Edelstein, H ; Shaefer, MS (SPRINGER, 2019-02-01)
    Human immunodeficiency virus (HIV)-associated neurocognitive disorders can persist in many patients despite achieving viral suppression while on antiretroviral therapy (ART). Neurocognitive function over 48 weeks was evaluated using a Cogstate test battery assessing psychomotor function, attention, learning, and working memory in 293 HIV-1-infected, ART-experienced, and virologically suppressed adults. The ASSURE study randomized participants 1:2 to remain on tenofovir/emtricitabine (TDF/FTC) and ritonavir-boosted atazanavir (ATV/r) or simplify to abacavir/lamivudine + atazanavir (ABC/3TC + ATV). Neurocognitive z-scores were computed using demographically adjusted normative data and were classified as "impaired" (defined as either a z-score ≤ - 2 or having 2 or more standardized individual test z-scores ≤ - 1); while higher scores (equaling better performance) were classified as "normal". By z-scores, 54.7% of participants had impaired neurocognition at baseline and 50.2% at week 48. There were no significant differences (p < 0.05) in the baseline-adjusted performance between treatment groups for any individual test or by z-score. Specific demographic and medical risk factors were evaluated by univariate analysis for impact on neurocognitive performance. Factors with p < 0.10 were evaluated by backwards regression analysis to identify neurocognition-correlated factors after accounting for treatment, assessment, and baseline. Four risk factors at baseline for impaired neurocognition were initially identified: lower CD4 nadir lymphocyte counts, higher Framingham risk scores, and interleukin-6 levels, and a history of psychiatric disorder not otherwise specified, however none were found to moderate the effect of treatment on neurocognition. In this aviremic, treatment-experienced population, baseline-adjusted neurocognitive function remained stable and equivalent over 48 weeks with both TDF/FTC + ATV/r-treated and in the ART-simplified ABC/3TC + ATV treatment groups.
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    The relationship between depression and cognitive function in adults with cardiovascular risk: Evidence from a randomised attention-controlled trial
    LaMonica, HM ; Biddle, DJ ; Naismith, SL ; Hickie, IB ; Maruff, P ; Glozier, N ; Gualtieri, C (PUBLIC LIBRARY SCIENCE, 2018-09-05)
    BACKGROUND AND AIM: This study assessed the association between depressive symptom severity and cognition in middle-to-older aged adults with mild-to-moderate depression and cardiovascular risk factors using an online test battery (CogState) and whether changes in depressive symptoms over 3 months were associated with changes in cognition. METHODS: Participants (mean age = 57.8) with cardiovascular risk and mild-to-moderate depressive symptoms completed measures of psychomotor speed, learning, and executive function prior to (n = 445)_and after (n = 334) online depression or attention control interventions. The symptom severity-cognition relationship was examined both cross-sectionally and prospectively. RESULTS: Participants exhibited significantly reduced psychomotor speed and variable impairments on measures of learning and executive functioning relative to normative data. However, there was no association of depression severity with cognition at baseline or of change in depressive symptoms with change in cognitive performance. LIMITATIONS: Participants were well-educated, which may have protected against cognitive decline. Attrition may limit generalisability, though is unlikely to explain the lack of association between depression symptoms and cognition. CONCLUSIONS: Adults with comorbid mild-to-moderate depressive symptoms and cardiovascular risks performed less well than age-matched normative data on three online cognitive tests; however, we were unable to show any symptom-cognition association cross-sectionally or longitudinally, despite significant improvements in depressive symptoms. This challenges the generalisability of such associations found in more severely unwell clinical samples to those with a broader depressive symptom profile, or suggests that underlying cardiovascular disease may account for the association seen in some clinical studies. This has implications for scaling up selective prevention of cognitive decline.
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    Minimal Cognitive Impairment in UK HIV-Positive Men Who Have Sex With Men: Effect of Case Definitions and Comparison With the General Population and HIV-Negative Men
    McDonnell, J ; Haddow, L ; Daskalopoulou, M ; Lampe, F ; Speakman, A ; Gilson, R ; Phillips, A ; Sherr, L ; Wayal, S ; Harrison, J ; Antinori, A ; Maruff, P ; Schembri, A ; Johnson, M ; Collins, S ; Rodger, A (LIPPINCOTT WILLIAMS & WILKINS, 2014-10-01)
    BACKGROUND: To determine the prevalence of neurocognitive impairment (NCI) in UK HIV-positive and HIV-negative men who have sex with men (MSM). METHODS: HIV-positive and HIV-negative participants were recruited to a cross-sectional study from 2 London clinics and completed computer-assisted neuropsychological tests and questionnaires of depression, anxiety, and activities of daily living. Published definitions of HIV-associated neurocognitive disorders (HAND) and global deficit scores were used. Age- and education-adjusted neuropsychological test scores were directly compared with reference population data. RESULTS: A total of 248 HIV-positive and 45 HIV-negative MSM participated. In the HIV-positive group, median time since diagnosis was 9.4 years, median CD4 count was 550 cells per cubic millimeter, and 88% were on antiretroviral therapy. Prevalence of HAND was 21.0% in HIV-positive MSM (13.7% asymptomatic neurocognitive impairment, 6.5% mild neurocognitive disorder, and 0.8% HIV-associated dementia). Using a global deficit score threshold of 0.5, the prevalence of NCI was 31.5% (when averaged over 5 neuropsychological domains) and 40.3% (over 10 neuropsychological test scores). These results were not significantly different from the HIV-negative study sample. No consistent pattern of impairment was seen in HIV-positive patients relative to general male population data (n = 380). CONCLUSIONS: We found a prevalence of HAND and degree of impairment on neuropsychological testing of HIV-positive MSM that could represent a normal population distribution. These findings suggest that NCI may be overestimated in HIV-positive MSM, and that the attribution of NCI to HIV infection implied by the term HAND requires revision.