Ecological validity of cognitive fluctuations in dementia with Lewy bodies.

OBJECTIVES: Cognitive fluctuations are a core clinical feature of dementia with Lewy bodies (DLB), but their contribution to the everyday functioning difficulties evident DLB are not well understood. The current study evaluated whether intraindividual variability across a battery of neurocognitive tests (intraindividual variability-dispersion) and daily cognitive fluctuations as measured by informant report are associated with worse daily functioning in DLB. METHODS: The study sample included 97 participants with consensus-defined DLB from the National Alzheimer's Coordinating Center (NACC). Intraindividual variability-dispersion was measured using the coefficient of variation, which divides the standard deviation of an individual's performance scores across 12 normed neurocognitive indices from the NACC neuropsychological battery by that individual's performance mean. Informants reported on daily cognitive fluctuations using the Mayo Fluctuations Scale (MFS) and on daily functioning using the functional activities questionnaire (FAQ). RESULTS: Logistic regression identified a large univariate association of intraindividual variability-dispersion and presence of daily cognitive fluctuations on the MFS (Odds Ratio = 73.27, 95% Confidence Interval = 1.38, 3,895.05). Multiple linear regression demonstrated that higher intraindividual variability-dispersion and presence of daily cognitive fluctuations as assessed by the MFS were significantly and independently related to worse daily functioning (FAQ scores). CONCLUSIONS: Among those with DLB, informant-rated daily cognitive fluctuations and cognitive fluctuations measured in the clinic (as indexed by intraindividual variability-dispersion across a battery of tests) were independently associated with poorer everyday functioning. These data demonstrate ecological validity in measures of cognitive fluctuations in DLB.

Indirect Effects of Negative Mood on Opioid Misuse and Dependence via Anxiety Sensitivity Subfacets: Evidence from Adults Reporting Chronic Pain.

Background: Opioid misuse in the context of pain management exacts a significant public health burden. Past work has established linkages between negative mood (i.e., symptoms of anxiety and depression) and opioid misuse/dependence, yet the mechanisms underlying these associations have received little scientific investigation. Anxiety sensitivity (AS), the fear of the negative consequences of internal states, may be relevant to better understanding negative mood-opioid relations among adults with chronic pain. Methods: Simultaneous indirect effects of negative mood on opioid misuse and opioid dependence via lower-order factors of AS (physical, cognitive, and social concerns) were examined cross-sectionally in the present study. The study sample consisted of 428 adults (74.1% female, Mage = 38.27 years, SD = 11.06) who self-reported current moderate to severe chronic pain and opioid use for chronic pain. Results: Results indicated that negative mood was (in part) indirectly related to opioid misuse (in part) via AS physical and cognitive concerns and was (in part) indirectly related to opioid dependence via AS cognitive concerns only. No significant indirect effects via social concerns were observed. Discussion and Conclusions: Findings suggest the importance of further exploring the role of anxiety sensitivity cognitive and physical concerns in terms of opioid misuse and dependence among adults with chronic pain.

Long-term cognitive and academic outcomes among pediatric brain tumor survivors treated with proton versus photon radiotherapy.

BACKGROUND: Proton radiotherapy (PRT) may be associated with less neurocognitive risk than photon RT (XRT) for pediatric brain tumor survivors. We compared neurocognitive and academic outcomes in long-term survivors treated with XRT versus PRT. METHODS: Survivors underwent neurocognitive evaluation >1 year after craniospinal (CSI) or focal PRT or XRT. Groups were compared using separate one-way analyses of covariance for the CSI and focal groups. RESULTS: PRT (n = 58) and XRT (n = 30) subgroups were similar on gender (66% male), age at RT (median = 6.5 years), age at follow-up (median = 14.6 years), and government assistance status (32%). PRT and XRT focal groups differed on follow-up interval, shunt history, and total RT dose (all p < .05), whereas PRT and XRT CSI groups differed on follow-up interval, baseline neurocognitive performance score, boost volume, and CSI dose (all p < .05). The PRT focal group outperformed the XRT focal group on inhibition/switching (p = .04). The PRT CSI group outperformed the XRT CSI group on inattention/impulsivity (both p < .05). Several clinical variables (i.e., RT dose, boost field, baseline performance) predicted neurocognitive outcomes (all p < .05). The PRT focal group performed comparably to population means on most neurocognitive measures, while both CSI groups performed below expectation on multiple measures. The XRT CSI group was most impaired. All groups fell below expectation on processing speed, fine motor, and academic fluency (most p < .01). CONCLUSIONS: Findings suggest generally favorable neurocognitive and academic long-term outcomes following focal PRT. Impairment was greatest following CSI regardless of modality. Dosimetry and baseline characteristics are important determinants of outcome alone or in combination with modality.

The relationship between sex-related alcohol expectancies and hazardous drinking among persons with HIV disease.

Hazardous drinking is a clinically significant problem among persons with HIV (PWH) disease, and is associated with a number of poor outcomes. Hazardous drinking among PWH is associated with risky substance use and sexual behavior, but little work has examined factors that may be associated with greater hazardous drinking and subsequent risky sexual behaviors among PWH. Research among the general population suggests that sex-related alcohol expectancies, defined as drinking to enhance sexual experience, increase sexual risk-taking, and disinhibition of sexual behavior, are associated with greater hazardous alcohol use and risky sexual behavior, but these relations have not been explored among PWH. Therefore, the current study examined the associations of sex-related alcohol expectancies with hazardous alcohol consumption, dependence, and problems among 146 PWH (Mage = 50.99, SD = 9.41) \ enrolled in a clinical trial examining a personalized feedback intervention to reduce hazardous drinking in primary HIV care. Results showed that only sexual disinhibition-related alcohol expectancies were significantly associated with the criterion variables, such that greater drinking alcohol for sexual disinhibition was associated with greater hazardous drinking behaviors. These results sit on the backdrop of a larger literature documenting the links between disinhibition and hazardous alcohol use and provide explanatory specificity to PWH who are hazardous drinkers.

Long-term neuromuscular outcomes of west nile virus infection: A clinical and electromyographic evaluation of patients with a history of infection.

INTRODUCTION: Neuromuscular clinical manifestations during acute West Nile virus (WNV) infection are well documented; however, long-term neurologic outcomes still require investigation. METHODS: We conducted a long-term follow-up study in patients with history of WNV infection. Of the 117 patients who participated in neurologic and neurocognitive evaluations, 30 were referred for neuromuscular and electrodiagnostic evaluation based on abnormal findings. RESULTS: We found that 33% of these patients (10 of 30) showed abnormalities on nerve conduction and/or needle electromyography due to primary or secondary outcomes of WNV infection. Most common electrodiagnostic findings and causes of long-term disability were related to anterior horn cell poliomyelitis (WNV poliomyelitis). Electrical data on these patient populations were similar to those observed in chronic poliomyelitis. DISCUSSION: With more than 16,000 cases of WNV neuroinvasive disease reported across the USA since 1999, understanding clinical outcomes from infection will provide a resource for physicians managing long-term care of these patients. Muscle Nerve 57: 77-82, 2018.

Baseline Neurocognitive Functioning Predicts Viral Load Suppression at 1-Year Follow-Up Among Newly Diagnosed HIV Infected Patients.

The current prospective observational study evaluated the impact of baseline neurocognitive impairment on future viral load suppression among antiretroviral medication naive persons newly diagnosed with HIV infection. We used the Montreal Cognitive Assessment (MoCA) score less than 26, to identify patients with neurocognitive deficits. Of the 138 patients enrolled; virologic suppression was seen in 61% of the participants, while 72% of the participants had a MoCA score less than 26 at baseline. Variables significantly associated with low MoCA score included higher age (p < 0.01) and presence of depression (p < 0.01). After adjusting for these variables, MoCA score less than 26 was significantly associated with a higher risk of failing achieve viral load suppression (adjusted OR 2.7; 95% CI 1.09-6.69). Baseline neurocognitive deficit as measured by MoCA was associated with a higher risk for failing to achieve viral load suppression at one-year follow-up.

Positive Psychological Factors are Linked to Successful Cognitive Aging Among Older Persons Living with HIV/AIDS.

We aimed to characterize successful cognitive aging (SCA) among older HIV-infected (HIV+) and HIV-uninfected (HIV-) adults, and to determine associations with positive psychological factors and health-related quality of life (HRQoL). Ninety-nine HIV+ and 46 HIV- older adults (≥ 50 years) completed measures of neurocognition, positive psychological factors, and HRQoL. Using study-defined SCA criteria (i.e., no cognitive or everyday impairment or major depressive disorder), we compared positive psychological factors and HRQoL across four groups: HIV+/SCA+, HIV+/SCA-, HIV-/SCA+, HIV-/SCA-. SCA was identified in 29% of the HIV+ sample compared to 61% of the HIV- sample (p < 0.01). HIV+/SCA+ participants had higher scores on 8 of 10 measures of positive psychological factors as well as better HRQoL (ps < 0.05) as compared to the HIV+/SCA- group. Furthermore, the HIV+/SCA+ participants had comparable scores on these factors as HIV- adults. Fewer HIV+ than HIV- participants met SCA criteria; however, the level of positive psychological factors among the HIV+/SCA+ group was comparable to the HIV- sample. Our findings present opportunities for interventions to optimize positive psychological factors and potentially improve SCA among older HIV+ adults.

RESUMEN: Nuestro objetivo fue caracterizar el envejecimiento cognitivo exitoso (ECE) entre personas mayores VIH+ y VIH−, y determinar asociaciones con factores psicológicos positivos y con la calidad de vida relacionada a la salud (CVrS). Noventa y nueve personas mayores (de 50 años o más) VIH+ y 46 VIH− completaron indicadores de neurocognición, de factores psicológicos positivos y de CVrS. Mediante la utilización de criterios de ECE definidos por el presente estudio (p. ej. la ausencia de deterioro cognitivo, impedimentos en el funcionamiento cotidiano, o trastorno depresivo mayor) comparamos los factores psicológicos positivos y la CVrS entre cuatro grupos: VIH+/ECE+, VIH+/ECE−, VIH−/ECE+, VIH−/ECE−. El ECE fue identificado en 29% de la muestra de VIH+ comparado con 61% de la muestra de VIH− (p < 0,01). Los participantes VIH+/ECE+ obtuvieron puntuaciones más altas en 8 de los 10 indicadores de factores psicológicos positivos, así como mejor CVrS (ps < 0,05), comparado con el grupo VIH+/ECE−. Además, los participantes VIH+/ECE+ obtuvieron valores comparables a los de los adultos VIH− en estos factores. Una proporción menor de participantes VIH+ que VIH− cumplieron criterios de ECE; sin embargo, el nivel de los factores psicológicos positivos en el grupo VIH+/ECE+ fue comparable a la muestra de la población VIH−. Nuestros resultados presentan oportunidades de intervención para optimizar los factores psicológicos positivos y potencialmente mejorar el ECE entre los adultos mayores con VIH.

Increased cell-free mitochondrial DNA is a marker of ongoing inflammation and better neurocognitive function in virologically suppressed HIV-infected individuals.

Cell-free mitochondrial DNA (mtDNA) is a highly immunogenic molecule that is associated with several inflammatory conditions and with neurocognitive impairment during untreated HIV infection. Here, we investigate how cell-free mtDNA in cerebrospinal fluid (CSF) is associated with inflammation, neuronal damage, and neurocognitive functioning in the context of long-term suppressive antiretroviral therapy (ART). We quantified the levels of cell-free mtDNA in the CSF from 41 HIV-infected individuals with completely suppressed HIV RNA levels in blood plasma (<50 copies/mL) by droplet digital PCR. We measured soluble CD14, soluble CD163, interferon γ-induced protein 10 (IP-10), monocyte chemoattractant protein-1 (MCP-1), interleukin 6 (IL-6), interleukin 8 (IL-8), tumor necrosis factor-α (TNF-α), neopterin, and neurofilament light chain (NFL) by immunoassays in CSF supernatant or blood plasma. Higher levels of mtDNA in CSF were associated with higher levels of MCP-1 (r = 0.56, p < 0.01) in CSF and TNF-α (r = 0.43, p < 0.01) and IL-8 (r = 0.44, p < 0.01) in blood plasma. Subjects with a previous diagnosis of AIDS showed significantly higher levels of mtDNA (p < 0.01) than subjects without AIDS. The associations between mtDNA and MCP-1 in CSF and TNF-α in blood remained significant after adjusting for previous diagnosis of AIDS (p < 0.01). Additionally, higher levels of mtDNA were associated with a lower CD4 nadir (r = -0.41, p < 0.01) and lower current CD4% (r = -0.34, p = 0.03). Paradoxically, higher levels of mtDNA in CSF were significantly associated with better neurocognitive performance (r = 0.43, p = 0.02) and with less neuronal damage (i.e. lower NFL). Higher cell-free mtDNA is associated with inflammation during treated HIV infection, but the impact on neurocognitive functioning and neuronal damage remains unclear and may differ in the setting of suppressive ART.

Effect of Retrieval Practice on Short-Term and Long-Term Retention in HIV+ Individuals.

OBJECTIVES: Episodic memory deficits are both common and impactful among persons infected with HIV; however, we know little about how to improve such deficits in the laboratory or in real life. Retrieval practice, by which retrieval of newly learned material improves subsequent recall more than simple restudy, is a robust memory boosting strategy that is effective in both healthy and clinical populations. In this study, we investigated the benefits of retrieval practice in 52 people living with HIV and 21 seronegatives. METHODS: In a within-subjects design, all participants studied 48 verbal paired associates in 3 learning conditions: Massed-Restudy, Spaced-Restudy, and Spaced-Testing. Retention of verbal paired associates was assessed after short- (30 min) and long- (30 days) delay intervals. RESULTS: After a short delay, both HIV+ persons and seronegatives benefited from retrieval practice more so than massed and spaced restudy. The same pattern of results was observed specifically for HIV+ persons with clinical levels of memory impairment. The long-term retention interval data evidenced a floor effect that precluded further analysis. CONCLUSIONS: This study provides evidence that retrieval practice improves verbal episodic memory more than some other mnemonic strategies among HIV+ persons. (JINS, 2017, 23, 214-222).

Latent Toxoplasma Infection and Higher Toxoplasma gondii Immunoglobulin G Levels Are Associated With Worse Neurocognitive Functioning in HIV-Infected Adults.

BACKGROUND: Human immunodeficiency virus (HIV)-associated neurocognitive disorders persist despite suppressive antiretroviral therapy (ART). Because latent Toxoplasma infection (LTI) may adversely impact brain function, we investigated its impact on neurocognitive impairment (NCI) in people living with HIV disease. METHODS: Two hundred sixty-three HIV-infected adults underwent comprehensive neurocognitive assessments and had anti-Toxoplasma gondii immunoglobulin G (anti-Toxo IgG) measured by qualitative and quantitative enzyme-linked immunosorbent assays. RESULTS: Participants were mostly middle-aged white men who were taking ART (70%). LTI was detected in 30 (11.4%) participants and was associated with a significantly greater prevalence of global NCI (LTI positive [LTI+] = 57% and LTI negative [LTI-] = 34%) (odds ratio, 1.67; 95% confidence interval, 1.17-2.40; P = .017). Deficits were more prevalent in the LTI+ vs the LTI- group in 6 of 7 cognitive domains with statistical significance reached for delayed recall (P < .01). The probability of NCI increased with higher CD4+ T-cell counts among LTI+ individuals but with lower CD4+ T-cell counts in LTI- persons. A strong correlation (r = .93) between anti-Toxo IgG levels and global deficit score was found in a subgroup of 9 patients. Biomarkers indicative of central nervous system inflammation did not differ between LTI+ and LTI- participants. CONCLUSIONS: In this cross-sectional analysis, LTI was associated with NCI, especially in those with higher CD4+ T-cell counts. Longitudinal studies to investigate the role of neuroinflammation and neuronal injury in LTI patients with NCI and trials of anti-Toxoplasma therapy should be pursued.

Antiretroviral treatment initiation does not differentially alter neurocognitive functioning over time in youth with behaviorally acquired HIV.

Although youth living with behaviorally acquired HIV (YLWH) are at risk for cognitive impairments, the relationship of impairments to HIV and potential to improve with antiretroviral therapy (ART) are unclear. This prospective observational study was designed to examine the impact of initiation and timing of ART on neurocognitive functioning in YLWH in the Adolescent Medicine Trials Network for HIV/AIDS Interventions. Treatment naïve YLWH age 18-24 completed baseline and four additional assessments of attention/working memory, complex executive, and motor functioning over 3 years. Group 1 co-enrolled in an early ART initiation study and initiated ART at enrollment CD4 >350 (n = 56); group 2 had CD4 >350 and were not initiating ART (n = 66); group 3 initiated ART with CD4 <350 (n = 59) per standard of care treatment guidelines at the time. Treatment was de-intensified to boosted protease inhibitor monotherapy at 48 weeks for those in group 1 with suppressed viral load. Covariates included demographic, behavioral, and medical history variables. Analyses used hierarchical linear modeling. All groups showed improved performance with peak at 96 weeks in all three functional domains. Trajectories of change were not significantly associated with treatment, timing of treatment initiation, or ART de-intensification. Demographic variables and comorbidities were associated with baseline functioning but did not directly interact with change over time. In conclusion, YLWH showed improvement in neurocognitive functioning over time that may be related to practice effects and nonspecific impact of study participation. Neither improvement nor decline in functioning was associated with timing of ART initiation or therapy de-intensification.

Neurocognitive change in the era of HIV combination antiretroviral therapy: the longitudinal CHARTER study.

BACKGROUND: Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) can show variable clinical trajectories. Previous longitudinal studies of HAND typically have been brief, did not use adequate normative standards, or were conducted in the context of a clinical trial, thereby limiting our understanding of incident neurocognitive (NC) decline and recovery. METHODS: We investigated the incidence and predictors of NC change over 16-72 (mean, 35) months in 436 HIV-infected participants in the CNS HIV Anti-Retroviral Therapy Effects Research cohort. Comprehensive laboratory, neuromedical, and NC assessments were obtained every 6 months. Published, regression-based norms for NC change were used to generate overall change status (decline vs stable vs improved) at each study visit. Survival analysis was used to examine the predictors of time to NC change. RESULTS: Ninety-nine participants (22.7%) declined, 265 (60.8%) remained stable, and 72 (16.5%) improved. In multivariable analyses, predictors of NC improvements or declines included time-dependent treatment status and indicators of disease severity (current hematocrit, albumin, total protein, aspartate aminotransferase), and baseline demographics and estimated premorbid intelligence quotient, non-HIV-related comorbidities, current depressive symptoms, and lifetime psychiatric diagnoses (overall model P < .0001). CONCLUSIONS: NC change is common in HIV infection and appears to be driven by a complex set of risk factors involving HIV disease, its treatment, and comorbid conditions.

PROPERTIES OF A COMBINED MEASURE OF READING AND WRITING: THE ASSESSMENT OF WRITING, SELF-MONITORING, AND READING (AWSM READER).

There is significant overlap between reading and writing, but no known standardized measure assesses these jointly. The goal of the present study is to evaluate the properties of a novel measure, the Assessment of Writing, Self-Monitoring, and Reading (AWSM Reader), that simultaneously evaluates both reading comprehension and writing. In doing so, we evaluate reliability (Cronbach's alpha) and various aspects of construct-related validity, including separate criterion measures of reading and writing, and the AWSM Reader's relations with other variables, including language and executive function (EF), both of which are implicated for both reading and writing. Participants were 377 3rd, 4th, and 5th graders with or at-risk for reading and writing difficulties. Reliability was low for the AWSM Reader reading comprehension (α = .58), but good for writing (α = .75-.80). Criterion-related validity indices revealed moderate correlations with other standardized and commonly used reading and writing measures, r = .47 to .50 (all ps < .001). Additionally, validity data supported the relations of both language and EF to AWSM Reader reading and writing, with EF showing unique prediction in both reading and writing domains. Results provide initial support for the measure per se but stress the difficulty in constructing combined reading and writing measures; directions are given for future work. Results also add to data on the contributions of language and EF to both reading and writing.

Functional interactions of HIV-infection and methamphetamine dependence during motor programming.

Methamphetamine (METH) dependence is frequently comorbid with HIV infection and both have been linked to alterations of brain structure and function. In a previous study, we showed that the brain volume loss characteristic of HIV infection contrasts with METH-related volume increases in striatum and parietal cortex, suggesting distinct neurobiological responses to HIV and METH (Jernigan et al., 2005). Functional magnetic resonance imaging (fMRI) has the potential to reveal functional interactions between the effects of HIV and METH. In the present study, 50 participants were studied in four groups: an HIV+ group, a recently METH-dependent group, a dually affected group, and a group of unaffected community comparison subjects. An fMRI paradigm consisting of motor sequencing tasks of varying levels of complexity was administered to examine blood oxygenation level dependent (BOLD) changes. Within all groups, activity increased significantly with increasing task complexity in large clusters within sensorimotor and parietal cortex, basal ganglia, cerebellum, and cingulate. The task complexity effect was regressed on HIV status, METH status, and the HIV×METH interaction term in a simultaneous multiple regression. HIV was associated with less complexity-related activation in striatum, whereas METH was associated with less complexity-related activation in parietal regions. Significant interaction effects were observed in both cortical and subcortical regions; and, contrary to expectations, the complexity-related activation was less aberrant in dually affected than in single risk participants, in spite of comparable levels of neurocognitive impairment among the clinical groups. Thus, HIV and METH dependence, perhaps through their effects on dopaminergic systems, may have opposing functional effects on neural circuits involved in motor programming.

Visual memory in methamphetamine-dependent individuals: deficient strategic control of encoding and retrieval.

OBJECTIVE: Chronic use of methamphetamine (MA) has moderate effects on neurocognitive functions associated with frontal systems, including the executive aspects of verbal episodic memory. Extending this literature, the current study examined the effects of MA on visual episodic memory with the hypothesis that a profile of deficient strategic encoding and retrieval processes would be revealed for visuospatial information (i.e., simple geometric designs), including possible differential effects on source versus item recall. METHOD: The sample comprised 114 MA-dependent (MA+) and 110 demographically-matched MA-nondependent comparison participants (MA-) who completed the Brief Visuospatial Memory Test-Revised (BVMT-R), which was scored for standard learning and memory indices, as well as novel item (i.e., figure) and source (i.e., location) memory indices. RESULTS: Results revealed a profile of impaired immediate and delayed free recall (p<0.05) in the context of preserved learning slope, retention, and recognition discriminability in the MA+ group. The MA+ group also performed more poorly than MA- participants on Item visual memory (p<0.05) but not Source visual memory (p>0.05), and no group by task-type interaction was observed (p>0.05). Item visual memory demonstrated significant associations with executive dysfunction, deficits in working memory, and shorter length of abstinence from MA use (p<0.05). CONCLUSIONS: These visual memory findings are commensurate with studies reporting deficient strategic verbal encoding and retrieval in MA users that are posited to reflect the vulnerability of frontostriatal circuits to the neurotoxic effects of MA. Potential clinical implications of these visual memory deficits are discussed.

Dispersion-based cognitive intra-individual variability in dementia with Lewy bodies.

OBJECTIVE: Cognitive fluctuations are characteristic of dementia with Lewy bodies (DLB) but challenging to measure. Dispersion-based intra-individual variability (IIV-d) captures neurocognitive performance fluctuations across a test battery and may be sensitive to cognitive fluctuations but has not been studied in DLB. METHOD: We report on 5,976 participants that completed the uniform data set 3.0 neuropsychological battery (UDS3NB). IIV-d was calculated via the intra-individual standard deviation across 12 primary UDS3NB indicators. Separate models using mean USD3NB score and the Montreal cognitive assessment (MoCA) total score tested the reproducibility of the incremental value of IIV-d over-and-above global cognition. Binary logistic regressions tested whether IIV-d could classify individuals with and without clinician-rated cognitive fluctuations. Multinomial logistic regressions tested whether IIV-d could differentiate participants with DLB, participants with Alzheimer's disease (AD), and participants with healthy cognition (CH), as well as the incremental diagnostic utility of IIV-d over-and-above clinician-rated cognitive fluctuations. RESULTS: IIV-d exhibited large univariate associations with clinician-rated and non-clinician-informant reported cognitive fluctuations, which persisted when adjusting for MoCA but not the full battery mean. Of diagnostic relevance, greater IIV-d was consistently associated with DLB and AD relative to CH over-and-above global cognition and clinician-rated cognitive fluctuations. Greater IIV-d was less consistently associated with an increased probability of DLB relative to AD when controlling for global cognition. CONCLUSIONS: IIV-d accurately differentiates DLB from CH over-and-above global cognition and clinician-rated cognitive fluctuations. IIV-d may supplement a thorough clinical interview of cognitive fluctuations and serve as a standardized performance-based indicator of this transdiagnostic phenomenon. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Predictors of rate of cognitive decline in patients with amnestic mild cognitive impairment.

OBJECTIVE: Amnestic mild cognitive impairment (MCI) is a known risk factor for conversion to Alzheimer's disease (AD). Although substantial research has been conducted on the general profile of amnestic MCI subjects and predictors of conversion to AD, research on predictors of rate of decline has been considerably less extensive. The present study sought to more systematically and comprehensively examine predictors of rate of cognitive decline in a longitudinal sample of individuals with MCI, including age, genetic vulnerability, baseline cognitive performance, and baseline neuropsychiatric severity. METHOD: Participants with single or multi-domain amnestic MCI (N = 151) were assessed at baseline and for a mean of 1.32 follow-up visits (mean interval from baseline to last follow-up = 1.61 years). RESULTS: Results showed that carriers of the ApoE ε4 allele declined more quickly on all three dementia severity measures compared to non-carriers. Older individuals did not decline more rapidly in dementia severity. Participants with lower executive functions composite scores and greater memory impairment severity at baseline predicted faster decline on dementia severity measures. Contrary to hypotheses, those with lower levels of depression at baseline declined more rapidly on dementia severity measures compared to those with higher levels of depression. CONCLUSION: Identifying potential predictors of rate of decline from amnestic MCI to AD could be clinically meaningful for prognostic purposes, understanding risk and protective factors, as well as guiding future treatments and clinical trials that could aim to target and delay progression among those patients who are vulnerable to more quickly convert to AD.

Differential Associations Between BDNF and Memory Across Older Black and White Adults With HIV Disease.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) shows consistent associations with memory across many clinical populations, including dementia. Less is understood about the association between BDNF and memory functioning in people living with HIV (PWH). METHODS: A sample of 173 adults aged 50+ (n = 100 HIV+ and n = 73 HIV seronegative) completed a comprehensive neurobehavioral assessment and blood draw. Linear regressions predicting memory domains (learning, delayed recall, and recognition) were conducted including race (White vs. Black/African American), HIV status, BDNF, and their interactions. RESULTS: For learning and delayed recall, significant (P < 0.05) main effects for race and interactions for BDNF x race and HIV status x race were found, whereas for recognition, only a BDNF x race interaction emerged. In adjusted models, BDNF x race interactions remained for learning and delayed recall. To determine effect size, correlations were conducted between BDNF and memory domains stratified by HIV serostatus and race, and small-medium associations between BDNF and learning and delayed recall (rho = 0.29, P < 0.01; rho = 0.22, P = 0.045), but no recognition (rho = 0.12, P = 0.29) were found among Black/African American PWH. BDNF was not significantly associated with memory domains in White PWH or either HIV- sample. Follow-up analyses showed BDNF-memory specificity, such that race X BDNF interactions did not emerge for other cognitive domains. CONCLUSIONS: While limited by cross-sectional design among a small sample, particularly of White individuals, results indicate that BDNF may serve as a promising biomarker reflecting memory functioning in PWH, particularly Black/African Americans. Further work is needed to replicate findings and determine mechanisms for racial differences in BDNF associations with memory.

HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors.

Combination antiretroviral therapy (CART) has greatly reduced medical morbidity and mortality with HIV infection, but high rates of HIV-associated neurocognitive disorders (HAND) continue to be reported. Because large HIV-infected (HIV+) and uninfected (HIV-) groups have not been studied with similar methods in the pre-CART and CART eras, it is unclear whether CART has changed the prevalence, nature, and clinical correlates of HAND. We used comparable methods of subject screening and assessments to classify neurocognitive impairment (NCI) in large groups of HIV + and HIV - participants from the pre-CART era (1988-1995; N = 857) and CART era (2000-2007; N = 937). Impairment rate increased with successive disease stages (CDC stages A, B, and C) in both eras: 25%, 42%, and 52% in pre-CART era and 36%, 40%, and 45% in CART era. In the medically asymptomatic stage (CDC-A), NCI was significantly more common in the CART era. Low nadir CD4 predicted NCI in both eras, whereas degree of current immunosuppression, estimated duration of infection, and viral suppression in CSF (on treatment) were related to impairment only pre-CART. Pattern of NCI also differed: pre-CART had more impairment in motor skills, cognitive speed, and verbal fluency, whereas CART era involved more memory (learning) and executive function impairment. High rates of mild NCI persist at all stages of HIV infection, despite improved viral suppression and immune reconstitution with CART. The consistent association of NCI with nadir CD4 across eras suggests that earlier treatment to prevent severe immunosuppression may also help prevent HAND. Clinical trials targeting HAND prevention should specifically examine timing of ART initiation.

The Structure of Processing Speed in Children and its Impact on Reading.

The present study had two aims. First, we set out to evaluate the structure of processing speed in children by comparing five alternative models: two conceptual models (a unitary model, a complexity model) and three methodological models (a stimulus material model, an output response model, and a timing modality model). Second, we then used the resulting models to predict multiple types of reading, a highly important developmental outcome, using other well-known predictors as covariates. Participants were 844 children enrolled in third through fifth grade in urban public elementary schools who received 16 measures of processing speed that varied in the above dimensions. A two-factor complexity model that differentiated between simple and complex processing speed was the preferred model and fit the data well. Both types of PS predicted reading fluency, and complex (but not simple) PS predicted single word reading and comprehension. Results offer insight to the structure of processing speed, its relation to closely related concepts (such as executive function), and provide nuance to the understanding of the way processing speed influences reading.