Neurologic Complications in Adult Cancer Survivorship.

Over the past decade, the improvement in cancer diagnostics and therapeutics has extended the overall survival of patients diagnosed with cancer including brain cancer. However, despite these unprecedented medical successes, patients continue to experience numerous neurologic complications after treatment that interfere with their independence, functionality, and overall quality of life. These include, among others, cognitive impairment, endocrinopathies, peripheral and cranial neuropathies, and vasculopathy. This article describes the long-term neurologic complications cancer survivors commonly experience to increase awareness of these complications and discuss treatments when available. Further research is necessary to understanding of mechanisms of neurologic injury and advance diagnosis and treatment. Effective patient education, monitoring, and managing neurologic issues after cancer treatment may improve independence, functionality, and quality of life during survivorship.

MoCA Intraindividual Cognitive Variability in Older Adults With Type 1 Diabetes.

Older adults with type 1 diabetes (T1D) may have an elevated risk of developing Alzheimer disease and related dementia. Higher intraindividual cognitive variability (IICV) has been proposed as a novel risk factor of Alzheimer disease and related dementia. Here, we examined the association between cross-domain IICV measured using the Montreal Cognitive Assessment (MoCA) and cognitive impairment measured using traditional neuropsychological tests in older individuals with T1D. Participants with T1D (N=201) completed both the MoCA and a battery of traditional neuropsychological tests. Participants with cognitive impairment, determined using traditional tests, had significantly higher IICV scores and significantly lower total MoCA scores ( P <0.001). However, the effect of the total score was greater than that of the IICV score on the likelihood of cognitive impairment (total odds ratio=3.50, IICV odds ratio=2.03, P <0.001). The MoCA total score performed better than the MoCA IICV score in identifying T1D individuals classified with cognitive impairment.

Executive functions mediate the association between alcohol use and declarative memory symptoms in daily life.

Alcohol use is associated with memory problems in young adults with HIV, but the cognitive mechanisms of that association are not known. Sixty adults (aged 19-24 years) living with HIV were administered the Alcohol, Smoking, and Substance Involvement Screening Test to assess alcohol use, Behavior Rating Inventory of Executive Function for self-reported executive functions, and the Prospective and Retrospective Memory Questionnaire (PRMQ) for dailiy memory functioning. Controlling for mood, self-reported executive functions fully mediated the relationship between alcohol use and memory (indirect effect b=.568, 95%CI [.209,.888]). Findings suggest that self-reported executive dysregulation of memory processes (e.g., Strategic encoding and retrieval) may drive the effects of alcohol use on daily memory symptoms.

"Do I Have a Memory Problem? I Can't Recall": An Evaluation of Measurement Invariance in Subjective Reporting of Memory Symptoms among Persons with and without Objective HIV-Associated Memory Impairment.

OBJECTIVE: Memory symptoms and objective impairment are common in HIV disease and are associated with disability. A paradoxical issue is that objective episodic memory failures can interfere with accurate recall of memory symptoms. The present study assessed whether responses on a self-report scale of memory symptoms demonstrate measurement invariance in persons with and without objective HIV-associated memory impairment. METHOD: In total, 505 persons with HIV completed the Prospective and Retrospective Memory Questionnaire (PRMQ). Objective memory impairment (n = 141) was determined using a 1-SD cutoff on clinical tests of episodic memory. PRMQ measurement invariance was assessed by confirmatory factor analyses examining a one-factor model with increasing cross-group equality constraints imposed on factor loadings and item thresholds (i.e., configural, weak, and strong invariance). RESULTS: Configural model fit indicated that identical items measured a one-factor model for both groups. Comparison to the weak model indicated that factor loadings were equivalent across groups. However, there was evidence of partial strong invariance, with two PRMQ item thresholds differing across memory impairment groups. Post hoc analyses using a 1.5-SD memory impairment cutoff (n = 77) revealed both partial weak and partial strong invariance, such that PRMQ item loadings differed across memory groups for three items. CONCLUSIONS: The PRMQ demonstrated a robust factor structure among persons with and without objective HIV-associated memory impairment. However, on select PRMQ items, individuals with memory impairment reported observed scores that were relatively higher than their latent score, while items were more strongly associated with the memory factor in a group with greater memory impairment.

Frequency and Correlates of Subjective Cognitive Impairment in HIV Disease.

The increasing prevalence of older adults living with HIV has raised growing concerns about a possible rise in the incidence of neurocognitive disorders due to HIV and other age-related factors. In typical aging, subjective cognitive impairment (SCI) among individuals with normal neurocognitive functioning may be an early manifestation of an incipient neurocognitive disorder. The current study examined the frequency and correlates of SCI in 188 HIV-infected adults without performance-based neurocognitive deficits or a current psychiatric disorder and 133 HIV seronegative comparison participants. All participants completed the Prospective and Retrospective Memory Questionnaire and Profile of Mood States Confusion/Bewilderment scale. Consistent with the diagnostic criteria proposed by Jessen et al. (Alzheimers Dement 10(6):844-852, 2014), participants were classified with SCI if their scores on either of the self-reported measures was greater than 1.5 SD above the normative mean. A logistic regression controlling for current mood complaints and lifetime history of substance use disorders revealed that HIV infection increased the odds of SCI (odds ratio= 4.5 [1.6, 15.4], p = 0.004). Among HIV+ individuals, SCI was associated with lower performance-based learning and delayed memory scores (Cohen's d range 0.41-0.42.) and poorer global everyday functioning (odds ratio= 8.5 [2.6, 15.9]), but not HIV disease severity (ps > 0.10). In a sample of individuals without neurocognitive impairment or elevated mood symptoms, HIV disease was associated with a nearly fivefold increased odds of SCI compared to seronegative individuals, which may indicate an increased risk for developing major neurocognitive disorders as these HIV+ individuals age.

Does intra-individual neurocognitive variability relate to neuroinvasive disease and quality of life in West Nile Virus?

West Nile Virus (WNV) can be a neuroinvasive pathogen that may produce persistent mild-to-moderate neurocognitive impairments in some infected persons. Intra-individual variability (IIV) is an index of a person's performance across a neuropsychological test or battery, which is an indicator of neurocognitive control and integrity of prefrontal systems. The present study examined possible associations of IIV to neurological health and well-being in WNV infection. Participants included 84 adults with a range of clinical WNV disease (31 West Nile Encephalitis, 16 West Nile Meningitis, 37 West Nile Fever) who completed the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). IIV was operationalized as covariance of variation (CoV), or the intra-individual standard deviation across 5 age-adjusted RBANS standard scores divided by the mean of standard scores. Participants were assessed for health-related quality of life (QoL) using the RAND 36-item short form health survey (SF-36). Analyses revealed that the West Nile Encephalitis group had higher neurocognitive CoV compared to the West Nile Fever group, and this difference was associated with a medium effect size (Cohen's d = .52). Mixed linear models controlling for estimated IQ, activities of daily living, depression, neuroinvasive disease groups, and fatigue showed that higher RBANS CoV was associated with lower physical, but not mental health QoL. In persons with WNV infection, there is a modest association between elevations in IIV and encephalitis, and even subtle disruptions in neuropsychological functioning show relationships with important self-reported functioning as measured by physical health quality of life. Future studies should examine whether IIV predicts long-term health outcomes (e.g., mortality) in individuals infected with WNV.

A comparison of the sensitivity, stability, and reliability of three diagnostic schemes for HIV-associated neurocognitive disorders.

HIV-associated neurocognitive disorders (HAND) occur in approximately 50% of HIV-infected individuals, yet available diagnostic criteria yield varying prevalence rates. This study examined the frequency, reliability, and sensitivity to everyday functioning problems of three HAND diagnostic criteria (DSM-5, Frascati, Gisslén). Participants included 361 adults with HIV disease and 199 seronegative adults. Neurocognitive status as defined by each of the three diagnostic systems was determined via a comprehensive neuropsychological battery. Everyday functioning was evaluated through self-report and clinician ratings. Results of logistic regressions revealed an association of HIV serostatus with Frascati-defined neurocognitive impairment (p = .027, OR = 1.7[1.1, 2.7]), but not DSM-5 or Gisslén-defined criteria (ps > .05). Frascati and DSM-5 criteria demonstrated agreement on 71% of observations, Frascati and Gisslén showed agreement on 80%, and DSM-5 and Gisslén criteria showed agreement on 46%, though reliability across the three criteria was poor. Only Frascati-defined neurocognitive impairment significantly predicted everyday functioning problems (p = .002, OR = 2.3[1.4, 3.8]). However, when both neurocognitive and complaint criteria were considered, the DSM-5 guidelines demonstrated significant relationships to everyday functioning, serostatus, and also increased reliability overtime compared to neurocognitive criteria alone (all ps < .05). A subset (n = 118) of the HIV+ group was assessed again after 14.0 (2.2) months. DSM-5 criteria evidenced significantly higher rates of incident neurocognitive disorder compared to both Frascati (p = .003) and Gisslén (p = .021) guidelines, while there were fewer remitting neurocognitive disorder diagnoses when Gisslén criteria were applied to the study sample compared to Frascati (p = .04). Future studies should aim to identify gold standard biological markers (e.g., neuropathology) and clinical outcomes associated with specific diagnostic criteria.

Accelerated and accentuated neurocognitive aging in HIV infection.

There is debate as to whether the neurocognitive changes associated with HIV infection represent an acceleration of the typical aging process or more simply reflect a greater accentuated risk for age-related declines. We aimed to determine whether accelerated neurocognitive aging is observable in a sample of older HIV-infected individuals compared to age-matched seronegatives and older old (i.e., aged ≥65) seronegative adults. Participants in a cross-sectional design included 48 HIV-seronegative (O-) and 40 HIV-positive (O+) participants between the ages of 50-65 (mean ages = 55 and 56, respectively) and 40 HIV-seronegative participants aged ≥65 (OO-; mean age = 74) who were comparable for other demographics. All participants were administered a brief neurocognitive battery of attention, episodic memory, speeded executive functions, and confrontation naming (i.e., Boston Naming Test). The O+ group performed more poorly than the O- group (i.e., accentuated aging), but not differently from the OO- on digit span and initial recall of a supraspan word list, consistent with an accelerating aging profile. However, the O+ group's performance was comparable to the O- group on all other neurocognitive tests (ps > 0.05). These data partially support a model of accelerated neurocognitive aging in HIV infection, which was observed in the domain of auditory verbal attention, but not in the areas of memory, language, or speeded executive functions. Future studies should examine whether HIV-infected adults over 65 evidence accelerated aging in downstream neurocognitive domains and subsequent everyday functioning outcomes.

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).

Spatial pattern separation differences in older adult carriers and non-carriers for the apolipoprotein E epsilon 4 allele.

We examined the performance of healthy young (n=57) and older adults (n=43) genotyped as apolipoprotein E-ε4 (APOE-ε4) carriers or APOE-ε4 non-carriers on a delayed match-to-sample task involving varying degrees of spatial interference hypothesized to assess spatial pattern separation. Older adult ε4 carriers were further divided into "impaired" and "unimpaired" groups based on their performance on a standardized test of verbal memory. We found that performance on the spatial pattern separation test increased as a function of decreased spatial interference across all groups. The older ε4 carriers in the impaired group performed significantly worse (p<.05) than unimpaired ε4 carriers, ε4 non-carriers, and young adults. The data suggest that spatial pattern separation may be less efficient in a subset of healthy older adults with subtle memory decline who are carriers of the ε4 allele. However, pattern separation performance may be comparable to that of young adults in a subset of older adult ε4 carriers and more broadly among non-carriers. Our findings offer additional evidence that pattern separation may vary in older adults, and they provide novel insight into pattern separation efficiency in ε4-positive older adults.

Elevated rates of mild cognitive impairment in HIV disease.

With the rising number of individuals in their 50s and 60s who are infected with HIV, concerns have emerged about possible increases in the rates of non-HIV-associated dementias. The current study examined the prevalence of mild cognitive impairment (MCI) in older HIV-infected adults, since MCI is an intermediate state between typical cognitive aging and dementia that emerges in this age range. Participants included 75 adults with HIV disease aged 50 years and older who were on combination antiretroviral therapy (cART) and had undetectable plasma viral loads and 80 demographically similar HIV-seronegative comparison subjects. Participants completed a research neuropsychological evaluation that was used to classify MCI according to the comprehensive diagnostic scheme described by Bondi et al. (J Alzheimers Dis 42:275-289, 2014). HIV-infected persons were over seven times more likely to have an MCI designation (16 %) than their seronegative counterparts (2.5 %). Within the HIV+ cohort, MCI had minimal overlap with diagnoses of asymptomatic neurocognitive impairment and was significantly associated with older age, lower Karnofsky Scale of Performance Scores, and mild difficulties performing instrumental activities of daily living (iADLs). HIV infection in older adults is associated with a notably elevated concurrent risk of MCI, which may increase the likelihood of developing non-HIV-associated dementias as this population ages further.

Health literacy mediates the effects of educational attainment on online pharmacy navigation skills in older adults with HIV disease.

ObjectiveThe Internet serves an increasingly critical role in health behaviors for older adults with chronic medical conditions. Guided by theories of health behaviors and literacy, this study examined whether the relationship between educational attainment and online pharmacy skills in older persons with HIV disease (PWH) is mediated by health literacy. Design: Participants included 98 PWH age 50 and older who completed the Test of Online Pharmacy Skills (TOPS), which required them to navigate an experimenter-controlled online pharmacy to perform several naturalistic tasks (e.g., refill an existing prescription). Participants also completed the Medication-Management Test-Revised (MMT-R). Results: Mediation analyses revealed a significant indirect effect of education on both online pharmacy accuracy and MMT-R, which was fully mediated by health literacy. In contrast, there was no direct or indirect effect of education on online pharmacy speed when health literacy was included as a mediator. Conclusion: Health literacy plays an important role in the relationship between years of education attained and the ability of older PWH to successfully navigate online pharmacy tasks and manage their medications. Future studies might examine whether interventions to improve electronic health literacy among older PWH who have lower educational attainment have beneficial effects on online health behaviors.

Subjective cognitive decline disrupts aspects of prospective memory in older adults with HIV disease.

Subjective cognitive decline (SCD) is a risk factor for dementia that may occur at higher rates in people with HIV (PWH). Prospective memory (PM) is an aspect of cognition that may help us better understand how SCD impacts daily life. Paricipants were 62 PWH aged ≥ 50 years and 33 seronegative individuals. SCD was operationalized as normatively elevated cognitive symptoms on standardized questionnaires, but with normatively unimpaired performance-based cognition and no current affective disorders. PM was measured with the Comprehensive Assessment of Prospective Memory (CAPM), the Cambridge Test of Prospective Memory (CAMPROMPT), and an experimental computerized time-based PM task. A logistic regression revealed that older PWH had a three-fold increased likelihood for SCD. Among the PWH, SCD was associated with more frequent PM symptoms and poorer accuracy on the time-based scale of the CAMPROMPT. These findings suggest that SCD disrupts PM in older PWH.

Poorer prospective memory performance is associated with reduced time monitoring among OEF/OIF/OND Veterans with a history of blast-related mild traumatic brain injury.

Objective:Prospective memory (PM) or "remembering to remember" has been shown to be reduced in Veterans with histories of mild traumatic brain injury (mTBI), particularly on tasks with high strategic demands such as recalling time-based information in the absence of external cues. This study examined whether time monitoring during a PM task was reduced in Veterans with a history of mTBI and was associated with time-based PM performance. Method:Veterans with a history of mTBI (n = 49) and Veterans without a history of TBI (n = 16) completed the Memory for Intentions Screening Test (MIST) as a measure of PM during which their time monitoring (i.e. number of clock checks) was recorded. Results:Adjusting for age, education, depression, and PTSD symptoms, negative binomial regression revealed that the mTBI group checked the clock less frequently compared to the control group (Cohen's d = 0.84, p = 0.005). Within the mTBI group, less frequent time monitoring across the entire MIST task was associated with poorer time-based MIST performance (rs = .57, p < 0.001), but not with event-based MIST (rs = .04, p = 0.768). Conclusions:Veterans with a history of mTBI evidenced significantly reduced time monitoring during a PM task compared to Veterans without a history mTBI, which was associated with strategically-demanding PM. Current findings provide that mTBI-associated difficulties with strategic aspects of PM may be due to reduced time monitoring. Future studies are needed to determine if reduced time monitoring also contributes to mTBI-associated PM difficulties in the real-world (e.g. medication non-adherence).

Associations between Intra-Individual Neurocognitive Variability and Prospective Memory in Veterans with Mild Traumatic Brain Injury History and Posttraumatic Stress Disorder.

OBJECTIVE: Mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) frequently co-occur and are associated with neurocognitive intra-individual variability (IIV) and difficulty with prospective memory (PM). The current study aimed to examine associations between IIV and PM in this comorbid group. METHOD: Fifty veterans with a history of blast mTBI and current comorbid PTSD completed a standardized neurocognitive battery to measure IIV, and the Memory for Intentions Screening Test measuring PM. RESULTS: Adjusting for age, education, and race, higher IIV was associated with poorer time-based PM (p < .001, f2 = .34), but not event-based PM. In a subset of the sample with self-report data, higher IIV was associated with poorer self-reported retrospective memory, but not PM. CONCLUSIONS: Cognitive variability on a standardized neuropsychological battery was associated with strategically demanding PM, which is an ecologically relevant ability and highlights the possible connection between subtle cognitive difficulties in-clinic and those experienced in daily life.

Gender disparities in the author bylines of articles published in clinical neuropsychology journals from 1985 to 2019.

Objective: Women are becoming more prevalent in clinical neuropsychology, but gender bias and disparities persist across multiple professional domains. This study examined potential gender disparities in historical authorship trends across commonly read journals in clinical neuropsychology. Method: Analyses were conducted on 10,531 articles published in six clinical neuropsychology journals from 1985 to 2019. Each author was coded as either a man or a woman using the OpenGenderTracking Project database. Results: On average, women comprised 43.3% (±30.6) of the authors listed in clinical neuropsychology article bylines and were lead and/or corresponding author on 50.3% of these papers. Findings varied by journal, with Child Neuropsychology having the best representation of women across several study metrics. Women comprised an increasing proportion of authors over time and the gender gap in clinical neuropsychology is smaller than was recently reported for the broader field of psychology; nevertheless, the recent rates of women as authors lag behind the prevalence of women in clinical neuropsychology. Encouragingly, gender was not associated with the number of times an article was cited. Articles that included women in leadership roles had significantly more authors overall and specifically more women authors. Conclusions: Women are under-represented as authors in clinical neuropsychology journals, but they are becoming more common and their papers are cited just as frequently as men. Efforts to increase women as research mentors and sponsors may help to further close the publishing gender gap in clinical neuropsychology.

Future and past autobiographical memory in persons with HIV disease.

Objective: While HIV disease is associated with impairment in declarative memory, the ability of people with HIV (PWH) to describe past and future autobiographical events is not known. Method: Participants included 63 PWH and 28 seronegative individuals ages 50-78 who completed standardized neurocognitive and everyday functioning assessments. Participants described four events from the recent past and four imagined events in the near future, details from which were classified as internal or external to the main event. Result: PWH produced fewer autobiographical details with small-to-medium effect sizes but did not differ from seronegative participants in meta-cognitive ratings of their performance. Performance of the study groups did not vary across past or future probes or internal versus external details; however, within the entire sample, past events were described in greater detail than future events, and more external than internal details were produced. Within the PWH group, the production of fewer internal details for future events was moderately associated with poorer prospective memory, executive dysfunction, and errors on a laboratory-based task of medication management. Conclusion: Older PWH may experience difficulty generating autobiographical details from the past and simulated events in the future, which may be related to executive dyscontrol of memory processes. Future studies might examine the role of future thinking in health behaviors such as medication adherence and retention in healthcare among PWH. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Prospective memory partially mediates the association between aging and everyday functioning.

Objective: Older adults commonly experience declines in everyday functioning, the reasons for which are multifactorial. Prospective memory (PM), or remembering to carry out intended actions, can be an executively demanding cognitive process that declines with older age and is independently associated with a variety of everyday functions (e.g. taking medication). This study examined the hypothesis that PM mediates the relationship between older age and poorer everyday functioning.Method: A total of 468 community-dwelling adults (ages 18-75) with a range of medical comorbidities (e.g. viral infection) were classified as dependent on four well-validated measures of manifest everyday functioning: activities of daily living, employment status, the Karnofsky Scale of Performance Status, and self-reported cognitive symptoms. Participants completed the Memory for Intentions Test (MIsT) to measure PM, alongside clinical tests of executive functions and retrospective memory.Results: Controlling for education and comorbidities, bootstrap analysis revealed a significant direct effect of age on everyday functioning and a significant mediated effect of age on everyday functioning through the indirect effect of time-based b = .006 [.003, .010] and event-based PM (b = .005, [.002, .009]), as well as slightly smaller effects for executive functions (b = .003, [.001, .005]) and retrospective memory (b = .002, [.001, .005]).Conclusions: These cross-sectional data suggest that executively demanding aspects of declarative memory play an important partial mediating role between an individual factor (i.e. age) and daily life activities, and highlight the possible benefit of targeting PM for improving everyday functioning in older adults.

Where have I heard that before? A validity study of source memory indices from the California Verbal Learning Test - Second edition.

Objective: We investigated the construct and criterion validity of the source memory (SM) indices within the California Verbal Learning Test-II (CVLT-II).Method: Participants included 77 individuals with HIV-associated neurocognitive disorders (HAND+), 287 HIV + neurocognitively normal individuals (HAND-) and 203 seronegative HIV comparisons (HIV-). CVLT-II SM impairment status (normative scores ≤1 standard deviation) was determined using Total Across-List Intrusions and Source Recognition Discriminability (d'). Participants also completed a comprehensive neuropsychological battery, assessments of everyday functioning and experimental measures of SM.Results: CVLT-II SM impairment was significantly associated with increased errors on experimental SM measures and lower scores on measures of passage recall and executive functions, but not visuospatial skills. In a logistic regression controlling for clinicodemographic factors, CVLT-II SM impairment was a significant independent predictor of HAND, with the HAND + group showing higher rates of SM impairment than both the HAND - and HIV - groups. Finally, CVLT-II SM impairment was significantly related to a composite measure of everyday functioning, but this effect disappeared after adjusting for covariates. Note that, the overall pattern of findings across this study also held when CVLT-3 normative standards were applied to the SM indices.Conclusions: Results provide initial support for the construct and criterion validity of a CVLT-II SM index in the setting of HIV disease. Future studies should examine the validity of CVLT-II SM variables in other neuropsychological populations.

Medication Management Capacity and Its Neurocognitive Correlates in Huntington's Disease.

OBJECTIVE: Although medication management is a necessary daily activity for individuals with Huntington's disease (HD), medication management abilities and their relation to cognitive functioning have not been evaluated. METHOD: Twenty individuals with HD and 20 healthy adults (HA) completed the Medication Management Abilities Assessment (MMAA). Individuals with HD also completed a self-report medication management measure and neuropsychological tests assessing executive function, retrospective memory, and prospective memory. RESULTS: Individuals with HD performed significantly poorer and made more undertaking errors on the MMAA as compared to HA. No group differences were found in overtaking errors. In the HD group, significant associations were found between undertaking errors and perceived medication management ability as well as between MMAA task performance and measures assessing prospective memory and executive functions. CONCLUSIONS: Medication management capacity was negatively affected in individuals with HD and may be associated with difficulty remembering to take medications in the future.