Patients with temporal lobe epilepsy (TLE) commonly show memory deficits on neuropsychological tests. The BVMT-R is a widely used test of visual learning and memory that involves accurately reproducing an array of figures in the correct special location. The present study examined performance processes of visual memory in presurgical patients with TLE, including item (i.e., accuracy) and associative memory (i.e., location), which have been shown to be dissociable in studies of visual memory in other neurologic populations.

Participants included nine patients with left TLE (67% female; 67% left-handed; mean age = 46.15 years, range = 24-55; mean education = 14.8 years, range = 9-18) and six patients with right TLE (17% female; 33% left-handed; mean age = 57.64 years, range = 22-62; mean education = 15.52 years, range 11-18). Mean duration of epilepsy was 19 years. Participants had an average of two failed anti-seizure medications prior to surgery. TLE groups were compared to 22 healthy controls (36% female; 14% left-handed; mean age = 33.68 years, range = 2253; mean education = 17.66 years, range = 1620). All participants completed comprehensive neuropsychological testing at a large Northeastern medical center. The BVMT-R was scored using standard and novel scoring paradigms. All data were retrospectively reviewed from archival datasets.

MANCOVA results indicated a significant multivariate main effect for group membership and standard BVMT-R scoring after controlling for level of education, Wilks’ A = 0.59, F(4, 64) = 4.91, p = .002. The multivariate partial eta squared (np2) of .58 indicated a strong relationship between group membership and both immediate and delayed recall, with the control group performing better overall. The TLE groups did not perform significantly different from each other. A significant multivariate main effect for group and novel BVMT-R scoring was found (also controlling for education), Wilks’ A = 0.42, F(8, 58) = 3.97, p = .001. Overall, the control group demonstrated better item learning with no significant difference between TLE groups observed. Both the control (M = (16.5, SD = 2.04) and left TLE (M = 12.33, SD = 4.03) showed stronger associative learning compared to the right TLE group (M = 10.2, SD = 4.27). For item and location delayed recall, controls (M = 4.82, SD = 1.62) had more accurate recall compared to left TLE (M = 1.56, SD = 2.04) with a trend toward better performance compared to the right TLE patients (M = 2.6, SD = 1.82); the TLE groups performed similarly. No difference was observed for associative delayed recall between the three groups.

Patients with right TLE showed worse associative learning compared to left TLE, while performance was generally comparable to their right TLE counterparts on other novel BVMT-R scoring paradigms. Unsurprisingly, patients with TLE performed worse on BVMT-R using standard scoring procedures, though no lateralizing effect was observed. While these findings suggest that associative visual learning weakness may be characteristic of right TLE, findings should be interpreted cautiously the given small sample size and demographic considerations (i.e., uneven gender distribution, lack of data on ethnicity/race).

Anterior temporal lobectomy is a common surgical approach for medication-resistant temporal lobe epilepsy (TLE). Prior studies have shown inconsistent findings regarding the utility of presurgical intracarotid sodium amobarbital testing (IAT; also known as Wada test) and neuroimaging in predicting postoperative seizure control. In the present study, we evaluated the predictive utility of IAT, as well as structural magnetic resonance imaging (MRI) and positron emission tomography (PET), on long-term (3-years) seizure outcome following surgery for TLE.

Patients consisted of 107 adults (mean age=38.6, SD=12.2; mean education=13.3 years, SD=2.0; female=47.7%; White=100%) with TLE (mean epilepsy duration =23.0 years, SD=15.7; left TLE surgery=50.5%). We examined whether demographic, clinical (side of resection, resection type [selective vs. non-selective], hemisphere of language dominance, epilepsy duration), and presurgical studies (normal vs. abnormal MRI, normal vs. abnormal PET, correctly lateralizing vs. incorrectly lateralizing IAT) were associated with absolute (cross-sectional) seizure outcome (i.e., freedom vs. recurrence) with a series of chi-squared and t-tests. Additionally, we determined whether presurgical evaluations predicted time to seizure recurrence (longitudinal outcome) over a three-year period with univariate Cox regression models, and we compared survival curves with Mantel-Cox (log rank) tests.

Demographic and clinical variables (including type [selective vs. whole lobectomy] and side of resection) were not associated with seizure outcome. No associations were found among the presurgical variables. Presurgical MRI was not associated with cross-sectional (OR=1.5, p=.557, 95% CI=0.4-5.7) or longitudinal (HR=1.2, p=.641, 95% CI=0.4-3.9) seizure outcome. Normal PET scan (OR= 4.8, p=.045, 95% CI=1.0-24.3) and IAT incorrectly lateralizing to seizure focus (OR=3.9, p=.018, 95% CI=1.2-12.9) were associated with higher odds of seizure recurrence. Furthermore, normal PET scan (HR=3.6, p=.028, 95% CI =1.0-13.5) and incorrectly lateralized IAT (HR= 2.8, p=.012, 95% CI=1.2-7.0) were presurgical predictors of earlier seizure recurrence within three years of TLE surgery. Log rank tests indicated that survival functions were significantly different between patients with normal vs. abnormal PET and incorrectly vs. correctly lateralizing IAT such that these had seizure relapse five and seven months earlier on average (respectively).

Presurgical normal PET scan and incorrectly lateralizing IAT were associated with increased risk of post-surgical seizure recurrence and shorter time-to-seizure relapse.

Methamphetamine and cannabis are two widely used substances with possibly opposing effects on aspects of central nervous system functioning. Use of these substances is prevalent among people with HIV (PWH), though their combined effects on HIV-associated neurocognitive impairment (NCI) are unknown. Adverse effects of methamphetamine use on cognition are well documented. Cannabis may disturb cognition acutely, though its longer-term effects in PWH are not well understood. Our prior analysis of people without HIV (PWoH) found that cotemporaneous cannabis use was associated with better neurocognitive outcomes among methamphetamine users. The aim of this study was to assess how lifetime cannabis and methamphetamine use disorder relate to neurocognitive outcomes in PWH.

HIV-positive participants (n=472) were on average 45.6±11.5 years of age, male (86.4%), White (60.6%), and educated 13.9±2.5 years. Most participants were on ART (81.9%) and virally suppressed (70%). Participants were stratified by lifetime methamphetamine (M-/M+) and cannabis (C-/C+) DSM-IV abuse/dependence disorder into four groups: M-C- (n=187), M-C+ (n=68), M+C-, (n=82) and M+C+ (n=135) and completed a comprehensive neurobehavioral assessment. Demographically corrected T-scores and deficit scores were used for analyses. Group differences in global and domain NC performances (i.e., T-scores) were examined using multiple linear regression, holding constant covariates that were associated with study groups and/or cognition. Specifically, M+ participants displayed higher rates of Hepatitis C infection (p=.004), higher current depressive symptom scores (p<.001), and higher rates of detectable plasma HIV RNA (p=.014). Multiple logistic regression was used to test for group differences in probability of neurocognitive impairment (i.e., deficit scores>0.5), including the same covariates. Pooling data with a sample of HIV-negative participants (n=423), we used generalized linear mixed effect models to examine how neurocognitive performance and impairment profiles varied by methamphetamine and/or cannabis use group, HIV disease characteristics, and their interactions.

Compared to M+C+, M+C- performed worse on measures of executive functions (ß=-3.17), learning (ß=-3.95), memory (ß=-5.58), and working memory (ß=-4.05) and were more likely to be classified as impaired in the learning (OR=2.93), memory (OR=5.24), and working memory (OR=2.48) domains. M-C- performed better than M+C+ on measures of learning (ß=3.46) and memory (ß=5.19), but worse than M-C+ on measures of executive functions (ß=-3.90), learning (ß=-3.32), memory (ß=-3.38), and working memory (ß=-3.38). Generalized linear mixed effect models indicate that detectable plasma HIV RNA (ß=-1.85) and low nadir CD4 T-cell counts (nadir CD4<200; ß=-1.07) were associated with worse neurocognitive performance, and these effects did not differ in size or direction by substance use group.

In PWH, lifetime methamphetamine use disorder and both current and legacy markers of HIV disease severity are associated with worse neurocognitive outcomes. Cannabis use disorder does not appear to exacerbate methamphetamine-related deficits in PWH. Instead, results are consistent with findings from preclinical studies that cannabis use may protect against methamphetamine’s deleterious effects. Profile analysis models showed that participants with a history of cannabis use disorder display better overall neurocognitive performance than comparison (M-C-) participants. Mechanisms underlying a potential protective effect of cannabis may be elucidated by examining the temporal relationship between cannabis and methamphetamine consumption and neurocognitive performance.

Many people with HIV (PWH) are at risk for age-related neurodegenerative disorders such as Alzheimer’s disease (AD). Studies on the association between cognition, neuroimaging outcomes, and the Apolipoprotein E4 (APOE4) genotype, which is associated with greater risk of AD, have yielded mixed results in PWH; however, many of these studies have examined a wide age range of PWH and have not examined APOE by race interactions that are observed in HIV-negative older adults. Thus, we examined how APOE status relates to cognition and medial temporal lobe (MTL) structures (implicated in AD pathogenesis) in mid- to older-aged PWH. In exploratory analyses, we also examined race (African American (AA)/Black and non-Hispanic (NH) White) by APOE status interactions on cognition and MTL structures.

The analysis included 88 PWH between the ages of 45 and 68 (mean age=51±5.9 years; 86% male; 51% AA/Black, 38% NH-White, 9% Hispanic/Latinx, 2% other) from the CNS HIV Antiretroviral Therapy Effects Research multi-site study. Participants underwent APOE genotyping, neuropsychological testing, and structural MRI; APOE groups were defined as APOE4+ (at least one APOE4 allele) and APOE4- (no APOE4 alleles). Eighty-nine percent of participants were on antiretroviral therapy, 74% had undetectable plasma HIV RNA (<50 copies/ml), and 25% were APOE4+ (32% AA/Black/15% NH-White). Neuropsychological testing assessed seven domains, and demographically-corrected T-scores were calculated. FreeSurfer 7.1.1 was used to measure MTL structures (hippocampal volume, entorhinal cortex thickness, and parahippocampal thickness) and the effect of scanner was regressed out prior to analyses. Multivariable linear regressions tested the association between APOE status and cognitive and imaging outcomes. Models examining cognition covaried for comorbid conditions and HIV disease characteristics related to global cognition (i.e., AIDS status, lifetime methamphetamine use disorder). Models examining the MTL covaried for age, sex, and

relevant imaging covariates (i.e., intracranial volume or mean cortical thickness).

APOE4+ carriers had worse learning (ß=-0.27, p=.01) and delayed recall (ß=-0.25, p=.02) compared to the APOE4- group, but APOE status was not significantly associated with any other domain (ps>0.24). APOE4+ status was also associated with thinner entorhinal cortex (ß=-0.24, p=.02). APOE status was not significantly associated with hippocampal volume (ß=-0.08, p=0.32) or parahippocampal thickness (ß=-0.18, p=.08). Lastly, race interacted with APOE status such that the negative association between APOE4+ status and cognition was stronger in NH-White PWH as compared to AA/Black PWH in learning, delayed recall, and verbal fluency (ps<0.05). There were no APOE by race interactions for any MTL structures (ps>0.10).

Findings suggest that APOE4 carrier status is associated with worse episodic memory and thinner entorhinal cortex in mid- to older-aged PWH. While APOE4+ groups were small, we found that APOE4 carrier status had a larger association with cognition in NH-White PWH as compared to AA/Black PWH, consistent with studies demonstrating an attenuated effect of APOE4 in older AA/Black HIV-negative older adults. These findings further highlight the importance of recruiting diverse samples and suggest exploring other genetic markers (e.g., ABCA7) that may be more predictive of AD in some races to better understand AD risk in diverse groups of PWH.

Patients with Parkinson’s disease (PD) commonly show deficits on tests of visuospatial functioning. The Identi-Fi is a new measure of visual organization and recognition composed of two components. The Visual Recognition (VR) subtest asks persons to identify an object that has been broken its pieces and rearranged, akin to the Hooper Visual Organization Test, but using updated and colorful pictures. The Visual Matching (VM) subtest involves showing the same stimuli, but the examinee must select the correct response from among five choices (1 correct and 4 foils), placing greater demand on visuospatial discrimination. Together, the two subtests comprise the Visual Organization Index (VOI), reflecting overall visual processing and organization ability. The present study examined performance on the Identi-Fi in patients with PD and its association with other aspects of cognition.

Participants were 23 patients with PD (95% male; mean age = 69.7 years [SD = 7.8], range = 47-79) and 12 patients with cognitive concerns (CC) who were intact on neuropsychological testing (excluding consideration of Identi-Fi scores; 50% male, mean age = 71.08 [SD = 6.27], range = 60-78) seen for a neuropsychological evaluation at a large Northeastern medical center. As part of a larger battery, patients completed the Identi-Fi, Trail Making Test (TMT), Category Fluency, Test of Premorbid Functioning (TOPF), and Brief Visuospatial Memory Test, Revised (BVMT-R).

The PD group performed significantly worse than the CC group on VR and VM, as well as VOI, of the Identi-Fi (p < .001). Within the PD group, poorer VR, VM, and VOI performance was associated with lower scores on the TOPF (p < .05), BVMT-R learning (p < .05) and delayed recall (p < .05), as well as TMT Parts A and B (p < .05). VR was significantly correlated with Category Fluency (p < .05), while a trend was seen for the association between VOI and Category Fluency (p = .094).

Identi-Fi performance was worse in the PD group than the CC group, which is consistent with prior research indicating that visuospatial processing is often abnormal in patients with PD. Furthermore, findings indicate that poorer performance on the Identi-Fi in the PD group is associated with poorer cognitive functioning in other domains (i.e., visuospatial learning and memory, processing speed, cognitive flexibility, and semantic fluency), as well as lower premorbid intellectual functioning. While these findings suggest that the Identi-Fi is useful in identifying visuospatial dysfunction in PD, findings should be interpreted with caution given the small sample sizes and uneven gender distribution

Although some animal research suggests possible sex differences in response to THC exposure (e.g., Cooper & Craft, 2018), there are limited human studies. One study found that among individuals rarely using cannabis, when given similar amounts of oral and vaporized THC females report greater subjective intoxication compared to males (Sholler et al., 2020). However, in a study of daily users, females reported indistinguishable levels of intoxication compared to males after smoking similar amounts (Cooper & Haney, 2014), while males and females using 1–4x/week showed similar levels of intoxication, despite females having lower blood THC and metabolite concentrations (Matheson et al., 2020). It is important to elucidate sex differences in biological indicators of cannabis intoxication given potential driving/workplace implications as states increasingly legalize use. The current study examined if when closely matching males and females on cannabis use variables there are predictable sex differences in residual whole blood THC and metabolite concentrations, and THC/metabolites, subjective appraisals of intoxication, and driving performance following acute cannabis consumption.

The current study was part of a randomized clinical trial (Marcotte et al., 2022). Participants smoked ad libitum THC cigarettes and then completed driving simulations, blood draws, and subjective measures of intoxication. The main outcomes were the change in Composite Drive Score (CDS; global measure of driving performance) from baseline, whole blood THC, 11-OH-THC, and THC-COOH levels (ng/mL), and subjective ratings of how “high” participants felt (0 = not at all, 100 = extremely). For this analysis of participants receiving active THC, males were matched to females on 1) estimated THC exposure (g) in the last 6 months (24M, 24F) or 2) whole blood THC concentrations immediately post-smoking (23M, 23F).

When matched on THC exposure in the past 6 months (overall mean of 46 grams; p = .99), there were no sex differences in any cannabinoid/metabolite concentrations at baseline (all p > .83) or after cannabis administration (all p > .72). Nor were there differences in the change in CDS from pre-to-post-smoking (p = .26) or subjective “highness” ratings (p = .53). When matched on whole blood THC concentrations immediately after smoking (mean of 34 ng/mL for both sexes, p = .99), no differences were found in CDS change from pre-to-post smoking (p = .81), THC metabolite concentrations (all p > .25), or subjective “highness” ratings (p = .56). For both analyses, males and females did not differ in BMI (both p > .7).

When male/female cannabis users are well-matched on use history, we find no significant differences in cannabinoid concentrations following a mean of 5 days of abstinence, suggesting that there are no clear biological differences in carryover residual effects. We also find no significant sex differences following ad libitum smoking in driving performance, subjective ratings of “highness,” nor whole blood THC and metabolite concentrations, indicating that there are no biological differences in acute response to THC. This improves upon previous research by closely matching participants over a wider range of use intensity variables, although the small sample size precludes definitive conclusions.

Patients with Post-Acute COVID Syndrome (PACS) are reported to commonly experience a variety of cognitive, physical, and neuropsychiatric symptoms well beyond the acute phase of the illness. Notably, concerns involving mood, fatigue, and physical symptoms (e.g., pain, headaches) following COVID-19 appears to be especially prevalent. It is unclear, however, the extent to which such symptoms are associated with cognitive problems in patients with PACS. In the present study, we examined the prevalence of cognitive impairment in a sample of patients with PACS, as well as the relationship between cognitive functioning and several non-cognitive symptoms.

Participants were 38 patients with PACS [71.1% female; mean age = 48.03 years (SD = 11.60) and years of education = 15.26 years (SD = 2.60)] seen for a neuropsychological evaluation at a large Northeastern medical center at least three months from the time of COVID-19 diagnosis (per PCR test). As part of a larger battery, patients completed the Hopkins Verbal Learning Test- Revised (HVLT, learning and delayed recall), Trail Making Test (TMT; time to complete parts A and B), Controlled Oral Word Association Test (COWAT total correct), and Animals (total correct). They also were administered the Chalder Fatigue Scale-11 (CFS-11), Beck Depression Inventory-II (BDI-II), Beck Anxiety Inventory (BAI), and Patient Health Questionnaire (PHQ-15). The percentage of patients with scores in the impaired range (z < -1.5) on cognitive tests was determined. Correlations between cognitive and non-cognitive measures were also examined.

The most frequent impairment was seen for COWAT (21.2%), followed by TMT-A and TMT-B (both 13.9%), then category fluency (9.1%). No patients were impaired on HVLT-R Learning and only one (4%) for HVLT-R Delayed Recall. Overall, the sample endorsed considerable depression, anxiety, fatigue, as well as physical symptoms. Greater fatigue was associated with worse verbal learning, processing speed, cognitive flexibility, and verbal fluency (letter and category). Worse physical symptom severity was related to poorer verbal delayed recall and cognitive flexibility. Greater anxiety was also associated with worse cognitive flexibility, while more severe depression was related to poorer category fluency.

In our sample of patients with PACS, seen for evaluation several months since contracting COVID-19, phonemic fluency was the most common cognitive impairment, though less than a quarter were impaired on any given cognitive test. Importantly, several associations were observed between cognitive test performance and non-cognitive symptoms commonly endorsed by patients with PACS. These findings highlight the importance of assessing multiple factors potentially contributing to cognitive impairment in these patients. Interventions designed to address such symptoms may be helpful in ameliorating cognitive functioning in those with PACS.

Mild cognitive impairment (MCI) is characterized by subjective and objective memory concerns, though additional cognitive concerns are commonly reported, including changes in executive functions (EF). Rabin et al. (2006) showed that a sample of research participants with MCI endorsed problems with their EFs, especially working memory. Similarly, those with subjective cognitive dysfunction (SCD) also reported greater difficulty with aspects of their EF than a healthy comparison sample of older adults (HC). In the present study, we investigated subjective EF in clinical samples of older adults with MCI or SCD, which represents a more naturalistic sample relative to a research sample. Furthermore, we evaluated whether subjective EF varied in these groups depending on whether patients were "young-old" versus "old-old" given prior research indicating objective cognitive differences between these age groups.

Participants were 135 older adults (53 MCI, 52 SCD, and 30 HC) matched for age (p = .116) and education (p = .863). Dichotomous categorization of age used the sample median (72 years) as cutoff score with 72 participants in the young-old group (mean age = 65.8 ± 4.7 years) and 63 in the old-old group (mean age = 78.1 ± 3.7 years). Participants completed the Behavior Rating Inventory of Executive Function-Adult (BRIEF-A), assessing executive functions in everyday life over the past month. The BRIEF-A yields an overall score (Global Executive Composite [GEC]) composed of two index scores (Behavioral Regulation Index [BRI] and Metacognition Index [MI]) and nine clinical scales (Inhibit, Shift, Emotional Control, Self-Monitor, Initiate, Working Memory, Plan/Organize, Task Monitor, and Organization of Materials). A diagnosis by age-group multivariate analysis of variance (MANOVA) with post-hoc comparisons for diagnosis using a Tukey HSD correction was conducted using SPSS Version 24.

MCI and SCD groups endorsed worse EF on all three index scores (ps < .005) and all nine clinical scales (ps < .05) relative to the HC group, and the MCI group reported worse initiation relative to the SCD group. Additionally, worse executive functions on all three index scores (ps < .05) and four clinical scales (ps < .05; emotional control, self-monitoring, planning/organization, and task monitoring) were reported by the young-old group relative to the old-old group. No diagnosis by age-group interactions were observed.

Problems with aspects of EF were endorsed by older adults with MCI and SCD compared to HCs across all indices and clinical scales; however, only initiation was reported to be worse in MCI than those with SCD. Additionally, the young-old group endorsed having worse EF than the old-old group across BRIEF-A indices and several more specific aspects of EF, without a moderating effect of diagnosis. These findings highlight the importance of assessing subjective EF in older adults, as they may be early indicators of cognitive change, prior to objective evidence of cognitive decline. Furthermore, results also point to differences in how the young-old and old-old perceive their EF in everyday life.

Methamphetamine and cannabis are two widely used, and frequently co-used, substances with possibly opposing effects on the central nervous system. Evidence of neurocognitive deficits related to use is robust for methamphetamine and mixed for cannabis. Findings regarding their combined use are inconclusive. We aimed to compare neurocognitive performance in people with lifetime cannabis or methamphetamine use disorder diagnoses, or both, relative to people without substance use disorders.

423 (71.9% male, aged 44.6 ± 14.2 years) participants, stratified by presence or absence of lifetime methamphetamine (M−/M+) and/or cannabis (C−/C+) DSM-IV abuse/dependence, completed a comprehensive neuropsychological, substance use, and psychiatric assessment. Neurocognitive domain T-scores and impairment rates were examined using multiple linear and binomial regression, respectively, controlling for covariates that may impact cognition.

Globally, M+C+ performed worse than M−C− but better than M+C−. M+C+ outperformed M+C− on measures of verbal fluency, information processing speed, learning, memory, and working memory. M−C+ did not display lower performance than M−C− globally or on any domain measures, and M−C+ even performed better than M−C− on measures of learning, memory, and working memory.

Our findings are consistent with prior work showing that methamphetamine use confers risk for worse neurocognitive outcomes, and that cannabis use does not appear to exacerbate and may even reduce this risk. People with a history of cannabis use disorders performed similarly to our nonsubstance using comparison group and outperformed them in some domains. These findings warrant further investigation as to whether cannabis use may ameliorate methamphetamine neurotoxicity.

Recent cannabis exposure has been associated with lower rates of neurocognitive impairment in people with HIV (PWH). Cannabis’s anti-inflammatory properties may underlie this relationship by reducing chronic neuroinflammation in PWH. This study examined relations between cannabis use and inflammatory biomarkers in cerebrospinal fluid (CSF) and plasma, and cognitive correlates of these biomarkers within a community-based sample of PWH.

263 individuals were categorized into four groups: HIV− non-cannabis users (n = 65), HIV+ non-cannabis users (n = 105), HIV+ moderate cannabis users (n = 62), and HIV+ daily cannabis users (n = 31). Differences in pro-inflammatory biomarkers (IL-6, MCP-1/CCL2, IP-10/CXCL10, sCD14, sTNFR-II, TNF-α) by study group were determined by Kruskal–Wallis tests. Multivariable linear regressions examined relationships between biomarkers and seven cognitive domains, adjusting for age, sex/gender, race, education, and current CD4 count.

HIV+ daily cannabis users showed lower MCP-1 and IP-10 levels in CSF compared to HIV+ non-cannabis users (p = .015; p = .039) and were similar to HIV− non-cannabis users. Plasma biomarkers showed no differences by cannabis use. Among PWH, lower CSF MCP-1 and lower CSF IP-10 were associated with better learning performance (all ps < .05).

Current daily cannabis use was associated with lower levels of pro-inflammatory chemokines implicated in HIV pathogenesis and these chemokines were linked to the cognitive domain of learning which is commonly impaired in PWH. Cannabinoid-related reductions of MCP-1 and IP-10, if confirmed, suggest a role for medicinal cannabis in the mitigation of persistent inflammation and cognitive impacts of HIV.

Frascati international research criteria for HIV-associated neurocognitive disorders (HAND) are controversial; some investigators have argued that Frascati criteria are too liberal, resulting in a high false positive rate. Meyer et al. recommended more conservative revisions to HAND criteria, including exploring other commonly used methodologies for neurocognitive impairment (NCI) in HIV including the global deficit score (GDS). This study compares NCI classifications by Frascati, Meyer, and GDS methods, in relation to neuroimaging markers of brain integrity in HIV.

Two hundred forty-one people living with HIV (PLWH) without current substance use disorder or severe (confounding) comorbid conditions underwent comprehensive neurocognitive testing and brain structural magnetic resonance imaging and magnetic resonance spectroscopy. Participants were classified using Frascati criteria versus Meyer criteria: concordant unimpaired [Frascati(Un)/Meyer(Un)], concordant impaired [Frascati(Imp)/Meyer(Imp)], or discordant [Frascati(Imp)/Meyer(Un)] which were impaired via Frascati criteria but unimpaired via Meyer criteria. To investigate the GDS versus Meyer criteria, the same groupings were utilized using GDS criteria instead of Frascati criteria.

When examining Frascati versus Meyer criteria, discordant Frascati(Imp)/Meyer(Un) individuals had less cortical gray matter, greater sulcal cerebrospinal fluid volume, and greater evidence of neuroinflammation (i.e., choline) than concordant Frascati(Un)/Meyer(Un) individuals. GDS versus Meyer comparisons indicated that discordant GDS(Imp)/Meyer(Un) individuals had less cortical gray matter and lower levels of energy metabolism (i.e., creatine) than concordant GDS(Un)/Meyer(Un) individuals. In both sets of analyses, the discordant group did not differ from the concordant impaired group on any neuroimaging measure.

The Meyer criteria failed to capture a substantial portion of PLWH with brain abnormalities. These findings support continued use of Frascati or GDS criteria to detect HIV-associated CNS dysfunction.