Identifying persons with HIV (PWH) at increased risk for Alzheimer’s disease (AD) is complicated because memory deficits are common in HIV-associated neurocognitive disorders (HAND) and a defining feature of amnestic mild cognitive impairment (aMCI; a precursor to AD). Recognition memory deficits may be useful in differentiating these etiologies. Therefore, neuroimaging correlates of different memory deficits (i.e., recall, recognition) and their longitudinal trajectories in PWH were examined.

We examined 92 PWH from the CHARTER Program, ages 45–68, without severe comorbid conditions, who received baseline structural MRI and baseline and longitudinal neuropsychological testing. Linear and logistic regression examined neuroanatomical correlates (i.e., cortical thickness and volumes of regions associated with HAND and/or AD) of memory performance at baseline and multilevel modeling examined neuroanatomical correlates of memory decline (average follow-up = 6.5 years).

At baseline, thinner pars opercularis cortex was associated with impaired recognition (p = 0.012; p = 0.060 after correcting for multiple comparisons). Worse delayed recall was associated with thinner pars opercularis (p = 0.001) and thinner rostral middle frontal cortex (p = 0.006) cross sectionally even after correcting for multiple comparisons. Delayed recall and recognition were not associated with medial temporal lobe (MTL), basal ganglia, or other prefrontal structures. Recognition impairment was variable over time, and there was little decline in delayed recall. Baseline MTL and prefrontal structures were not associated with delayed recall.

Episodic memory was associated with prefrontal structures, and MTL and prefrontal structures did not predict memory decline. There was relative stability in memory over time. Findings suggest that episodic memory is more related to frontal structures, rather than encroaching AD pathology, in middle-aged PWH. Additional research should clarify if recognition is useful clinically to differentiate aMCI and HAND.

Family involvement in the lives of people who have dementia and live in long-term care is important, but family members may face challenges communicating and connecting with their loved one as dementia progresses. A type of therapeutic humor (Laughter Care) delivered by trained specialists aims to engage people with dementia who reside in long-term care through creative play and laughter. This study aimed to explore the perceptions of Laughter Care Specialists (LCSs) regarding families’ engagement with the program.

Semi-structured interviews were conducted with LCSs (n = 8) and analyzed inductively using thematic analysis.

Family members were reported to initially have varied degrees of openness toward Laughter Care, but often become more accepting after observing positive engagement with the person with dementia. Family members were perceived to benefit from the program through witnessing the person with dementia enjoy joyous and light interactions, learn new ways of communicating and connecting with the person with dementia, and engage in positive interactions at end of life.

Laughter Care may provide family members with novel ways of communicating and connecting with people who have dementia at end of life as well as comfort into bereavement.

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.

Functional near-infrared spectroscopy (fNIRS) is a non-invasive functional neuroimaging method that takes advantage of the optical properties of hemoglobin to provide an indirect measure of brain activation via task-related relative changes in oxygenated hemoglobin (HbO). Its advantage over fMRI is that fNIRS is portable and can be used while walking and talking. In this study, we used fNIRS to measure brain activity in prefrontal and motor region of interests (ROIs) during single- and dual-task walking, with the goal of identifying neural correlates.

Nineteen healthy young adults [mean age=25.4 (SD=4.6) years; 14 female] engaged in five tasks: standing single-task cognition (serial-3 subtraction); single-task walking at a self-selected comfortable speed on a 24.5m oval-shaped course (overground walking) and on a treadmill; and dual-task cognition+walking on the same overground course and treadmill (8 trials/condition: 20 seconds standing rest, 30 seconds task). Performance on the cognitive task was quantified as the number of correct subtractions, number of incorrect subtractions, number of self-corrected errors, and percent accuracy over the 8 trials. Walking speed (m/sec) was recorded for all walking conditions. fNIRS data were collected on a system consisting of 16 sources, 15 detectors, and 8 short-separation detectors in the following ROIs: right and left lateral frontal (RLF, LLF), right and left medial frontal (RMF, LMF), right and left medial superior frontal (RMSF, LMSF), and right and left motor (RM, LM). Lateral and medial refer to ROIs’ relative positions on lateral prefrontal cortex. fNIRS data were analyzed in Homer3 using a spline motion correction and the iterative weighted least squares method in the general linear model. Correlations between the cognitive/speed variables and ROI HbO data were applied using a Bonferroni adjustment for multiple comparisons.

Subjects with missing cognitive data were excluded from analyses, resulting in sample sizes of 18 for the single-task cognition, dual-task overground walking, and dual-task treadmill walking conditions. During dual-task overground walking, there was a significant positive correlation between walking speed and relative change in HbO in RMSF [r(18)=.51, p<.05] and RM [r(18)=.53, p<.05)]. There was a significant negative correlation between total number of correct subtractions and relative change in HbO in LMSF ([r(18)=-.75, p<.05] and LM [r(18)=-.52, p<.05] during dual-task overground walking. No other significant correlations were identified.

These results indicate that there is lateralization of the cognitive and motor components of overground dual-task walking. The right hemisphere appears to be more active the faster people walk during the dual-task. By contrast, the left hemisphere appears to be less active when people are working faster on the cognitive task (i.e., serial-3 subtraction). The latter results suggest that automaticity of the cognitive task (i.e., more total correct subtractions) is related to decreased brain activity in the left hemisphere. Future research will investigate whether there is a change in cognitive automaticity over trials and if there are changes in lateralization patterns in neurodegenerative disorders that are known to differentially affect the hemispheres (e.g., Parkinson’s disease).

Limited data is available on the prognosis of patients with FND concerning their ability to return to work.

To identify factors associated with the ability to return to work in patients with FND following treatment and rehabilitation.

We retrospectively assessed the employment outcomes of 79 consecutively evaluated patients. Patients were referred at the inception of an FND Program for adults. The majority of patients were unemployed, on sickness leave and or disability benefits at the time of their referral (n=71). Their median age was 48 years. Most patients were of female gender (n=50), in a relationship (n=53), with no dependants (n=64). Most patients had a referral diagnosis of mixed functional neurological symptoms (n=35), presenting with a combination of motor, sensory, cogniform or dissociative seizure symptoms. Among patients distinct phenomenological presentations, the most common referral diagnosis was functional sensory disorder (n=16). Twenty two patients had a concurrent structural neurological disorder. Seven patients had an accident compensation claim, and twenty had a workers’ compensation or employment insurance claim at the time of referral.

Approximately 30 % of patients were able to return to some work (n=24) within five years or less, and all those who were in employment at the time of the referral continued to hold a job for the duration of their treatment. We identified a negative correlation between patients’ ability to return to work and the length of employment interruption, with patients more recently out of work (within a year prior to the referral) being most able to return to work (odds ratio = 2; 95% CI, 1.2 to 3.8). We previously analyzed employment figures at 18 months of the service operation. Return to work was moderately lower at that point at 19%, but with maintained negative correlation with the length of employment interruption.

There was a negative correlation between having a work-related financial claim and the ability to return to work (p <0.001). There was no statistically significant correlation between demographic variables (gender, age, relationship status, or having dependants) and the ability to return to work, nor was there a statistically significant correlation between the phenomenology of Functional Neurological Disorder (motor, sensory, cogniform, non-epileptic attack disorder or mixed) and the ability to return to work.

Early and continuous treatment of employed or recently unemployed patients with Functional Neurological Disorder is associated with better occupational outcomes. Having a work-related compensation claim is correlated with negative occupational outcomes. There is a need for further research into occupational rehabilitation, specially for patients receiving work-related compensation claim.

None Declared

To evaluate the potential superiority of donanemab vs. aducanumab on the percentage of participants with amyloid plaque clearance (≤24.1 Centiloids [CL]) at 6 months in patients with early symptomatic Alzheimer's disease (AD) in phase 3 TRAILBLAZER-ALZ-4 study. The amyloid cascade in AD involves the production and deposition of amyloid beta (Aβ) as an early and necessary event in the pathogenesis of AD.

Participants (n = 148) were randomized 1:1 to receive donanemab (700 mg IV Q4W [first 3 doses], then 1400 mg IV Q4W [subsequent doses]) or aducanumab (per USPI: 1 mg/kg IV Q4W [first 2 doses], 3 mg/kg IV Q4W [next 2 doses], 6 mg/kg IV Q4W [next 2 doses] and 10 mg/kg IV Q4W [subsequent doses]).

Baseline demographics and characteristics were well-balanced across treatment arms (donanemab [N = 71], aducanumab [N = 69]). Twenty-seven donanemab-treated and 28 aducanumab-treated participants defined as having intermediate tau.

Upon assessment of florbetapir F18 PET scans (6 months), 37.9% donanemab-treated vs. 1.6% aducanumab-treated participants achieved amyloid clearance (p < 0.001). In the intermediate tau subpopulation, 38.5% donanemab-treated vs. 3.8% aducanumab-treated participants achieved amyloid clearance (p = 0.008).

Percent change in brain amyloid levels were −65.2%±3.9% (baseline: 98.29 ± 27.83 CL) and −17.0%±4.0% (baseline: 102.40 ± 35.49 CL) in donanemab and aducanumab arms, respectively (p < 0.001). In the intermediate tau subpopulation, percent change in brain amyloid levels were −63.9%±7.4% (baseline: 104.97 ± 25.68 CL) and −25.4%±7.8% (baseline: 102.23 ± 28.13 CL) in donanemab and aducanumab arms, respectively (p ≤ 0.001).

62.0% of donanemab-treated and 66.7% of aducanumab-treated participants reported an adverse event (AE), there were no serious AEs due to ARIA in donanemab arm and 1.4% serious AEs (one event) due to ARIA were reported in aducanumab arm.

This study provides the first active comparator data on amyloid plaque clearance in patients with early symptomatic AD. Significantly higher number of participants reached amyloid clearance and amyloid plaque reductions with donanemab vs. aducanumab at 6 months.

Previously presented at the Clinical Trials on Alzheimer's Disease - 15th Conference, 2022.

Emotional functioning is linked to HIV-associated neurocognitive impairment, yet research on this association among diverse people with HIV (PWH) is scant. We examined emotional health and its association with neurocognition in Hispanic and White PWH.

Participants included 107 Hispanic (41% primarily Spanish-speakers; 80% Mexican heritage/origin) and 216 White PWH (Overall age: M = 53.62, SD = 12.19; 86% male; 63% AIDS; 92% on antiretroviral therapy). Emotional health was assessed via the National Institute of Health Toolbox (NIHTB)-Emotion Battery, which yields T-scores for three factor-based summary scores (negative affect, social satisfaction, and psychological well-being) and 13 individual component scales. Neurocognition was measured via demographically adjusted fluid cognition T-scores from the NIHTB-cognition battery.

27%–39% of the sample had problematic socioemotional summary scores. Hispanic PWH showed less loneliness, better social satisfaction, higher meaning and purpose, and better psychological well-being than Whites (ps <.05). Within Hispanics, Spanish-speakers showed better meaning and purpose, higher psychological well-being summary score, less anger hostility, but greater fear affect than English speakers. Only in Whites, worse negative affect (fear affect, perceived stress, and sadness) was associated with worse neurocognition (p <.05); and in both groups, worse social satisfaction (emotional support, friendship, and perceived rejection) was linked with worse neurocognition (p <.05).

Adverse emotional health is common among PWH, with subgroups of Hispanics showing relative strengths in some domains. Aspects of emotional health differentially relate to neurocogntition among PWH and cross-culturally. Understanding these varying associations is an important step towards the development of culturally relevant interventions that promote neurocognitive health among Hispanic PWH.