Validity of Digital Assessments in Screening for HIV-Related Cognitive Impairment: a Review.

Purpose of reviewWhile traditional neuropsychological tests are the gold standard in screening for HIV-related cognitive impairment, computerized neuropsychological assessment devices (CNADs) offer an alternative to these time- and resource-intensive batteries and may prove to be particularly useful for remote assessments or longitudinal monitoring. This review seeks to describe the benefits, limitations, and validity of CNADs in the evaluation of HIV-associated neurocognitive disorder (HAND).Recent findingsWe identified eight CNADs that have undergone validity testing for cognitive impairment in the setting of HIV. Included among these are batteries that have been modeled after the traditional neuropsychological exam, as well as others that implement new technologies, such as simulated reality and daily ecological assessments in their testing. Currently, these digital batteries do not yet have the ability to supplant gold standard neuropsychological tests in screening for HAND. However, many have the potential to become effective clinical screening tools

Caregiving for Patients With Frontotemporal Dementia in Latin America

Latin America is a vast heterogeneous territory where chronic diseases such as mild cognitive impairment or dementia are becoming higher. Frontotemporal dementia (FTD) prevalence in this region is estimated to be around 12-18 cases per thousand persons. However, this prevalence is underestimated given the lack of awareness of FTD even among healthcare professionals. Family members are responsible for the care of patients with FTD at home. These caregivers deliver care despite being ill-equipped and living in the context of austerity policies and social inequities. They often face unsurmountable financial and social burdens that are specific to the region. The most important step to support caregivers in Latin America is to increase awareness of the disease at all levels. Healthcare diplomacy is fundamental to create joint efforts that push policies forward to protect caregivers of FTD patients

Longitudinal brain atrophy patterns and neuropsychological performance in older adults with HIV-associated neurocognitive disorder compared with early Alzheimer's disease

Older HIV-infected patients are at risk for both HIV-associated neurocognitive disorder (HAND) and Alzheimer's disease. We investigated neuroimaging and neuropsychological performance of 61 virally suppressed older adults with HAND (mean (SD) age 64.3 (3.9) years), 53 demographically matched individuals with mild cognitive impairment of the Alzheimer's type (MCI-AD; 65.0 [4.8]), and 89 healthy controls (65.0 [4.3]) cross-sectionally and over 20 months. At the baseline, both disease groups exhibited lower volumes in multiple cortical and subcortical regions compared with controls. Hippocampal volume differentiated MCI-AD from HAND. Cognitively, MCI-AD performed worse on memory and language compared with HAND. Adjusted longitudinal models revealed greater diffuse brain atrophy in MCI-AD compared with controls, whereas HAND showed greater atrophy in frontal gray matter and cerebellum compared with controls. Comparing HAND with MCI-AD showed similar atrophy rates in all brain regions explored, with no significant findings. MCI-AD exhibited more pronounced language decline compared with HAND. These findings reveal the need for further work on unique cognitive phenotypes and neuroimaging signatures of HAND compared with early AD, providing preliminary clinical insight for differential diagnosis of age-related brain dysfunction in geriatric neuroHIV

Geriatric Syndromes in Older Adults Living with HIV and Cognitive Impairment

ObjectivesNearly half of the population living with human immunodeficiency virus (HIV) in the United States is now older than 50 years with at least 6% over age 65. Between 35% and 50% live with mild to moderate cognitive impairment. Older persons living with HIV (PLWH) also have a substantial burden of HIV-associated non-acquired immunodeficiency syndrome medical conditions and are at risk for frailty, geriatric syndromes, and early mortality compared with HIV-uninfected peers. We sought to define the magnitude of geriatric conditions and multimorbidity in PLWH older than 60 years who are living with symptomatic cognitive impairment. In a subset of participants, we examined associations between these geriatric conditions.DesignRetrospective cohort study.SettingHIV Elders Study at the University of California, San Francisco, Memory and Aging Center.ParticipantsParticipants were HIV infected, virally suppressed, 60 years or older, and clinically diagnosed with mild neurocognitive disorder (MND).MeasurementsWe conducted standardized assessment of geriatric conditions and everyday function and investigated multimorbidity burden using the Veterans Aging Cohort Study (VACS) index.ResultsAmong 141 older PLWH with MND, 58% report incontinence, 55% meet criteria for pre-frailty, and a substantial proportion report dependence with instrumental activities of daily living (52%) or activities of daily living (41%). The mean VACS index score is 33 (standard deviation = 14), suggesting a 13.8% 5-year all-cause mortality risk.ConclusionsOlder PLWH with symptomatic cognitive impairment carry a substantial burden of other geriatric conditions. Our work supports the need for comprehensive geriatric systems of care for cognitively impaired individuals aging with HIV. J Am Geriatr Soc 67:1913-1916, 2019

A neuropathologic diagnosis of Alzheimer's disease in an older adult with HIV-associated neurocognitive disorder.

We discuss the challenges associated with diagnosing neurodegenerative disorders in older adults living with HIV, illustrated through a case report where neurologic co-diagnosis of Alzheimer's disease (AD) and HIV-associated Neurocognitive Disorder (HAND) are considered. The patient was followed and evaluated for over 4 years and underwent post-mortem neuropathologic evaluation. Further work is needed to identify diagnostic tests that can adequately distinguish HAND from early stage neurodegenerative disorders among older adults living with HIV and cognitive changes

Associations Between Plasma Immunomodulatory and Inflammatory Mediators With VACS Index Scores Among Older HIV-Infected Adults on Antiretroviral Therapy.

The prevalence of age-related comorbidities is increased in people living with HIV, even in those well-controlled on combination antiretroviral therapy (ART). Persistent immune activation and inflammation may play pivotal roles in the pathogenesis; however, the burden of morbidities in the older HIV infected population may be exacerbated and driven by distinct mechanisms. In a cross sectional study of 45 HIV-infected participants 60 years or older, we examined the relationships between 14 immunomodulatory and inflammatory factors and the Veterans Aging Cohort Study (VACS) Index, a metric of multimorbidity and mortality comprised of age, CD4 count, hemoglobin, Fibrosis-4 [FIB-4], and estimated glomerular filtration rate [eGFR], by linear regression analysis. All participants were virally suppressed (<50 HIV RNA copies/mL), on ART, and primarily Caucasian (86.7%), and male (91.1%). Plasma levels of monocyte/macrophage-associated (neopterin, IP-10, sCD163, sCD14, and MCP-1) and glycan-binding immunomodulatory factors (galectin (Gal)-1, Gal-3, and Gal-9) were assessed, as well as inflammatory biomarkers previously linked to the VACS Index (i.e., CRP, cystatin C, TNF-α, TNFRI, IL-6, and D-dimer) for comparison. In regression analysis, higher VACS index scores were associated with higher levels of neopterin, cystatin C, TNFRI, and Gal-9 (all p < 0.05), potentially driven by correlations found with individual VACS components, including age, CD4 count, FIB-4, and eGFR. Gal-9, cystatin C, and TNFRI directly correlated with the extent of multimorbidity. Multiple correlations among markers were observed, suggesting an interplay of overlapping, but distinct, pathways. Collectively, in addition to cystatin C and TNFRI, both galectin-9 and neopterin, independently emerged as novel fluid markers of the VACS Index and burden of comorbidity and may further guide in understanding pathogenic mechanisms of age-related disorders in older HIV-infected individuals on suppressive ART

Plasma inflammatory biomarkers link to diffusion tensor imaging metrics in virally suppressed HIV-infected individuals.

ObjectiveInflammation may contribute to brain white matter health in people living with HIV who report cognitive symptoms despite adherence to combination antiretroviral therapy and viral suppression. We explored relationships between diffusion tensor imaging (DTI) metrics of white matter, plasma biomarkers of immune activation, and cognitive function in the HIV-infected population.DesignRetrospective study of older adults living with HIV who are combination antiretroviral therapy adherent, virally suppressed, and self-report cognitive symptoms.MethodsMRI, blood draws, and standardized neuropsychological test scores were collected from HIV-infected individuals. DTI metrics (fractional anisotropy, mean diffusivity, radial diffusivity, axial diffusivity) and plasma biomarkers (soluble CD163, soluble CD14, neopterin, IFN γ-induced protein 10, monocyte chemoattractant protein 1) were quantified. Statistical analysis explored associations between biomarker levels or neuropsychological test scores and DTI metrics using region of interest analyses and a voxelwise approach.ResultsA total of 43 participants with median (interquartile range) age of 64 (62-66 years), CD4 cell count of 600 (400-760 cell/μl) who were all virally suppressed (<100 copies/ml) were selected. Higher levels of monocyte chemoattractant protein 1 associated with lower fractional anisotropy and higher mean diffusivity (P < 0.05) across white matter tracts including corpus callosum, corona radiata, and superior longitudinal fasciculus. Higher neopterin associated with higher mean diffusivity in the genu of corpus callosum, and higher soluble CD14 associated with lower fractional anisotropy in the bilateral superior corona radiata (P < 0.05). Worse global performance and speed domain scores associated with higher mean diffusivity and lower fractional anisotropy, and worse executive domain scores associated with lower fractional anisotropy (P < 0.05).ConclusionElevated inflammatory plasma biomarkers link to white matter abnormalities among virally suppressed individuals. DTI abnormalities associate to cognitive performance. We conclude that inflammatory processes impact clinically relevant brain health indices despite viral suppression

Classification of Alzheimer's disease and frontotemporal dementia using routine clinical and cognitive measures across multicentric underrepresented samples: a cross sectional observational studyResearch in context

Summary: Background: Global brain health initiatives call for improving methods for the diagnosis of Alzheimer's disease (AD) and frontotemporal dementia (FTD) in underrepresented populations. However, diagnostic procedures in upper-middle-income countries (UMICs) and lower-middle income countries (LMICs), such as Latin American countries (LAC), face multiple challenges. These include the heterogeneity in diagnostic methods, lack of clinical harmonisation, and limited access to biomarkers. Methods: This cross-sectional observational study aimed to identify the best combination of predictors to discriminate between AD and FTD using demographic, clinical and cognitive data among 1794 participants [904 diagnosed with AD, 282 diagnosed with FTD, and 606 healthy controls (HCs)] collected in 11 clinical centres across five LAC (ReDLat cohort). Findings: A fully automated computational approach included classical statistical methods, support vector machine procedures, and machine learning techniques (random forest and sequential feature selection procedures). Results demonstrated an accurate classification of patients with AD and FTD and HCs. A machine learning model produced the best values to differentiate AD from FTD patients with an accuracy = 0.91. The top features included social cognition, neuropsychiatric symptoms, executive functioning performance, and cognitive screening; with secondary contributions from age, educational attainment, and sex. Interpretation: Results demonstrate that data-driven techniques applied in archival clinical datasets could enhance diagnostic procedures in regions with limited resources. These results also suggest specific fine-grained cognitive and behavioural measures may aid in the diagnosis of AD and FTD in LAC. Moreover, our results highlight an opportunity for harmonisation of clinical tools for dementia diagnosis in the region. Funding: This work was supported by the Multi-Partner Consortium to Expand Dementia Research in Latin America (ReDLat), funded by NIA/NIH (R01AG057234), Alzheimer's Association (SG-20-725707-ReDLat), Rainwater Foundation, Takeda (CW2680521), Global Brain Health Institute; as well as CONICET; FONCYT-PICT (2017-1818, 2017-1820); PIIECC, Facultad de Humanidades, Usach; Sistema General de Regalías de Colombia (BPIN2018000100059), Universidad del Valle (CI 5316); ANID/FONDECYT Regular (1210195, 1210176, 1210176); ANID/FONDAP (15150012); ANID/PIA/ANILLOS ACT210096; and Alzheimer's Association GBHI ALZ UK-22-865742

The Multi-Partner Consortium to Expand Dementia Research in Latin America (ReDLat): Driving Multicentric Research and Implementation Science

Dementia is becoming increasingly prevalent in Latin America, contrasting with stable or declining rates in North America and Europe. This scenario places unprecedented clinical, social, and economic burden upon patients, families, and health systems. The challenges prove particularly pressing for conditions with highly specific diagnostic and management demands, such as frontotemporal dementia. Here we introduce a research and networking initiative designed to tackle these ensuing hurdles, the Multi-partner consortium to expand dementia research in Latin America (ReDLat). First, we present ReDLat's regional research framework, aimed at identifying the unique genetic, social, and economic factors driving the presentation of frontotemporal dementia and Alzheimer's disease in Latin America relative to the US. We describe ongoing ReDLat studies in various fields and ongoing research extensions. Then, we introduce actions coordinated by ReDLat and the Latin America and Caribbean Consortium on Dementia (LAC-CD) to develop culturally appropriate diagnostic tools, regional visibility and capacity building, diplomatic coordination in local priority areas, and a knowledge-to-action framework toward a regional action plan. Together, these research and networking initiatives will help to establish strong cross-national bonds, support the implementation of regional dementia plans, enhance health systems' infrastructure, and increase translational research collaborations across the continent