Purpose of Review
While 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 Findings
We 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.
Summary
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.
Mild cognitive difficulties and progressive brain atrophy are observed in older people living with HIV (PLWH) despite persistent viral suppression. Whether cerebrovascular disease (CVD) risk factors ...and white matter hyperintensity (WMH) volume correspond to the observed progressive brain atrophy is not well understood.
Longitudinal structural brain atrophy rates and WMH volume were examined among 57 HIV-infected participants and 40 demographically similar HIV-uninfected controls over an average (SD) of 3.4 (1.7) years. We investigated associations between CVD burden (presence of diabetes, hypertension, hyperlipidemia, obesity, smoking history, and atrial fibrillation) and WMH with atrophy over time.
The mean (SD) age was 64.8 (4.3) years for PLWH and 66.4 (3.2) years for controls. Participants and controls were similar in age and sex (P > 0.05). PLWH were persistently suppressed (VL <375 copies/mL with 93% <75 copies/mL). The total number of CVD risk factors did not associate with atrophy rates in any regions of interests examined; however, body mass index independently associated with progressive atrophy in the right precentral gyrus (β = -0.30; P = 0.023), parietal lobe (β = -0.28; P = 0.030), and frontal lobe atrophy (β = -0.27; P = 0.026) of the HIV-infected group. No associations were found in the HIV-uninfected group. In both groups, baseline WMH was associated with progressive atrophy rates bilaterally in the parietal gray in the HIV-infected group (β = -0.30; P = 0.034) and the HIV-uninfected participants (β = -0.37; P = 0.033).
Body mass index and WMH are associated with atrophy in selective brain regions. However, CVD burden seems to partially contribute to progressive brain atrophy in older individuals regardless of HIV status, with similar effect sizes. Thus, CVD alone is unlikely to explain accelerated atrophy rates observed in virally suppressed PLWH. In older individuals, addressing modifiable CVD risk factors remains important to optimize brain health.
OBJECTIVE:Inflammation 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.
DESIGN:Retrospective study of older adults living with HIV who are combination antiretroviral therapy adherent, virally suppressed, and self-report cognitive symptoms.
METHODS:MRI, 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.
RESULTS:A 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).
CONCLUSION:Elevated 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.
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.
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
< 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.
clinically relevant methods to identify individuals at risk for impaired daily living abilities secondary to neurocognitive impairment (ADLs) remain elusive. This is especially true for complex ...clinical conditions such as HIV-Associated Neurocognitive Disorders (HAND). The aim of this study was to identify novel and modifiable factors that have potential to improve diagnostic accuracy of ADL risk, with the long-term goal of guiding future interventions to minimize ADL disruption.
study participants included 79 people with HIV (PWH; mean age = 63; range = 55–80) enrolled in neuroHIV studies at University California San Francisco (UCSF) between 2016 and 2019. All participants were virally suppressed and exhibited objective evidence of neurocognitive impairment. ADL status was defined as either normative (n = 39) or at risk (n = 40) based on a task-based protocol. Gradient boosted multivariate regression (GBM) was employed to identify the combination of variables that differentiated ADL subgroup classification. Predictor variables included demographic factors, HIV disease severity indices, brain white matter integrity quantified using diffusion tensor imaging, cognitive test performance, and health co-morbidities. Model performance was examined using average Area Under the Curve (AUC) with repeated five-fold cross validation.
the univariate GBM yielded an average AUC of 83% using Wide Range Achievement test 4 (WRAT-4) reading score, self-reported thought confusion and difficulty reading, radial diffusivity (RD) in the left external capsule, fractional anisotropy (FA) in the left cingulate gyrus, and Stroop performance. The model allowing for two-way interactions modestly improved classification performance (AUC of 88%) and revealed synergies between race, reading ability, cognitive performance, and neuroimaging metrics in the genu and uncinate fasciculus. Conversion of Neuropsychological Assessment Battery Daily Living Module (NAB-DLM) performance from raw scores into T scores amplified differences between White and non-White study participants.
demographic and sociocultural factors are critical determinants of ADL risk status among older PWH who meet diagnostic criteria for neurocognitive impairment. Task-based ADL assessment that relies heavily on reading proficiency may artificially inflate the frequency/severity of ADL impairment among diverse clinical populations. Culturally relevant measures of ADL status are needed for individuals with acquired neurocognitive disorders, including HAND.
Background
White matter hyperintensities (WMHs) are imaging abnormalities of white matter noted by hyperintense signals on fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging ...(MRI). When present among patients with CVRF (hypertension, diabetes, hypercholesteremia and smoking), WMHs are interpreted as cerebral vascular changes. However, WMHs in older individuals can be a feature of late onset leukodystrophies or varied neurodegenerative diseases such as Alzheimer disease (AD), Parkinson’s disease, and Frontotemporal Lobar Degeneration (FTLD). Additionally, WMHs can be present before symptom onset in neurodegenerative disorders and have been linked to the presence of some mutations, including progranulin (GRN). A clearer understanding of the underling etiology of WMHs in bvFTD and svPPA may improve management and treatment considerations.
Methods
In this cross‐sectional study, we included all participants meeting research diagnostic criteria for bvFTD (n = 152) and svPPA (n = 49) from ongoing studies at the UCSF Memory and Aging Center between the dates of September 2008 and December 2021 in comparison to a group of healthy controls enrolled at the same center with similar imaging parameters (n = 152, 1:1 matching for age and sex). All participants underwent a 3T FLAIR MRI and automated quantification of WMHs was performed. Linear regression analyses were performed to determine if WMHs were more frequent in participants with bvFTD or svPPA in comparison to controls and to explore associations with CVRF.
Results
After adjusting for age, sex, apolipoprotein E4 (APO‐E 4) status, and intracranial volume (ICV), both groups demonstrated a higher burden compared to controls (bvFTD (p = 0.012, R2 = 0.146) and svPPA (p = 0.008, R2 = 0.329). Modeling cardiovascular risk factors (CVRFs) as none or at least one, we did not find an association between CVRFs and WMH volume in models adjusting for ICV, ApoE4, and age among those with svPPA and bvFTD combined (p = 0.450).
Conclusion
Individuals with bvFTD and svPPA appear to face a greater burden of WMHs compared to age‐ and sex‐matched healthy controls. WMHs in bvFTD and svPPA do not appear to be related CVRF.
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.
•Subcortical and cortical atrophy occurs in both HIV-associated neurocognitive disorder (HAND) and mild cognitive impairment of the Alzheimer's type (MCI-AD).•Baseline hippocampal volumes differentiate MCI-AD and HAND.•At the baseline, MCI-AD performs worse on memory and language compared with HAND.•Longitudinal results demonstrate faster atrophy in MCI-AD than HAND.•MCI-AD show faster language decline than HAND.
Objectives
Nearly 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.
Design
Retrospective cohort study.
Setting
HIV Elders Study at the University of California, San Francisco, Memory and Aging Center.
Participants
Participants were HIV infected, virally suppressed, 60 years or older, and clinically diagnosed with mild neurocognitive disorder (MND).
Measurements
We conducted standardized assessment of geriatric conditions and everyday function and investigated multimorbidity burden using the Veterans Aging Cohort Study (VACS) index.
Results
Among 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.
Conclusions
Older 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
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