Using data from NIH Research Portfolio Online Reporting Tools (RePORT) and recently assembled prevalence estimates of 6 major neurologic diseases, we compared the relative prevalences and the annual NIH support levels for 6 major neurologic disorders: Alzheimer disease, amyotrophic lateral sclerosis (ALS), epilepsy, multiple sclerosis, Parkinson disease, and stroke. Compared to these other major neurologic disorders, epilepsy research is funded at a persistently lower rate based on relative disease prevalences. Relative NIH funding for these other disorders in 2010 adjusted for prevalence ranged from 1.7x (stroke) to 61.1x (ALS) greater than epilepsy. The disparity cannot be explained by differences in the overall impact of these diseases on US citizens. Greater transparency in the review and funding process is needed to disclose the reason for this disparity.
Objectives: Memory impairment is one of the most prominent cognitive deficits in temporal lobe epilepsy (TLE). The overall goal of this study was to explore the contribution of cortical and hippocampal (subfield) damage to impairment of auditory immediate recall (AIMrecall), auditory delayed recall (ADMrecall), and auditory delayed recognition (ADMrecog) of the Wechsler Memory Scale III (WMS-III) in TLE with (TLE-MTS) and without hippocampal sclerosis (TLE-no). It was hypothesized that volume loss in different subfields determines memory impairment in TLE-MTS and temporal neocortical thinning in TLE-no. Methods: T1 whole brain and T2-weighted hippocampal magnetic resonance imaging and WMS-III were acquired in 22 controls, 18 TLE-MTS, and 25 TLE-no. Hippocampal subfields were determined on the T2 image. Free surfer was used to obtain cortical thickness averages of temporal, frontal, and parietal cortical regions of interest (ROI). MANOVA and stepwise regression analysis were used to identify hippocampal subfields and cortical ROI significantly contributing to AIMrecall, ADMrecall, and ADMrecog.
Results: In TLE-MTS, AIMrecall was associated with cornu ammonis 3 (CA3) and dentate (CA3&DG) and pars opercularis, ADMrecall with CA1 and pars triangularis, and ADMrecog with CA1. In TLE-no, AIMrecall was associated with CA3&DG and fusiform gyrus (FUSI), and ADMrecall and ADMrecog were associated with FUSI.
Conclusion: The study provided the evidence for different structural correlates of the verbal memory impairment in TLE-MTS and TLE-no. In TLE-MTS, the memory impairment was mainly associated by subfield-specific hippocampal and inferior frontal cortical damage. In TLE-no, the impairment was associated by mesial-temporal cortical and to a lesser degree hippocampal damage.
HIV-associated neurocognitive disorder (HAND) is a common condition in both developed and developing nations, but its cause is largely unknown. Previous research has inconsistently linked Alzheimer’s disease (AD), viral burden, and inflammation to the onset of HAND in HIV-infected individuals. Here we simultaneously measured cerebrospinal fluid (CSF) levels of established amyloid and tau biomarkers for AD, viral copy numbers, and six key cytokines in 41 HIV-infected individuals off combination anti-retroviral therapy (14 with HAND) who underwent detailed clinical and neuropsychological characterization, and compared their CSF patterns with those from young healthy subjects, older healthy subjects with normal cognition, and older people with AD. HAND was associated with the lowest CSF levels of phosphorylated tau (p-Tau181) after accounting for age and race. We also found very high CSF levels of the pro-inflammatory interferon gamma-induced protein 10 (IP-10/CXCL10) in HIV regardless of cognition, but elevated CSF interleukin 8 (IL-8/CXCL8) only in HIV-NC but not HAND. Eleven HIV-infected subjects underwent repeat CSF collection six months later and showed strongly correlated longitudinal changes in p-Tau181 and IL-8 levels (R = 0.841). These data suggest reduced IL-8 relative to IP-10 and reduced p-Tau181 to characterize HAND.
HIV-associated neurocognitive disorders (HANDs) continue to be common and are associated with increased morbidity and mortality. However, the underlying mechanisms in the combination antiretroviral therapy (cART) era are not fully understood. Interferon alpha (IFNα) is an antiviral cytokine found to be elevated in the cerebrospinal fluid (CSF) of individuals with advanced HIV-associated dementia in the pre-cART era. In this cross-sectional study, we investigated the association between IFNα and neurocognitive performance in ambulatory HIV-infected individuals with milder impairment. An eight-test neuropsychological battery representing six cognitive domains was administered. Individual scores were adjusted for demographic characteristics, and a composite neuropsychological score (NPT-8) was calculated. IFNα and CSF neurofilament light chain (NFL) levels were measured using enzyme-linked immunosorbent assay (ELISA). There were 15 chronically infected participants with a history of significant immunocompromise (median nadir CD4+ of 49 cells/μl). Most participants were neurocognitively impaired (mean global deficit score of 0.86). CSF IFNα negatively correlated with three individual tests (Trailmaking A, Trailmaking B, and Stroop Color-Word) as well as the composite NPT-8 score (r = −0.67, p = 0.006). These negative correlations persisted in multivariable analyses adjusting for chronic hepatitis B and C. Additionally, CSF IFNα correlated strongly with CSF NFL, a marker of neuronal damage (rho = 0.748, p = 0.0013). These results extend findings from individuals with severe HIV-associated dementia in the pre-cART era and suggest that IFNα may continue to play a role in HAND pathogenesis during the cART era. Further investigation into the role of IFNα is indicated.
Given the high prevalence of HIV-associated neurocognitive disorders (HAND), we examined the performance of a novel computerized cognitive assessment device (NCAD) for the evaluation of neurocognitive impairment in the setting of HIV. In addition to a standard 8-test neuropsychological battery, each participant underwent testing with the NCAD, which requires approximately 20 min and has been shown to accurately measure neurocognition in elderly individuals. The NCAD yields seven subtest scores in addition to an overall predictive score that is calculated based on subtest results. Thirty-nine HIV-infected participants were included in this study; the majority of which (71.8 %) had undetectable plasma HIV RNA levels and a history of significant immunocompromise (median nadir CD4+ count 34 cells/μl). The mean composite neuropsychological score (NPT-8) was 46.07, and mean global deficit score (GDS) was 0.59. NCAD total subtest accuracy correlated significantly with NPT-8 (Pearson correlation r = 0.59, p & #lt; 0.0001) as well as GDS (Spearman’s rho = −0.36, p = 0.02). NCAD predictive score also correlated significantly with NPT-8 (Spearman’s rho = −0.5601, p = 0.0016) and GDS (Spearman’s rho = 0.45, p = 0.0144). When using the most recent nosology of HAND criteria for neurocognitive impairment, the area under the curve (AUC) for NCAD total subtest accuracy was 0.7562 (p = 0.012), while the AUC for the HIV dementia scale was 0.508 (p = 0.930). While not as comprehensive as a full neuropsychological battery, the NCAD shows promise as a rapid screening tool for HIV-infected individuals, and additional research of this device is indicated.