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BACKGROUND: Alcohol use disorder (AUD) affects 283 million people worldwide and its prevalence is increasing. Despite the role of the cerebellum in executive control and its sensitivity to alcohol, few studies have assessed its involvement in AUD-relevant functional networks. The goal of this study is to compare resting-state functional connectivity (FC) patterns in abstinent adults with a history of AUD and controls (CTL). We hypothesized that group differences in cerebro-cerebellar FC would be present, particularly within the frontoparietal/executive control network (FPN). METHODS: Twenty-eight participants completed a resting-state functional magnetic resonance imaging (rsfMRI) study. CTL participants had no history of AUD, comorbid psychological conditions, or recent heavy drinking and/or drug use. AUD participants had a history of AUD, with sobriety for at least 30 days prior to data collection. Multivariate pattern analysis, an agnostic, whole-brain approach, was used to identify regions with significant differences in FC between groups. Seed-based analyses were then conducted to determine the directionality and extent of these FC differences. Associations between FC strength and executive function were assessed using correlations with Wisconsin Card Sorting Test (WCST) performance. RESULTS: There were significant group differences in FC in nodes of the FPN, ventral attention network, and default mode network. Post hoc analyses predominantly identified FC differences within the cerebro-cerebellar FPN, with AUD showing significantly less FC within the FPN. In AUD, FC strength between FPN clusters identified in the multivariate pattern analysis (MVPA) analysis (Left Crus II, Right Frontal Cortex) was positively associated with performance on the WCST. CONCLUSIONS: Our results show less engagement of the FPN in individuals with AUD than in CTL. FC strength within this network was positively associated with performance on the WCST. These findings suggest that long-term heavy drinking alters cerebro-cerebellar FC, particularly within networks that are involved in executive function.
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INTRODUCTION: Growing evidence suggests that some common infections are causally associated with cognitive impairment; however, less is known about the burden of multiple infections. METHODS: We investigated the cross-sectional association of positive antibody tests for herpes simplex virus, cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella zoster virus (VZV), and Toxoplasma gondii (TOX) with Mini-Mental State Examination (MMSE) and delayed verbal recall performance in 575 adults aged 41-97 from the Baltimore Epidemiologic Catchment Area Study. RESULTS: In multivariable-adjusted zero-inflated Poisson (ZIP) regression models, positive antibody tests for CMV (p = .011) and herpes simplex virus (p = .018) were individually associated with poorer MMSE performance (p = .011). A greater number of positive antibody tests among the five tested was associated with worse MMSE performance (p = .001). DISCUSSION: CMV, herpes simplex virus, and the global burden of multiple common infections were independently associated with poorer cognitive performance. Additional research that investigates whether the global burden of infection predicts cognitive decline and Alzheimer's disease biomarker changes is needed to confirm these findings.
Subject(s)
Cytomegalovirus Infections , Epstein-Barr Virus Infections , Adult , Humans , Follow-Up Studies , Cross-Sectional Studies , Baltimore/epidemiology , Herpesvirus 4, Human , Herpesvirus 3, Human , Cytomegalovirus , Cytomegalovirus Infections/complications , Cytomegalovirus Infections/epidemiology , CognitionABSTRACT
OBJECTIVES: Multiple exposures to gadolinium-based contrast agents (GBCAs) is known to be associated with gadolinium deposition in the brain in certain patients. Such deposition has been correlated with specific brain MRI findings, although most available data is in patients with underlying neurologic disorders. We aim to prospectively evaluate brain MRI signal changes as well as neurologic and neuropsychologic testing results in women undergoing screening breast MRI. METHODS: In this IRB-approved, HIPAA-compliant prospective study, 9 women with 5 or more exposures to linear and/or macrocyclic GBCA due to screening breast MRI underwent noncontrast brain MRI, neurologic exam and neuropsychologic testing. Women with underlying neurologic, psychologic, hepatic or renal disorders were excluded. RESULTS: The mean total number of GBCA exposures was 8 (standard deviation 2.7), with 63/72 (87%) of the exposures being linear agents. There was no association between brain MRI signal changes and abnormalities on neurologic or neuropsychologic examination. There was no association between total number of GBCA exposures and abnormalities on neurologic or neuropsychologic examination. CONCLUSION: In this prospective exploratory study of 9 women with 5 or more GBCA exposures due to screening breast MRI, there was no association between brain MRI signal changes and clinical abnormalities on neurologic or neuropsychologic examination. While larger studies are needed in this patient population, the lack of clinical impact of multiple GBCA exposures in this study is reassuring.
Subject(s)
Contrast Media , Organometallic Compounds , Humans , Female , Contrast Media/adverse effects , Gadolinium , Prospective Studies , Magnetic Resonance Imaging/methods , Brain/diagnostic imaging , Retrospective StudiesABSTRACT
BACKGROUND: Falls are highly common in patients with Alzheimer's disease (AD); around two-thirds of AD patients fall annually. Fall events are major drivers of injury, early institutionalization, and shorter survival. Balance and mobility impairment are among the most important fall risk factors in AD patients. Vestibular therapy (VT) is an effective rehabilitation intervention in improving balance and fall risk through vestibular function, but not often used in AD. We want to evaluate the feasibility of using VT to reduce falls and improve balance function in patients with AD and drive use of an existing, potentially beneficial therapy in a patient population whose high level of vestibular deficits is currently unaddressed. METHODS: The proposed pilot clinical trial will be a parallel-group randomized controlled trial. Patients with a diagnosis of mild-moderate AD, age ≥ 60, and the presence of a caregiver will be recruited from the Johns Hopkins Memory and Alzheimer's Treatment Center. Eligible patients will be offered vestibular testing. Patients with vestibular loss will be offered participation in the VT trial. One-hundred AD patients with vestibular loss will be enrolled and randomized 1:1 into the control and intervention arms of the trial. All patients will undergo baseline balance and cognitive assessment, followed by 8 weeks of active control therapy or VT, consisting of ~25-min office sessions with a vestibular therapist. Patients will be tracked for falls and undergo follow-up balance and cognitive assessment at 8 and 52 weeks (1 year) to assess the potential short-term and longer-term effects, respectively, of VT on balance and cognition. The main outcomes of this trial are falls, balance (using the Berg Balance Scale and the Timed Up and Go test), and cognition (using the clock drawing test, the Card Rotations test, the Money Road Map test, and the triangle completion task). DISCUSSION: As the population ages and the number of individuals with AD in the US grows to a projected 14 million in 2050, managing falls in AD will continue to grow as a critical public health concern; this trial assesses feasibility of a potential solution. TRIAL REGISTRATION: ClinicalTrial.Gov identifier - NCT03799991 . Registered 01 August 2019.
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STUDY OBJECTIVES: Trauma exposure likely contributes to poor sleep, but relatively few studies have empirically tested this, instead focusing on posttraumatic stress disorder. Moreover, little is known about sex differences in sleep after trauma. The current study used a cross-sectional and retrospective design to test hypotheses that trauma exposure would be associated with subsequent insomnia symptoms, particularly among women, even after accounting for important covariates. METHOD: Data from Wave 3 (1993-1996) of the Baltimore Epidemiologic Catchment Area Study (N = 1920) were used to examine associations between remote (prior to past year) and recent (past year) trauma and current sleep disturbance (insomnia, hypersomnia symptoms) in the total sample (Mage= 55, 63.2% women, 57.7% white), and separately in men and women. Sensitivity analyses were conducted among individuals with no pretrauma sleep disturbance to examine incident sleep disturbance. RESULTS: Among all participants, both remote (odds ratio [OR] = 1.95, 95% confidence interval [CI] [1.34, 2.85]) and recent (OR = 1.94, 95% CI [1.31, 2.87]) trauma exposure were associated with increased odds of insomnia (OR = 2.41, 95% CI [1.54, 3.76]) but not hypersomnia. Associations between trauma and insomnia were particularly strong among women, but null among men. The relationship between trauma exposure and insomnia symptoms persisted among individuals with no pretrauma history of insomnia. CONCLUSION: Results suggest women may be vulnerable to insomnia symptoms as sequelae of trauma. Future research should examine prospective associations between trauma and sleep in larger samples and how assessment and treatment of insomnia among women trauma survivors reduces the public health impact of trauma and poor sleep.
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Sleep Initiation and Maintenance Disorders , Sleep Wake Disorders , Baltimore/epidemiology , Cross-Sectional Studies , Female , Follow-Up Studies , Humans , Male , Retrospective Studies , Sleep Initiation and Maintenance Disorders/epidemiologyABSTRACT
BACKGROUND: Financial capacity (FC) is a complex ability commonly impaired in older individuals with cognitive impairment; however, the underlying neural mechanisms are not well understood. OBJECTIVE: To assess resting state functional connectivity using functional magnetic resonance imaging (rs-fMRI) in individuals with mild cognitive impairment (MCI) and impaired FC compared to cognitively normal older adults. METHODS: rs-fMRI scans were obtained from individuals with MCI (Nâ=â17) and normal older adults (Nâ=â15). All participants completed the Financial Capacity Instrument Short Form (FCI-SF) and neuropsychological assessments. Based on previous findings, the left angular gyrus (lAG) was used as the seed region. Connectivity correlation coefficients were calculated for each seed-based connection that showed significantly altered connectivity. A Pearson's correlation was calculated between the connectivity correlation values from relevant regions and FC and other cognitive measures. RESULTS: A total of 26 brain regions showed significantly increased functional connectivity with the lAG. Of these regions, 14 were identified as relevant to higher-level cognitive function for analysis. Pearson's correlations showed a significant negative correlation between the FCI-SF total score and increased connectivity between the IAG and the right temporal fusiform cortex (rTFC) (râ=â-0.455, pâ=â0.009). CONCLUSION: Results showed a significant correlation between FC and increased functional connectivity between the lAG and the rTFC in cognitively normal older adults compared to participants with MCI. These exploratory findings suggest that cognitive functions play important roles in FC as the functional connectivity between the lAG and rTFC was not associated with other tests of executive or visuospatial cognition.
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Cognitive Dysfunction , Aged , Brain , Humans , Magnetic Resonance Imaging/methods , Neuropsychological Tests , Parietal Lobe/diagnostic imagingSubject(s)
Caregivers , Parkinson Disease , Asia/epidemiology , Humans , Severity of Illness Index , Stress, PsychologicalABSTRACT
There are distinct trajectories to cognitive impairment among participants in the Multicenter AIDS Cohort Study (MACS). Here we analyzed the relationship between regional brain volumes and the individual trajectories to impairment in a subsample (n = 302) of the cohort. 302 (167 HIV-infected; mean age = 55.7 yrs.; mean education: 16.2 yrs.) of the men enrolled in the MACS MRI study contributed data to this analysis. We used voxel-based morphometry (VBM) to segment the brain images to analyze gray and white matter volume at the voxel-level. A Mixed Membership Trajectory Model had previously identified three distinct profiles, and each study participant had a membership weight for each of these three trajectories. We estimated VBM model parameters for 100 imputations, manually performed the post-hoc contrasts, and pooled the results. We examined the associations between brain volume at the voxel level and the MMTM membership weights for two profiles: one considered "unhealthy" and the other considered "Premature aging." The unhealthy profile was linked to the volume of the posterior cingulate gyrus/precuneus, the inferior frontal cortex, and the insula, whereas the premature aging profile was independently associated with the integrity of a portion of the precuneus. Trajectories to cognitive impairment are the result, in part, of atrophy in cortical regions linked to normal and pathological aging. These data suggest the possibility of predicting cognitive morbidity based on patterns of CNS atrophy.
Subject(s)
Cognitive Dysfunction , HIV Infections , Brain/diagnostic imaging , Cognitive Dysfunction/diagnostic imaging , Cohort Studies , Gray Matter/diagnostic imaging , HIV Infections/complications , HIV Infections/diagnostic imaging , Humans , Magnetic Resonance Imaging , Male , Middle AgedABSTRACT
INTRODUCTION: Alzheimer's disease (AD) is a disabling, common cause of dementia, and agitation is one of the most common and distressing symptoms for patients with AD. Escitalopram for agitation in Alzheimer's disease (S-CitAD) tests a novel, clinically derived therapeutic approach to treat agitation in patients with AD. METHODS: S-CitAD is a NIH-funded, investigator-initiated, randomized, multicenter clinical trial. Participants receive a structured psychosocial intervention (PSI) as standard of care. Participants without sufficient response to PSI are randomized to receive 15 mg escitalopram/day or a matching placebo in addition to PSI. Primary outcome is the Modified Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (mADCS-CGIC). DISCUSSION: S-CitAD will provide information about a practical, immediately available approach to treating agitation in patients with AD. S-CitAD may become a model of how to evaluate and predict treatment response in patients with AD and agitation as a neuropsychiatric symptom (ClinicalTrials.gov Identifier: NCT03108846).
Subject(s)
Alzheimer Disease/complications , Citalopram/therapeutic use , Psychomotor Agitation/drug therapy , Selective Serotonin Reuptake Inhibitors/therapeutic use , Aged , Aged, 80 and over , Alzheimer Disease/psychology , Double-Blind Method , Female , Humans , Male , Psychiatric Status Rating ScalesABSTRACT
BACKGROUND: Prevalence estimates of cognitive impairment in HIV disease vary widely. Here we used multivariate normative comparison (MNC) with identify individuals with impaired cognition, and to compare the results with those using the Frascati and Gisslén criteria. METHODS: The current project used data collected before October 2014 from bisexual/gay men from the Multicenter AIDS Cohort Study. A total of 2904 men (mean age 39.7 years, 52.7% seropositive) had complete data in six cognitive domains at their first neuropsychological evaluation. T-scores were computed for each domain and the MNC was applied to detect impairment among seronegative and seropositive groups. RESULTS: The MNC classified 6.26% of seronegative men as being impaired using a predetermined 5% false discovery rate. By contrast, the Frascati and the Gisslén criteria identified 24.54 and 11.36% of seronegative men as impaired. For seropositive men, the percentage impairment was 7.45, 25.73, and 11.69%, respectively, by the MNC, Frascati and Gisslén criteria. When we used seronegative men without medical comorbidities as the control group, the MNC, the Frascati and the Gisslén criteria identified 5.05, 27.07, and 4.21% of the seronegative men, and 4.34, 30.95, and 4.48% of the seropositive men as having cognitive impairment. For each method, serostatus was not associated with cognitive impairment. CONCLUSION: The MNC controls the false discovery rate and therefore avoids the low specificity that characterizes the Frascati and Gisslén criteria. More research is needed to evaluate the sensitivity of the MNC method in a seropositive population that may be sicker and older than the current study sample and that includes women.
Subject(s)
Cognitive Dysfunction/diagnosis , HIV Infections/complications , HIV Infections/psychology , Neuropsychological Tests , Adult , Anti-HIV Agents/therapeutic use , Bisexuality , Cognition , Cognitive Dysfunction/epidemiology , Cohort Studies , Cross-Sectional Studies , HIV Infections/drug therapy , HIV-1/isolation & purification , Homosexuality, Male , Humans , Male , Middle Aged , Prevalence , Sensitivity and Specificity , United States/epidemiologyABSTRACT
OBJECTIVE: Obesity is a common, modifiable cardiovascular and cerebrovascular risk factor. Among people with HIV, obesity may contribute to multisystem dysregulation including cognitive impairment. We examined body mass index (BMI) and central obesity (waist circumference [WC]) in association with domain-specific cognitive function and 10-year cognitive decline in men with HIV infection (MWH) vs HIV-uninfected (HIV-) men. METHODS: A total of 316 MWH and 656 HIV- Multicenter AIDS Cohort Study participants ≥40 years at baseline, with neuropsychological testing every 2 years and concurrent BMI and WC measurements, were included. MWH were included if taking ≥2 antiretroviral agents and had HIV-1 RNA <400 copies/mL at >80% of visits. Mixed-effects models included all visits from 1996 to 2015, stratified by HIV serostatus, and adjusted for sociodemographic, behavioral, and clinical characteristics. At baseline and follow-up, 8% of MWH and 15% of HIV- men and 41% of MWH and 56% of HIV- men were ≥60 years, respectively. RESULTS: Cross-sectionally, higher BMI was inversely associated with motor function in MWH and HIV- men, and attention/working memory in HIV- men. WC was inversely associated with motor function in MWH and HIV- men. Longitudinal associations indicated an obese BMI was associated with a less steep decline in motor function in MWH whereas in HIV- men, obesity was associated with a greater decline in motor function, learning, and memory. WC, or central obesity, showed similar patterns of associations. CONCLUSION: Higher adiposity is associated with lower cognition cross-sectionally and greater cognitive decline, particularly in HIV- men. Overweight and obesity may be important predictors of neurologic outcomes and avenues for prevention and intervention.
Subject(s)
Cognitive Dysfunction/epidemiology , HIV Infections/epidemiology , Obesity, Abdominal/epidemiology , Adult , Aged , Aged, 80 and over , Attention , Body Mass Index , Case-Control Studies , Humans , Male , Memory, Short-Term , Middle Aged , Movement , Obesity/epidemiology , Waist CircumferenceABSTRACT
OBJECTIVES: Despite treatment-related improvements in morbidity and mortality, HIV-1-infected (HIV+) individuals continue to face a wide range of HIV-associated medical and HIV-associated neurocognitive disorders. Little is known about the impact of cognitive impairment on patients' health-related quality of life (HRQoL). To address this, the current study examined the longitudinal relationship between cognitive functioning and HRQoL among HIV+ individuals. METHOD: The sample consisted of 1,306 HIV+ men enrolled in the Multicenter AIDS Cohort Study. Participants received biannual assessments of cognitive functioning (including tests of processing speed, executive functioning, attention/working memory, motor functioning, learning, and memory) and completed questionnaires assessing HRQoL and depression. Multilevel models were used to examine the longitudinal and cross-lagged relationship between HRQoL and cognition, independent of depression and HIV disease severity. RESULTS: There was a significant relationship between HRQoL and cognitive functioning both between and within subjects. Specifically, individuals who reported better HRQoL reported better cognitive functioning, and longitudinal change in cognition was positively related to change in HRQoL. There was a significant unidirectional-lagged relationship; cognition predicted HRQoL at subsequent visits, but HRQoL did not predict cognitive functioning at subsequent visits. Furthermore, analyses of severity of neurocognitive impairment revealed that transition to a more severe stage of cognitive impairment was associated with a decline in HRQoL. CONCLUSIONS: Overall, the current study suggests that changes in HRQoL are partially driven by changes in cognitive functioning. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Subject(s)
Cognition/physiology , Cognitive Dysfunction/diagnosis , HIV Seropositivity/psychology , Quality of Life/psychology , Adult , Attention/physiology , Cognitive Dysfunction/etiology , Cognitive Dysfunction/psychology , Executive Function/physiology , HIV Seropositivity/complications , Humans , Male , Memory/physiology , Middle Aged , Neuropsychological Tests , Surveys and QuestionnairesABSTRACT
INTRODUCTION: The reasons why women are at higher risk than men for developing dementia are unclear. Although studies implicate sex differences in the effect of stress on cognitive functioning, whether stressful life events are associated with subsequent cognitive decline has received scant research attention. METHODS: In Wave 3 (1993-1996) of the Baltimore Epidemiologic Catchment Area study, 337 men and 572 women (mean age = 47 years) reported recent (within the last year) and remote (from 1981 until 1 year ago) traumatic events (eg, combat) and stressful life events (eg, divorce/separation). At Waves 3 and 4 (2004-2005), they completed the Mini Mental State Examination (MMSE) and a word-list memory test. Multivariable models were used to examine the association between traumatic and stressful life events at Wave 3 and cognitive change by Wave 4. RESULTS: A greater number of recent stressful life events at Wave 3, but not of more remote stressful events, was associated with greater verbal memory decline by Wave 4 in women but not in men. Stressful events were not associated with change in MMSE, and there were no associations between traumatic events occurring at any time and subsequent memory or MMSE decline in either sex. CONCLUSIONS: Unlike men, middle-aged women with a greater number of recent stressful life events demonstrate memory decline over a decade later. Sex differences in cognitive vulnerability to stressful life events may underlie women's increased risk of memory impairment in late life, suggesting that stress reduction interventions may help prevent cognitive decline in women.
Subject(s)
Cognitive Dysfunction , Life Change Events , Stress, Psychological/complications , Adult , Aged , Baltimore/epidemiology , Cognitive Dysfunction/epidemiology , Cognitive Dysfunction/etiology , Female , Humans , Male , Memory Disorders/epidemiology , Memory Disorders/etiology , Mental Status and Dementia Tests , Middle Aged , Multivariate Analysis , Prevalence , Prospective Studies , Sex FactorsABSTRACT
Mild cognitive impairment (MCI) is a term used to describe individuals with cognitive impairment that is not severe enough to affect daily functioning (e.g. Petersen, 2004; Winblad et al., 2004). Although MCI has been used to describe cognitive abnormality due to any number of causes that can be progressive, stable, or reversible, it is most often considered to be a transition phase between normal cognition and dementia.
Subject(s)
Cognition Disorders , Cognitive Dysfunction , Dementia , Cognition , HumansABSTRACT
INTRODUCTION: HIV-associated neurocognitive disorders (HAND) are estimated to affect approximately 50% of infected individuals at any one time. Dispersion, a type of intraindividual variability in neurocognitive test performance, has been identified as a potential behavioral marker of HAND; however, the specificity of dispersion to HAND and how it is influenced by participant effort when taking neurocognitive tests remain unclear. METHOD: Data were analyzed from 996 (474 HIV-, 522 HIV+) men enrolled in the Multicenter AIDS Cohort Study (MACS). Dispersion was calculated based on the standard deviation of an individual's test scores within a single assessment. Effort was determined using the Visual Analogue Effort Scale. Predictors of dispersion were determined using stepwise linear regression. Dispersion was compared between the HIV serostatus groups using analysis of covariance (ANCOVA), considering demographic and psychosocial variables that differed between the groups. RESULTS: Contrary to our hypothesis, dispersion was not influenced by effort. Instead, poorer neurocognitive ability and race were the sole predictors of dispersion. Dispersion did not differ between the serostatus groups. CONCLUSIONS: Our results indicate that dispersion is a valid indicator of neurocognitive dysfunction that is not due to suboptimal effort; however, it is not specific to HIV and is therefore of limited utility as a behavioral marker of HIV-related neurocognitive impairment.
Subject(s)
AIDS Dementia Complex/psychology , Cognition/physiology , Energy Metabolism , HIV Seropositivity/psychology , Individuality , Psychomotor Performance/physiology , Adult , Cohort Studies , Depression/psychology , Ethnicity , Humans , Male , Middle Aged , Self ReportABSTRACT
The aim of this study was to describe sex differences in neuropsychiatric symptoms (NPSs) in patients with Alzheimer's disease (AD). Baseline scores on the Cohen-Mansfield Agitation Inventory, Neurobehavioral Rating Scale-Agitation subscale, and the Neuropsychiatric Inventory from patients with AD enrolled in a multicenter trial of citalopram for the treatment of agitation were analyzed. We found not only that patients with AD having agitation were likely to exhibit many other NPSs but also that the women in this study were more likely to exhibit a broader range of NPS than were the men. These results suggest greater heterogeneity in the clinical presentation of women compared to men, and thus in the potential targets for treatment in these patients. Further characterization of sex differences in NPS can inform future efforts aimed at establishing subtypes of patients for whom various treatment approaches will be most appropriate.
Subject(s)
Alzheimer Disease/complications , Behavioral Symptoms/psychology , Psychiatric Status Rating Scales/statistics & numerical data , Psychomotor Agitation/drug therapy , Activities of Daily Living , Aged , Alzheimer Disease/drug therapy , Citalopram/therapeutic use , Cross-Sectional Studies , Female , Humans , Male , Psychomotor Agitation/epidemiology , Psychomotor Agitation/etiology , Selective Serotonin Reuptake Inhibitors/therapeutic use , Severity of Illness Index , Sex FactorsABSTRACT
BACKGROUND: Given recent challenges in developing new treatments for Alzheimer dementia (AD), it is vital to explore alternate treatment targets, such as neuromodulation for circuit dysfunction. We previously reported an exploratory Phase IIb double-blind trial of deep brain stimulation targeting the fornix (DBS-f) in mild AD (the ADvance trial). We reported safety but no clinical benefits of DBS-f versus the delayed-on (sham) treatment in 42 participants after one year. However, secondary post hoc analyses of the one-year data suggested a possible DBS-f benefit for participants≥65 years. OBJECTIVE: To examine the long-term safety and clinical effects of sustained and delayed-on DBS-f treatment of mild AD after two years. METHODS: 42 participants underwent implantation of DBS-f electrodes, with half randomized to active DBS-f stimulation (early on) for two years and half to delayed-on (sham) stimulation after 1 year to provide 1 year of active DBS-f stimulation (delayed on). We evaluated safety and clinical outcomes over the two years of the trial. RESULTS: DBS-f had a favorable safety profile with similar rates of adverse events across both trial phases (years 1 and 2) and between treatment arms. There were no differences between treatment arms on any primary clinical outcomes. However, post-hoc age group analyses suggested a possible benefit among older (>65) participants. CONCLUSION: DBS-f was safe. Additional study of mechanisms of action and methods for titrating stimulation parameters will be needed to determine if DBS has potential as an AD treatment. Future efficacy studies should focus on patients over age 65.
Subject(s)
Alzheimer Disease/therapy , Deep Brain Stimulation/methods , Fornix, Brain/physiology , Aged , Aged, 80 and over , Female , Humans , Longitudinal Studies , Male , Neuropsychological Tests , Psychiatric Status Rating ScalesABSTRACT
BACKGROUND: Since the onset of combination antiretroviral therapy use, the incidence of HIV-associated dementia and of HIV encephalitis has fallen dramatically. The present study investigates the extent of white matter hyperintensities (WMHs) among individuals with HIV disease, and factors that predict their presence and their impact on psychomotor speed. METHODS: A total of 322 men participating in the Multicenter AIDS Cohort Study (185 HIV-infected, age: 57.5â±â6.0) underwent MRI scans of the brain. T1-weighted magnetization-prepared rapid gradient-echo (MP-RAGE) and T2-weighted Fluid Attenuated Inversion Recovery (FLAIR) images were obtained and processed using an automated method for identifying and measuring WMHs. WMH burden was expressed as the log10 transformed percentage of total white matter. RESULTS: There were no significant associations between WMHs and HIV disease. However, the extent of WMHs was predicted by age more than 60 (ßâ=â0.17), non-white race (ßâ=â0.14), glomerular filtration rate (ßâ=â-0.11), and the presence of diabetes (ßâ=â0.12). There were no interactions between HIV status and age (ßâ=â-0.03) or between age and diabetes (ßâ=â0.07). However, the interaction between HIV infection and diabetes was significant (ßâ=â0.26). The extent of WMHs was significantly associated with performance on measures of psychomotor speed (ßâ=â0.15). CONCLUSION: In today's therapeutic environment, in HIV-infected and HIV seronegative individuals, those factors which affect the cerebrovasculature are the best predictors of WMHs. Diabetes has a specific impact among HIV-infected, but not uninfected, men, suggesting the need for more aggressive treatment even in the prediabetes state, especially as WMHs affect cognitive functions.
Subject(s)
Brain/pathology , Cognition Disorders/epidemiology , Diabetes Complications , HIV Infections/complications , White Matter/pathology , Aged , Aged, 80 and over , Animals , Brain/diagnostic imaging , Cognition Disorders/pathology , Humans , Incidence , Magnetic Resonance Imaging , Male , Middle AgedABSTRACT
OBJECTIVE: Mild forms of HIV-associated neurocognitive disorder (HAND) remain prevalent in the combination antiretroviral therapy (cART) era. This study's objective was to identify neuropsychological subgroups within the Multicenter AIDS Cohort Study (MACS) based on the participant-based latent structure of cognitive function and to identify factors associated with subgroups. DESIGN: The MACS is a four-site longitudinal study of the natural and treated history of HIV disease among gay and bisexual men. METHODS: Using neuropsychological domain scores, we used a cluster variable selection algorithm to identify the optimal subset of domains with cluster information. Latent profile analysis was applied using scores from identified domains. Exploratory and posthoc analyses were conducted to identify factors associated with cluster membership and the drivers of the observed associations. RESULTS: Cluster variable selection identified all domains as containing cluster information except for Working Memory. A three-profile solution produced the best fit for the data. Profile 1 performed below average on all domains, Profile 2 performed average on executive functioning, motor, and speed and below average on learning and memory, Profile 3 performed at or above average across all domains. Several demographic, cognitive, and social factors were associated with profile membership; these associations were driven by differences between Profile 1 and the other profiles. CONCLUSION: There is an identifiable pattern of neuropsychological performance among MACS members determined by all domains except Working Memory. Neither HIV nor HIV-related biomarkers were related with cluster membership, consistent with other findings that cognitive performance patterns do not map directly onto HIV serostatus.
Subject(s)
AIDS Dementia Complex/pathology , HIV Infections/complications , Adult , Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , Humans , Longitudinal Studies , Male , Middle Aged , Neuropsychological TestsABSTRACT
OBJECTIVES: To determine the relationship between glycemic status and cognitive performance in men living with HIV (MLWH) and without HIV infection. DESIGN: A prospective HIV/AIDS cohort study in four US cities between 1999 and 2016. METHODS: Glycemic status was categorized as normal glucose, impaired fasting glucose, controlled diabetes mellitus and uncontrolled diabetes mellitus at each semiannual visit. Cognitive performance was evaluated using nine neuropsychological tests which measure attention, constructional ability, verbal learning, executive functioning, memory and psychomotor speed. Linear mixed models were used to assess the association between glycemic status and cognition. RESULTS: Overall, 900 MLWH and 1149 men without HIV were included. MLWH had significantly more person-visits with impaired fasting glucose (52.1 vs. 47.9%) and controlled diabetes mellitus (58.2 vs. 41.8%) than men without HIV (Pâ<â0.05). Compared with men with normal glucose, men with diabetes mellitus had significantly poorer performance on psychomotor speed, executive function and verbal learning (all Pâ<â0.05). There was no difference in cognition by HIV serostatus. The largest effect was observed in individuals with uncontrolled diabetes mellitus throughout the study period, equivalent to 16.5 and 13.4 years of aging on psychomotor speed and executive function, respectively, the effect of which remained significant after adjusting for HIV-related risk factors. Lower CD4+ nadir was also associated with worse cognitive performance. CONCLUSION: Abnormalities in glucose metabolism were more common among MLWH than men without HIV and were related to impaired cognitive performance. Metabolic status, along with advanced age and previous immunosuppression, may be important predictors of cognition in the modern antiretroviral therapy era.