Normative data for 8 neuropsychological tests in older blacks and whites from the atherosclerosis risk in communities (ARIC) study.

Accurate assessment of cognitive impairment requires comparison of cognitive performance in individuals to performance in a comparable healthy normative population. Few prior studies have included a large number of black participants and few have excluded participants from the normative sample with subclinical/latent neurological disease or dementia. This study provides age, race, and education-specific normative data for 8 cognitive tests derived from 320 black and 392 white participants aged 61 to 82 years (mean 71 y) in the Atherosclerosis Risk in Communities (ARIC) study without clinical or subclinical/latent neurological disease. Normative data are provided for the Delayed Word Recall Test, Logical Memory Parts I and II, the Word Fluency Test, Animal Naming, the Trail Making Test Parts A and B and the Digit Symbol Substitution Test. Age, race, and education-specific mean and -1.5 SD scores are given in tabular form and graphically, as well as regression-based equations to derive adjusted score cut-points. These robust normative data should enhance comparison across studies of cognitive aging, where these measures are widely used, and improve interpretation of performance on these tests for the diagnosis of cognitive impairment not only within the ARIC cohort, but also among older blacks and whites with similar demographics.

Impact of differential attrition on the association of education with cognitive change over 20 years of follow-up: the ARIC neurocognitive study.

Studies of long-term cognitive change should account for the potential effects of education on the outcome, since some studies have demonstrated an association of education with dementia risk. Evaluating cognitive change is more ideal than evaluating cognitive performance at a single time point, because it should be less susceptible to confounding. In this analysis of 14,020 persons from a US cohort study, the Atherosclerosis Risk in Communities (ARIC) Study, we measured change in performance on 3 cognitive tests over a 20-year period, from ages 48-67 years (1990-1992) through ages 70-89 years (2011-2013). Generalized estimating equations were used to evaluate the association between education and cognitive change in unweighted adjusted models, in models incorporating inverse probability of attrition weighting, and in models using cognitive scores imputed from the Telephone Interview for Cognitive Status for participants not examined in person. Education did not have a strong relationship with change in cognitive test performance, although the rate of decline was somewhat slower among persons with lower levels of education. Methods used to account for selective dropout only marginally changed these observed associations. Future studies of risk factors for cognitive impairment should focus on cognitive change, when possible, to allow for reduction of confounding by social or cultural factors.

Length of red cell unit storage and risk for delirium after cardiac surgery.

BACKGROUND: The time that red cell units are stored before transfusion may be associated with postoperative complications, although the evidence is conflicting. However, the association between the length of red cell unit storage and postoperative delirium has not been explored. We hypothesized that the length of storage of transfused red cell units would be associated with delirium after cardiac surgery. METHODS: We conducted a case-control study in which patients undergoing coronary artery bypass, valve, or ascending aorta surgery with cardiopulmonary bypass at Johns Hopkins from 2005 to 2011 were eligible for inclusion. Patients were excluded if they did not receive red cell units, received >4 red cell units during hospitalization, received any transfusion after the first postoperative day, or received red cell units that were not exclusively stored for ≤14 days or >14 days. Eighty-seven patients met transfusion-related inclusion criteria and developed postoperative delirium. Controls who did not develop delirium were selected from the same source population of eligible patients and were matched 1:1 based on age (± 5 years), 2- to 2.5-year band of date of surgery, and surgical procedure. For each patient, we calculated the average storage duration of all transfused red cell units. The primary outcome was odds of delirium in patients who were transfused red cell units with exclusive storage duration >14 days compared with that of ≤14 days. Secondary outcomes were odds of delirium with each increasing day of average red cell unit storage duration. We used conditional multivariable regression to test our hypotheses. RESULTS: In conditional multivariable analysis of 87 case-control pairs, there was no difference in the odds of patients developing delirium if they were transfused red cell units with an exclusive storage age >14 days compared with that ≤14 days (odds ratio [OR] 1.83; 95% confidence interval, 0.73-4.58, P = 0.20). Each additional day of average red cell unit storage beyond 14 days was associated with a 1.01- to 1.13-fold increase in the odds of postoperative delirium (OR, 1.07; P = 0.03). Each additional day of average storage beyond 21 days was associated with a 1.02- to 1.23-fold increase in the odds of postoperative delirium (OR, 1.12; P = 0.02). CONCLUSIONS: Transfusion of red cell units that have been stored for >14 days is not associated with increased odds of delirium. However, each additional day of storage >14 or 21 days may be associated with increased odds of postoperative delirium in patients undergoing cardiac surgery. More research is needed to further characterize the association between delirium and storage duration of transfused red cell units.

A novel computerized functional assessment for human immunodeficiency virus-associated neurocognitive disorder.

Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) is present in 30-60 % of HIV-positive (HIV+) individuals and can be assessed by neuropsychological testing and level of functional impairment. HAND diagnosis therefore requires accurate assessment of functional impairment. The Computer Assessment of Mild Cognitive Impairment (CAMCI) is a computer-based screening tool that includes performance-based measures of functional impairment. We sought to evaluate the CAMCI as a functional assessment tool in HAND. One hundred fourteen HIV+ patients and 38 HIV-negative (HIV-) patients underwent neuropsychological and CAMCI testing. Cognitive status for HIV+ subjects was classified using the Frascati criteria. HIV+ subjects grouped together and classified by cognitive impairment performed worse than HIV- subjects on several of the CAMCI tasks, including following directions to the supermarket (p = 0.05, p = 0.03), recalling which items to purchase (p = 0.01, p = 0.02), and remembering to stop at a supermarket (p < 0.01, p = 0.01) and the post office (p < 0.01, p = 0.03). After controlling for hepatitis C status and depression symptomatology, the tasks "following directions to the supermarket" and the "recalling which items to purchase" were no longer significant. The "remembering to run two separate errands" tasks retained their significance (p < 0.01 for both tasks). A subset of the CAMCI tasks therefore successfully differentiated HIV+ patients from HIV- individuals. Differences in hepatitis C status and depression symptomatology could account for some of the function assessment differences in the CAMCI. These results suggest the CAMCI could be a useful objective performance-based functional assessment in patients with HIV.

Neuropsychological test performance before and after HIV-1 seroconversion: the Multicenter AIDS Cohort Study.

The objective of this study is to compare neuropsychological test performance before and after HIV-1 seroconversion in order to identify possible acute changes in psychomotor speed, memory, attention, and concentration secondary to seroconversion. The study utilized mixed effects models to examine longitudinal neuropsychological test data. We conducted a nested cohort study of 362 male HIV-1 seroconverters enrolled in the Multicenter AIDS Cohort Study. We used linear mixed models with random subject effects to compare repeated neuropsychological test outcomes from 5 years before seroconversion to 2 years after seroconversion on the Trail Making Test (parts A and B), Symbol-Digit Test, Grooved Pegboard (dominant and non-dominant hands), Stroop Color-Interference Test, Rey Auditory Verbal Learning Test, and the CalCAP Reaction Time Test. We found no significant changes in the time-dependent score after seroconversion for the majority of neuropsychological tests used in the Multicenter AIDS Cohort Study. There was a significant change in time trend after seroconversion on part B of the Trail Making Test (p=0.042), but the difference only represented a 2 % decrease in performance. We found the following characteristics to be associated with worse neuropsychological test performance: lower education levels, history of depression, older age, and no previous neurocognitive testing (p< .05). Our results suggest that despite a 50 % decrease in CD4 cell count immediately following infection, HIV-1 does not appear to have a measurable effect on psychomotor or complex cognitive processing for up to 2 years following infection, using this set of neurocognitive measures.

Platelet decline as a predictor of brain injury in HIV infection.

An association between platelet decline and increased risk of progression to dementia has been observed in an advanced HIV infection cohort study. This investigation evaluated the prognostic significance of platelet decline for dementia, for psychomotor slowing, and for brain injury, as quantified in vivo, in a much larger population of HIV+ men. Platelet counts and neurocognitive data were available from biannual visits of 2,125 HIV+ men participating in the prospective, Multicenter AIDS Cohort Study from 1984 to 2009. Brain volumetric data were also available from an imaging substudy of 83 seropositive participants aged 50 and older. The association of platelet counts with neurocognitive outcome was assessed using Cox proportional hazard models where change in platelet count from baseline was a time-updated variable. Marked platelet decline was associated with increased risk of dementia in univariate analysis (hazard ratio [HR] = 2.5, 95% confidence interval [CI] = 1.8-3.5), but not after adjustment for CD4 cell count, HIV viral load, age, study site, hemoglobin, race, education, smoking, and alcohol use (HR = 1.4, 95% CI = 0.78-2.5). Platelet decline did not predict psychomotor slowing in either univariate (HR = 0.79, 95% CI = 0.58-1.08) or multivariate (HR = 1.10, 95% CI = 0.73-1.67) analysis. Analysis of brain volumetric data, however, indicated a relationship between platelet decline and reduced gray matter volume fraction in univariate (p = 0.06) and multivariate (p < 0.05) analyses. Platelet decline was not an independent predictor of dementia or psychomotor slowing, after adjusting for stage of disease. Findings from a structural brain imaging substudy of older participants, however, support a possible relationship between platelet decline and reduced gray matter.

A comparison of performance-based measures of function in HIV-associated neurocognitive disorders.

The objectives of this study are to compare the results of newer performance-based functional assessments in the study of HIV-associated neurocognitive disorders (HAND) and to correlate these functional assessments with specific levels of severity of HAND. One hundred fourteen HIV+ subjects in an existing cohort were evaluated with a medical history, neurological exam, neuropsychological test battery as well as subjective and novel objective measures of functional abilities. Self-reported measures of functional performance included the Karnofsky Performance Scale, a questionnaire for instrumental activities of daily living, and a questionnaire for physical quality of life measures. The newer objective functional performance assessments included the Columbia Medication Management and the San Diego Finances tests. These newer performance-based measures of function were assessed for their ability to predict level of HAND. The two objective measures of functional performance, The Columbia Medication Management Scale and the San Diego Finances Test, were both associated with levels of severity of HAND. The Karnofsky Performance Scale and the questionnaires for role and physical quality of life were subjective measures that were also associated with specific levels of HAND. Newer measures of functional performance can be used to objectively evaluate functional impairment in HAND and validate different levels of HAND.

Delirium after coronary artery bypass graft surgery and late mortality.

OBJECTIVE: Delirium is common after cardiac surgery, although under-recognized, and its long-term consequences are likely underestimated. The primary goal of this study was to determine whether patients with delirium after coronary artery bypass graft (CABG) surgery have higher long-term out-of-hospital mortality when compared with CABG patients without delirium. METHODS: We studied 5,034 consecutive patients undergoing CABG surgery at a single institution from 1997 to 2007. Presence or absence of neurologic complications, including delirium, was assessed prospectively. Survival analysis was performed to determine the role of delirium in the hazard of death, including a propensity score to adjust for potential confounders. These analyses were repeated to determine the association between postoperative stroke and long-term mortality. RESULTS: Individuals with delirium had an increased hazard of death (adjusted hazard ratio [HR], 1.65; 95% confidence interval [CI], 1.38-1.97) up to 10 years postoperatively, after adjustment for perioperative and vascular risk factors. Patients with postoperative stroke had a HR of 2.34 (95% CI, 1.87-2.92). The effect of delirium on subsequent mortality was the strongest among those without a prior stroke (HR 1.83 vs HR 1.11 [with a prior stroke] [p-interaction = 0.02]) or who were younger (HR 2.42 [<65 years old] vs HR 1.49 [>/=65 years old] [p-interaction = 0.04]). INTERPRETATION: Delirium after cardiac surgery is a strong independent predictor of mortality up to 10 years postoperatively, especially in younger individuals and in those without prior stroke. Future studies are needed to determine the impact of delirium prevention and/or treatment in long-term patient mortality.

Neuropsychological outcomes after coronary artery bypass grafting.

Short- and long-term cognitive declines after cardiac surgery with cardiopulmonary bypass have been reported, but the frequency, severity, nature, and etiology of postoperative cognitive changes have been difficult to quantify. Current studies have corrected the principal methodological shortcoming of earlier studies by including control groups, and have shown that while early postoperative cognitive decline does occur in some patients, it is generally mild and reversible by 3 months after surgery. Late cognitive changes do occur, but comparison with patients undergoing off-pump surgery or those being treated medically suggests that these changes are not specific to CABG or more specifically to the use of cardiopulmonary bypass.

Cognition 6 years after surgical or medical therapy for coronary artery disease.

OBJECTIVE: The choice of coronary artery bypass grafting (CABG) as an intervention for coronary artery disease has been clouded by concerns about postoperative cognitive decline. Long-term cognitive decline after CABG has been reported, but without appropriate control subjects, it is not known whether this decline is specific to CABG or related to other factors such as cerebrovascular disease. METHODS: This prospective, observational study of patients with diagnosed coronary artery disease included 152 CABG and 92 nonsurgical cardiac comparison patients from one institution. The main outcome measure was within-patient change in cognitive performance for eight cognitive domains from baseline to 12- and 72-month follow-up. RESULTS: Mild late cognitive decline was observed for both study groups, but despite greater than 80% power to detect a 0.2 standard deviation difference, there were no statistically significant differences between the surgical and nonsurgical patients in the degree of change from 12 to 72 months for any cognitive domain. There was also no difference between groups in the degree of change from baseline to 72 months or in the number of patients with a Mini-Mental State Examination score in the clinically impaired range at 72 months. INTERPRETATION: Late cognitive decline does occur in patients who have undergone CABG surgery, but the degree of this decline does not differ from that observed in patients of similar age with coronary artery disease who have not undergone CABG. Therefore, late cognitive decline after CABG is not specific to the use of cardiopulmonary bypass.

Early postoperative cognitive dysfunction and blood pressure during coronary artery bypass graft operation.

OBJECTIVE: To determine the relationship between change in blood pressure during coronary artery bypass graft operations and early cognitive dysfunction. DESIGN: Cohort study. SETTING: Quaternary care facility. Patients Fifteen patients undergoing coronary artery bypass graft operations who were at high risk for postoperative stroke. Preoperative and intraoperative mean arterial pressures (MAPs) were measured in all patients. Intervention A subset of patients underwent preoperative and postoperative magnetic resonance imaging. Main Outcome Measure Change in cognitive performance, using the Mini-Mental State Examination and other simple cognitive tests. RESULTS: A drop in MAP (preoperatively to intraoperatively) predicted a decrease in Mini-Mental State Examination score. When change in MAP was dichotomized (after excluding an outlier), subjects with a small decrease improved on the Mini-Mental State Examination by 1 point, whereas those with a large drop in MAP worsened by 1.4 points (P = .04). CONCLUSION: A drop in MAP from a preoperative baseline may put patients at risk for early cognitive dysfunction after a coronary artery bypass graft operation.

An evaluation of neurocognitive status and markers of immune activation as predictors of time to death in advanced HIV infection.

BACKGROUND: Several markers of immune activation have been identified as potential prognostic markers for human immunodeficiency virus (HIV)-associated morbidity and mortality, but the results from studies are conflicting. OBJECTIVE: To evaluate whether neurocognitive status and baseline levels of plasma and cerebrospinal fluid tumor necrosis factor alpha (TNF-alpha), macrophage chemoattractant protein 1 (MCP-1), matrix metalloproteinase 2 (MMP-2), or macrophage colony-stimulating factor (M-CSF) are associated with time to death in a cohort with advanced HIV infection. DESIGN: Cohort study. SETTING: Enrollees in the Northeast AIDS Dementia Study. PARTICIPANTS: Three hundred twenty-nine subjects who were positive for HIV-1 and had a CD4 cell count of less than 200/microL (or <300/microL but with cognitive impairment at baseline) were assessed for CD4 cell count, neurocognitive status, pertinent demographic and clinical variables, and plasma and cerebrospinal fluid HIV RNA, TNF-alpha, MCP-1, MMP-2, and M-CSF levels. MAIN OUTCOME MEASURES: Cox proportional hazards regression models were used to examine the associations between the variables of interest (using time-dependent covariates, where applicable) and time to death, adjusting for possible confounders. RESULTS: There were 50 deaths in the cohort after a median of 25.2 months of follow-up. The cumulative incidences of death were 7% at 1 year and 16% at 2 years. In Cox proportional hazards regression analyses adjusting for demographic, clinical, and immunological variables, HIV-associated dementia (hazard rate, 6.10; P = .001) was significantly associated with time to death; (log) plasma MCP-1 level (hazard rate, 3.38; P = .08) trended toward significance. CONCLUSION: In patients with advanced HIV infection, HIV-associated dementia is an independent predictor of time to death.

Effect of ageing on neurocognitive function by stage of HIV infection: evidence from the Multicenter AIDS Cohort Study.

BACKGROUND: The demographics of the HIV epidemic in the USA have shifted towards older age. We aimed to establish the relationship between the processes of ageing and HIV infection in neurocognitive impairment. METHODS: With longitudinal data from the Multicenter AIDS Cohort Study, a long-term prospective cohort study of the natural and treated history of HIV infection among men who have sex with men in the USA, we examined the effect of ageing, HIV infection (by disease stage), and their interaction on five neurocognitive domains: information processing speed, executive function, episodic memory, working memory, and motor function. We controlled for duration of serostatus in a subanalysis, as well as comorbidities and other factors that affect cognition. Analyses were by linear mixed models for longitudinal data. FINDINGS: 5086 participants (47 886 visits) were included in the analytic sample (2278 HIV-seropositive participants contributed 20 477 visits and 2808 HIV-seronegative control participants contributed 27 409 visits). In an a-priori multivariate analysis with control variables including comorbidities and time since seroconversion, significant, direct negative effects of ageing were noted on all neurocognitive domains (p<0·0001 for all). Similar effects were noted for late-stage HIV disease progression on information processing speed (p=0·002), executive function (p<0·0001), motor function (p<0·0001), and working memory (p=0·001). Deleterious interaction effects were also noted in the domains of episodic memory (p=0·03) and motor function (p=0·02). INTERPRETATION: A greater than expected effect of ageing on episodic memory and motor function with advanced stages of HIV infection suggests that these two domains are most susceptible to the progression of neurocognitive impairment caused by ageing in individuals with HIV. This deficit pattern suggests differential damage to the hippocampus and basal ganglia (specifically nigrostriatal pathways). Older individuals with HIV infection should be targeted for regular screening for HIV-associate neurocognitive disorder, particularly with tests referable to the episodic memory and motor domains. FUNDING: National Institute of Mental Health.

Stroke and encephalopathy after cardiac surgery: an update.

BACKGROUND AND PURPOSE: As a result of advances in surgical, anesthetic, and medical management, cardiac surgery can now be performed on older, sicker patients, some of whom have had prior cardiac interventions. As surgical mortality has declined in recent years, attention has focused on the complications of stroke and encephalopathy after cardiac surgery. SUMMARY OF REVIEW: Patients with preexisting cerebrovascular disease are at increased risk for these untoward neurological outcomes, which are associated with longer lengths of hospital stay, higher costs, and greater mortality. The mechanisms underlying these neurological events may include microemboli and hypoperfusion during surgery, and postoperative atrial fibrillation. Predictive models, based on information available before surgery, allow identification of these "high risk" patients. CONCLUSIONS: Establishing the degree of functionally significant vascular disease of the brain before surgery should be an essential part of the preoperative evaluation, particularly when modifications in surgical technique or novel neuroprotective agents are being evaluated.

Watershed strokes after cardiac surgery: diagnosis, etiology, and outcome.

BACKGROUND AND PURPOSE: Watershed strokes are more prevalent after cardiac surgery than in other stroke populations, but their mechanism in this setting is not understood. We investigated the role of intraoperative blood pressure in the development of watershed strokes and used MRI to evaluate diagnosis and outcomes associated with this stroke subtype. METHODS: From 1998 to 2003 we studied 98 patients with clinical stroke after cardiac surgery who underwent MRI with diffusion-weighted imaging. We used logistic regression to explore the relationship between mean arterial pressure and watershed infarcts, between watershed infarcts and outcome, and chi(2) analyses to compare detection by MRI versus CT of watershed infarcts. RESULTS: Bilateral watershed infarcts were present on 48% of MRIs and 22% of CTs (P<0.0001). Perioperative stroke patients with bilateral watershed infarcts, compared with those with other infarct patterns, were 17.3 times more likely to die, 12.5 and 6.2 times more likely to be discharged to a skilled nursing facility and to acute rehabilitation, respectively, than to be discharged home (P=0.0004). Patients with a decrease in mean arterial pressure of at least 10 mm Hg (intraoperative compared with preoperative) were 4.1 times more likely to have bilateral watershed infarcts than other infarct patterns. CONCLUSIONS: Bilateral watershed infarcts after cardiac surgery are most reliably detected by diffusion-weighted imaging MRI and are associated with poor short-term outcome, compared with other infarct types. The mechanism may include an intraoperative drop in blood pressure from a patient's baseline. These findings have implications for future clinical practice and research.

Cognitive and neurobehavioral dysfunction after cardiac bypass procedures.

From a cognitive standpoint, CABG as currently practiced appears to be safe for the great majority of patients, but transient changes involving memory, executive functions, and motor speed may still occur in a subset of patients during the first few days to weeks after CABG. The etiology most likely is multifactorial and includes a synergistic effect of microemboli, hypo-perfusion, and other variables associated with major surgery. Older age and degree of pre-existing cerebrovascular disease have been identified as important risk factors. The short-term cognitive changes appear to be reversible by 3 months after surgery for most patients. Late cognitive decline after CABG,occurring between 1 and 5 years after the surgery, has been well documented,but controlled studies demonstrating that this decline is specifically attributable to the use of cardiopulmonary bypass itself rather than to progression of underlying cerebrovascular disease or other age-related changes are pending.

A randomized trial of the impact of a programmable medication reminder device on quality of life in patients with AIDS.

This 6-month randomized controlled trial evaluated the impact on quality of life (QOL) of a medication reminder device for patients with HIV. Patients were eligible if they had taken three or fewer highly active antiretroviral therapy (HAART) regimens or were treatment naïve. The intervention group received the Disease Management Assistance System (DMAS), a prompting device that verbally reminds patients at medication times and electronically records doses, and a monthly 30 minute adherence educational session. Controls received education only. QOL was measured at baseline and 6 months using the Centers for Epidemiologic Studies Depression Scale (CES-D), Instrumental Activities of Daily Living (IADLs), and the Medical Outcomes Study HIV Health Survey (MOS-HIV). At baseline, 62 patients completed surveys (31 control, 31 DMAS); at month 6, 48 patients completed surveys (23 control, 25 DMAS). At month 6, controls had improved QOL scores for CES-D, IADLs, physical health, general health, pain, QOL, and role functioning, while participants in the DMAS arm had some deterioration in QOL scores. These differences persisted after controlling for demographics, baseline CD4, and adherence. DMAS was associated with improved adherence but decreased QOL.

Hypothetical Preclinical Alzheimer Disease Groups and Longitudinal Cognitive Change.

IMPORTANCE: Clinical trials testing treatments for Alzheimer disease (AD) are increasingly focused on cognitively normal individuals in the preclinical phase of the disease. To optimize observing a treatment effect, such trials need to enroll cognitively normal individuals likely to show cognitive decline over the duration of the trial. OBJECTIVE: To identify which group of cognitively normal individuals shows the greatest cognitive decline over time based on their cerebrospinal fluid biomarker profile. DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, cognitively normal participants were classified into 1 of the following 4 hypothetical preclinical AD groups using baseline cerebrospinal fluid levels of Aß and tau or Aß and phosphorylated tau (p-tau): stage 0 (high Aß and low tau), stage 1 (low Aß and low tau), stage 2 (low Aß and high tau), and suspected non-AD pathology (SNAP) (high Aß and high tau). The data presented herein were collected between August 1995 and August 2014. MAIN OUTCOMES AND MEASURES: An a priori cognitive composite score based on the following 4 tests previously shown to predict progression from normal cognition to symptom onset of mild cognitive impairment or dementia: Paired Associates immediate recall, Logical Memory delayed recall, Boston Naming, and Digit-Symbol Substitution. Linear mixed-effects models were used to compare the cognitive composite scores across the 4 groups over time, adjusting for baseline age, sex, education, and their interactions with time. RESULTS: Two hundred twenty-two cognitively normal participants were included in the analyses (mean follow-up, 11.0 years [range, 0-18.3 years] and mean baseline age, 56.9 years [range, 22.1-85.8 years]). Of these, 102 were stage 0, 46 were stage 1, 28 were stage 2, and 46 were SNAP. Individuals in stage 2 (low Aß and high tau [or p-tau]) had lower baseline cognitive scores and a greater decline in the cognitive composite score relative to the other 3 groups (ß ≤ -0.06 for all and P ≤ .001 for the rate of decline for all). Individuals in stage 0, stage 1, and SNAP did not differ from one another in cognitive performance at baseline or over time (11.0 years) and showed practice-related improvement in performance. The APOE ε4 genotype was not associated with baseline cognitive composite score or the rate of change in the cognitive composite score. CONCLUSIONS AND RELEVANCE: These results suggest that, to optimize observing a treatment effect, clinical trials enrolling cognitively normal individuals should selectively recruit participants with abnormal levels of both amyloid and tau (ie, stage 2) because this group would be expected to show the greatest cognitive decline over time if untreated.

The International HIV Dementia Scale: a new rapid screening test for HIV dementia.

OBJECTIVE: HIV dementia is an important neurological complication of advanced HIV infection. The use of a cross-cultural screening test to detect HIV dementia within the international community is critical for diagnosing this condition. The objective of this study was to evaluate the sensitivity and specificity of a new screening test for HIV dementia, the International HIV Dementia Scale (IHDS) in cohorts from the US and Uganda. DESIGN: Two cross-sectional cohort studies designed to evaluate for the presence of HIV dementia. METHODS: Sixty-six HIV-positive individuals in the US and 81 HIV-positive individuals in Uganda received the IHDS and full standardized neurological and neuropsychological assessments. The sensitivity and specificity of varying cut-off scores of the IHDS were evaluated in the two cohorts. RESULTS: In the US cohort, the mean IHDS score for HIV-positive individuals without dementia and with dementia were 10.6 and 9.3 respectively (P < 0.001). Using the cut-off of < or = 10, the sensitivity and specificity for HIV dementia with the IHDS were 80% and 57% respectively in the US cohort, and 80% and 55% respectively in the Uganda cohort. CONCLUSIONS: The IHDS may be a useful screening test to identify individuals at risk for HIV dementia in both the industrialized world and the developing world. Full neuropsychological testing should then be performed to confirm a diagnosis of HIV dementia.