Impact of Baseline Features and Risk Factor Control on Cognitive Function in the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis Trial.

BACKGROUND: Cerebrovascular disease is an important cause of cognitive impairment. The aim of this study is to report the relationship between cognitive function and risk factors at baseline and during follow-up in the Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis (SAMMPRIS) trial. METHODS: Subjects in the SAMMPRIS trial were included in this study. In order to have an assessment of cognitive function independent of stroke, patients with a stroke as a qualifying event whose deficits included aphasia or neglect were excluded from these analyses as were those with a cerebrovascular event during follow-up. The Montreal Cognitive Assessment (MoCA) score was used to assess cognitive impairment at baseline, 4 months, 12 months and closeout. Cognitive impairment was defined as MoCA < 26. A multivariate analysis was performed to determine what risk factors were independent predictors of cognitive function at baseline, 12 months and closeout. Among patients randomized to aggressive medical management only, the percentage of patients with cognitive impairment was compared between patients in versus out of target for each risk factor at 12 months and closeout. RESULTS: Of the 451 patients in SAMMPRIS, 371 patients met the inclusion criteria. MoCA < 26 was present in 55% at baseline. Older age and physical inactivity were associated with cognitive impairment at baseline. Older age, non-white race, lower baseline body mass index, and baseline cognitive impairment were associated with cognitive impairment at 12 months. In the aggressive medical management group, at 12 months, physical inactivity during follow-up was the strongest risk factor associated with cognitive impairment. CONCLUSION: Cognitive impairment is common in patients with severe symptomatic intracranial atherosclerosis. Physical inactivity at baseline and during follow-up is a strong predictor of cognitive impairment.

Is There Benefit from Stenting on Cognitive Function in Intracranial Atherosclerosis?

BACKGROUND: Revascularization of stenotic cerebral arteries is hypothesized to improve cognition by increasing cerebral perfusion. AIMS: We compared cognition impairment among patients treated with percutaneous angioplasty and stenting (PTAS) and aggressive medical management (AMM) versus AMM alone in the Stenting versus Aggressive Medical Therapy for Intracranial Arterial Stenosis (SAMMPRIS) Trial. METHODS: In SAMMPRIS, 451 patients with recent transient ischemic attack or stroke attributed to 70-99% intracranial stenosis were randomized to PTAS plus AMM or AMM alone. Patients who had stroke as the qualifying event with National Institutes of Health Stroke Scale indicating aphasia or neglect were excluded from these analyses. Patients with a cerebrovascular event (ischemic stroke, cerebral infarct with temporary signs or intracranial hemorrhage) during follow-up were excluded from follow-up visit analyses. The Montreal Cognitive Assessment (MoCA) score was used to assess cognition impairment at baseline, 4 months, 12 months and closeout. Cognitive impairment was defined as MoCA <26. Mean MoCA scores and the percentage of patients with cognitive impairment were compared between treatment groups at each time point using t tests and chi-square tests. Differences in MoCA mean at baseline and follow-up time points were compared using mixed model repeated measures ANOVA and Tukey-Kramer tests. RESULTS: There were no significant differences between the treatment groups for mean MoCA at any time point. Mean MoCA scores improved in both groups. The percentage of patients with cognitive impairment in the AMM versus PTAS groups was not significantly different at any time point. CONCLUSIONS: Revascularization with PTAS showed no improvement in cognitive impairment over AMM alone among patients who did not have recurrent cerebrovascular events during follow-up.

Racial differences in poststroke rehabilitation utilization and functional outcomes.

OBJECTIVE: To examine racial differences in poststroke rehabilitation utilization and functional outcomes. DESIGN: Observational follow-up study. SETTING: Designated stroke center. PARTICIPANTS: Stroke survivors (N=162; 106 whites and 56 blacks) surveyed at 1 year poststroke. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Twenty-question measure of activities of daily living (ADL) and instrumental activities of daily living (IADL) performance, life participation, and driving. One-year follow-up data collected from stroke survivors as part of the Stroke Education and Prevention-South Carolina Project were examined for racial disparities in rehabilitation utilization and functional outcomes. RESULTS: Analyses revealed no significant differences between blacks and whites for rehabilitation utilization. In multivariate comparisons controlling for stroke severity, blacks were less likely to report independence in overall functional performance and domain-specific measures of toileting, walking, transportation, laundry, and shopping. Blacks also reported less independence in driving at 1-year follow-up. CONCLUSIONS: Blacks were less likely to report independence in performing ADL and IADL at 1 year poststroke after controlling for stroke severity. Racial disparities were reported in ADL and IADL performance despite a lack of racial differences in rehabilitation utilization. Future studies are needed to further understand the reason for this disparity in reported functional independence.

Progressive Multifocal Leukoencephalopathy: Recent Advances and a Neuro-Ophthalmological Review.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a severe often fatal opportunistic infection of the central nervous system caused by reactivation of a ubiquitous polyoma virus, JC virus. Although typically characterized by multifocal asymmetric subcortical white matter lesions, it may be monofocal and affect the cortical gray matter. Among the broad spectrum of clinical manifestations that occurs with PML, visual complaints are common. EVIDENCE ACQUISITION: Combination of representative personally observed cases of PML and comprehensive review of case series of PML from 1958 through 2014. RESULTS: Neuro-ophthalmic signs and symptoms were reported in approximately 20%-50% of patients with PML and can be the presenting manifestation in half of these. A majority of these presentations occur from damage to cerebral visual pathways resulting in visual field defects, cortical blindness, and other disorders of visual association. Given the decreased frequency of infratentorial and cerebellar involvement, ocular motility disorders are less common. CONCLUSIONS: Visual complaints occur in patients with PML and are often the presenting sign. Awareness of this condition is helpful in avoiding unnecessary delays in the diagnosis of PML and management of the underlying condition. Recent guidelines have established criteria for diagnosis of PML in the high-risk patient population and strategies to mitigate the risk in these populations.

Persistent racial disparity in stroke hospitalization and economic impact in young adults in the buckle of stroke belt.

BACKGROUND AND PURPOSE: Mounting evidence points to a decline in stroke incidence. However, little is known about recent patterns of stroke hospitalization within the buckle of the stroke belt. This study aims to investigate the age- and race-specific secular trends in stroke hospitalization rates, inpatient stroke mortality rates, and related hospitalization charges during the past decade in South Carolina. METHODS: Patients from 2001 to 2010 were identified from the State Inpatient Hospital Discharge Database with a primary discharge diagnosis of stroke (International Classification of Diseases, Ninth Revision codes: 430-434, 436, 437.1). Age- and race-stroke-specific hospitalization rates, hospital charges, charges associated with racial disparity, and 30-day stroke mortality rates were compared between blacks and whites. RESULTS: Of the 84,179 stroke hospitalizations, 31,137 (37.0%) were from patients aged<65 years and 29,846 (35.5%) were blacks. Stroke hospitalization rates decreased in the older population (aged≥65 years) for both blacks and whites (P<0.001) but increased among the younger group (aged<65 years; P=0.004); however, this increase was mainly driven by a 17.3% rise among blacks (P=0.001), with no difference seen among whites (P=0.84). Of hospital charges totaling $2.77 billion, $453.2 million (16.4%) are associated with racial disparity (79.6% from patients aged<65 years). Thirty-day stroke mortality rates decreased in all age-race-stroke-specific groups (P<0.001). CONCLUSIONS: The stroke hospitalization rate increased in the young blacks only, which results in a severe and persistent racial disparity. It highlights the urgent need for a racial disparity reduction in the younger population to alleviate the healthcare burden.

Effect of methylphenidate on attention in apathetic AD patients in a randomized, placebo-controlled trial.

BACKGROUND: Little is known about the effect of methylphenidate (MPH) on attention in Alzheimer's disease (AD). MPH has shown to improve apathy in AD, and both apathy and attention have been related to dopaminergic function. The goal was to investigate MPH effects on attention in AD and assess the relationship between attention and apathy responses. METHODS: MPH (10 mg PO twice daily) or placebo was administered for six weeks in a randomized, double-blind trial in mild-to-moderate AD outpatients with apathy (Neuropsychiatric Inventory (NPI) Apathy ≥ 4). Attention was measured with the Wechsler Adult Intelligence Scale--Digit Span (DS) subtest (DS forward, selective attention) and apathy with the Apathy Evaluation Scale (AES). A mixed effects linear regression estimated the difference in change from baseline between treatment groups, defined as δ (MPH (DS week 6-DS baseline)) - (placebo (DS week 6-DS baseline)). RESULTS: In 60 patients (37 females, age = 76 ± 8, Mini-Mental State Examination (MMSE) = 20 ± 5, NPI Apathy = 7 ± 2), the change in DS forward (δ = 0.87 (95% CI: 0.06-1.68), p = 0.03) and DS total (δ = 1.01 (95% CI: 0.09-1.93), p = 0.03) favored MPH over placebo. Of 57 completers, 17 patients had improved apathy (≥3.3 points on the AES from baseline to end point) and 40 did not. There were no significant associations between AES and NPI Apathy with DS change scores in the MPH, placebo, AES responder, or non-responder groups. DS scores did not predict apathy response to MPH treatment. CONCLUSION: These results suggest MPH can improve attention and apathy in AD; however, the effects appear independent in this population.

The impact of ICD-9 revascularization procedure codes on estimates of racial disparities in ischemic stroke.

BACKGROUND: The use of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9) diagnostic codes can identify racial disparities in ischemic stroke hospitalizations; however, inclusion of revascularization procedure codes as acute stroke events may affect the magnitude of the risk difference. This study assesses the impact of excluding revascularization procedure codes in the ICD-9 definition of ischemic stroke, compared with the traditional inclusive definition, on racial disparity estimates for stroke incidence and recurrence. METHODS: Patients discharged with a diagnosis of ischemic stroke (ICD-9 codes 433.00-434.91 and 436) were identified from a statewide inpatient discharge database from 2010 to 2012. Race-age specific disparity estimates of stroke incidence and recurrence and 1-year cumulative recurrent stroke rates were compared between the routinely used traditional classification and a modified classification of stroke that excluded primary ICD-9 cerebral revascularization procedures codes (38.12, 00.61, and 00.63). RESULTS: The traditional classification identified 7878 stroke hospitalizations, whereas the modified classification resulted in 18% fewer hospitalizations (n = 6444). The age-specific black to white rate ratios were significantly higher in the modified than in the traditional classification for stroke incidence (rate ratio, 1.50; 95% confidence interval [CI], 1.43-1.58 vs. rate ratio, 1.24; 95% CI, 1.18-1.30, respectively). In whites, the 1-year cumulative recurrence rate was significantly reduced by 46% (45-64 years) and 49% (≥ 65 years) in the modified classification, largely explained by a higher rate of cerebral revascularization procedures among whites. There were nonsignificant reductions of 14% (45-64 years) and 19% (≥ 65 years) among blacks. CONCLUSIONS: Including cerebral revascularization procedure codes overestimates hospitalization rates for ischemic stroke and significantly underestimates the racial disparity estimates in stroke incidence and recurrence.

Impact of repeated sportive chokes on carotid intima media thickness and brain injury biomarkers in grappling athletes.

PURPOSE: Vascular neck compression techniques, referred to as 'chokes' in combat sports, reduce cerebral perfusion, causing loss of consciousness or voluntary submission by the choked athlete. Despite these chokes happening millions of times yearly around the world, there is scant research on their long-term effects. This pilot study evaluated whether repeated choking in submission grappling impacts the carotid intima media thickness (CIMT) and brain injury biomarkers (NFL, hGFAP, t-Tau, and UCH-L1). METHODS: Participants (n = 39, 29 male; ages 27-60 years) were assigned to one of two study arms: Grapplers (n = 20, 15 male) and 19 age/sex/body size matched controls. Grapplers had been exposed to >500 choke events while training for >5 years in a choke-inclusive sport. Exclusion criteria were recent TBI or deficits from a past TBI or stroke. Bilateral ultrasound measurement of the CIMT was performed, and blood was collected for quantitative analysis of four brain injury markers. Subgroup analyses were performed within the Grappler group to account for blunt head trauma as a possible confounder. RESULTS: There was no overall difference in CIMT measurements between Grapplers (mean 0.55 mm, SD 0.07) and Controls (mean 0.57 mm, SD 0.10) p = 0.498 [95% CI -0.04-0.08], nor were there CIMT differences between Grappler subgroups of blunt Trauma and No-Trauma. There were no significant differences in any biomarkers comparing Grapplers and Controls or comparing Grappler subgroups of Trauma and No-Trauma. CONCLUSION: This study found no significant difference in CIMT and serum brain injury biomarkers between controls and grapplers with extensive transient choke experience, nor between grapplers with extensive past blunt head trauma and those without.

Cognitive Assessment in Grappling Athletes Following Choke Versus Non-Choke Submissions.

PURPOSE: Participation in Brazilian jiu-jitsu (BJJ) and mixed martial arts has increased over the last 3 decades. These sports feature submission attacks, including strangles. These strangles, termed "chokes" in this context, primarily limit blood flow to the brain via compression of neck vasculature. There has been discussion in literature of the possibility of measurable cognitive effects following transient choking episodes. The present study used the King-Devick test (KDT) platform, a tablet-based reaction time and accuracy task designed to measure participants' number recognition, cognition, and verbal expression. This task requires functional vision, saccadic eye movements, comprehension and expression. METHODS: Volunteer participants were screened for exclusion (prior brain injury) criteria and survey information prior to testing. Athletes were tested with the KDT immediately prior to a BJJ training session, again immediately after succumbing to either a choke ("Choke" arm) or non-choke ("Non-Choke" arm) submission while sparring, and again after a 10-minute rest period following the post-submission test. Analysis was done on Test Failures, Total Test Times, and Individual Difference Scores between baseline and subsequent testing. RESULTS: 62 (32 Choke, 30 Non-Choke) participants were analyzed. There was no significant difference between Choke and Non-Choke in Test failures (X2(1,62) = 1.25, p = 0.263), Total Times (t(60) = 0.62, p = 0.540, 95% CI [-3.44, 6.51]), and Individual Difference Scores (t(60) = 0.29, p = 0.776, 95% CI [-2.41, 3.21]). CONCLUSIONS: There were no significant differences between study arms in any of the 3 analyzed measures. This suggests that cognitive functioning, as measured by the King-Devick test, is not affected by transient choking episodes.

Designing a trial to evaluate potential treatments for apathy in dementia: the apathy in dementia methylphenidate trial (ADMET).

BACKGROUND: Research on efficacious treatments for apathy in Alzheimer disease has been hindered by a lack of consensus diagnosis, difficulties in measurement, and studies with small sample sizes. METHODS: In designing the Apathy in Dementia Methylphenidate Trial (ADMET), a trial to evaluate the efficacy and safety of methylphenidate for the treatment of apathy in Alzheimer disease, we encountered the following issues: defining and measuring apathy, distinguishing apathy and depression, determining an appropriate test treatment, selecting relevant secondary outcomes, recruiting participants, and deciding on a suitable method for treatment unmasking. ADMET is a 6-week randomized, double-masked, placebo-controlled multicenter clinical trial with two parallel treatment groups assigned in a 1:1 ratio with randomization stratified by clinical center. The recruitment goal is 60 randomized participants over 2 years. The primary outcomes are change in apathy severity as measured by the Apathy Evaluation Scale and the Alzheimer Disease Cooperative Study-Clinical Global Impression of Change. CONCLUSION: The design decisions made for ADMET are important elements to be considered in trials assessing the safety and efficacy of medications for clinically significant apathy in Alzheimer disease.

Establishment of a predominantly African-American cohort for the study of Alzheimer's disease: the South Carolina Alzheimer's disease clinical core.

BACKGROUND/AIMS: The recruitment of culturally diverse subject populations into research studies, particularly African-Americans (AA), has been the focus of intense interest by many groups. METHODS: In this paper, we present the methodology utilized to create a predominantly AA cohort for the longitudinal study of risk factors in Alzheimer's disease (AD). The underlying strategy was that of identifying geographically diverse clinical venues within South Carolina (SC) where large numbers of AA patients already come to seek medical care. RESULTS: This strategy was successful, although recruitment rates for AA subjects (43.4%) still fell below those for white subjects (70.3%; p = 0.0025). Subject characteristics of AA subjects that chose to enroll were not substantially different from those that declined to participate. The demographic characteristics of this cohort were largely similar to those of the SC Alzheimer Disease Registry, a population-based database. The problems of standardization of subject recruitment and assessment across diverse clinical venues are also addressed. CONCLUSION: The utilization of geographically diverse sites for research recruitment where minorities already receive medical care is one practical solution to the problem of minority participation in research. Multi-site recruitment to improve minority recruitment can be accomplished with acceptable standardization and inter-rater reliability.

Preliminary examination of progression of Alzheimer's disease in a rural Southern African American cohort.

African Americans are at significantly increased risk for the development of Alzheimer's disease (AD), yet are seriously underrepresented in research trials. Preliminary experiences on a large scale, multi-site, 5-year longitudinal trial investigating the psychometric expression and progression of AD targeting an aging Southern rural cohort of African Americans are reported. Sixty-five participants, ranging from asymptomatic to severely demented, underwent extensive individual diagnostic and psychometric evaluation. Results indicated that cultural factors strongly influenced the data. Recruitment with asymptomatic volunteers were found to have greater educational attainment than other participant groups. Psychomotor measures showed greater impairment in African Americans compared to Caucasians suggesting increased cerebrovascular burden. African Americans' performance on the Boston Naming Test and the Wechsler Test of Adult Reading tests were significantly different than performance of Caucasian groups. The findings demonstrated that a better understanding of sociocultural factors associated with AD in the African American population may facilitate the development of primary and secondary preventions, especially when considering the role of cerebrovascular comorbidity which is a modifiable risk factor.

Demographic and biologic influences on survival in whites and blacks: 40 years of follow-up in the Charleston Heart Study.

BACKGROUND: In the United States, life expectancy is significantly lower among blacks than whites. We examined whether socioeconomic status (SES) and cardiovascular disease (CVD) risk factors may help explain this disparity. METHODS: Forty years (1961 through 2000) of all-cause mortality data were obtained on a population-based cohort of 2,283 subjects in the Charleston Heart Study (CHS). We examined the influence of SES and CVD risk factors on all-cause mortality. RESULTS: Complete data were available on 98% of the original sample (647 white men, 728 white women, 423 black men, and 443 black women). After adjusting for SES and CVD risk factors, the hazard ratios (HRs) for white ethnicity were 1.14 (0.98 to 1.32) among men and 0.90 (0.75 to 1.08) among women, indicating that the mortality risk was 14% greater for white men and 10% lower for white women compared to their black counterparts. However the differences were not statistically significant. CONCLUSION: While there are marked contrasts in mortality among blacks and whites in the CHS, the differences can be largely explained by SES and CVD risk factors. Continued focus on improving and controlling cardiovascular disease risk factors may reduce ethnic disparities in survival.

A comparison of four embedded validity indices for the RBANS in a memory disorders clinic.

This examination of four embedded validity indices for the Repeated Battery for the Assessment of Neuropsychological Status (RBANS) explores the potential utility of integrating cognitive and self-reported depressive measures. Examined indices include the proposed RBANS Performance Validity Index (RBANS PVI) and the Charleston Revised Index of Effort for the RBANS (CRIER). The CRIER represented the novel integration of cognitive test performance and depression self-report information. The sample included 234 patients without dementia who could be identified as having demonstrated either valid or invalid responding, based on standardized criteria. Sensitivity and specificity for invalid responding varied widely, with the CRIER emerging as the best all-around index (sensitivity = 0.84, specificity = 0.90, AUC = 0.94). Findings support the use of embedded response validity indices, and suggest that the integration of cognitive and self-report depression data may optimize detection of invalid responding among older Veterans.

Oscillating Square Wave Transcranial Direct Current Stimulation (tDCS) Delivered During Slow Wave Sleep Does Not Improve Declarative Memory More Than Sham: A Randomized Sham Controlled Crossover Study.

BACKGROUND: A 2006 trial in healthy medical students found that anodal slow oscillating tDCS delivered bi-frontally during slow wave sleep had an enhancing effect in declarative, but not procedural memory. Although there have been supporting animal studies, and similar findings in pathological groups, this study has not been replicated, or refuted, in the intervening years. We therefore tested these earlier results for replication using similar methods with the exception of current waveform (square in our study, nearly sinusoidal in the original). OBJECTIVE/HYPOTHESIS: Our objective was to test the findings of a 2006 trial suggesting bi-frontal anodal tDCS during slow wave sleep enhances declarative memory. METHODS: Twelve students (mean age 25, 9 women) free of medical problems underwent two testing conditions (active, sham) in a randomized counterbalanced fashion. Active stimulation consisted of oscillating square wave tDCS delivered during early Non-Rapid Eye Movement (NREM) sleep. The sham condition consisted of setting-up the tDCS device and electrodes, but not turning it on during sleep. tDCS was delivered bi-frontally with anodes placed at F3/F4, and cathodes placed at mastoids. Current density was 0.517 mA/cm(2), and oscillated between zero and maximal current at a frequency of 0.75 Hz. Stimulation occurred during five-five minute blocks with 1-min inter-block intervals (25 min total stimulation). The primary outcomes were both declarative memory consolidation measured by a paired word association test (PWA), and non-declarative memory, measured by a non-dominant finger-tapping test (FTT). We also recorded and analyzed sleep EEG. RESULTS: There was no difference in the number of paired word associations remembered before compared to after sleep [(active = 3.1 ± 3.0 SD more associations) (sham = 3.8 ± 3.1 SD more associations)]. Finger tapping improved, (non-significantly) following active stimulation [(3.6 ± 2.7 SD correctly typed sequences) compared to sham stimulation (2.3 ± 2.2 SD correctly typed sequences)]. CONCLUSION: In this study, we failed to find improvements in declarative or performance memory and could not replicate an earlier study using nearly identical settings. Specifically we failed to find a beneficial effect on either overnight declarative or non-declarative memory consolidation via square-wave oscillating tDCS intervention applied bi-frontally during early NREM sleep. It is unclear if the morphology of the tDCS pulse is critical in any memory related improvements.

Depression as a risk factor for Alzheimer disease: the MIRAGE Study.

BACKGROUND: Depression symptoms may be associated with the development of Alzheimer disease (AD). OBJECTIVES: To evaluate the association between depression symptoms and risk of AD, and to explore the temporal aspects of this association. SETTING: Academic institutions with specialized memory clinics. DESIGN: Cross-sectional, family-based, case-control study with standardized self- and proxy questionnaires to collect information on depression symptoms and other risk factors. PARTICIPANTS: A total of 1953 subjects with AD and 2093 of their unaffected relatives enrolled in the Multi-institutional Research in Alzheimer's Genetic Epidemiology Study. MAIN OUTCOME MEASURES: Odds ratios (ORs) of AD were estimated with and without depression symptoms, adjusted for age, sex, education, history of head trauma, and apolipoprotein E status. RESULTS: There was a significant association between depression symptoms and AD (adjusted OR, 2.13; 95% confidence interval [CI], 1.71-2.67). In families where depression symptoms first occurred within 1 year before the onset of AD, the association was higher (OR, 4.57; 95% CI, 2.87-7.31), while in the families where the depression symptoms first occurred more than 1 year before the onset of AD, the association was lower (OR, 1.38; 95% CI, 1.03-1.85). In families where depression symptoms first occurred more than 25 years before the onset of AD, there was still a modest association (OR, 1.71; 95% CI, 1.03-2.82). CONCLUSIONS: Depression symptoms before the onset of AD are associated with the development of AD, even in families where first depression symptoms occurred more than 25 years before the onset of AD. These data suggest that depression symptoms are a risk factor for later development of AD.

Association between apolipoprotein E genotype and Alzheimer disease in African American subjects.

BACKGROUND: The association between Alzheimer disease (AD) and genotypes at the apolipoprotein E (APOE) locus has been confirmed in numerous populations worldwide, but appears to be inconsistent in African American subjects. OBJECTIVE: To investigate the association between APOE genotypes and AD in elderly African American subjects. DESIGN: Clinic-based, multicenter case-control study and a family study. PARTICIPANTS: A total of 338 African American probands meeting criteria for probable or definite AD, 301 cognitively healthy, elderly unrelated control subjects (spouses and community volunteers), and 108 siblings of 88 AD probands. MAIN OUTCOME MEASURES: Odds of AD according to APOE genotype. RESULTS: Compared with individuals with the APOEepsilon3/epsilon3, the odds of having AD were significantly increased among those with 1 or more copies of the epsilon4 allele; the odds ratio (OR) for the epsilon3/epsilon4 genotype was 2.6 (95% confidence interval [CI], 1.8-3.7), and the OR for the epsilon4/epsilon4 genotype was 10.5 (95% CI, 5.1-21.8). These risks decreased substantially after 68 years of age. The risk for AD was lower among individuals with the epsilon2/epsilon3 genotype (OR, 0.41; 95% CI, 0.22-0.79). The patterns of association were similar in men and women. These results obtained from comparisons of unrelated AD patients and controls were bolstered by results of analysis of family data that showed preferential transmission of the epsilon4 allele to demented siblings (P<<.001) and of the epsilon2 allele to nondemented siblings (P=.005). CONCLUSIONS: The presence of 1 or 2 epsilon4 alleles is a determinant of AD risk in African American subjects. The age-related risk for decline associated with the epsilon4 allele and the apparent protective effect of the epsilon2 allele are similar to patterns observed in white subjects.

Phase III quality-of-life study results: impact on patients' quality of life to reducing xerostomia after radiotherapy for head-and-neck cancer--RTOG 97-09.

PURPOSE: To determine whether prevention of hyposalivation after curative radiotherapy (RT) to the head and neck improves patients' quality of life (QOL). METHODS AND MATERIALS: Patients were to receive at least 50 Gy to 50% of the volume of the major salivary glands, provide unstimulated and stimulated saliva samples, and complete the University of Washington head-and-neck QOL tool before RT and 3 and 6 months after RT. Patients were randomized to receive pilocarpine 5 mg or placebo q.i.d. RESULTS: A total of 249 patients was randomized between March 1998 and January 2000. Of these, 214 were eligible for QOL analysis. Patients were evenly distributed between arms by race, gender, tobacco use, tumor site, T stage (50% T2-T3), and salivary function. A Karnofsky performance status of 90% was more common in the pilocarpine arm. Twenty percent of the patients on the pilocarpine arm and 29% of the patients on the placebo arm were taking nutritional supplements. The placebo arm patients had greater mouth pain and chewing difficulties. Compliance for the QOL tool at 3 and 6 months was 65% and 50%, respectively. Despite statistically significant (p = 0.047 and p = 0.049, respectively) preservation of salivary function in the pilocarpine arm, patients on the pilocarpine arm reported difficulties with swallowing (75%), activity (80%), hyposalivation (64%), and taste (81%). No difference was noted between arms at 3 months in mucositis scores, with both arms demonstrating increased requirement for oral nutrients. CONCLUSION: Objective prevention of hyposalivation did not affect patients' assessment of salivary function or QOL because of the greater impact mucositis plays in QOL after RT.

Diagnostic challenges of using CSF assay of tau and beta-amyloid(42) in atypical degenerative dementias of the Alzheimer type.

This report presents three cases of atypical degenerative dementias in order to illustrate challenges associated with the use of biologic markers of Alzheimer's disease (AD) for diagnosis and management. Clinical diagnostic methods followed the NINCDS-ADRDA criteria for AD. Additional diagnostic studies included serial neurocognitive testing, MRI, neuroSPECT, ApoE genotyping, and a CSF assay of tau and beta-amyloid(42). For patient 1, both the clinical and biologic markers were consistent with AD. The patient was diagnosed with AD with a high degree of confidence, even though the base rate of nonfamilial AD at this age group (<55 years) is exceedingly rare. This case argues favorably for the use of biologic markers to aid in confirming a diagnosis in an atypical dementia. Patient 2 met the NINCDS-ADRDA criteria for AD, although with less confidence. Neurocognitive data indicated a progressive right hemispheric syndrome, insight was preserved, and ApoE was 3/3, but tau concentrations and beta-amyloid(42) were highly consistent with cut-offs for AD; the differential fell on the Pick's disease/frontotemporal degeneration spectrum. Patient 3 had no clinical evidence of the disease, even when evaluated via extensive neurocognitive testing over a 2-year interval. However, ApoE was 4/4, and CSF assay of tau and beta-amyloid(42) were within the AD range. Therefore, while the CSF assay of tau and beta-amyloid(42) markers was confirmatory of AD, each case was highly atypical. Results illustrate the lack of normative data available when using biologic markers for highly atypical cases, calling into question their usefulness for such patients. These cases illustrate the interplay between neuropsychological and biological markers in establishing neurodegenerative diagnoses.

A synopsis of the practice parameters on dementia from the american academy of neurology on the diagnosis of dementia.

OBJECTIVE: The objective of this paper is to review the current practice guidelines as developed by the American Academy of Neurology (AAN) for the diagnosis of dementia. DATA SOURCES: The data sources were the Report of the Quality Standards Subcommittee of the American Academy of Neurology paper, which was published in the May 2001 issue of the journal Neurology. STUDY SELECTION: The studies used in this paper are those reviewed by the AAN Practice Parameter Committee, which reviewed the literature for evidence-based human studies pertaining to the diagnosis of dementia. Studies on Alzheimer's disease (AD) included had to have more than 25 subjects. Each article was classified based on the quality of evidence. After review of the evidence, the committee drafted recommendations and placed the evidence into Practice Standards, Guidelines, or Options. DATA SYNTHESIS: The main results of this review were the guidelines for diagnosing dementia of various forms. To diagnose dementia, the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised (DSM-IIIR) should be used. For AD, the NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer s Disease and Related Disorders Association) criteria should be used. The Modified Hachinski Ischemic Score criteria can be used in the diagnosis of vascular dementia. The Consortium for DLB (Dementia with Lewy Bodies) criteria may be of use in clinical practice. Neuroimaging with a noncontrast CT or MRI scan in the routine initial evaluation of persons with dementia is appropriate; other methods of neuroimaging are not recommended at this time. Genetic testing and use of apolipoprotein E (ApoE) genotyping is not recommended at this time. Depression, B12 deficiency, and hypothyroidism should be screened for and treated in patients with dementia. Unless the patient lives in an area in the United States with a high rate of syphilis, screening for tertiary syphilis is not warranted. CONCLUSION: The guidelines and their clinical applications are pertinent and important knowledge for consultant pharmacists. This practice parameter will need to be updated every few years to include new studies and information that becomes available.