A survey of speech-language pathology service delivery in Australian schools.

PURPOSE: Speech-language pathologists (SLPs) work in Australian schools yet, little is documented about their service delivery practices. This study therefore explores Australian speech-language pathology service delivery in schools, inclusive of work activities, caseloads, and assessment and intervention practices. METHOD: An online survey comprising multiple choice, constant sum, Likert scale, and open text questions was completed by 105 SLPs. Quantitative data was analysed using descriptive statistics while open-text responses were analysed using content analysis. RESULT: Participants were predominantly government education department employees working in multiple schools, and caseloads ranged from 10 to 240 students for full-time SLPs. While responses varied considerably, some general trends emerged. Most time was spent on intervention, followed by non-contact tasks, and assessments, with differences across employment sectors. Language was the most common student need, followed by literacy and speech. Frequently reported factors contributing to client complexity and intervention frequency were co-occurring presentations, severity of student needs, caseload size, and impact on learning. Caseload manageability was a concern for participants who reported larger caseloads, spent more time in assessment or less time in therapy than others, and worked in education departments. CONCLUSION: Findings have implications for policy makers, professional bodies and employers, and provide direction for future systematic data collection.

Overcoming Barriers to Latino Participation in Alzheimer's Disease Research.

There is a critical need to increase Latino participation in research on Alzheimer's disease and related disorders (ADRD). Applying principles of community-based participatory research, we convened a community advisory board (CAB) to identify barriers and recommend strategies to increase participation of older Latinos in a longitudinal observational research study of ADRD at the Shiley-Marcos Alzheimer's Disease Research Center. Six major barriers were identified and programmatic changes to overcome them were implemented. Changes resulted in a nearly three-fold increase in the number of Latino individuals recruited, with the proportion of all newly recruited participants who were Latino increasing from 12.2% to 57.4%. Newer Latino recruits were more representative of the elderly Latino population in San Diego County than those recruited pre-CAB and remained highly agreeable to blood draw and neuroimaging, though less so to lumbar puncture and autopsy. Results demonstrate the value of CAB involvement in enhancing diversity in ADRD research.

Protocol for a seamless phase 2A-phase 2B randomized double-blind placebo-controlled trial to evaluate the safety and efficacy of benfotiamine in patients with early Alzheimer's disease (BenfoTeam).

BACKGROUND: Benfotiamine provides an important novel therapeutic direction in Alzheimer's disease (AD) with possible additive or synergistic effects to amyloid targeting therapeutic approaches. OBJECTIVE: To conduct a seamless phase 2A-2B proof of concept trial investigating tolerability, safety, and efficacy of benfotiamine, a prodrug of thiamine, as a first-in-class small molecule oral treatment for early AD. METHODS: This is the protocol for a randomized, double-blind, placebo-controlled 72-week clinical trial of benfotiamine in 406 participants with early AD. Phase 2A determines the highest safe and well-tolerated dose of benfotiamine to be carried forward to phase 2B. During phase 2A, real-time monitoring of pre-defined safety stopping criteria in the first approximately 150 enrollees will help determine which dose (600 mg or 1200 mg) will be carried forward into phase 2B. The phase 2A primary analysis will test whether the rate of tolerability events (TEs) is unacceptably high in the high-dose arm compared to placebo. The primary safety endpoint in phase 2A is the rate of TEs compared between active and placebo arms, at each dose. The completion of phase 2A will seamlessly transition to phase 2B without pausing or stopping the trial. Phase 2B will assess efficacy and longer-term safety of benfotiamine in a larger group of participants through 72 weeks of treatment, at the selected dose. The co-primary efficacy endpoints in phase 2B are CDR-Sum of Boxes and ADAS-Cog13. Secondary endpoints include safety and tolerability measures; pharmacokinetic measures of thiamine and its esters, erythrocyte transketolase activity as blood markers of efficacy of drug delivery; ADCS-ADL-MCI; and MoCA. CONCLUSION: The BenfoTeam trial utilizes an innovative seamless phase 2A-2B design to achieve proof of concept. It includes an adaptive dose decision rule, thus optimizing exposure to the highest and best-tolerated dose. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06223360, registered on January 25, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT06223360.

Comparison of the telephone-Montreal Cognitive Assessment (T-MoCA) and Telephone Interview for Cognitive Status (TICS) as screening tests for early Alzheimer's disease.

INTRODUCTION: Remote screening for cognitive impairment associated with Alzheimer's disease (AD) has grown in importance with the expected rise in prevalence of AD in an aging population and with new potential treatment options. METHODS: The Telephone Interview for Cognitive Status (TICS) and new telephone adaptation of the Montreal Cognitive Assessment (T-MoCA) were administered to participants independently classified through in-person clinical evaluation as cognitively normal (CN; n = 167), mild cognitive impairment (MCI; n = 25), or dementia (n = 23). Cerebrospinal fluid AD biomarkers were measured (n = 79). RESULTS: TICS and T-MoCA were highly correlated (r = 0.787; P < 0.001): groups differed on both (CN

Optimal Weighting of Preclinical Alzheimer's Cognitive Composite (PACC) Scales to Improve their Performance as Outcome Measures for Alzheimer's Disease Clinical Trials.

Introduction: Cognitive composite scales constructed by combining existing neuropsychometric tests are seeing wide application as endpoints for clinical trials and cohort studies of Alzheimer's disease (AD) predementia conditions. Preclinical Alzheimer's Cognitive Composite (PACC) scales are composite scores calculated as the sum of the component test scores weighted by the reciprocal of their standard deviations at the baseline visit. Reciprocal standard deviation is an arbitrary weighting in this context, and may be an inefficient utilization of the data contained in the component measures. Mathematically derived optimal composite weighting is a promising alternative. Methods: Sample size projections using standard power calculation formulas were used to describe the relative performance of component measures and their composites when used as endpoints for clinical trials. Power calculations were informed by (n=1,333) amnestic mild cognitive impaired participants in the National Alzheimer's Coordinating Center (NACC) Uniform Data Set. Results: A composite constructed using PACC reciprocal standard deviation weighting was both less sensitive to change than one of its component measures and less sensitive to change than its optimally weighted counterpart. In standard sample size calculations informed by NACC data, a clinical trial using the PACC weighting would require 38% more subjects than a composite calculated using optimal weighting. Discussion: These findings illustrate how reciprocal standard deviation weighting can result in inefficient cognitive composites, and underscore the importance of component weights to the performance of composite scales. In the future, optimal weighting parameters informed by accumulating clinical trial data may improve the efficiency of clinical trials in AD.

Association of Neurofibrillary Tangle Distribution With Age at Onset-Related Clinical Heterogeneity in Alzheimer Disease: An Autopsy Study.

BACKGROUND AND OBJECTIVE: Patients with earlier age at onset of sporadic Alzheimer disease (AD) are more likely than those with later onset to present with atypical clinical and cognitive features. We sought to determine whether this age-related clinical and cognitive heterogeneity is mediated by different topographic distributions of tau-aggregate neurofibrillary tangles (NFTs) or by variable amounts of concomitant non-AD neuropathology. METHODS: The relative distribution of NFT density in hippocampus and midfrontal neocortex was calculated, and α-synuclein, TAR DNA binding protein 43 (TDP-43), and microvascular copathologies were staged, in patients with severe AD and age at onset of 51-60 (n = 40), 61-70 (n = 41), and >70 (n = 40) years. Regression, mediation, and mixed effects models examined relationships of pathologic findings with clinical features and longitudinal cognitive decline. RESULTS: Patients with later age at onset of AD were less likely to present with nonmemory complaints (odds ratio [OR] 0.46 per decade, 95% confidence interval [CI] 0.22-0.88), psychiatric symptoms (ß = -0.66, 95% CI -1.15 to -0.17), and functional impairment (ß = -1.25, 95% CI -2.34 to -0.16). TDP-43 (OR 2.00, 95% CI 1.23-3.35) and microvascular copathology (OR 2.02, 95% CI 1.24-3.40) were more common in later onset AD, and α-synuclein copathology was not related to age at onset. NFT density in midfrontal cortex (ß = -0.51, 95% CI -0.72 to -0.31) and midfrontal/hippocampal NFT ratio (ß = -0.18, 95% CI -0.26 to -0.10) were lower in those with later age at onset. Executive function (ß = 0.48, 95% CI 0.09-0.90) and visuospatial cognitive deficits (ß = 0.97, 95% CI 0.46-1.46) were less impaired in patients with later age at onset. Mediation analyses showed that the effect of age at onset on severity of executive function deficits was mediated by midfrontal/hippocampal NFT ratio (ß = 0.21, 95% CI 0.08-0.38) and not by concomitant non-AD pathologies. Midfrontal/hippocampal NFT ratio also mediated an association between earlier age at onset and faster decline on tests of global cognition, executive function, and visuospatial abilities. DISCUSSION: Worse executive dysfunction and faster cognitive decline in people with sporadic AD with earlier rather than later age at onset is mediated by greater relative midfrontal neocortical to hippocampal NFT burden and not by concomitant non-AD neuropathology.

Impact of potential modifications to Alzheimer's disease clinical trials in response to disruption by COVID-19: a simulation study.

BACKGROUND: The COVID-19 pandemic disrupted Alzheimer disease randomized clinical trials (RCTs), forcing investigators to make changes in the conduct of such trials while endeavoring to maintain their validity. Changing ongoing RCTs carries risks for biases and threats to validity. To understand the impact of exigent modifications due to COVID-19, we examined several scenarios in symptomatic and disease modification trials that could be made. METHODS: We identified both symptomatic and disease modification Alzheimer disease RCTs as exemplars of those that would be affected by the pandemic and considered the types of changes that sponsors could make to each. We modeled three scenarios for each of the types of trials using existing datasets, adjusting enrollment, follow-ups, and dropouts to examine the potential effects COVID-19-related changes. Simulations were performed that accounted for completion and dropout patterns using linear mixed effects models, modeling time as continuous and categorical. The statistical power of the scenarios was determined. RESULTS: Truncating both symptomatic and disease modification trials led to underpowered trials. By contrast, adapting the trials by extending the treatment period, temporarily stopping treatment, delaying outcomes assessments, and performing remote assessment allowed for increased statistical power nearly to the level originally planned. DISCUSSION: These analyses support the idea that disrupted trials under common scenarios are better continued and extended even in the face of dropouts, treatment disruptions, missing outcomes, and other exigencies and that adaptations can be made that maintain the trials' validity. We suggest some adaptive methods to do this noting that some changes become under-powered to detect the original effect sizes and expected outcomes. These analyses provide insight to better plan trials that are resilient to unexpected changes to the medical, social, and political milieu.

A thematic analysis of influences on parents' autism intervention decisions.

BACKGROUND: Factors impacting parents' selection of interventions for their child on the autism spectrum need to be understood in order to better support decision-making. The aim of the current study was to explore parent-reported influences on decisions. METHOD: A sample of 14 Australian parents (13 mothers; 1 father) of a child (4-11 years) diagnosed on the autism spectrum were interviewed about their decisions regarding the use of interventions. A thematic analysis was used to identify prominent themes. FINDINGS: A total of three themes, comprising 11 subthemes were identified. The primary themes were: finding interventions; meeting child and family needs; and acceptability and access. CONCLUSION: Parents' responses highlighted influences on decisions to use evidence-based practices (e.g., behavioural therapies and social skills programs), as well as those with limited empirical support (e.g., animal-assisted therapy and dietary intervention). Influences frequently reported in extant research were reported by parents in this study (e.g., recommendations, logistics of access, and children's individual needs) as well as issues that warrant further investigation (e.g., coping with challenges and stress, importance of intervention intensity, and consideration of the whole family).

A survey of smartphone and interactive video technology use by participants in Alzheimer's disease research: Implications for remote cognitive assessment.

INTRODUCTION: Participants from a longitudinal cohort study were surveyed to evaluate the practical feasibility of remote cognitive assessment. METHODS: All active participants/informants at the University of California San Diego Alzheimer's Disease Research Center were invited to complete a nine-question survey assessing technology access/use and willingness to do cognitive testing remotely. RESULTS: Three hundred sixty-nine of 450 potential participants/informants (82%) completed the survey. Overall, internet access (88%), device ownership (77%), and willingness to do cognitive testing remotely (72%) were high. Device access was higher among those with normal cognition (85%) or cognitive impairment (85%) than those with dementia (52%), as was willingness to do remote cognitive testing (84%, 74%, 39%, respectively). Latinos were less likely than non-Latinos to have internet or device access but were comparable in willingness to do remote testing. DISCUSSION: Remote cognitive assessment using interactive video technology is a practicable option for nondemented participants in longitudinal studies; however, additional resources will be required to ensure representative participation of Latinos.

Development of a novel cognitive composite outcome to assess therapeutic effects of exercise in the EXERT trial for adults with MCI: The ADAS-Cog-Exec.

INTRODUCTION: Use of cognitive composites as primary outcome measures is increasingly common in clinical trials of preclinical and prodromal Alzheimer's disease (AD). Composite outcomes can decrease intra-individual variability, resulting in improved sensitivity to detect longitudinal change and increased statistical power. We developed a novel composite outcome, the ADAS-Cog-Exec, for use in the EXERT trial-a Phase 3 randomized, controlled, 12-month exercise intervention in mild cognitive impairment (MCI). METHODS: Three combinations of cognitive measures selected from the Alzheimer's Disease Assessment Scale-Cognitive Subscale version 13 (ADAS-Cog13), tests of executive function, and the Clinical Dementia Rating (CDR) were created based on previously documented sensitivity to longitudinal change in MCI and to the effects of exercise. Optimally weighted composites of each combination were modeled using data from the ADNI-1 MCI cohort. Ten-fold cross-validation was performed to obtain a bias-corrected mean to standard deviation ratio (MSDR). The cognitive composites were assessed for their sensitivity to detect 12-month change in MCI. RESULTS: The MSDR of 12-month change for each of the composite outcomes tested exceeded that of the ADAS-Cog13 total score. The composite with the highest MSDR (MSDR = 0.48) and associated statistical power included scores on ADAS-Cog13 Word Recall, Delayed Word Recall, Orientation, and Number Cancellation subtests; Trail-Making Tests A & B, Digit Symbol Substitution and Category Fluency; and cognitive components of the CDR (Memory, Orientation, Judgement & Problem Solving). DISCUSSION: An optimally weighted cognitive composite measure was identified and validated for use in EXERT. This composite contained selected subtests from the ADAS-Cog13, additional measures of executive function, and box scores for cognitive components of the CDR. Because this composite score demonstrated high sensitivity to longitudinal change in MCI it will be used as the primary outcome measure for the EXERT trial.

Women can bear a bigger burden: ante- and post-mortem evidence for reserve in the face of tau.

In this study, we aimed to assess whether women are able to withstand more tau before exhibiting verbal memory impairment. Using data from 121 amyloid-ß-positive Alzheimer's Disease Neuroimaging Initiative participants, we fit a linear model with Rey Auditory Verbal Learning Test score as the response variable and tau-PET standard uptake value ratio as the predictor and took the residuals as an estimate of verbal memory reserve for each subject. Women demonstrated higher reserve (i.e. residuals), whether the Learning (t = 2.78, P = 0.006) or Delay (t = 2.14, P = 0.03) score from the Rey Auditory Verbal Learning Test was used as a measure of verbal memory ability. To validate these findings, we examined 662 National Alzheimer's Coordinating Center participants with a C2/C3 score (Consortium to Establish a Registry for Alzheimer's Disease) at autopsy. We stratified our National Alzheimer's Coordinating Center sample into Braak 1/2, Braak 3/4 and Braak 5/6 subgroups. Within each subgroup, we compared Logical Memory scores between men and women. Men had worse verbal memory scores within the Braak 1/2 (Logical Memory Immediate: ß = -5.960 ± 1.517, P < 0.001, Logical Memory Delay: ß = -5.703 ± 1.677, P = 0.002) and Braak 3/4 (Logical Memory Immediate: ß = -2.900 ± 0.938, P = 0.002, Logical Memory Delay: ß = -2.672 ± 0.955, P = 0.006) subgroups. There were no sex differences in Logical Memory performance within the Braak 5/6 subgroup (Logical Memory Immediate: ß = -0.314 ± 0.328, P = 0.34, Logical Memory Delay: ß = -0.195 ± 0.287, P = 0.50). Taken together, our results point to a sex-related verbal memory reserve.

Cognitive heterogeneity in probable Alzheimer disease: Clinical and neuropathologic features.

OBJECTIVE: To identify heterogeneity in cognitive profiles of patients with probable Alzheimer disease (AD) who have mild to moderate dementia and satisfy inclusion and exclusion criteria for a typical AD clinical trial, and to determine whether cognitive profiles are systematically related to the clinical course and neuropathologic features of the disease. METHODS: Neuropsychological test data from patients with mild to moderate probable AD (n = 4,711) were obtained from the National Alzheimer's Coordinating Center. Inclusion and exclusion criteria usually used in AD clinical trials were applied. Principal component analysis and model-based clustering were used to identify cognitive profiles in a subset of patients with autopsy-verified AD (n = 800) and validated in the overall (nonautopsy) sample and an independent cohort with similar test data. Relationships between cognitive profile, clinical characteristics, and rate of decline were examined with mixed-effects models. RESULTS: In the autopsy-confirmed sample, 79.6% of patients had a typical AD cognitive profile (greater impairment of episodic memory than other cognitive functions), and 20.4% had an atypical profile (comparable impairment across cognitive domains). Similar results were obtained in the overall (typical 79.8%, atypical 20.2%) and validation (typical 71.8%, atypical 28.2%) samples. Atypicality was associated with younger age, male sex, lower probability of APOE ε4, less severe global dementia, higher depression scores, lower Braak stage at autopsy, and slower cognitive decline. CONCLUSION: We can reliably identify distinct cognitive profiles among patients with clinically diagnosed probable AD that are associated with tangle pathology and with different rates of decline. This may have implications for clinical trials in AD, especially therapies targeting tau.

The Multilingual Naming Test (MINT) as a Measure of Picture Naming Ability in Alzheimer's Disease.

OBJECTIVE: The present study investigated the ability of the Multilingual Naming Test (MINT), a picture naming test recently added to the National Alzheimer's Coordinating Center's (NACC) Uniform Data Set neuropsychological test battery, to detect naming impairment (i.e., dysnomia) across stages of Alzheimer's disease (AD). METHOD: Data from the initial administration of the MINT were obtained on NACC participants who were cognitively normal (N = 3,981) or diagnosed with mild cognitive impairment (N = 852) or dementia (N = 1,148) with presumed etiology of AD. Dementia severity was rated using the Clinical Dementia Rating (CDR) scale. RESULTS: Cross-sectional multiple regression analyses revealed significant effects of diagnostic group, sex, education, age, and race on naming scores. Planned comparisons collapsing across age and education groups revealed significant group differences in naming scores across levels of dementia severity. ROC curve analyses showed good diagnostic accuracy of MINT scores for distinguishing cognitively normal controls from AD dementia, but not from MCI. Within the cognitively normal group, there was a robust interaction between age and education such that naming scores exhibited the most precipitous drop across age groups for the least educated participants. Additionally, education effects were stronger in African-Americans than in Whites (a race-by-education interaction), and race effects were stronger in older than in younger age groups (a race-by-age interaction). CONCLUSIONS: The MINT successfully detects naming deficits at different levels of cognitive impairment in patients with MCI or AD dementia, but comparison to age, sex, race, and education-corrected norms to determine impairment is essential.

Word-list intrusion errors predict progression to mild cognitive impairment.

OBJECTIVE: Preclinical Alzheimer's disease (AD) defined by a positive AD biomarker in the presence of normal cognition is presumed to precede mild cognitive impairment (MCI). Subtle cognitive deficits and cognitive inefficiencies in preclinical AD may be detected through process and error scores on neuropsychological tests in those at risk for progression to MCI. METHOD: Cognitively normal participants (n = 525) from the Alzheimer's Disease Neuroimaging Initiative were followed for up to 5 years and classified as either stable normal (n = 305) or progressed to MCI (n = 220). Cox regressions were used to determine whether baseline process scores on the Rey Auditory Verbal Learning Test (AVLT; intrusion errors, learning slope, proactive interference, retroactive interference) predicted progression to MCI and a Clinical Dementia Rating (CDR) score of 1 after considering demographic characteristics, apolipoprotein E ε4 status, cerebrospinal fluid AD biomarkers, ischemia risk, mood, functional difficulty, and standard neuropsychological total test scores for the model. RESULTS: Baseline AVLT intrusion errors predicted progression to MCI (hazard ratio = 1.04, 95% confidence interval 1.01-1.07, p = .008) and improved model fit after the other valuable predictors were already in the model, χ2(df = 1) = 6.330, p = .012. AVLT intrusion errors also predicted progression to CDR = 1 (hazard ratio = 1.10, 95% confidence interval 1.02-1.18, p = .016) and again improved model fit, χ2(df = 1) = 4.682, p = .030. CONCLUSIONS: Intrusion errors on the AVLT contribute unique value for predicting progression from normal cognition to MCI and normal cognition to mild dementia (CDR = 1). Intrusion errors appear to reflect subtle change and inefficiencies in cognition that precede impairment detected by neuropsychological total scores. (PsycINFO Database Record

Potential implications of practice effects in Alzheimer's disease prevention trials.

INTRODUCTION: Practice effects (PEs) present a potential confound in clinical trials with cognitive outcomes. A single-blind placebo run-in design, with repeated cognitive outcome assessments before randomization to treatment, can minimize effects of practice on trial outcome. METHODS: We investigated the potential implications of PEs in Alzheimer's disease prevention trials using placebo arm data from the Alzheimer's Disease Cooperative Study donepezil/vitamin E trial in mild cognitive impairment. Frequent ADAS-Cog measurements early in the trial allowed us to compare two competing trial designs: a 19-month trial with randomization after initial assessment, versus a 15-month trial with a 4-month single-blind placebo run-in and randomization after the second administration of the ADAS-Cog. Standard power calculations assuming a mixed-model repeated-measure analysis plan were used to calculate sample size requirements for a hypothetical future trial designed to detect a 50% slowing of cognitive decline. RESULTS: On average, ADAS-Cog 13 scores improved at first follow-up, consistent with a PE and progressively worsened thereafter. The observed change for a 19-month trial (1.18 points) was substantively smaller than that for a 15-month trial with 4-month run-in (1.79 points). To detect a 50% slowing in progression under the standard design (i.e., a 0.59 point slowing), a future trial would require 3.4 times more subjects than would be required to detect the comparable percent slowing (i.e., 0.90 points) with the run-in design. DISCUSSION: Assuming the improvement at first follow-up observed in this trial represents PEs, the rate of change from the second assessment forward is a more accurate representation of symptom progression in this population and is the appropriate reference point for describing treatment effects characterized as percent slowing of symptom progression; failure to accommodate this leads to an oversized clinical trial. We conclude that PEs are an important potential consideration when planning future trials.

Predicting literacy in children with a high-functioning autism spectrum disorder.

The most commonly reported reading profile for children with a high-functioning autism spectrum disorder (HFASD) is one of intact decoding combined with reduced reading comprehension. Whether or not the variables that predict decoding and reading comprehension for children with a HFASD are exactly the same as those identified for a non-ASD population is unknown. Therefore, the ability of cognition, phonological processing, oral language, and vision to predict decoding and reading comprehension was investigated. Regression analysis revealed that cognition, phonological processing, and syntax predicted decoding and reading comprehension for the HFASD and non-ASD groups. One notable difference was that semantics predicted literacy for the non-ASD children but not their HFASD peers.

Evaluating cognition in an elderly cohort via telephone assessment.

OBJECTIVE: Longitudinal neuropsychological assessment provides the opportunity to observe the earliest transition to cognitive impairment in healthy, elderly individuals. We examined the feasibility, and its comparability to in-person assessment, of a telephone administered battery of established neuropsychological measures of cognitive functioning in healthy, elderly women. METHODS: Fifty-four women (age = 79 +/- 7.7; education = 15.4 +/- 3.3) who were in self-reported good health were recruited from senior centers and other community sources. A two-way cross-over design was used in which participants were randomly assigned to receive either (1) in-person neuropsychological assessment followed by telephone assessment and (2) telephone assessment followed by in-person assessment, separated by approximately 4 weeks. Linear regression models were used to determine whether there were performance differences by method (in-person vs. telephone), and equivalence testing assessed comparability of the two methods. RESULTS: There were no statistically significant differences in performance between in-person and telephone assessments on most neuropsychological tests, with the exception of digit span backward, Oral Trail Making Test Part A, and delayed recall on the SRT, the latter likely related to non-comparable exposure (6-trials in-person vs. 3-trials telephone). Equivalence testing differences fell in the pre-specified clinical equivalence zones, providing evidence of comparability of the two methods. CONCLUSIONS: These pilot data support telephone administration of a neuropsychological battery that yields comparable performance to in-person assessment with respect to most instruments. Significant differences in scores on some measures suggest care should be taken in selecting specific measures used in a neuropsychological battery administered by telephone.

Cardiovascular risk and memory in non-demented elderly women.

OBJECTIVE: To determine whether cardiovascular (CV) risk is associated with subtle memory deficits in non-demented, healthy older women with a family history of Alzheimer disease (AD). METHODS: Baseline data of 375 participants from a randomized, double-blind placebo-controlled primary prevention trial to test the efficacy of hormone replacement therapy in delaying AD and cognitive decline were analyzed. All subjects were women over 65 with a family history of AD who had normal cognition and no active heart disease at baseline. A baseline memory composite score was calculated, consisting of immediate and delayed recall of verbal and nonverbal material. Multiple linear regression was performed to examine the association of relative CV risk with memory functioning; age, ethnicity and education level were included as covariates. RESULTS: Mean baseline memory composite score was significantly higher in those with low relative CHD risk than those with high relative CHD risk. CONCLUSION: These findings suggest that subtle elevation of CHD risk may negatively affect memory functioning even in otherwise healthy, non-demented older women without a history of heart disease.

A multi-center, randomized, double blind placebo-controlled trial of estrogens to prevent Alzheimer's disease and loss of memory in women: design and baseline characteristics.

BACKGROUND: Observational studies and small clinical trials suggested that hormone replacement therapy (HRT) decreases risk of cognitive loss and Alzheimer's disease (AD) in postmenopausal women and may have value in primary prevention. PURPOSE: A clinical trial was designed to determine if HRT delays AD or memory loss. This report describes the rationale and original design of the trial and details extensive modifications that were required to respond to unanticipated findings that emerged from other studies during the course of the trial. METHODS: The trial was designed as a multi-center, placebo-controlled primary prevention trial for women 65 years of age or older with a family history of dementia. Recruitment from local sites was supplemented by centralized efforts to use names of Medicare beneficiaries. Inclusion criteria included good general health and intact memory functioning. Participants were randomized to HRT or placebo in a 1:1 ratio. Assignment was stratified by hysterectomy status and site. The primary outcomes were incident AD and memory decline on neuropsychological testing. RESULTS: Enrollment began in March 1998. In response to the Women's Health Initiative (WHI) May 2002 report of increased incidence of heart disease, stroke, pulmonary embolism, and breast cancer among women randomized to HRT, participants were re-consented with a revised consent form. Procedural modifications, including discontinuation of study medication and a modification of the planned primary outcome based on a final enrollment below the target enrollment (N = 477), were enacted in response to the subsequent WHI Memory Study report of increased risk of dementia and poorer cognitive function with HRT. The mean length of treatment exposure prior to discontinuation was 2.14 years. Participants' mean age at baseline was 72.8; mean education was 14.2 years. Minority participation was 19% and 34% had a hysterectomy. The study continues to follow these participants for a total of 5 years blind to the original medication assignment. LIMITATIONS: Results reported from the WHI during the course of this study mandated extensive procedural modifications, including discontinuing recruitment before completion and halting study medication. Alternative strategies for study redesign that were considered are discussed.