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4 Traumatic Brain Injury Does Not Alter the Course of Neurocognitive Functioning Later in Life
- Jeff Schaffert, Hsueh-Sheng Chiang, Hudaisa Fatima, Christian LoBue, John Hart, Munro Cullum
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- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 105-106
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Objective:
History of traumatic brain injury (TBI) is associated with increased risk of dementia, but few studies have evaluated whether TBI history alters the course of neurocognitive decline, and existing literature on this topic is limited to short follow-up and smaller samples. The primary aim of this study was to evaluate whether a history of TBI (TBI+) influences neurocognitive decline later-in-life among older adults with or without cognitive impairment [i.e., normally aging, Mild Cognitive Impairment (MCI), or dementia].
Participants and Methods:Participants included individuals from the National Alzheimer’s Coordinating Center (NACC) who were at least 50 years old and with 3 to 6 visits (M number of visits = 4.43). Participants with any self-reported history of TBI (n = 1,467) were matched 1:1 to individuals with no reported history of TBI (TBI-) from a sample of approximately 45,000 participants using case-control matching based on age (+/- 2 years), sex, education, race, ethnicity, cognitive diagnosis [cognitively normal (CN), MCI, or all-cause dementia], etiology of cognitive impairment, functional decline (Clinical Dementia Rating Scale, CDR), number of Apolipoprotein E4 (APOE ε4) alleles, and number of annual visits (3 to 6). Mixed linear models were used to assess longitudinal neuropsychological test composites (using NACC normative data) of executive functioning/attention/speed (EFAS), language, and memory in TBI+ and TBI- participants. Interactions between TBI and demographics, APOE ε4 status, and cognitive diagnosis were also examined.
Results:Following matching procedures, TBI+ (n=1467) and TBI- (n=1467) groups were nearly identical in age (TBI+ M = 71.59, SD = 8.49; TBI- M = 71.63, SD = 8.44), education (TBI+ M = 16.12, SD = 2.59; TBI- M = 16.10, SD = 2.52), sex (both 55% male), race (both 90% White), ethnicity (both 98% non-Hispanic), APOE ε4 alleles (both 0 = 62%, 1 = 33%, 2 = 5%), baseline cognitive diagnoses (both CN = 60%, MCI = 18%, dementia = 12%), and global CDR (TBI+ M = 0.30, SD = 0.38, TBI- M = 0.30, SD = 0.38). At baseline, groups had similar Z-scores of in EFAS (TBI+ Mefas = -0.02, SD = 1.21; TBI- Mefas = -0.04, SD = 1.27), language (TBI+ MLanguage = -0.48, SD = 0.98; TBI- MLanguage = -0.55, SD = 1.05), and memory (TBI+ MMemory = -0.45, SD = 1.28; TBI- MMemory = -0.45, SD =1.28). The course of change in neuropsychological functioning worsened longitudinally, but did not differ between TBI groups (p’s > .110). There were no significant interactions between TBI history and age, sex, education, race/ethnicity, number of APOE ε4 status, or cognitive diagnosis (all p’s > .027).
Conclusions:In this matched case-control design, our findings suggest that a history of TBI, regardless of demographic factors, APOE ε4 status, and cognitive diagnosis, does not significantly alter the course of neurocognitive functioning later-in-life in older adults with and without cognitive impairment. Future clinicopathological longitudinal studies with well characterized TBI histories and the associated clinical course are needed to help clarify the mechanism by which TBI may increase dementia risk for some individuals, without affecting course of decline.
96 The Proportion of Patients with Cerebrospinal Fluid Biomarkers Consistent with Alzheimer’s Disease in a Cohort with Suspected Normal Pressure Hydrocephalus
- Hudaisa Fatima, Trung P Nguyen, Anne Carlew, Munro Cullum, Jonathan White, Robert Ruchinskas
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- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 396-397
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Objective:
Normal pressure hydrocephalus (NPH) is characterized by pathologically enlarged ventricles without elevated cerebrospinal fluid (CSF) pressure along with a triad of clinical symptoms including gait disturbances, urinary incontinence, and cognitive impairment. NPH is evaluated with lumbar drain trials (LDTs) where CSF is removed over several days to determine if patients would benefit from ventricular shunting. Candidate selection and success for these surgeries remains challenging because other diseases such as Alzheimer’s disease (AD) share common features with NPH in cognitive impairment and enlarged ventricles. Prior research has found that 20%-40% of presumed NPH cases have AD pathology as determined by brain biopsy or autopsy. CSF biomarkers of AD can be altered in NPH and are not always conclusive, complicating the interpretation of results when formulating diagnoses and prognoses. Studies to refine the analyses of AD CSF biomarkers in NPH are needed. We aimed to examine the frequency of CSF biomarker results among patients presenting for NPH evaluations with LDTs.
Participants and Methods:62 patients presented for LDTs upon physician recommendations. CSF specimens were sent to Mayo Clinic Laboratories for Alzheimer Disease Evaluation (ADEVL) that utilizes Elecsys (Lenexa, KS) CSF electrochemiluminescence immunoassays (Roche Diagnostics, Basel, Switzerland) to measure levels of amyloid-beta 42 (Aβ42), total tau (t-tau), and phosphorylatedtau (p-tau), and p-tau:Aβ42 ratio. Results were classified based on interpretation through the Amyloid/Tau/Neurodegeneration (ATN) framework1: 1) AD - biomarker profile consistent with AD pathologic change, 2) non-AD profile - biomarker levels normal or inconsistent with AD pathologic change, or 3) indeterminate - biomarkers were incongruous with only one or two abnormal levels of Aβ42, t-tau, p-tau, or ptau: Aβ42. Indeterminate cases may represent altered protein levels due to CSF dynamics or AD-related pathologic change. In reviewing recent research on CSF dynamics and AD biomarkers in NPH2 a p-tau threshold of 15 pg/mL was derived and implemented such that cases with Aß42 <=1026 pg/mL and p-tau <15 pg/mL were designated as suspected non-AD, and those with Aß42 <=1026 pg/mL and p-tau >15 pg/mL were designated suspected AD.
Results:Of the 62 LDT cases, 12 (19.35%) were classified as AD, 31 (50%) were indeterminate and 22 (35.48%) were non-AD. Of the 31 indeterminate cases, 21 (33.87% of the overall sample) were suspected non-AD and 7 (11.29% of the full sample) were categorized as suspected AD.
Conclusions:Our findings show that 20%-30% of patients presenting for LDT showed evidence for AD-type pathologic change, consistent with prior reports of AD pathology in cases of possible NPH. Half of all LDT cases had indeterminate AD CSF biomarker results, the interpretations of which were confounded by the potential alterations of CSF biomarkers levels due to NPH independent of AD. Our findings emphasize the need to establish better approaches to interpreting CSF AD biomarkers in evaluating NPH. Future research should examine the discriminative utility of CSF AD biomarkers and the selected p-tau threshold in indeterminate cases for predicting response to LDT and shunting.
31 Machine Learning Algorithm to Predict Duration to Full Time Care after Alzheimer's Disease Diagnosis
- Jessica H Helphrey, Jayme M Palka, Jake Rossmango, Hudaisa Fatima, Michael Conley, Anthony Longoria, Jennifer Sawyer, Jeffrey Schaffert, Anne Carlew, Munro Cullum, Laura Lacritz, John Hart, Hsueh-Sheng Chiang, Trung Nguyen, Alka Khera, Christian LoBue
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, p. 241
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Objective:
Patients and their families often ask clinicians to estimate when full-time care (FTC) will be needed after Alzheimer's Disease (AD) is diagnosed. Although a few algorithms predictive algorithms for duration to FTC have been created, these have not been widely adopted for clinical use due to questions regarding precision from limited sample sizes and lack of an easy, user friendly prediction model. Our objective was to develop a clinically relevant, data-driven predictive model using machine learning to estimate time to FTC in AD based on information gathered from a) clinical interview alone, and b) clinical interview plus neuropsychological data.
Participants and Methods:The National Alzheimer's Coordinating Center dataset was used to examine 3,809 participants (M age at AD diagnosis = 76.05, SD = 9.76; 47.10% male; 87.20% Caucasian) with AD dementia who were aged >50 years, had no history of stroke, and not dependent on others for basic activities of daily living at time of diagnosis based on qualitative self or informant report. To develop a predictive model for time until FTC, supervised machine learning algorithms (e.g., gradient descent, gradient boosting) were implemented. In Model 1, 29 variables captured at the time of AD diagnosis and often gathered in a clinical interview, including sociodemographic factors, psychiatric conditions, medical history, and MMSE, were included. In Model 2, additional neuropsychological variables assessing episodic memory, language, attention, executive function, and processing speed were added. To train and test the algorithm(s), data were split into a 70:30 ratio. Prediction optimization was examined via cross validation using 1000 bootstrapped samples. Model evaluation included assessment of confusion matrices and calculation of accuracy and precision.
Results:The average time to requiring FTC after AD diagnosis was 3.32 years (Range = 0.53-14.57 years). For the clinical interview only model (Model 1), younger age of onset, use of cholinesterase inhibitor medication, incontinence, and apathy were among the clinical variables that significantly predicted duration to FTC, with the largest effects shown for living alone, a positive family history of dementia, and lower MMSE score. In Model 2, the clinical predictors remained significant, and lower Boston Naming Test and Digit-Symbol Coding scores showed the largest effects in predicting duration to FTC among the neuropsychological measures. Final prediction models were further tested using five randomly selected cases. The average estimated time to FTC using the clinical interview model was within an average of 5.2 months of the recorded event and within an average of 5.8 months for the model with neuropsychological data.
Conclusions:Predicting when individuals diagnosed with AD will need FTC is important as the transition often carries significant financial costs related to caregiving. Duration to FTC was predicted by clinical and neuropsychological variables that are easily obtained during standard dementia evaluations. Implementation of the model for prediction of FTC in cases showed encouraging prognostic accuracy. The two models show promise as a first step towards creation of a user friendly prediction calculator that could help clinicians better counsel patients on when FTC after AD diagnosis may occur, though the development of separate models for use in more diverse populations will be essential.
52 Bayesian Logistic Regression Bias Adjustment for Data Observed without a Gold Standard: A Simulation Study of Clinical Alzheimer’s Disease
- William F Goette, Hudaisa Fatima, Jeff Schaffert, Anne R Carlew, Heidi Rossetti, Laura H Lacritz, C. Munro Cullum
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 259-260
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Objective:
Definitive diagnosis of Alzheimer’s disease (AD) is often unavailable, so clinical diagnoses with some degree of inaccuracy are often used in research instead. When researchers test methods that may improve clinical accuracy, the error in initial diagnosis can penalize predictions that are more accurate to true diagnoses but differ from clinical diagnoses. To address this challenge, the current study investigated the use of a simple bias adjustment for use in logistic regression that accounts for known inaccuracy in initial diagnoses.
Participants and Methods:A Bayesian logistic regression model was developed to predict unobserved/true diagnostic status given the sensitivity and specificity of an imperfect reference. This model considers cases as a mixture of true (with rate = sensitivity) and false positives (rate = 1 - specificity) while controls are mixtures of true (rate = specificity) and false negatives (rate = 1 - sensitivity). This bias adjustment was tested using Monte Carlo simulations over four conditions that varied the accuracy of clinical diagnoses. Conditions utilized 1000 iterations each generating a random dataset of n = 1000 based on a true logistic model with an intercept and three arbitrary predictors. Coefficients for parameters were randomly selected in each iteration and used to produce a set of two diagnoses: true diagnoses and observed diagnoses with imperfect accuracy. Sensitivity and specificity of the simulated clinical diagnosis varied with each of the four conditions (C): C1 = (0.77, 0.60), C2 = (0.87, 0.44), C3 = (0.71, 0.71), and C4 = (0.83, 0.55), which are derived from published values for clinical AD diagnoses against autopsy-confirmed pathology. Unadjusted and bias-adjusted logistic regressions were then fit to the simulated data to determine the models’ accuracy in estimating regression parameters and prediction of true diagnosis.
Results:Under all conditions, the bias-adjusted logistic regression model outperformed its unadjusted counterpart. Root mean square error (the variability of estimated coefficients around their true parameter values) ranged from 0.23 to 0.79 for the unadjusted model versus 0.24 to 0.29 for the bias-adjusted model. The empirical coverage rate (the proportion of 95% credible intervals that include their true parameter) ranged from 0.00 to 0.47 for the unadjusted model versus 0.95 to 0.96 for the bias-adjusted model. Finally, the bias-adjusted model produced the best overall diagnostic accuracy with correct classification of true diagnostic values about 78% of the time versus 62-72% without adjustment.
Conclusions:Results of this simulation study, which used published AD sensitivity and specificity statistics, provide evidence that bias-adjustments to logistic regression models are needed when research involves diagnoses from an imperfect standard. Results showed that unadjusted methods rarely identified true effects with credible intervals for coefficients including the true value anywhere from never to less than half of the time. Additional simulations are needed to examine the bias-adjusted model’s performance under additional conditions. Future research is needed to extend the bias adjustment to multinomial logistic regressions and to scenarios where the rate of misdiagnosis is unknown. Such methods may be valuable for improving detection of other neurological disorders with greater diagnostic error as well.
87 Not Normal but not MCI: Course of Memory over time
- Michael Conley, Jeff Schaffert, Anthony Longoria, Jessica Helphrey, C Munro Cullum, Laura Lacritz
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- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 389-390
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Objective:
A diagnosis of mild cognitive impairment (MCI) requires memory complaint and objective memory impairment. However, some individuals report subjective memory complaints (SMC) despite having intact memory performance, while others demonstrate subtle impairment on memory testing but have no memory complaints; neither case would meet criteria for MCI. This study aimed to compare memory performances over time in individuals who do not meet traditional MCI criteria to those with normal cognition and those who converted to MCI.
Participants and Methods:Diagnoses for a longitudinal sample from the Texas Alzheimer’s Research and Care Consortium were reviewed by a consensus panel of neuropsychologists and neurologists and reclassified at time of last visit. Diagnostic categories included SMC (i.e., memory complaint but no impairment on testing), objective cognitive impairment but no complaint (Impaired but not MCI), normal control (NC), MCI, and dementia. In this study, 827 participants were divided into 4 groups: 1) NC over 5 visits (n=511, 71% female; 42% Latinx/Hispanic), 2) baseline NC to amnestic MCI (n=62; 63% female; 57% Latinx/Hispanic), 3) SMC at last visit (n=133; 58% female; 70% Latinx/Hispanic), and 4) impaired but not MCI at last visit (n=121; 71% female; 60% Latinx/Hispanic). A memory composite (z-score) was created from the CERAD list-learning task (immediate, delayed, and recognition-discrimination) and Wechsler Memory Scale (Immediate and Delayed Logical Memory and Visual Reproduction) to evaluate memory performance over time. A linear mixed-model adjusting for age, education, sex, ethnicity, and number of APOE e4 alleles evaluated memory performance across 5 visits for the groups. To assess if depression followed a similar course, a linear mixed-model evaluated Geriatric Depression Scale (GDS) scores over time.
Results:At baseline, groups differed by age (F=22.82; p<.001), education (F=8.60; p<.001), MMSE scores (F=9.38; p<.001), GDS-30 scores (F=3.56; p=.015), and memory composites (F=24.29; p<.001). A significant group X time interaction was observed (F=4.83, p<.001). Memory performance improved in both the SMC and the NC groups, remained stable in the impaired but not MCI group, and declined (as expected) in those who converted to amnestic MCI. Depression scores also showed a significant group X time interaction (F=2.43; p=.004), in which the NC to MCI group endorsed slightly more depression symptoms over time, while other groups declined or remained stable.
Conclusions:Memory trajectories in this diverse sample differed across groups. Individuals with SMC but without objective memory impairment and normal controls showed some improvement in memory over time, presumably due to practice effects. Those with subtle memory impairments but no complaint (i.e., did not meet MCI criteria) remained stable and those who converted to amnestic MCI had worse memory across time. The stability of memory performances in the impaired not MCI group suggests these subtle memory inefficiencies may be longstanding or unperceived. However, because our sample achieved retrospective diagnoses of SMC and impaired not MCI, it will be important for future studies to prospectively follow these groups to determine which risk factors may predict progression to MCI and what impact ethnicity may have on these trajectories.
97 Looking in the Webcam Reflection: A Scoping Review of Videoconferencing-Based Teleneuropsychological Assessment Since the Start of the COVID-19 Pandemic
- Joshua T Fox-Fuller, Preeti Sunderaraman, C. Munro Cullum, Yakeel T. Quiroz
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 770-771
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Objective:
Following the start of the SARS-COV-2 (COVID-19) pandemic there was a rapid uptake in teleneuropsychology (TeleNP). Many clinicians and researchers used videoconferencing technologies (e.g., Zoom®) to conduct remote neuropsychological assessments. Prior reviews (e.g., Marra et al., 2020) have indicated promise for the use of videoconference-based approaches to cognitive assessment under certain circumstances, though arguably nobody foresaw the widespread use of teleNP during the pandemic. Given the rapid expansion in the teleNP literature in the past couple of years, in this scoping review we specifically discuss research updates made during the COVID-19 pandemic pertaining to teleNP assessment of adults conducted via videoconferencing and their potential clinical applications.
Participants and Methods:GoogleScholar and PubMed were used to search for peer-reviewed original research articles published between January 1, 2020 (i.e., the approximate beginning of the COVID-19 pandemic) and August 1, 2022. Broad search terms were used pertaining to teleNP, remote cognitive assessment, videoconferencing, and neuropsychological assessment, resulting in 16 articles.
Results:Though most of the included studies were based in the United States (n=5), there was international representation across studies (Chile=1; United Kingdom=1; Australia=2; New Zealand=1; France=2; Greece=1; Japan=2, Singapore=1). All of the identified articles examined TeleNP-related research questions using cognitive tests administered via videoconferencing that have been previously studied in-person to varying degrees. Several of the studies focused on psychometric characterization (i.e., reliability and validity) of the examined tests when delivered via videoconferencing, whereas others focused on demonstrating the relative equivalence of neuropsychological scores obtained via videoconferencing versus in-person evaluations.
Conclusions:Formal psychometric studies of traditional in-person neuropsychological tests delivered via videoconferencing since the start of the COVID-19 pandemic suggest that this remote modality of assessment is generally reliable and valid. Moreover, multiple recent studies have demonstrated relative equivalence of neuropsychological scores obtained via videoconferencing versus neuropsychological test scores obtained in-person. When considered alongside teleNP research conducted prior to the COVID-19 pandemic (e.g. Cullum et al., 2014), recent studies on videoconference-based neuropsychological assessment indicate that videoconferencing may not necessarily be a complete substitute for an in-person comprehensive evaluation given the inherent limitations of the procedure. However, teleNP via videoconferencing may be a promising tool in the neuropsychologist’s toolbox because it can help reduce common barriers to in-person neuropsychological assessment (e.g., travel time to clinics). Additional research on videoconferencing-based cognitive assessment is needed, especially in low-and-middle income countries (LMIC) and diverse populations where there may be more economic barriers to remote neuropsychological assessment relative to more economically-developed countries. Notably it is possible that research from LMIC may have been missed through the screening processes used in this review (e.g., inclusion of articles written in English).
3 Separating Memory Impairment from Other Neuropsychological Deficits on the CVLT-II
- William F Goette, Jeff Schaffert, Anne R Carlew, David Denney, Heidi Rossetti, C. Munro Cullum, Laura H Lacritz
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, p. 678
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Objective:
Learning curve patterns on list-learning tasks can help clinicians determine the nature of memory difficulties, as an “impaired” score may actually reflect attention and/or executive difficulties rather than a true memory impairment. Though such pattern analysis is often qualitative, there are quantitative methods to assess these concepts that have been generally underutilized. This study aimed to develop a model that decomposes learning over repeated trials into separate cognitive processes and then include other testing data to predict performance at each trial as a function of general cognitive functioning.
Participants and Methods:Data for CVLT-II learning trials were obtained from an outpatient neuropsychology service within an academic medical center referred for clinical reasons. Participants with a cognitive diagnosis of non-demented (ND) or probable Alzheimer’s disease (AD) were included. The final sample consisted of 323 ND [Mage = 58.6 (14.8); Medu = 15.4 (2.7); 55.7% female] and 915 AD [Mage = 72.6 (9.0); Medu = 14.2 (3.1); 60.1% female cases. A Bayesian non-linear beta-binomial multilevel model was used, which uses three parameters to predict CVLT-II recall-by-trial: verbal attention span (VAS), maximal learning potential (MLP), and learning rate (LR). Briefly, VAS predicts expected first trial performance while MLP, conversely, predicts the expected best performance as trials are repeated, and LR weights the influence of VAS versus MLR over repeated trials. Predictors of these parameters included age, education, sex, race, and clinical diagnosis, in addition to raw scores on Trail Making Test Parts A and B, phonemic (FAS) fluency, animal fluency, Boston Naming Test, Wisconsin Card Sorting Test (WCST) Categories Completed, and then age-adjusted scaled scores from WAIS-IV Digit Span, Block Design, Vocabulary, and Coding. Random intercepts were included for each parameter and extracted for comparison of residual differences by diagnosis.
Results:The model explained 84% of the variance in CVLT-II raw scores. VAS reduced with age and time-to-complete Trails B but improved with both verbal fluencies and confrontation naming. MLP increased as a function of WAIS Digit Span, animal fluency, confrontation naming, and WCST categories completed. Finally, LR was greater for females and WAIS-IV Coding and Vocabulary performances but reduced with age. Participants with AD had lower estimates of all three parameters: Cohen’s d = 2.49 (VAS) - 3.48 (LR), though including demographic and neuropsychological tests attenuated differences, Cohen’s d = 0.34 (LR) - 0.95 (MLP).
Conclusions:The resulting model highlights how non-memory neuropsychological deficits affect list-learning test performance. At the same time, the model demonstrated that memory patterns on the CVLT-II can still be identified beyond other confounding deficits since having AD affected all parameters independent of other cognitive impairments. The modeling approach can generate conditional learning curves for individual patient data, and when multiple diagnoses are included in the model, a person-fit statistic can be computed to return the mostly likely diagnosis for an individual. The model can also be used in research to quantify or adjust for the effect of other patient data (e.g., neuroimaging, biomarkers, medications).
50 Sex differences in psychological features in adolescents after concussion
- Hannah M. Doggett, Linda S. Hynan, Cheryl H. Silver, Danyah Ahmed, Logan Shurtz, Ingrid Tamez, C. Munro Cullum, Mathew A. Stokes
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- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 155-156
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Objective:
Few concussion studies have investigated the psychological domain of concussions. Of the 22 postconcussion symptoms assessed on the Graded Symptom Checklist of the SCAT-5, five do not overlap with core symptoms of anxiety and depression. 43% of patients report at least one psychiatric symptom, the median is four after injury. Previous studies focus on total scores and not individual items; furthermore, few consider resilience as part of psychological factors that impact recovery. This research aims to describe general and specific characteristics of psychological functioning in males/females ages 12-18 after concussion to help guide treatment. We compared total scores for each measure between males/females and looked at the differences between the genders for individual items in each measure.
Participants and Methods:Participants were evaluated at an outpatient concussion clinic participating in the North Texas Concussion Registry (ConTex; N=1238, 53% female, mean age=15.4 years, SD=1.16 years). The Generalized Anxiety Disorder 7-item Scale (GAD-7, the Patient Health Questionnaire-8 (PHQ-8), the Brief Resilience Scale (BRS), and the Pittsburgh Sleep Quality Index (PSQI) were used to determine levels of anxiety, depression, resilience, and sleep quality.
Results:Utilizing Mann-Whitney U tests (median, interquartile range) to examine group distributions for the GAD-7, PHQ-8, and BRS, females had significantly higher scores than males for the GAD (p<0.001; Female: 4, 1-9 v. Male: 2, 0-5) and PHQ (p<0.001; Female: 5, 210 v. Male: 3, 1-7). For the BRS, total scores for females were significantly lower than males (p<0.001; Female: 3.67, 3-4 v. Male: 3.83, 3.214.33). The PSQI media score was significantly different between males and females: item 2, p=.016 and item 4 p=.007 using an exact sampling distribution for U. Pearson Chi square tests were used to examine sex differences for each item of the psychological measures. Items 1-7 within the GAD-7 were significant between sexes (i.e. male or female). The seven items assess (1) Feelings of nervousness, (2) Inability to stop/control worry, (3) Worrying too much about different things, (4) Trouble relaxing, (5) Inability to sit still due to restlessness, (6) Irritability, and (7) Feeling afraid. Items 2-8 within the PHQ were significant between sexes. The items assess (2) Feeling down/depressed/hopeless, (3) Trouble falling/staying asleep, (4) Feeling tired/no energy, (5) Appetite changes, (6) Lowered/poor self-esteem, (7) Concentration issues, and (8) Feeling slowed down or unable to be still. There was a statistically significant difference between genders and Items 2 and 4 within the BRS were significant between sexes. The items assess (2) Difficulty surviving hard times and (4) Difficulty snapping back from something bad.
Conclusions:Like other studies, this study found females have higher levels of negative affect (i.e., depressive and anxious symptoms). Females displayed lower resilience and reported poorer sleep. By analyzing psychiatric measures, treatment protocols can be tailored to address specific problems, and mental health difficulties can be mitigated by teaching specific coping techniques. These results suggest clinicians should consistently be providing education on depression, anxiety, sleep, and resilience, particularly to female patients, who appear at greater risk for psychological distress.
78 Preliminary Exploration of a Novel Speech Analysis Algorithm to Detect Cognitive Impairment in a Spanish Population
- Alyssa N Kaser, Jeff Schaffert, Munro Cullum, Javier Jimenez-Raboso, Pablo de la Guardia, Peru Gabirondo, Alberto J Coca, Laura Lacritz
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- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 482-483
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Objective:
Early detection of mild cognitive impairment (MCI) and dementia is crucial for initiation of treatment and access to appropriate care. While comprehensive neuropsychological assessment is often an intrinsic part of the diagnostic process, access to services may be limited and cannot be utilized effectively on a large scale. For these reasons, cognitive screening instruments are used as brief and cost-effective methods to identify individuals who require further evaluation. Novel technologies and automated software systems to screen for cognitive changes in older individuals are evolving as new avenues for early detection. The present study presents preliminary data on a new technology that uses automated linguistic analysis software to screen for MCI and dementia.
Participants and Methods:Data were collected from 148 Spanish-speaking individuals recruited in Spain (MAge=74.4, MEducation=12.93, 56.7% females) of whom 78 were diagnosed as cognitively normal [CN; Mmmse = 28.51 (1.39)], 49 as MCI [MMMSE = 25.65 (2.94)], and 21 as all-cause dementia [MMMSE = 22.52 (2.06)]. Participants were recorded performing various verbal tasks [Animal fluency, phonemic (F) fluency, Cookie Theft Description, and CERAD list learning task]. Recordings were processed via text-transcription and sound signal processing techniques to capture neuropsychological variables and audio characteristics. Features from each task were used in the development of an algorithm (for that task) to compute a score between 0 or 1 (healthy to more impairment), and a fifth algorithm was constructed using audio characteristics from all tasks. These five classifiers were combined algorithmically to provide the final algorithm. Receiver Operating Characteristic (ROC) analysis was conducted to determine sensitivity and specificity of predicted algorithm performance [CN vs. impaired (MCI or dementia)] against clinical diagnoses, and additional general linear modeling was used to test whether age, sex, education, and multilingualism significantly predicted logistically transformed weighted algorithm scores.
Results:Scores were transformed to logit scores, with significant differences in mean logit scores between all groups (p <.001). Logit-inverse transformation of mean logit scores (possible range 0 -1) resulted in values of 0.06 for CN, 0.90 for MCI, and 0.99 for all-cause dementia groups. ROC curve analyses revealed the algorithm obtained a total area under the curve of 0.92, with an overall accuracy of 86.8%, a sensitivity of 0.92, and specificity of 0.82. Age was identified as a significant predictor (beta = 0.22; p <0.01) of algorithm output, whereas years of education (beta = -0.04; p = 0.64), sex (beta = 0.38; p = 0.02, did not survive correction for type-1 error), and multilingualism (beta = -0.24; p = 0.22) were non-significant.
Conclusions:These findings provide initial support for the utility of an automated speech analysis algorithm to detect cognitive impairment quickly and efficiently in a Spanish-speaking population. Although sociodemographic variables were not included in the algorithm, age significantly predicted algorithm output, and should be further explored to determine if age-adjusted formulas would improve algorithm accuracy for younger versus older individuals. Additional research is needed to validate this novel methodology in other languages, as this may represent a promising cross-cultural screening method for MCI and dementia detection.
23 The Utility of Global versus Domain-specific Neuropsychological Test Score Dispersion as Markers of Cognitive Decline
- Hudaisa Fatima, Jeff Schaffert, Anne Carlew, Will Goette, Jessica Helphrey, Laura Lacritz, Heidi Rossetti, C. Munro Cullum
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- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 233-234
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Objective:
Higher baseline dispersion (intra-individual variability) across neuropsychological test scores at a single time-point has been associated with more rapid cognitive decline, onset of Mild Cognitive Impairment (MCI) and Alzheimer’s disease (AD), faster rates of hippocampal and entorhinal atrophy, and increased AD neuropathology. Comparison between predictions made from test score dispersion within a cognitive domain versus global, cross-domain dispersion is understudied. Global dispersion may be influenced by ability-and test-specific characteristics. This study examined the performance of global versus domain-specific dispersion metrics to identify which is most predictive of cognitive decline over time.
Participants and Methods:Data for baseline and five follow-up visits of 308 participants with normal cognition (Mage=73.90, SD=8.12) were selected from the National Alzheimer’s Coordinating Center (NACC) Dataset. Participants were required to have no focal neurological deficits, or history of depression, stroke, or heart attack. Diagnoses and progression to MCI and/or dementia were determined at each visit through consensus conferences. Raw neuropsychological scores were standardized using NACC norms. Global baseline dispersion was defined as the intraindividual standard deviation (ISD) across the 10 scores in the NACC battery. Domain-specific dispersions were calculated by constructing composites and ISD was computed across tests sampling their respective domains (executive functioning/attention/processing speed [EFAS], language, and memory; see Table 1 for details on these tests). Higher values on each of these metrics reflect greater dispersion. Multinomial logistic regression model fit statistics and parameter estimates were compared across four different models (global, EFAS, Language, and Memory dispersion) covarying for age, years of education, sex, race, ethnicity, and ApoE4 status. Models were compared using the Likelihood Ratio Test (LRT) and the Akaike Information Criteria (AIC) of Models statistics.
Results:Of the 308 participants, 70 (22.7%) progressed to MCI, and 82 (26.6%) progressed to dementia. Tables 1 and 2 show the results of the logistic regressions for the four models. All models fit the data well, with statistically significant predictions of conversion. Model 1 (global dispersion) showed a better fit than domain-specific models of dispersion per LRT and AIC values. Consistent with the results from mean differences between groups, parameter estimates showed that only global dispersion and EFAS dispersion significantly predicted conversion to dementia (when included with other covariates in models), with higher dispersion reflecting a greater risk of conversion.
Conclusions:In this sample, baseline global and EFAS dispersion measures significantly predicted conversion to dementia. Although global dispersion was a stronger predictor of dementia progression, findings suggest that executive functioning performance may be driving this relationship. A single index of global variability, from the calculation of standard deviation across test scores, may be supplementary for clinicians when distinguishing individuals at risk for dementia progression. None of the models were predictive of conversion to MCI. Further research is required to examine cognitive variability differences among patients who progress to MCI and patient-specific factors that may relate to test score dispersion and its utility in predicting the progression of symptoms.
Validation of a Bayesian Diagnostic and Inferential Model for Evidence-Based Neuropsychological Practice
- William F. Goette, Anne R. Carlew, Jeff Schaffert, Ben K. Mokhtari, C. Munro Cullum
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue 2 / February 2023
- Published online by Cambridge University Press:
- 07 April 2022, pp. 182-192
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Objective:
Evidence-based diagnostic methods have clinical and research applications in neuropsychology. A flexible Bayesian model was developed to yield diagnostic posttest probabilities from a single person’s neuropsychological score profile by utilizing sample descriptive statistics of the test battery across diagnostic populations of interest.
Methods:Three studies examined the model’s performance. One simulation examined estimation accuracy of true z-scores. A diagnostic accuracy simulation utilized descriptive statistics from two popular neuropsychological tests, the Wechsler Adult Intelligence Scale–IV (WAIS-IV) and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The final simulation examined posterior predictive accuracy of scores to those reported in the WAIS manual.
Results:The model produced minimally biased z-score estimates (root mean square errors: .02–.18) with appropriate credible intervals (95% credible interval empirical coverage rates: .94–1.00). The model correctly classified 80.87% of simulated normal, mild cognitive impairment, and Alzheimer’s disease cases using a four subtest WAIS-IV and the RBANS compared to accuracies of 60.67–65.60% from alternative methods. The posterior predictions of raw scores closely aligned to percentile estimates published in the WAIS-IV manual.
Conclusion:This model permits estimation of posttest probabilities for various combinations of neuropsychological tests across any number of clinical populations with the principal limitation being the accessibility of applicable reference samples. The model produced minimally biased estimates of true z-scores, high diagnostic classification rates, and accurate predictions of multiple reported percentiles while using only simple descriptive statistics from reference samples. Future nonsimulation research on clinical data is needed to fully explore the utility of such diagnostic prediction models.
Evaluation of the Effects of Severe Depression on Global Cognitive Function and Memory
- Shawn M. McClintock, C. Munro Cullum, Mustafa M. Husain, A. John Rush, Rebedca G. Knapp, Martina Mueller, Georgios Petrides, Shirlene Sampson, Charles H. Kellner
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- Journal:
- CNS Spectrums / Volume 15 / Issue 5 / May 2010
- Published online by Cambridge University Press:
- 07 November 2014, pp. 304-313
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Introduction: Major depressive disorder (MDD) is thought to negatively impact cognitive function; however, the relationship has not been well explored.
Objective: This study examined the association between depression severity and global cognitive function and memory in subjects with severe, treatment-resistant MDD.
Methods: We enrolled 66 subjects with Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosed unipolar MDD in a multicenter trial to assess the efficacy and neurocognitive effects of electroconvulsive therapy (ECT). We measured depression severity with the 24 item Hamilton Rating Scale for Depression (HRSD24). Neuropsychologic measures included the Mini Mental State Examination (MMSE), Rey Auditory Verbal Learning Test (RAVLT), and the Complex Figure Test (CFT). Correlational and regression analyses were conducted to explore associations between depression severity and cognitive function.
Results: The mean age of the subjects was 53.6 years (SD=15.8), 65% were female, and mean HRSD24 was 33.9 (SD=6.7). Mean demographic-corrected T-scores for each neurocognitive measure were in the average to borderline range, and HRSD24 values were unrelated to performance on the MMSE, RAVLT immediate and delayed recall, and CFT immediate and delayed recall.
Conclusion: In this sample of severely depressed subjects referred for ECT, depression severity was unrelated to global cognitive function or memory. Future research should examine the interactions between other depressive characteristics and neurocognitive function.
Teleneuropsychology: Evidence for Video Teleconference-Based Neuropsychological Assessment
- C. Munro Cullum, L.S. Hynan, M. Grosch, M. Parikh, M.F. Weiner
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- Journal:
- Journal of the International Neuropsychological Society / Volume 20 / Issue 10 / November 2014
- Published online by Cambridge University Press:
- 24 October 2014, pp. 1028-1033
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The use of videoconference technology to deliver health care diagnostics and treatment continues to grow at a rapid pace. Telepsychiatry and telepsychology applications are well-accepted by patients and providers, and both diagnostic and treatment outcomes have generally been similar to traditional face-to-face interactions. Preliminary applications of videoconference-based neuropsychological assessment (teleneuropsychology) have yielded promising results in the feasibility and reliability of several standard tests, although large-scale studies are lacking. This investigation was conducted to determine the reliability of video teleconference (VTC) - based neuropsychological assessment using a brief battery of standard neuropsychological tests commonly used in the evaluation of known or suspected dementia. Tests included the Mini-Mental State Examination (MMSE), Hopkins Verbal Learning Test-Revised, Digit Span forward and backward, short form Boston Naming Test, Letter and Category Fluency, and Clock Drawing. Tests were administered via VTC and in-person to subjects, counterbalanced using alternate test forms and standard instructions. Two hundred two adult subjects were tested in both rural and urban settings, including 83 with cognitive impairment and 119 healthy controls. We found highly similar results across VTC and in-person conditions, with significant intraclass correlations (mean=.74; range: 0.55–0.91) between test scores. Findings remained consistent in subjects with or without cognitive impairment and in persons with MMSE scores as low as 15. VTC-based neuropsychological testing is a valid and reliable alternative to traditional face-to-face assessment using selected measures. More VTC-based studies using additional tests in different populations are needed to fully explore the utility of this new testing medium. (JINS, 2014, 20, 1–6)
Contributors
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- By C. Alan Anderson, Celso Arango, David B. Arciniegas, Igor Bombin, Robert W. Buchanan, C. Robert Cloninger, Joshua Cosman, C. Munro Cullum, Felipe DeBrigard, Steven L. Dubovsky, Robert Feinstein, Lynne Fenton, Christopher M. Filley, Laura A. Flashman, Morris Freedman, Oliver Freudenreich, Kimberly L. Frey, Lauren C. Frey, Kelly S. Giovanello, Deborah A. Hall, John Hart, Kenneth M. Heilman, Katherine L. Howard, Robin A. Hurley, Daniel I. Kaufer, Sita Kedia, James P. Kelly, B. K. Kleinschmidt-DeMasters, Benzi M. Kluger, David G. Lichter, Deborah M. Little, Deborah M. Lucas, Thomas W. McAllister, Mario F. Mendez, Doron Merims, Steven G. Ojemann, Fred Ovsiew, Brian D. Power, Bruce H. Price, Gila Z. Reckess, Martin L. Reite, Matthew Rizzo, Donald C. Rojas, Michael Henry Rosenbloom, Elliott D. Ross, Jeremy D. Schmahmann, Stuart A. Schneck, Jonathan M. Silver, Mark C. Spitz, Sergio E. Starkstein, Katherine H. Taber, Robert L. Trestman, Hal S. Wortzel
- Edited by David B. Arciniegas, C. Alan Anderson, Christopher M. Filley
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- Book:
- Behavioral Neurology & Neuropsychiatry
- Published online:
- 05 February 2013
- Print publication:
- 24 January 2013, pp vii-x
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24 - Neuropsychologicalassessment
- from Section II - Neurobehavioral and Neuropsychiatric Assessment
- Edited by David B. Arciniegas, C. Alan Anderson, Christopher M. Filley
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- Behavioral Neurology & Neuropsychiatry
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- 05 February 2013
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- 24 January 2013, pp 394-405
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Summary
This chapter reviews conceptual issues and definitions of the executive function. It is argued that executive function is a multidimensional construct and it is suggested that subspecialists in Behavioral neurology (BN) & Neuropsychiatry (NP) regard executive function principally as a cognitive domain. Executive function requires the integrated actions of the frontal-subcortical circuits, open-loop connections to other neocortical areas, limbic and paralimbic structures, thalamic nuclei, pontocerebellar networks, modulatory neurochemical projections from mesencephalic and ventral forebrain structures, and the white matter connections within and between all of these areas. As such, executive dysfunction is more accurately understood as dysfunction within or across these networks. The distributed structural and functional anatomy of executive function renders it vulnerable to disruption by many conditions affecting the brain. Finally, the chapter briefly discusses neuropsychological tests and bedside assessments of executive function.
Gist Distinctions in Healthy Cognitive Aging Versus Mild Alzheimer's Disease
- Sandra B. Chapman, Raksha Anand, Garen Sparks, C. Munro Cullum
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- Journal:
- Brain Impairment / Volume 7 / Issue 3 / 01 December 2006
- Published online by Cambridge University Press:
- 21 February 2012, pp. 223-233
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There is limited understanding of the effects of normal and abnormal aging on gist-based memory in relation to the massive evidence regarding detail-based memory. This void is striking given the widely accepted view that memory is rarely veridical, but most often abstracted. The present study examined the effects of healthy advanced aging and mild Alzheimer's disease (AD) on three distinct forms of gist. Two of these gist forms involved a passage: transformed gist (global generalised meaning of a passage) and main-idea gist (main points of a passage). The third gist form involved a word list: categorical gist (clustering of words according to semantic categories during list recall). These gist forms were assessed in immediate and delayed recall conditions. A total of 36 participants were included: 12 cognitively healthy young seniors (65–79 years), 12 cognitively healthy old seniors (80–95 years), and 12 young seniors with mild AD (65–79 years). The findings revealed that age and dementia did not equally affect all three forms of gist. Specifically, transformed gist was relatively maintained in the cognitively healthy senior groups as compared to the other two gist forms (main-idea gist and categorical gist), whereas all three gist forms were impaired in individuals with AD. The present study suggests that transformed gist operates differently than detail-based memory in the cognitively healthy senior groups. These findings have important theoretical implications in terms of informing existing models on the interrelationship between gist and detail-based memory and clinical implications in diagnosis of AD.
Diffusion Tensor Imaging Biomarkers for Traumatic Axonal Injury: Analysis of Three Analytic Methods
- Carlos D. Marquez de la Plata, Fanpei Gloria Yang, Jun Yi Wang, Kamini Krishnan, Khamid Bakhadirov, Christopher Paliotta, Sina Aslan, Michael D. Devous, Sr., Carol Moore, Caryn Harper, Roderick McColl, C. Munro Cullum, Ramon Diaz-Arrastia
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- Journal:
- Journal of the International Neuropsychological Society / Volume 17 / Issue 1 / January 2011
- Published online by Cambridge University Press:
- 12 November 2010, pp. 24-35
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Traumatic axonal injury (TAI) is a common mechanism of traumatic brain injury not readily identified using conventional neuroimaging modalities. Novel imaging modalities such as diffusion tensor imaging (DTI) can detect microstructural compromise in white matter (WM) in various clinical populations including TAI. DTI-derived data can be analyzed using global methods (i.e., WM histogram or voxel-based approaches) or a regional approach (i.e., tractography). While each of these methods produce qualitatively comparable results, it is not clear which is most useful in clinical research and ultimately in clinical practice. This study compared three methods of analyzing DTI-derived data with regard to detection of WM injury and their association with clinical outcomes. Thirty patients with TAI and 19 demographically similar normal controls were scanned using a 3 Tesla magnet. Patients were scanned approximately eight months postinjury, and underwent an outcomes assessment at that time. Histogram analysis of fractional anisotropy (FA) and mean diffusivity showed global WM integrity differences between patients and controls. Voxel-based and tractography analyses showed significant decreases in FA within centroaxial structures involved in TAI. All three techniques were associated with functional and cognitive outcomes. DTI measures of microstructural integrity appear robust, as the three analysis techniques studied showed adequate utility for detecting WM injury. (JINS, 2011, 17, 000–000)
Bifrontal, bitemporal and right unilateral electrode placement in ECT: randomised trial
- Charles H. Kellner, Rebecca Knapp, Mustafa M. Husain, Keith Rasmussen, Shirlene Sampson, Munro Cullum, Shawn M. McClintock, Kristen G. Tobias, Celena Martino, Martina Mueller, Samuel H. Bailine, Max Fink, Georgios Petrides
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- Journal:
- The British Journal of Psychiatry / Volume 196 / Issue 3 / March 2010
- Published online by Cambridge University Press:
- 02 January 2018, pp. 226-234
- Print publication:
- March 2010
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Background
Electroconvulsive therapy (ECT) is an effective treatment for major depression. Optimising efficacy and minimising cognitive impairment are goals of ongoing technical refinements.
AimsTo compare the efficacy and cognitive effects of a novel electrode placement, bifrontal, with two standard electrode placements, bitemporal and right unilateral in ECT.
MethodThis multicentre randomised, double-blind, controlled trial (NCT00069407) was carried out from 2001 to 2006. A total of 230 individuals with major depression, bipolar and unipolar, were randomly assigned to one of three electrode placements during a course of ECT: bifrontal at one and a half times seizure threshold, bitemporal at one and a half times seizure threshold and right unilateral at six times seizure threshold.
ResultsAll three electrode placements resulted in both clinically and statistically significant antidepressant outcomes. Remission rates were 55% (95% CI 43–66%) with right unilateral, 61% with bifrontal (95% CI 50–71%) and 64% (95% CI 53–75%) with bitemporal. Bitemporal resulted in a more rapid decline in symptom ratings over the early course of treatment. Cognitive data revealed few differences between the electrode placements on a variety of neuropsychological instruments.
ConclusionsEach electrode placement is a very effective antidepressant treatment when given with appropriate electrical dosing. Bitemporal leads to more rapid symptom reduction and should be considered the preferred placement for urgent clinical situations. The cognitive profile of bifrontal is not substantially different from that of bitemporal.
Effects of bilingualism on verbal learning and memory in Hispanic adults
- Josette G. Harris, C. Munro Cullum, Antonio E. Puente
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- Journal:
- Journal of the International Neuropsychological Society / Volume 1 / Issue 1 / January 1995
- Published online by Cambridge University Press:
- 26 February 2009, pp. 10-16
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The effect of bilingualism on qualitative aspects of verbal learning and memory was investigated. Equivalent list learning tests in English and Spanish were carefully constructed, and compared across two bilingual Hispanic groups of Mexican origin that differed in their level of English proficiency (“balanced” and “nonbalanced” bilinguals) and a group of monolingual English-speaking non-Hispanic subjects. Groups were matched for age, education, and gender composition. Nonbalanced bilinguals assessed in English utilized semantic clustering to the same extent as monolinguals, but learned fewer words overall, and demonstrated lower retention scores compared to monolinguals. Comparisons of groups assessed in their dominant languages, however, revealed no significant differences on any of the learning and memory indices examined. In addition to comparisons with standard clinical memory indices, assessment issues concerning bilingual individuals are addressed. (JINS, 1995, I, 10–16.)
Episodic memory function in advanced aging and early Alzheimer's disease
- C. Munro Cullum, C. M. Filley, E. Kozora
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- Journal:
- Journal of the International Neuropsychological Society / Volume 1 / Issue 1 / January 1995
- Published online by Cambridge University Press:
- 26 February 2009, pp. 100-103
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Despite some well-documented differences, normal aging and Alzheimer's disease (AD) share a number of common neuropathological and neuropsychological features. Many of the reported differences are largely quantitative in nature and there is often overlap between the respective distributions of these populations. To assess the issue of overlap and distinguishing features in memory functions between these groups, and to minimize aging effects per se, samples of older individuals in good health (ages 75–95 yr) and younger patients in the early stages of AD (age < 75 yr) were selected to be similar in global cognitive functioning. Despite comparable language and visuospatial scores, these preliminary results suggest important qualitative differences in episodic memory functions between these conditions, even when “low-functioning” or “at-risk” controls are compared with early AD patients. These findings furthermore highlight some of the challenges in defining “normality” among the oldest segment of our population. (JINS, 1995, I, 100–103.)