Development and Validity of Norms for Cognitive Dispersion on the Uniform Data Set 3.0 Neuropsychological Battery.

OBJECTIVE: Cognitive dispersion indexes intraindividual variability in performance across a battery of neuropsychological tests. Measures of dispersion show promise as markers of cognitive dyscontrol and everyday functioning difficulties; however, they have limited practical applicability due to a lack of normative data. This study aimed to develop and evaluate normed scores for cognitive dispersion among older adults. METHOD: We analyzed data from 4,283 cognitively normal participants aged ≥50 years from the Uniform Data Set (UDS) 3.0. We describe methods for calculating intraindividual standard deviation (ISD) and coefficient of variation (CoV), as well as associated unadjusted scaled scores and demographically adjusted z-scores. We also examined the ability of ISD and CoV scores to differentiate between cognitively normal individuals (n = 4,283) and those with cognitive impairment due to Lewy body disease (n = 282). RESULTS: We generated normative tables to map raw ISD and CoV scores onto a normal distribution of scaled scores. Cognitive dispersion indices were associated with age, education, and race/ethnicity but not sex. Regression equations were used to develop a freely accessible Excel calculator for deriving demographically adjusted normed scores for ISD and CoV. All measures of dispersion demonstrated excellent diagnostic utility when evaluated by the area under the curve produced from receiver operating characteristic curves. CONCLUSIONS: Results of this study provide evidence for the clinical utility of sample-based and demographically adjusted normative standards for cognitive dispersion on the UDS 3.0. These standards can be used to guide interpretation of intraindividual variability among older adults in clinical and research settings.

The Technology in Caring Questionnaire: Development and Psychometric Properties.

OBJECTIVE: We developed the Technology in Caring Questionnaire (TCQ) to assess the use of technology-based strategies by dementia caregivers. METHODS: One hundred caregivers completed a survey that included TCQ items along with measures of technology proficiency and patient and caregiver-centered outcomes. RESULTS: The final 34-item TCQ scale had adequate to excellent internal consistency (raw Cronbach alpha = 0.75; standardized Cronbach alpha = 0.95; Guttman lambda-6 = 0.97). TCQ scores demonstrated modest convergent associations with scores from measures of smartphone ( r = 0.265, P < 0.01) and computer proficiency ( r = 0.230, P < 0.05) but a strong association with overall technology experience scores ( r = 0.578, P < 0.001). Elevated TCQ scores were associated with reduced informant-reported cognitive symptoms ( B = -0.003, P < 0.05), increased ability of caregivers to find support and information ( B = 0.03, P < 0.001), and increased direct care strain ( B = 0.03, P < 0.05), after controlling for dementia severity and demographics. CONCLUSION: The TCQ has good psychometric properties for the assessment of technology-based care strategies among dementia caregivers. Findings imply that the use of technologies may aid in symptom management and finding support and information but may also increase caregiver strain.

Internet-Enabled Behaviors in Older Adults During the Pandemic: Patterns of Use, Psychosocial Impacts, and Plans for Continued Utilization.

In response to social distancing measures during the COVID-19 pandemic, there was a need to increase the frequency of internet enabled behaviors (IEBs). To date, little is known about how the pandemic impacted IEBs in older adults, a population that has historically been linked to lower digital literacy and utilization. We administered an online survey between April and July 2021 to 298 adults who were over age 50 (mean age = 73 years; 93.5% non-Hispanic white; 94% smart phone owners; 83.5% retired). Older adults self-reported IEBs for social, shopping, medical, and leisure activities during the pandemic, plans for continued use of these behaviors, and completed measures of psychosocial functioning. 66.8% of respondents reported an overall increase in IEBs during the pandemic, most notably for online meeting attendance. More frequent online meeting use was associated with less depression (r = -0.12, p = .04) and less loneliness (r = -0.14, p = .02). With regard to plans for continued use, 82.5% of the sample reported at least one IEB (M = 2.18, SD = 1.65) that they increased during the pandemic and planned to maintain over time (e.g., online shopping for household goods). Plans for continued use were more likely in participants who used IEBs more overall during the pandemic (r = 0.56, p < .001), and who frequently sought technical support on search engines (r = 0.22, p < .001), or online video sites (r = 0.16, p = .006). In summary, IEBs during the pandemic were associated with favorable psychosocial functioning and expectations for continued use in this sample of predominantly white older adults who had some baseline technological familiarity.

Ecological validity of cognitive fluctuations in dementia with Lewy bodies.

OBJECTIVES: Cognitive fluctuations are a core clinical feature of dementia with Lewy bodies (DLB), but their contribution to the everyday functioning difficulties evident DLB are not well understood. The current study evaluated whether intraindividual variability across a battery of neurocognitive tests (intraindividual variability-dispersion) and daily cognitive fluctuations as measured by informant report are associated with worse daily functioning in DLB. METHODS: The study sample included 97 participants with consensus-defined DLB from the National Alzheimer's Coordinating Center (NACC). Intraindividual variability-dispersion was measured using the coefficient of variation, which divides the standard deviation of an individual's performance scores across 12 normed neurocognitive indices from the NACC neuropsychological battery by that individual's performance mean. Informants reported on daily cognitive fluctuations using the Mayo Fluctuations Scale (MFS) and on daily functioning using the functional activities questionnaire (FAQ). RESULTS: Logistic regression identified a large univariate association of intraindividual variability-dispersion and presence of daily cognitive fluctuations on the MFS (Odds Ratio = 73.27, 95% Confidence Interval = 1.38, 3,895.05). Multiple linear regression demonstrated that higher intraindividual variability-dispersion and presence of daily cognitive fluctuations as assessed by the MFS were significantly and independently related to worse daily functioning (FAQ scores). CONCLUSIONS: Among those with DLB, informant-rated daily cognitive fluctuations and cognitive fluctuations measured in the clinic (as indexed by intraindividual variability-dispersion across a battery of tests) were independently associated with poorer everyday functioning. These data demonstrate ecological validity in measures of cognitive fluctuations in DLB.

A survey of neuropsychological assessment feedback practices among neuropsychologists.

OBJECTIVE: Feedback on neuropsychological assessment is a critical part of clinical practice, but there are few empirical papers on neuropsychological feedback practices. We sought to fill this gap in the literature by surveying practicing neuropsychologists in the United States. Questions addressed how they provide verbal and written feedback to patients and referral sources. Survey questions also addressed billing practices and training in the provision of feedback. METHODS: A survey was developed using Qualtrics XM to survey currently licensed, independently practicing clinical neuropsychologists in the United States about their feedback practices. The survey was completed by 184 individuals. RESULTS: Nearly all respondents reported that they provide verbal feedback to patients, most often in-person, within three weeks following testing. Typically, verbal feedback sessions with patients last 45 min. Verbal feedback was provided to referrals by about half of our sample, typically via a brief phone call. Most participants also reported providing written feedback to both the patient and referring provider, most commonly via the written report within three weeks after testing. Regarding billing, most respondents use neuropsychological testing evaluation codes. The COVID-19 pandemic appeared to have had a limited impact on the perceived effectiveness and quality of verbal feedback sessions. Finally, respondents reported that across major stages of professional development, training in the provision of feedback gradually increased but was considered inadequate by many participants. CONCLUSIONS: Results provide an empirical summary of the "state of current practice" for providing neuropsychological assessment feedback. Further experimental research is needed to develop an evidence-base for effective feedback practices.

Limited connectedness of spontaneous speech may be a marker of dementia due to Alzheimer's disease.

The study evaluated the connectedness of spontaneous speech production in individuals with dementia as a potential predictor of dementia severity. Data were derived from the baseline sample of 143 individuals with dementia in the English Pitt corpus. Dementia severity was assessed via the Mini Mental Status Exam, the Mattis Dementia Rating Scale, and the Blessed Dementia Scale. Language abilities were evaluated using verbal fluency and picture description tasks. Graph analysis was carried out for the picture description task using the computational tool SpeechGraphs to calculate connectedness. Results demonstrated that higher educational attainment, higher verbal fluency and strongly-connected spontaneous speech were associated with better cognitive function. Results suggest that automated language processing approaches, such as graph structure analysis, may provide a faster and ecologically valid method of detecting dementia symptoms.

Career development in pragmatic clinical trials to improve care for people living with dementia.

The growing number of people living with dementia (PLWD) requires a coordinated clinical response to deliver pragmatic, evidence-based interventions in frontline care settings. However, infrastructure to support such a response is lacking. Moreover, there are too few researchers conducting rigorous embedded pragmatic clinical trials (ePCTs) to make the vision of high quality, widely accessible dementia care a reality. National Institute on Aging (NIA) Imbedded Pragmatic Alzheimer's disease and Related Dementias Clinical Trials (IMPACT) Collaboratory seeks to improve the pipeline of early career researchers qualified to lead ePCTs by funding career development awards. Even with support from the Collaboratory, awardees face practical and methodological challenges to success, recently exacerbated by the COVID-19 pandemic. We first describe the training opportunities and support network for the IMPACT CDA recipients. This report then describes the unique career development challenges faced by early-career researchers involved in ePCTs for dementia care. Topics addressed include challenges in establishing a laboratory, academic promotion, mentoring and professional development, and work-life balance. Concrete suggestions to address these challenges are offered for early-career investigators, their mentors, and their supporting institutions. While some of these challenges are faced by researchers in other fields, this report seeks to provide a roadmap for expanding the work of the IMPACT Collaboratory and initiating future efforts to recruit, train, and retain talented early-career researchers involved in ePCTs for dementia care.

Recent Advances in Neuropsychological Test Interpretation for Clinical Practice.

Much attention in the field of clinical neuropsychology has focused on adapting to the modern healthcare environment by advancing telehealth and promoting technological innovation in assessment. Perhaps as important (but less discussed) are advances in the development and interpretation of normative neuropsychological test data. These techniques can yield improvement in diagnostic decision-making and treatment planning with little additional cost. Brooks and colleagues (Can Psychol 50: 196-209, 2009) eloquently summarized best practices in normative data creation and interpretation, providing a practical overview of norm development, measurement error, the base rates of low scores, and methods for assessing change. Since the publication of this seminal work, there have been several important advances in research on development and interpretation of normative neuropsychological test data, which may be less familiar to the practicing clinician. Specifically, we provide a review of the literature on regression-based normed scores, item response theory, multivariate base rates, summary/factor scores, cognitive intraindividual variability, and measuring change over time. For each topic, we include (1) an overview of the method, (2) a rapid review of the recent literature, (3) a relevant case example, and (4) a discussion of limitations and controversies. Our goal was to provide a primer for use of normative neuropsychological test data in neuropsychological practice.

The impact of technology-based compensatory behaviors on subjective cognitive decline in older adults with a family history of dementia.

The current study examined whether greater use of technology to help with daily tasks is associated with less subjective cognitive decline (SCD), especially in individuals with a family history of Alzheimer's disease (AD). Individuals over the age of 50 (n = 102; age range 50-85) completed surveys about their digital and analog approaches to daily tasks, physical activity, and SCD. Participants with and without family histories of AD were matched on age, education, sex, and family history of AD using the R package MatchIt. There was no main effect of technology-based behavioral strategies on SCD (p = 0.259). However, a family history of AD moderated the association between technology use and SCD even when controlling for another protective lifestyle factor, physical activity. In individuals with a family history of AD, more reliance on technology-based behavioral strategies was associated with less SCD (p = 0.018), but this relationship was not significant in individuals without family history of AD (p = 0.511). Our findings suggest that technology-based behavioral strategies are associated with less SCD in individuals with a family history of AD, independent of another protective lifestyle factor. Future recommendations provided by healthcare providers to address SCD in cognitively unimpaired older adults might include focusing on technological assistance.

Technology use and subjective cognitive concerns in older adults.

OBJECTIVES: How technology impacts the day to day cognitive functioning of older adults is a matter of some debate. On the one hand, the use of technologies such as smartphones and social media, may lead to more subjective cognitive concerns (SCC) by promoting distractibility and reliance on devices to perform memory tasks. However, continued digital engagement in older adults may also be related to better cognitive functioning. Given these competing viewpoints, our study evaluated if frequency of digital device use was associated with greater or less subjective cognitive concerns. METHOD: Participants were 219 adults over the age of 65 (mean age =75 years) who had internet access. Measures assessing frequency of digital device use along with SCC were administered. Hierarchical multiple regression was used to gage association between frequency of device use and SCC, controlling for relevant demographic and lifestyle factors. RESULTS: Increased frequency of digital device use was associated with less SCC, over and above the influence of demographic factors, across cognitive (but especially in executive) domains. This effect was observed for general device usage, with no statistically significant associations were observed between texting/video call, social media use and SCC. DISCUSSION: Results were broadly consistent with the technological reserve hypothesis in that digital engagement was associated with better experienced cognitive functioning in older adults. While device use may contribute to distractibility in certain cases, the current results add to a burgeoning literature that digital engagement may be a protective factor for cognitive changes with age.

Examining racial disparities in the diagnosis of mild cognitive impairment.

Black individuals are less likely to receive an accurate diagnosis of mild cognitive impairment (MCI) than their White counterparts, possibly because diagnoses are typically made by a physician, often without reference to objective neuropsychological test data. We examined racial differences in actuarial MCI diagnoses among individuals diagnosed with MCI via semi-structured clinical interview (the Clinical Dementia Rating) to examine for possible biases in the diagnostic process. Participants were drawn from the National Alzheimer's Coordinating Center Uniform Data Set and included 491 individuals self-identifying as Black and 2,818 individuals self-identifying as White. Chi-square tests were used to examine racial differences in rates of low scores for each cognitive test (domains assessed included attention, processing speed/executive functioning, memory, language, and visual skills). Next, we tested for racial differences in probability of meeting actuarial criteria for MCI by race. Compared to Black participants diagnosed with MCI via clinical interview, White individuals diagnosed with MCI via clinical interview demonstrated significantly higher rates of low demographically-adjusted z-scores on tests of memory, attention, processing speed, and verbal fluency. Furthermore, White individuals were significantly more likely to meet actuarial criteria for MCI (71.60%) than Black individuals (57.90%). Results suggest there may be bias in MCI classification based on semi-structured interview, leading to over diagnosis among Black individuals and/or under diagnosis among White individuals. Examination of neuropsychological test data and use of actuarial approaches may reduce racial disparities in the diagnosis of MCI. Nonetheless, issues related to race-based norming and differential symptom presentations complicate interpretation of results.

The impact of conventional versus robust norming on cognitive characterization and clinical classification of MCI and dementia.

We examined the impact of conventional versus robust normative approaches on cognitive characterization and clinical classification of MCI versus dementia. The sample included participants from the National Alzheimer's Coordinating Center Uniform Data Set. Separate demographically adjusted z-scores for cognitive tests were derived from conventional (n = 4273) and robust (n = 602) normative groups. To assess the impact of deriving scores from a conventional versus robust normative group on cognitive characterization, we examined likelihood of having a low score on each neuropsychological test. Next, we created receiver operating characteristic (ROC) curves for the ability of normed scores derived from each normative group to differentiate between MCI (n = 3570) and dementia (n = 1564). We examined the impact of choice of normative group on classification accuracy by comparing sensitivity and specificity values and areas under the curves (AUC). Compared with using a conventional normative group, using a robust normative group resulted in a higher likelihood of low cognitive scores for individuals classified with MCI and dementia. Comparison of the classification accuracy for distinguishing MCI from dementia did not suggest a statistically significant advantage for either normative approach (Z = -0.29, p = .77; AUC = 0.86 for conventional and AUC = 0.86 for robust). In summary, these results indicate that using a robust normative group increases the likelihood of characterizing cognitive performance as low. However, there is not a clear advantage of using a robust over a conventional normative group when differentiating between MCI and dementia.

Psychometric properties of the Autonomic Symptoms Checklist in the Lewy body disease module of the uniform dataset.

INTRODUCTION: Autonomic dysfunction is an important feature of Lewy Body Dementia (DLB), but measurement of autonomic symptoms has been limited in both previous research and clinical practice. Accurate measurement of autonomic dysfunction has the potential to improve our understanding of the course and progression of DLB, given that autonomic symptoms typically precede cognitive impairment and are associated with functional impairment. The primary aim of this study was to examine the psychometric properties of the two versions (3.0 and 3.1) of the NACC LBD-module Autonomic Symptom Checklist (ASC). METHODS: Psychometric analyses of the ASC (internal consistency, reliability, factor structure, and validity) were conducted on data acquired from 245 individuals with DLB from the NACC database. ASC V3.0 was contrasted on these attributes to V3.1. RESULTS: Results suggested an underlying factor structure for the ASC, and confirmatory factor analysis (CFA) revealed 3 factors, which generally aligned with discrete autonomic systems. The ASC V3.0 and CFA-identified scales were comparable in terms of reliability, which were both improved relative to the ASC V3.1. In terms of ecological validity, CFA-identified items related to gastrointestinal/thermoregulation symptoms were significantly more associated with functional outcomes compared to the unitary ASC. CONCLUSION: Findings underscore the importance of differentiation within the autonomic system. Future research into autonomic symptom classes and lab-based pathophysiological measurement of autonomic dysfunction in DLB has the potential to support early identification and inform treatment planning.

Dispersion-based cognitive intra-individual variability in dementia with Lewy bodies.

OBJECTIVE: Cognitive fluctuations are characteristic of dementia with Lewy bodies (DLB) but challenging to measure. Dispersion-based intra-individual variability (IIV-d) captures neurocognitive performance fluctuations across a test battery and may be sensitive to cognitive fluctuations but has not been studied in DLB. METHOD: We report on 5,976 participants that completed the uniform data set 3.0 neuropsychological battery (UDS3NB). IIV-d was calculated via the intra-individual standard deviation across 12 primary UDS3NB indicators. Separate models using mean USD3NB score and the Montreal cognitive assessment (MoCA) total score tested the reproducibility of the incremental value of IIV-d over-and-above global cognition. Binary logistic regressions tested whether IIV-d could classify individuals with and without clinician-rated cognitive fluctuations. Multinomial logistic regressions tested whether IIV-d could differentiate participants with DLB, participants with Alzheimer's disease (AD), and participants with healthy cognition (CH), as well as the incremental diagnostic utility of IIV-d over-and-above clinician-rated cognitive fluctuations. RESULTS: IIV-d exhibited large univariate associations with clinician-rated and non-clinician-informant reported cognitive fluctuations, which persisted when adjusting for MoCA but not the full battery mean. Of diagnostic relevance, greater IIV-d was consistently associated with DLB and AD relative to CH over-and-above global cognition and clinician-rated cognitive fluctuations. Greater IIV-d was less consistently associated with an increased probability of DLB relative to AD when controlling for global cognition. CONCLUSIONS: IIV-d accurately differentiates DLB from CH over-and-above global cognition and clinician-rated cognitive fluctuations. IIV-d may supplement a thorough clinical interview of cognitive fluctuations and serve as a standardized performance-based indicator of this transdiagnostic phenomenon. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Comparison of Azure Kinect overground gait spatiotemporal parameters to marker based optical motion capture.

BACKGROUND: Instrumented measurement of spatiotemporal parameters during walking can provide valuable information on an individual's overall function and health. Efficient, inexpensive, and accurate measurement of overground walking spatiotemporal parameters would be a critical component of providing point-of-care assessments of gait function, concussion recovery, fall-risk, and cognitive decline. Depth cameras combined with skeleton pose tracking algorithms, such as the Microsoft Kinect with body tracking software, have been used to measure walking spatiotemporal parameters. However, the ability of the latest generation Microsoft Kinect sensor, the Azure Kinect, to accurately measure overground walking spatiotemporal parameters has not been evaluated in the literature. RESEARCH QUESTION: The purpose of this work was to compare overground walking spatiotemporal parameters measurements from a 12 camera Vicon optical motion capture system to measurements of a single Azure Kinect with body tracking SDK (software development kit). METHODS: Spatiotemporal parameters of overground walking were simultaneously collected on twenty young healthy participants. Stride length, stride time, step length and step width were derived from ankle joint center locations and measurements from the two instruments were compared using descriptive statistics, scatter plots, Pearson correlation analyses, and Bland-Altman analyses. RESULTS: Pearson correlation coefficients were greater than 0.87 for all spatiotemporal parameters with most parameters demonstrating very strong (> 0.9) agreement. The mean of the differences for stride length between measurements was 35.6 mm for the left limb and 39.1 mm for the right limb, both of which are less than 3% of average stride length. Mean of the differences for step width and stride time were less than 2% and 1% of their averages respectively. SIGNIFICANCE: A single Microsoft Azure Kinect with body tracking SDK can provide clinically relevant measurement of walking spatiotemporal parameters, providing accessible and objective measurements that can improve clinical decision making across a variety of patient populations.

The ecological validity of the Uniform Data Set 3.0 neuropsychological battery in individuals with mild cognitive impairment and dementia.

Objective: Ecological validity refers to the ability of neuropsychological measures to predict real world performance. Questions remain as to the ecological validity of commonly used measures, particularly regarding their relationships to global versus specific activities of daily living among those with neurodegenerative disease. We explored these issues through the lens of the Uniform Data Set 3.0 Neuropsychological battery (UDS3NB) in individuals with mild cognitive impairment and dementia. Method: UDS3NB and informant rated Functional Activities Questionnaire scales were evaluated from 2,253 individuals with mild cognitive impairment and dementia. Ordinal regression equations were used to explore the relationships of demographic and cognitive variables with overall and specific instrumental activities of daily living. Results: Delayed recall for visual and verbal material, and performance on trail making tests were consistent predictors of global and specific functions. Specific skills (i.e. naming or figure copy) showed differential relationships with specific activities, while phonemic fluency was not related to any particular activity. Conclusions: Measures in the UDS3NB predicted activities of daily living in individuals with MCI and dementia, providing initial support for the ecological validity of these tests. Specifically, measures that tap core deficits of Alzheimer's disease, such as delayed recall and sequencing/shifting, are consistent predictors of performance in daily tasks.

Neuropsychological functioning in dysgenesis of the corpus callosum with colpocephaly.

Dysgenesis of the corpus callosum is a rare developmental abnormality in brain structure that is associated with changes in physical appearance, as well as behavioral and cognitive consequences. A relatively commonly co-occurring structural abnormality with callosal dysgenesis is colpocephaly, characterized by enlargement of the posterior lateral ventricles and reductions in posterior brain volume. Although some case studies of individuals with this combination of structural malformations exist, they do not often report results of neuropsychological evaluation. Furthermore, those that do contain neuropsychological data may be of limited generalizability due to unique patient characteristics. The current manuscript overcomes these limitations by presenting the case of a 55-year-old male with callosal dysgenesis and colpocephaly identified in adulthood. The paper includes a full profile of his performance on a comprehensive neuropsychological test battery with discussion of differential diagnosis and treatment planning. Findings indicated low average intellectual abilities with deficits in processing speed, executive functions, and social cognition, consistent with expectations based on callosal dysgenesis. One surprising finding was that despite the significant posterior involvement of colpocephaly, visuospatial skills were a relative strength. The manuscript provides a clear characterization of callosal dysgenesis with colpocephaly to facilitate future clinical comparisons and set the stage for future research on this rare neuromorphological presentation.

Neuropsychological Equivalence of the Clinical Diagnosis of Mild Cognitive Impairment in the National Alzheimer's Coordinating Center Uniform Data Set and Alzheimer's Disease Neuroimaging Initiative.

INTRODUCTION: Our understanding of Alzheimer's disease may be improved by harmonizing data from large cohort studies of older adults. Differences in the way clinical conditions, like mild cognitive impairment (MCI), are diagnosed may lead to variability among participants that share the same diagnostic label. This variability presents a challenge for cohort harmonization and may lead to inconsistency in research findings. Little research to date has explored the equivalence of the diagnostic label of MCI across 2 of the largest and most influential cohort studies in the USA: the National Alzheimer's Coordinating Center (NACC) and the Alzheimer's Disease Neuroimaging Initiative (ADNI). METHODS: Participants with MCI due to presumed Alzheimer's disease from the NACC Uniform Data Set (n = 789) and ADNI (n = 131) were compared on demographic, psychological, and functional variables, as well as on an abbreviated neuropsychological battery common to the 2 data sets. RESULTS: Though similar in terms of age, education, and functional status, the NACC sample was more diverse (17.4% non-White participants vs. 7.6% in ADNI; χ2 = 7.923, p = 0.005) and tended to perform worse on some cognitive tests. In particular, participants diagnosed with MCI in NACC were more likely to have clinically significant impairments on language measures (26.36-31.18%) than MCI participants in ADNI (16.03-19.85%). DISCUSSION: The current findings suggest important differences in cognitive performances between 2 large MCI cohorts, likely reflective of differences in diagnostic criteria used in these 2 studies, as well as differences in sample compositions. Such diagnostic heterogeneity may make harmonizing data across these cohorts challenging. However, application of shared psychometric criteria across studies may lead to closer equivalence of MCI groups. Such approaches could pave the way for cohort harmonization and enable "big data" analytic approaches to understanding Alzhei-mer's to be developed.

Empirically defining the preclinical stages of the Alzheimer's continuum in the Alzheimer's Disease Neuroimaging Initiative.

AIM: The National Institute on Aging and the Alzheimer's Association published new research criteria defining the Alzheimer's continuum (AC) by the presence of positive amyloid-ß biomarkers. Symptom severity of those on the AC is staged across six levels, including two preclinical stages (stages 1 and 2). AC stage 2 is defined by the presence of at least one of the following: (i) transitional cognitive decline; (ii) subjective cognitive decline; or (iii) neurobehavioural symptoms. In contrast, AC stage 1 is defined by the absence of symptoms. METHODS: Initial empirical definitions for each symptom class were developed. These empirical criteria were then applied in a sample of 285 cognitively normal, amyloid-positive individuals from the Alzheimer's Disease Neuroimaging Initiative for purposes of AC stage 1 and 2 classification. RESULTS: In this sample, 56.10% of participants were asymptomatic and classified as AC stage 1. In contrast, 42.46% of individuals were positive for at least one symptom class: 22.11% for transitional cognitive decline, 20.35% for subjective cognitive decline, and 14.74% for neurobehavioural symptoms. AC stage was a predictor of cognitive/functional decline over 4 years of follow up in a longitudinal growth model (B = 0.33, P < 0.001). CONCLUSIONS: Results provide a methodology to operationalize the National Institute on Aging and the Alzheimer's Association AC stage 1 and 2 criteria and include preliminary evidence of the validity of this approach. The methods outlined in this manuscript can be used to test hypotheses regarding prodromal Alzheimer's disease, as well as implemented in clinical trial selection procedures.

How impaired is too impaired? Exploring futile neuropsychological test patterns as a function of dementia severity and cognitive screening scores.

Some older adults cannot meaningfully participate in the testing portion of a neuropsychological evaluation due to significant cognitive impairments. There are limited empirical data on this topic. Thus, the current study sought to provide an operational definition for a futile testing profile and examine cognitive severity status and cognitive screening scores as predictors of testing futility at both baseline and first follow-up evaluations. We analysed data from 9,263 older adults from the National Alzheimer's Coordinating Center Uniform Data Set. Futile testing profiles occurred rarely at baseline (7.40%). There was a strong relationship between cognitive severity status and the prevalence of futile testing profiles, χ2 (4) = 3559.77, p < .001. Over 90% of individuals with severe dementia were unable to participate meaningfully in testing. Severity range on the Montreal Cognitive Assessment (MoCA) also demonstrated a strong relationship with testing futility, χ2 (3) = 3962.35, p < .001. The rate of futile testing profiles was similar at follow-up (7.90%). There was a strong association between baseline dementia severity and likelihood of demonstrating a futile testing profile at follow-up, χ2 (4) = 1513.40, p < .001. Over 90% of individuals with severe dementia, who were initially able to participate meaningfully testing, no longer could at follow-up. Similarly, there was a strong relationship between baseline MoCA score band and likelihood of demonstrating a futile testing profile at follow-up, χ2 (3) = 1627.37, p < .001. Results can help to guide decisions about optimizing use of limited neuropsychological assessment resources.