NIH Toolbox® Episodic Memory Measure Differentiates Older Adults with Exceptional Memory Capacity from those with Average-for-Age Cognition.

OBJECTIVE: Older adults with exceptional memory function, designated "SuperAgers," include individuals over age 80, with episodic memory at least as good as individuals ages 50s-60s. The Northwestern University SuperAging cohort is defined by performance on an established test of verbal memory. The purpose of this study was to determine if superior verbal memory extends to nonverbal memory in SuperAgers by examining differences in the National Institutes of Health Toolbox® (NIHTB) between older adults with exceptional memory and those with average-for-age cognition. METHOD: SuperAgers (n = 46) and cognitively average-for-age older adults (n = 31) completed a comprehensive neuropsychological battery and the NIHTB Cognition module. Multiple linear regressions were used to examine differences on subtests between groups. RESULTS: There was a significant effect of group on the Picture Sequence Memory score, (p = .007), such that SuperAgers had higher scores than cognitively average-for-age older adults. There were no other group effects across other non-episodic memory NIHTB Cognition measures. CONCLUSIONS: Findings from this study demonstrated stronger performance on the memory measure of the NIHTB in SuperAgers compared to cognitively average-for-age older adults demonstrating superior memory in not only verbal but also nonverbal episodic memory in this group. Additionally, this study adds to the literature validating the NIHTB in older adults, particularly in a novel population of adults over age 80 with exceptional memory.

Baseline characterization of the ARMADA (Assessing Reliable Measurement in Alzheimer's Disease) study cohorts.

INTRODUCTION: The National Institutes of Health (NIH) Toolbox (NIHTB) provides computerized measures of cognition, emotion, sensation, and motor abilities across the lifespan. The ARMADA (Assessing Reliable Measurement in Alzheimer's Disease and Cognitive Aging) study validated the NIHTB in individuals across the cognitive aging spectrum. This article reports the characteristics of our sample of participants. METHODS: Participants were recruited across nine sites and classified clinically as cognitively normal (NC), with mild cognitive impairment (MCI), or with dementia of the Alzheimer's type (DAT.) They completed the NIHTB at multiple time points and many had at least one Alzheimer's biomarker previously obtained. RESULTS: Groups differed with respect to dementia severity levels, as anticipated, but were well-matched across many demographic characteristics. DISCUSSION: The ARMADA study demographics and baseline characteristics provide a suitable sample for validating the NIHTB across the cognitive aging spectrum. Other enriched samples (African American participants, Spanish NIHTB, 85+ years of age) will be reported elsewhere. HIGHLIGHTS: There is a need for assessments that can detect the early stages of cognitive decline in older adults. The ARMADA (Assessing Reliable Measurement in Alzheimer's Disease and Cognitive Aging) study will validate the National Institutes of Health (NIH) Toolbox across the aging spectrum, including mild cognitive impairment (MCI) and dementia of the Alzheimer's type (DAT). Here we report the characteristics of participants. Groups were well-matched across most demographic characteristics, and clinical characteristics differed as expected. ARMADA study cohorts reflect their respective clinical syndromes for validating the NIH Toolbox.

ARMADA: Assessing reliable measurement in Alzheimer's disease and cognitive aging project methods.

INTRODUCTION: Early detection of cognitive decline in older adults is a public health priority. Advancing Reliable Measurement in Alzheimer's Disease and Cognitive Aging (ARMADA), a multisite study, is validating cognition, emotion, motor, and sensory modules of the National Institutes of Health Toolbox for Assessment of Neurological and Behavioral Function (NIHTB) in the aging spectrum from cognitively normal to dementia of the Alzheimer's type (DAT). METHODS: Participants 65 to 85 years old, in demographic groups racially proportional to the general US population, are recruited in one of three groups to validate the NIHTB: cognitively normal, amnestic mild cognitive impairment (aMCI), or mild DAT. Additional special emphasis cohorts include (1) Blacks in the three clinical groups; (2) Spanish-speakers in the three clinical groups; (3) cognitively normal, population-proportional, over age 85. DISCUSSION: Longitudinal study will determine whether NIHTB can predict cognitive decline and is associated with Alzheimer's disease biomarkers. Here, we detail the methods for the ARMADA study.

Measuring Multidimensional Aspects of Health in the Oldest Old Using the NIH Toolbox: Results From the ARMADA Study.

OBJECTIVE: The percentage of older adults living into their 80s and beyond is expanding rapidly. Characterization of typical cognitive performance in this population is complicated by a dearth of normative data for the oldest old. Additionally, little attention has been paid to other aspects of health, such as motor, sensory, and emotional functioning, that may interact with cognitive changes to predict quality of life and well-being. The current study used the NIH Toolbox (NIHTB) to determine age group differences between persons aged 65-84 and 85+ with normal cognition. METHOD: Participants were recruited in two age bands (i.e., 65-84 and 85+). All participants completed the NIHTB Cognition, Motor, Sensation, and Emotion modules. Independent-samples t-tests determined age group differences with post-hoc adjustments using Bonferroni corrections. All subtest and composite scores were then regressed on age and other demographic covariates. RESULTS: The 65-84 group obtained significantly higher scores than the 85+ group across all cognitive measures except oral reading, all motor measures except gait speed, and all sensation measures except pain interference. Age remained a significant predictor after controlling for covariates. Age was not significantly associated with differences in emotion scores. CONCLUSIONS: Results support the use of the NIHTB in persons over 85 with normal cognition. As expected, fluid reasoning abilities and certain motor and sensory functions decreased with age in the oldest old. Inclusion of motor and sensation batteries is warranted when studying trajectories of aging in the oldest old to allow for multidimensional characterization of health.

The Paradox in Positive and Negative Aspects of Emotional Functioning Among Older Adults with Early Stages of Cognitive Impairment.

Introduction: Emotional functioning in older adults is influenced by normal aging and cognitive impairment, likely heterogeneous across positive versus negative aspects of emotional functioning. Little is known about positive emotional experiences at the early stages of cognitive impairment. Methods: We assessed different aspects of emotional functioning among 448 participants aged 65+ (Normal Control (NC) = 276, Mild Cognitive Impairment (MCI) = 103, and mild dementia of the Alzheimer type (mild DAT) = 69) and tested moderators. Results: Compared to NC, older adults with MCI and mild DAT have maintained many positive aspects of emotional functioning, despite higher levels of negative affect, sadness, and loneliness. Among the oldest-old, the mild DAT group experienced higher fear and lower self-efficacy. Discussion: Older adults at early stages of cognitive impairment can experience positive aspects of emotional functioning, such as positive affect, purpose, and life satisfaction, all of which are important buildable psychological resources for coping.

Reduced task-evoked pupillary response in preparation for an executive cognitive control response among individuals across the psychosis spectrum.

Task-evoked pupillary response (TEPR) is a measure of physiological arousal modulated by cognitive demand. Healthy individuals demonstrate greater TEPR prior to correct versus error antisaccade trials and correct antisaccade versus visually guided saccade (VGS) trials. The relationship between TEPR and antisaccade performance in individuals with psychotic disorders and their relatives has not been investigated. Probands with schizophrenia, schizoaffective disorder, psychotic bipolar disorder, their first-degree relatives, and controls from the B-SNIP study completed antisaccade and VGS tasks. TEPR prior to execution of responses on these tasks was evaluated among controls compared to probands and relatives according to diagnostic groups and neurobiologically defined subgroups (biotypes). Controls demonstrated greater TEPR on antisaccade correct versus error versus VGS trials. TEPR was not differentiated between antisaccade correct versus error trials in bipolar or schizophrenia probands, though was greater on antisaccade compared to prosaccade trials. There was no modulation of TEPR in schizoaffective probands. Relatives of schizophrenia and schizoaffective probands and those with elevated psychosis spectrum traits failed to demonstrate differential TEPR on antisaccade correct versus error trials. No proband or relative biotypes demonstrated differential TEPR on antisaccade correct versus error trials, and only proband biotype 3 and relative biotypes 3 and 2 demonstrated greater TEPR on antisaccade versus VGS trials. Our findings suggest that aberrant modulation of preparatory activity prior to saccade execution contributes to impaired executive cognitive control across the psychosis spectrum, including nonpsychotic relatives with elevated clinical risk. Reduced pupillary modulation under cognitive challenge may thus be a biomarker for the psychosis phenotype.

Eye movements as a measure of word comprehension deficits in primary progressive aphasia.

INTRODUCTION: Eye movement studies can uncover subtle aspects of language processing impairment in individuals with primary progressive aphasia (PPA), who may have difficulty understanding words. This study examined eye movement patterns on a word-object matching task in response to varying levels of word-knowledge in PPA. METHODS: Participants with semantic and non-semantic PPA completed an object-matching task, where a word was presented and participants then selected the corresponding pictured object from an array. Afterwards, participants defined words for trials to which they incorrectly pointed. Linear mixed-effects analyses examined fixation differences on targets and related and unrelated foils. RESULTS: On incorrectly-pointed trials, participants demonstrated greater fixation duration on related foils, demonstrating intra-category blurring. For words that could not be defined, there was similar fixation duration on related and unrelated foils, demonstrating inter-category semantic blurring. DISCUSSION: This study demonstrated that fixation patterns reflect varying levels of word knowledge in PPA.

Cognitive Empathy and Longitudinal Changes in Temporo-Parietal Junction Thickness in Schizophrenia.

Objective: Deficits in cognitive empathy are well-documented in individuals with schizophrenia and are related to reduced community functioning. The temporoparietal junction (TPJ) is closely linked to cognitive empathy. We compared the relationship between baseline cognitive empathy and changes in TPJ thickness over 24 months between individuals with schizophrenia and healthy controls. Methods: Individuals with schizophrenia (n = 29) and healthy controls (n = 26) completed a cognitive empathy task and underwent structural neuroimaging at baseline and approximately 24 months later. Symmetrized percent change scores were calculated for right and left TPJ, as well as whole-brain volume, and compared between groups. Task accuracy was examined as a predictor of percent change in TPJ thickness and whole-brain volume in each group. Results: Individuals with schizophrenia demonstrated poorer accuracy on the cognitive empathy task (p < 0.001) and thinner TPJ cortex relative to controls at both time points (p = 0.01). In schizophrenia, greater task accuracy was uniquely related to less thinning of the TPJ over time (p = 0.02); task accuracy did not explain changes in left TPJ or whole-brain volume. Among controls, task accuracy did not explain changes in right or left TPJ, or whole-brain volume. Conclusions: Our findings suggest that greater cognitive empathy may explain sustained integrity of the right TPJ in individuals with schizophrenia, suggesting a contributory substrate for the long-term maintenance of this process in psychosis. Cognitive empathy was not related to changes in whole-brain volume, demonstrating the unique role of the TPJ in cognitive empathy.

Phasic alerting enhances spatial orienting in healthy aging but not in mild cognitive impairment.

OBJECTIVE: Previous studies in young adults have demonstrated strong functional links between phasic alerting and exogenous orienting. The present study examined changes in the dynamic interaction between these attentional networks in healthy aging and in amnestic mild cognitive impairment. METHOD: Healthy young adults, healthy older adults, and patients with amnestic mild cognitive impairment (MCI) were asked to identify as quickly as possible the color of a target stimulus that appeared within one of 2 peripheral boxes. Orienting was manipulated by a brief flashing of the same (valid cue) or opposite (invalid cue) box in which the target subsequently appeared. Alerting was manipulated by presenting an auditory white noise burst simultaneously with the visual orienting cue on half of the trials. RESULTS: All 3 groups displayed significant alerting and orienting effects but differed in the nature of the interaction between alerting and orienting. As expected, young adults displayed increased orienting under high alerting conditions through a selective enhancement of validly cued targets. While older adults displayed a greater effect of alerting on orienting compared to young adults, MCI patients did not display a significant interaction between attentional networks. CONCLUSIONS: Results provide support for the presence of increased compensatory interactions between attentional networks in healthy aging that may be no longer effective with the emergence of clinical symptoms in MCI. The demonstration of qualitatively distinct effects of healthy aging and MCI suggests that behavioral tests of attentional network interactions may serve as cognitive markers in individuals at increased risk for developing AD. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

The effect of high vs. low dose lurasidone on eye movement biomarkers of prefrontal abilities in treatment-resistant schizophrenia.

OBJECTIVE: Eye movement (EM) measures can serve as biomarkers to evaluate pharmacological effects on brain systems involved in cognition. In recent onset schizophrenia, antipsychotic treatment can improve attentional control on the antisaccade task and exacerbate working memory impairment on the memory guided saccade task; effects in treatment-resistant schizophrenia (TRS) are less clear. This study evaluated the effects of high versus low dose lurasidone on EM performance in TRS. METHODS: TRS patients completed EM testing: 1) at baseline, on existing medication regimen (n = 42), 2) after 6 weeks of low dose (80 mg) lurasidone (n = 38), 3) after 12 weeks following randomization to low (80 mg) or high dose (240 mg) lurasidone (n = 27), and 4) after 24 weeks of treatment (n = 23). EM testing included prosaccade, antisaccade, and memory guided saccade tasks. RESULTS: Six weeks of lurasidone resulted in increased prosaccade saccade latency and reduced antisaccade errors, with no change in memory guided saccade accuracy. After randomization, prosaccade and antisaccade latencies increased in only the high dose group, with no change in antisaccade errors in both groups. Memory guided saccade error increased in the high dose group and remained stable in the low dose group. CONCLUSION: Among TRS, stabilization on low dose lurasidone was associated with improved executive control of attention reflected by reduced antisaccade errors. High dose lurasidone resulted in prolonged speed of reflexive and executive shifts of attention and reduced spatial working memory relative to low dose. These findings indicate that EM measures are helpful biomarkers of dose-dependent antipsychotic treatment effects on executive cognitive abilities in TRS.