Andrew J. Aschenbrenner

Clinical and psychological characteristics of the initial cohort of the Dominantly Inherited Alzheimer Network (DIAN).

OBJECTIVE The purpose was to describe clinical, cognitive, and personality characteristics at baseline assessment of 249 participants, 19 to 60 years of age, in a multinational longitudinal study of autosomal dominant Alzheimers disease (ADAD). METHOD Participants (74% cognitively normal) were from ADAD families with mutations in 1 of 3 genes (APP, PSEN1, or PSEN2). Mixed model analyses, including family as a random variable and controlling for years from expected time of symptomatic onset of ADAD based on parental age at onset, compared 3 groups (cognitively normal mutation noncarriers, cognitively normal mutation carriers, very mildly impaired mutation carriers). RESULTS Global cognitive deficits similar to those observed in late-life sporadic Alzheimers disease (AD) existed in very mild ADAD compared with cognitively normal carriers and noncarriers on all but 2 measures (Digit Span Backward, Letter Fluency for FAS) of episodic memory, semantic memory, working memory, attention, and speeded visuospatial abilities. Demented individuals were less extraverted, open, and conscientious than cognitively normal participants on the International Personality Item Pool. Differences in the relation between 3 measures (Logical Memory, Digit Symbol, attention switching) and time to expected age at symptomatic onset indicate that cognitive deficits on some measures can be detected in mutation carriers prior to symptomatic AD, and hence should be useful markers in subsequent longitudinal follow-up. CONCLUSIONS Overall cognitive and personality deficits in very mild ADAD are similar to those seen in sporadic AD. Cognitive deficits also occur in asymptomatic mutation carriers who are closer to the expected time of dementia onset.

Additive effects of word frequency and stimulus quality: the influence of trial history and data transformations.

A counterintuitive and theoretically important pattern of results in the visual word recognition literature is that both word frequency and stimulus quality produce large but additive effects in lexical decision performance. The additive nature of these effects has recently been called into question by Masson and Kliegl (in press), who used linear mixed effects modeling to provide evidence that the additive effects were actually being driven by previous trial history. Because Masson and Kliegl also included semantic priming as a factor in their study and recent evidence has shown that semantic priming can moderate the additivity of word frequency and stimulus quality (Scaltritti, Balota, & Peressotti, 2012), we reanalyzed data from 3 published studies to determine if previous trial history moderated the additive pattern when semantic priming was not also manipulated. The results indicated that previous trial history did not influence the joint influence of word frequency and stimulus quality. More important, and independent of Masson and Kliegls conclusions, we also show how a common transformation used in linear mixed effects analyses to normalize the residuals can systematically alter the way in which two variables combine to influence performance. Specifically, using transformed, rather than raw reaction times, consistently produces more underadditive patterns.

A behavioral database for masked form priming

Reading involves a process of matching an orthographic input with stored representations in lexical memory. The masked priming paradigm has become a standard tool for investigating this process. Use of existing results from this paradigm can be limited by the precision of the data and the need for cross-experiment comparisons that lack normal experimental controls. Here, we present a single, large, high-precision, multicondition experiment to address these problems. Over 1,000 participants from 14 sites responded to 840 trials involving 28 different types of orthographically related primes (e.g., castfe–CASTLE) in a lexical decision task, as well as completing measures of spelling and vocabulary. The data were indeed highly sensitive to differences between conditions: After correction for multiple comparisons, prime type condition differences of 2.90 ms and above reached significance at the 5% level. This article presents the method of data collection and preliminary findings from these data, which included replications of the most widely agreed-upon differences between prime types, further evidence for systematic individual differences in susceptibility to priming, and new evidence regarding lexical properties associated with a target word’s susceptibility to priming. These analyses will form a basis for the use of these data in quantitative model fitting and evaluation and for future exploration of these data that will inform and motivate new experiments.

Alzheimer Disease Cerebrospinal Fluid Biomarkers Moderate Baseline Differences and Predict Longitudinal Change in Attentional Control and Episodic Memory Composites in the Adult Children Study.

Cognitive measures that are sensitive to biological markers of Alzheimer disease (AD) pathology are needed to (a) facilitate preclinical staging, (b) identify individuals who are at the highest risk for developing clinical symptoms, and (c) serve as endpoints for evaluating the efficacy of interventions. The present study assesses the utility of two cognitive composite scores of attentional control and episodic memory as markers for preclinical AD pathology in a group of cognitively normal older adults (N = 238), as part of the Adult Children Study. All participants were given a baseline cognitive assessment and follow-up assessments every 3 years over an 8-year period, as well as a lumbar puncture within 2 years of the initial assessment to collect cerebrospinal fluid (CSF) and amyloid tracer Pittsburgh compound-B scan for amyloid imaging. Results indicated that attentional control was correlated with levels of Aβ42 at the initial assessment whereas episodic memory was not. Longitudinally, individuals with high CSF tau exhibited a decline in both attention and episodic memory over the course of the study. These results indicate that measures of attentional control and episodic memory can be used to evaluate cognitive decline in preclinical AD and provide support that CSF tau may be a key mechanism driving longitudinal cognitive change.

Interactive Effects of Working Memory and Trial History on Stroop Interference in Cognitively Healthy Aging

Past studies have suggested that Stroop interference increases with age; however the robustness of this effect after controlling for processing speed has been questioned. Both working memory (WM) and the congruency of the immediately preceding trial have also been shown to moderate the magnitude of Stroop interference. Specifically, interference is smaller both for individuals with higher working memory capacity and following an incongruent trial. At present, it is unclear whether and how these 3 variables (age, WM and previous congruency) interact to predict interference effects in the standard Stroop color-naming task. We present analyses of Stroop interference in a large database of Stroop color-naming trials from a lifespan sample of well-screened, cognitively healthy, older adults. Our results indicated age-related increases in interference (after controlling for processing speed) that were exaggerated for individuals with low WM. This relationship between age and WM occurred primarily when the immediately preceding trial was congruent. Following an incongruent trial, interference increased consistently with age, regardless of WM. Taken together, these results support previous accounts of multiple mechanisms underlying control in the Stroop task and provide insight into how each component is jointly affected by age, WM, and trial history.

A Diffusion Model Analysis of Episodic Recognition in Preclinical Individuals With a Family History for Alzheimer's Disease: The Adult Children Study

OBJECTIVE A family history of Alzheimers disease (AD) increases the risk of developing AD and can influence the accumulation of well-established AD biomarkers. There is some evidence that family history can influence episodic memory performance even in cognitively normal individuals. We attempted to replicate the effect of family history on episodic memory and used a specific computational model of binary decision making (the diffusion model) to understand precisely how family history influences cognition. Finally, we assessed the sensitivity of model parameters to family history controlling for standard neuropsychological test performance. METHOD Across 2 experiments, cognitively healthy participants from the Adult Children Study completed an episodic recognition test consisting of high- and low-frequency words. The diffusion model was applied to decompose accuracy and reaction time (RT) into latent parameters which were analyzed as a function of family history. RESULTS In both experiments, individuals with a family history of AD exhibited lower recognition accuracy and this occurred in the absence of an apolipoprotein E (APOE) ε4 allele. The diffusion model revealed this difference was due to changes in the quality of information accumulation (the drift rate) and not differences in response caution or other model parameters. This difference remained after controlling for several standard neuropsychological tests. CONCLUSIONS These results confirm that the presence of a family history of AD confers a subtle cognitive deficit in episodic memory as reflected by decreased drift rate that cannot be attributed to APOE. This measure may serve as a novel cognitive marker of preclinical AD.

The first letter position effect in visual word recognition: The role of spatial attention.

A prominent question in visual word recognition is whether letters within a word are processed in parallel or in a left to right sequence. Although most contemporary models posit parallel processing, this notion seems at odds with well-established serial position effects in word identification that indicate preferential processing for the initial letter. The present study reports 4 experiments designed to further probe the locus of the first position processing advantage. The paradigm involved masked target words presented for short durations and required participants to subsequently select from 2 alternatives, 1 which was identical to the target and 1 that differed by a single letter. Experiment 1 manipulated the case between the target and the alternatives to ensure that previous evidence for a first position effect was not due to simple perceptual matching. The results continued to yield a robust first position advantage. Experiment 2 attempted to eliminate postperceptual decision processes as the explanatory mechanism by presenting single letters as targets and requiring participants to select an entire word that contained the target letter at different positions. Here the first position advantage was eliminated, suggesting postperceptual decision processes do not underlie the effect. The final 2 experiments presented masked stimuli either all vertically (Experiment 3) or randomly intermixed vertical and horizontal orientation (Experiment 4). In both cases, a robust first position advantage was still obtained. The authors consider alternative interpretations of this effect and suggest that these results are consistent with a rapid deployment of spatial attention to the beginning of a target string which occurs poststimulus onset.

Dynamic adjustment of lexical processing in the lexical decision task: Cross-trial sequence effects

There has been growing interest in dynamic changes in the lexical processing system across trials, which have typically been assessed via linear mixed effect modelling. In the current study, we explore the influence of previous trial lexicality and previous trial perceptual degradation on the effect of lexicality and degradation on the current trial. The results of analyses of three datasets (two previously published studies and a new study) provide evidence for a robust four-way interaction among previous trial lexicality and degradation and current trial lexicality and degradation effects. Discussion emphasizes how priming of relevant dimensions (clear vs. degraded or word vs. nonword) within the experimental context modulates the influence of degradation on the current trial as a function of lexicality. These results suggest that in lexical decision there are robust lingering effects of the previous stimulus and response that carry over to the current stimulus and response, and participants cannot tune task-related systems to only the present trial. Importantly, although these complex relationships are theoretically important regarding lexical and decision level processes, these complexities also reinforce Keith Rayner’s emphasis on on-line eye-tracking measures during reading as the most straightforward window into word-level processes engaged during reading.

Dynamic adjustments of attentional control in healthy aging.

In standard attentional control tasks, interference effects are reduced following incongruent trials compared to congruent trials, a phenomenon known as the congruency sequence effect (CSE). Typical explanations of this effect suggest the CSE is due to changes in levels of control across adjacent trials. This interpretation has been questioned by the finding that older adults, individuals with impaired attentional control systems, have been shown to produce larger CSEs in the Stroop task compared with younger adult controls. In 2 experiments, we investigate the generality of this finding by examining how the CSE changes in healthy aging in 3 standard attentional control tasks—Stroop, Simon, and flanker—while controlling for additional confounds that have plagued some of the past literature. In both experiments, older adult participants exhibited a larger CSE in the Stroop task, replicating recent research, but smaller CSEs in both the Simon and flanker paradigms. These results are interpreted as reflecting a pathway priming mechanism in the Stroop task but a control adjustment process in Simon and flanker. Hence, there appears to be different mechanisms underlying the CSE which are engaged based on the type of attentional selection that is required by the task. More generally, these results question the use of the CSE in the Stroop task as a measure of dynamic adjustments in attentional control and highlight the importance of consideration of task-specific control systems underlying the CSE.

Task-switching errors show sensitivity to preclinical Alzheimer's disease biomarkers

identify early presymptomatic change and could also be a measure of disease progression. This study therefore investigates retinal changes in both presymptomatic and symptomatic subjects across all three genetic mutations (GRN, MAPT, C9orf72). Methods:We have recruited nine cases so far including two affected participants (2 C9orf72 mutations) and 7 presymptomatic participants: 4 mutation positive gene carriers and 3 mutation negative controls. We measured automated peripapillary retinal nerve fibre layer (RNFL) thickness acquired using spectral-domain optical coherence tomography (Optos OCT SLO) and averaged the RNFL thickness of all interpretable scans. Results: Average RNFL thickness for affected cases was 88.5 (standard deviation (sd) 1⁄4 2.1) mm. For the presymptomatic cases average RNFL thickness was 103.8 (8.0) mm for mutation positive carriers and 106.0 (10.2) mm for mutation negative controls. Conclusions: Preliminary analysis suggests that RNFL thinning may be seen in symptomatic genetic FTD. There is also a trend for decreased thickness in mutation positive carriers although this was not significantly different from controls. Further analysis in a larger group is needed to see at what point abnormalities may be seen during the presymptomatic phase and whether there are differences between the different genetic groups.