Embodied cognition comes of age: A processing advantage for action words is modulated by aging and the task.

Processing action words (e.g., fork, throw) engages neurocognitive motor representations, consistent with embodied cognition principles. Despite age-related neurocognitive changes that could affect action words, and a rapidly aging population, the impact of healthy aging on action-word processing is poorly understood. Previous research suggests that in lexical tasks demanding semantic access, such as picture naming, higher motor-relatedness can enhance performance (e.g., fork vs. pier)-particularly in older adults, perhaps due to the age-related relative sparing of motor-semantic circuitry, which can support action words. However, motor-relatedness was recently found to affect performance in younger but not older adults in lexical decision. We hypothesized this was due to decreased semantic access in this task, especially in older adults. Here we tested effects of motor-relatedness on 2,174 words in younger and older adults not only in lexical decision but also in reading aloud, in which semantic access is minimal. Mixed-effects regression, controlling for phonological, lexical, and semantic variables, yielded results consistent with our predictions. In lexical decision, younger adults were faster and more accurate at words with higher-motor relatedness, whereas older adults showed no motor-relatedness effects. In reading aloud, neither age group showed such effects. Multiple sensitivity analyses demonstrated that the patterns were robust. Altogether, whereas previous research indicates that in lexical tasks demanding semantic access, higher motor-relatedness can enhance performance, especially in older adults, evidence now suggests that such effects are attenuated with decreased semantic access, which in turn depends on the task as well as aging itself. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Naturalistic assessment of reaction time variability in older adults at risk for Alzheimer's disease.

OBJECTIVE: Maintaining attention underlies many aspects of cognition and becomes compromised early in neurodegenerative diseases like Alzheimer's disease (AD). The consistency of maintaining attention can be measured with reaction time (RT) variability. Previous work has focused on measuring such fluctuations during in-clinic testing, but recent developments in remote, smartphone-based cognitive assessments can allow one to test if these fluctuations in attention are evident in naturalistic settings and if they are sensitive to traditional clinical and cognitive markers of AD. METHOD: Three hundred and seventy older adults (aged 75.8 +/- 5.8 years) completed a week of remote daily testing on the Ambulatory Research in Cognition (ARC) smartphone platform and also completed clinical, genetic, and conventional in-clinic cognitive assessments. RT variability was assessed in a brief (20-40 seconds) processing speed task using two different measures of variability, the Coefficient of Variation (CoV) and the Root Mean Squared Successive Difference (RMSSD) of RTs on correct trials. RESULTS: Symptomatic participants showed greater variability compared to cognitively normal participants. When restricted to cognitively normal participants, APOE ε4 carriers exhibited greater variability than noncarriers. Both CoV and RMSSD showed significant, and similar, correlations with several in-clinic cognitive composites. Finally, both RT variability measures significantly mediated the relationship between APOE ε4 status and several in-clinic cognition composites. CONCLUSIONS: Attentional fluctuations over 20-40 seconds assessed in daily life, are sensitive to clinical status and genetic risk for AD. RT variability appears to be an important predictor of cognitive deficits during the preclinical disease stage.

Precipitating Mechanisms of Falls in Preclinical Alzheimer's Disease.

Background: Individuals with Alzheimer's disease (AD) are more than twice as likely to incur a serious fall as the general population of older adults. Although AD is commonly associated with cognitive changes, impairments in other clinical measures such as strength or functional mobility (i.e., gait and balance) may precede symptomatic cognitive impairment in preclinical AD and lead to increased fall risk. Objective: To examine mechanisms (i.e., functional mobility, cognition, AD biomarkers) associated with increased falls in cognitively normal older adults. Methods: This 1-year study was part of an ongoing longitudinal cohort study. We examined the relationships among falls, clinical measures of functional mobility and cognition, and neuroimaging AD biomarkers in cognitively normal older adults. We also investigated which domain(s) best predicted fall propensity and severity through multiple regression models. Results: A total of 182 older adults were included (mean age 75 years, 53% female). A total of 227 falls were reported over the year; falls per person ranged from 0-16 with a median of 1. Measures of functional mobility were the best predictors of fall propensity and severity. Cognition and AD biomarkers were associated with each other but not with the fall outcome measures. Conclusion: These results suggest that, although subtle changes in cognition may be more closely associated with AD neuropathology, functional mobility indicators better predict falls in cognitively normal older adults. This study adds to our understanding of the mechanisms underlying falls in older adults and could lead to the development of targeted fall prevention strategies.

Unsupervised high-frequency smartphone-based cognitive assessments are reliable, valid, and feasible in older adults at risk for Alzheimer's disease.

OBJECTIVE: Smartphones have the potential for capturing subtle changes in cognition that characterize preclinical Alzheimer's disease (AD) in older adults. The Ambulatory Research in Cognition (ARC) smartphone application is based on principles from ecological momentary assessment (EMA) and administers brief tests of associative memory, processing speed, and working memory up to 4 times per day over 7 consecutive days. ARC was designed to be administered unsupervised using participants' personal devices in their everyday environments. METHODS: We evaluated the reliability and validity of ARC in a sample of 268 cognitively normal older adults (ages 65-97 years) and 22 individuals with very mild dementia (ages 61-88 years). Participants completed at least one 7-day cycle of ARC testing and conventional cognitive assessments; most also completed cerebrospinal fluid, amyloid and tau positron emission tomography, and structural magnetic resonance imaging studies. RESULTS: First, ARC tasks were reliable as between-person reliability across the 7-day cycle and test-retest reliabilities at 6-month and 1-year follow-ups all exceeded 0.85. Second, ARC demonstrated construct validity as evidenced by correlations with conventional cognitive measures (r = 0.53 between composite scores). Third, ARC measures correlated with AD biomarker burden at baseline to a similar degree as conventional cognitive measures. Finally, the intensive 7-day cycle indicated that ARC was feasible (86.50% approached chose to enroll), well tolerated (80.42% adherence, 4.83% dropout), and was rated favorably by older adult participants. CONCLUSIONS: Overall, the results suggest that ARC is reliable and valid and represents a feasible tool for assessing cognitive changes associated with the earliest stages of AD.

Effects of Mindfulness Training and Exercise on Cognitive Function in Older Adults: A Randomized Clinical Trial.

Importance: Episodic memory and executive function are essential aspects of cognitive functioning that decline with aging. This decline may be ameliorable with lifestyle interventions. Objective: To determine whether mindfulness-based stress reduction (MBSR), exercise, or a combination of both improve cognitive function in older adults. Design, Setting, and Participants: This 2 × 2 factorial randomized clinical trial was conducted at 2 US sites (Washington University in St Louis and University of California, San Diego). A total of 585 older adults (aged 65-84 y) with subjective cognitive concerns, but not dementia, were randomized (enrollment from November 19, 2015, to January 23, 2019; final follow-up on March 16, 2020). Interventions: Participants were randomized to undergo the following interventions: MBSR with a target of 60 minutes daily of meditation (n = 150); exercise with aerobic, strength, and functional components with a target of at least 300 minutes weekly (n = 138); combined MBSR and exercise (n = 144); or a health education control group (n = 153). Interventions lasted 18 months and consisted of group-based classes and home practice. Main Outcomes and Measures: The 2 primary outcomes were composites of episodic memory and executive function (standardized to a mean [SD] of 0 [1]; higher composite scores indicate better cognitive performance) from neuropsychological testing; the primary end point was 6 months and the secondary end point was 18 months. There were 5 reported secondary outcomes: hippocampal volume and dorsolateral prefrontal cortex thickness and surface area from structural magnetic resonance imaging and functional cognitive capacity and self-reported cognitive concerns. Results: Among 585 randomized participants (mean age, 71.5 years; 424 [72.5%] women), 568 (97.1%) completed 6 months in the trial and 475 (81.2%) completed 18 months. At 6 months, there was no significant effect of mindfulness training or exercise on episodic memory (MBSR vs no MBSR: 0.44 vs 0.48; mean difference, -0.04 points [95% CI, -0.15 to 0.07]; P = .50; exercise vs no exercise: 0.49 vs 0.42; difference, 0.07 [95% CI, -0.04 to 0.17]; P = .23) or executive function (MBSR vs no MBSR: 0.39 vs 0.31; mean difference, 0.08 points [95% CI, -0.02 to 0.19]; P = .12; exercise vs no exercise: 0.39 vs 0.32; difference, 0.07 [95% CI, -0.03 to 0.18]; P = .17) and there were no intervention effects at the secondary end point of 18 months. There was no significant interaction between mindfulness training and exercise (P = .93 for memory and P = .29 for executive function) at 6 months. Of the 5 prespecified secondary outcomes, none showed a significant improvement with either intervention compared with those not receiving the intervention. Conclusions and Relevance: Among older adults with subjective cognitive concerns, mindfulness training, exercise, or both did not result in significant differences in improvement in episodic memory or executive function at 6 months. The findings do not support the use of these interventions for improving cognition in older adults with subjective cognitive concerns. Trial Registration: ClinicalTrials.gov Identifier: NCT02665481.

Wakeful Rest Benefits Recall, but Not Recognition, of Incidentally Encoded Memory Stimuli in Younger and Older Adults.

Older adults exhibit deficits in episodic memory tasks, which have often been attributed to encoding or retrieval deficits, with little attention to consolidation mechanisms. More recently, researchers have attempted to measure consolidation in the context of a behavioral experiment using the wakeful rest paradigm (i.e., a brief, quiet period of minimal stimulation, which facilitates memory performance, compared to a distractor task). Critically, older adults might not produce this effect, given established age differences in other episodic memory processes and mind-wandering. In three experiments, we directly compared younger and older adults in modified versions of the wakeful rest paradigm. Critically, we utilized incidental encoding procedures (all experiments) and abstract shape stimuli (in Experiment 3) to limit the possibility of retrieval practice or maintenance rehearsal as potential confounding mechanisms in producing the wakeful rest effect. Wakeful rest reliably and equally benefited recall of incidentally encoded words in both younger and older adults. In contrast, wakeful rest had no benefit for standard accuracy measures of recognition performance in verbal stimuli, although there was an effect in response latencies for non-verbal stimuli. Overall, these results suggest that the benefits of wakeful rest on episodic retrieval are preserved across age groups, and hence support age-independence in potential consolidation mechanisms as measured by wakeful rest. Further, these benefits do not appear to be dependent on the intentionality of encoding or variations in distractor task types. Finally, the lack of wakeful rest benefits on recognition performance might be driven by theoretical constraints on the effect or methodological limitations of recognition memory testing in the current paradigm.

Targeted memory reactivation and consolidation-like processes during mind-wandering in younger and older adults.

Mind-wandering (MW) is a universal cognitive process that is estimated to comprise ~30% of our everyday thoughts. Despite its prevalence, the functional utility of MW remains a scientific blind spot. The present study sought to investigate whether MW serves a functional role in cognition. Specifically, we investigated whether MW contributes to memory consolidation-like processes, and if age differences in the ability to reactivate episodic memories during MW may contribute to age-related declines in episodic memory. Younger and older adults encoded paired associates, received targeted reactivation cues during an interval filled with a task that promotes MW, and were tested on their memory for the cued and uncued stimuli from the initial encoding task. Thought probes were presented during the retention (MW) interval to assess participants' thought contents. Across four experiments, we compared the effect of different cue modalities (i.e., auditory, visual) on cued recall performance, and examined both correct retrieval RTs as well as accuracy. Across experiments, there was evidence that stimuli that were cued during the MW task were correctly retrieved more quickly than uncued stimuli and that this effect was more robust for younger adults than older adults. Additionally, the more MW a participant reported during the retention interval, the stronger the cuing effect they produced during retrieval. The results from these experiments are interpreted within a retrieval facilitation framework wherein cues serve to reactivate the earlier traces during MW, and this reactivation benefits retrieval speed for cued items compared with uncued items. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

A Critical Review of Network-Based and Distributional Approaches to Semantic Memory Structure and Processes.

Some of the earliest work on understanding how concepts are organized in memory used a network-based approach, where words or concepts are represented as nodes, and relationships between words are represented by links between nodes. Over the past two decades, advances in network science and graph theoretical methods have led to the development of computational semantic networks. This review provides a modern perspective on how computational semantic networks have proven to be useful tools to investigate the structure of semantic memory as well as search and retrieval processes within semantic memory, to ultimately model performance in a wide variety of cognitive tasks. Regarding representation, the review focuses on the distinctions and similarities between network-based (based on behavioral norms) approaches and more recent distributional (based on natural language corpora) semantic models, and the potential overlap between the two approaches. Capturing the type of relation between concepts appears to be particularly important in this modeling endeavor. Regarding processes, the review focuses on random walk models and the degree to which retrieval processes demand attention in pursuit of given task goals, which dovetails with the type of relation retrieved during tasks. Ultimately, this review provides a critical assessment of how the network perspective can be reconciled with distributional and machine-learning-based perspectives to meaning representation, and describes how cognitive network science provides a useful conceptual toolkit to probe both the structure and retrieval processes within semantic memory.

Semantic Memory Search and Retrieval in a Novel Cooperative Word Game: A Comparison of Associative and Distributional Semantic Models.

Considerable work during the past two decades has focused on modeling the structure of semantic memory, although the performance of these models in complex and unconstrained semantic tasks remains relatively understudied. We introduce a two-player cooperative word game, Connector (based on the boardgame Codenames), and investigate whether similarity metrics derived from two large databases of human free association norms, the University of South Florida norms and the Small World of Words norms, and two distributional semantic models based on large language corpora (word2vec and GloVe) predict performance in this game. Participant dyads were presented with 20-item word boards with word pairs of varying relatedness. The speaker received a word pair from the board (e.g., exam-algebra) and generated a one-word semantic clue (e.g., math), which was used by the guesser to identify the word pair on the board across three attempts. Response times to generate the clue, as well as accuracy and latencies for the guessed word pair, were strongly predicted by the cosine similarity between word pairs and clues in random walk-based associative models, and to a lesser degree by the distributional models, suggesting that conceptual representations activated during free association were better able to capture search and retrieval processes in the game. Further, the speaker adjusted subsequent clues based on the first attempt by the guesser, who in turn benefited from the adjustment in clues, suggesting a cooperative influence in the game that was effectively captured by both associative and distributional models. These results indicate that both associative and distributional models can capture relatively unconstrained search processes in a cooperative game setting, and Connector is particularly suited to examine communication and semantic search processes.

Re-examining age differences in the Stroop effect: The importance of the trees in the forest (plot).

Despite several meta-analyses suggesting that age differences in attentional control are "greatly exaggerated," there have been multiple reports of disproportionate age differences in the Stroop effect. The Stroop task is widely accepted as the gold standard for assessing attentional control and has been critical in comparisons across development and in studies of neuropsychological patient groups. However, accounting for group differences in processing speed is a notorious challenge in interpreting reaction time (RT) data. Within the aging literature, prior meta-analyses have relied on Brinley and State-Trace techniques to account for overall processing speed differences in evaluating the effects of within-participant manipulations. Such analyses are based on mean performance per group per study and have been criticized as potentially being insensitive to within-participant manipulations. In order to further examine possible age differences in Stroop performance, we amassed a dataset from 33 different computerized, color-naming Stroop task studies with available trial-level data from 2,896 participants. We conducted meta-regression analyses on a wide set of dependent measures that control for general slowing, tested for publication bias, and examined four potential methodological moderators. We also conducted linear mixed-effect modeling allowing the intercept to vary randomly for each participant, thereby accounting for individual differences in processing speed. All analyses, with the exception of the Brinley and State-Trace techniques, produced clear evidence supporting a disproportionate age difference in the Stroop effect above and beyond the effects of general slowing. Discussion highlights the importance of trial-level data in accounting for group differences in processing speed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Cerebrospinal fluid Aß42 moderates the relationship between brain functional network dynamics and cognitive intraindividual variability.

As Alzheimer's disease (AD) pathology accumulates, resting-state functional connectivity (rs-fc) within and between brain networks decreases, and fluctuations in cognitive performance known as intraindividual variability (IIV) increase. Here, we assessed the relationship between IIV and anticorrelations in rs-fc between the default mode network (DMN)-dorsal attention network (DAN) in cognitively normal older adults and symptomatic AD participants. We also evaluated the relationship between cerebrospinal fluid (CSF) biomarkers of AD (amyloid-beta [Aß42] and tau) and IIV-anticorrelation in rs-fc. We observed that cognitive IIV and anticorrelations between DMN × DAN were higher in individuals with AD compared with cognitively normal participants. As DMN × DAN relationship became more positive, cognitive IIV increased, indicating that stronger anticorrelations between networks support more consistent cognitive performance. Moderation analyses indicated that continuous CSF Aß42, but not CSF total tau, moderated the relationship between cognitive IIV and DMN × DAN, collectively demonstrating that greater amyloid burden and alterations in functional network dynamics are associated with cognitive changes seen in AD. These findings are valuable, as they suggest that amyloid affects cognitive functioning during the early stages of AD.

Sharper in the morning: Cognitive time of day effects revealed with high-frequency smartphone testing.

Decades of research has established a shift from an "eveningness" preference to a "morningness" preference with increasing age. Accordingly, older adults typically have better cognition in morning hours compared to evening hours. We present the first known attempt to capture circadian fluctuations in cognition in individuals at risk for Alzheimer disease (AD) using a remotely administered smartphone assessment that samples cognition rapidly and repeatedly over several days. Older adults (N = 169, aged 61-94 years; 93% cognitively normal) completed four brief smartphone-based testing sessions per day for 7 consecutive days at quasi-random time intervals, assessing associate memory, processing speed, and visual working memory. Scores completed during early hours were averaged for comparison with averaged scores completed during later hours. Mixed effects models evaluated time of day effects on cognition. Additional models included clinical status and cerebrospinal fluid (CSF) biomarkers for beta amyloid (Aß42) and phosphorylated tau181 (pTau). Models with terms for age, gender, education, APOE ε4 status, and clinical status revealed significantly worse performance on associate memory in evening hours compared to morning hours. Contemporaneously reported mood and fatigue levels did not moderate relationships. Using CSF data to classify individuals with and without significant AD pathology, there were no group differences in performance in morning hours, but subtle impairment emerged in associate memory in evening hours in those with CSF-confirmed AD pathology. These findings indicate that memory is worse in evening hours in older adults, that this pattern is consistent across several days, and is independent of measures of mood and fatigue. Further, they provide preliminary evidence of a "cognitive sundowning" in the very earliest stages of AD. Time of day may be an important consideration for assessments in observational studies and clinical trials in AD populations.

Evaluating Cognitive Relationships with Resting-State and Task-driven Blood Oxygen Level-Dependent Variability.

Recent functional magnetic resonance imaging studies have reported that moment-to-moment variability in the blood oxygen level-dependent (BOLD) signal is positively associated with task performance and, thus, may reflect a behaviorally sensitive signal. However, it is not clear whether estimates of resting-state and task-driven BOLD variability are differentially related to cognition, as they may be driven by distinct sources of variance in the BOLD signal. Moreover, other studies have suggested that age differences in resting-state BOLD variability may be particularly sensitive to individual differences in cardiovascular, rather than neural, factors. In this study, we tested relationships between measures of behavioral task performance and BOLD variability during both resting-state and task-driven runs of a Stroop and an animacy judgment task in a large, well-characterized sample of cognitively normal middle-aged to older adults. Resting-state BOLD variability was related to composite measures of global cognition and attentional control, but these relationships were eliminated after correction for age or cardiovascular estimates. In contrast, task-driven BOLD variability was related to attentional control measured both inside and outside the scanner, and importantly, these relationships persisted after correction for age and cardiovascular measures. Overall, these results suggest that BOLD variability is a behaviorally sensitive signal. However, resting-state and task-driven estimates of BOLD variability may differ in the degree to which they are sensitive to age-related, cardiovascular, and neural mechanisms.

Evaluating resting-state BOLD variability in relation to biomarkers of preclinical Alzheimer's disease.

Recent functional magnetic resonance imaging studies have demonstrated that moment-to-moment variability in the blood oxygen level-dependent (BOLD) signal is related to age differences, cognition, and symptomatic Alzheimer's disease (AD). However, no studies have examined BOLD variability in the context of preclinical AD. We tested relationships between resting-state BOLD variability and biomarkers of amyloidosis, tauopathy, and neurodegeneration in a large (N = 321), well-characterized sample of cognitively normal adults (age = 39-93), using multivariate machine learning techniques. Furthermore, we controlled for cardiovascular health factors, which may contaminate resting-state BOLD variability estimates. BOLD variability, particularly in the default mode network, was related to cerebrospinal fluid (CSF) amyloid-ß42 but was not related to CSF phosphorylated tau-181. Furthermore, BOLD variability estimates were also related to markers of neurodegeneration, including CSF neurofilament light protein, hippocampal volume, and a cortical thickness composite. Notably, relationships with hippocampal volume and cortical thickness survived correction for cardiovascular health and also contributed to age-related differences in BOLD variability. Thus, BOLD variability may be sensitive to preclinical pathology, including amyloidosis and neurodegeneration in AD-sensitive areas.

Predicting dysfunctional age-related task activations from resting-state network alterations.

Alzheimer's disease (AD) is linked to changes in fMRI task activations and fMRI resting-state functional connectivity (restFC), which can emerge early in the illness timecourse. These fMRI correlates of unhealthy aging have been studied in largely separate subfields. Taking inspiration from neural network simulations, we propose a unifying mechanism wherein restFC alterations associated with AD disrupt the flow of activations between brain regions, leading to aberrant task activations. We apply this activity flow model in a large sample of clinically normal older adults, which was segregated into healthy (low-risk) and at-risk subgroups based on established imaging (positron emission tomography amyloid) and genetic (apolipoprotein) AD risk factors. Modeling the flow of healthy activations over at-risk AD connectivity effectively transformed the healthy aged activations into unhealthy (at-risk) aged activations. This enabled reliable prediction of at-risk AD task activations, and these predicted activations were related to individual differences in task behavior. These results support activity flow over altered intrinsic functional connections as a mechanism underlying Alzheimer's-related dysfunction, even in very early stages of the illness. Beyond these mechanistic insights, this approach raises clinical potential by enabling prediction of task activations and associated cognitive dysfunction in individuals without requiring them to perform in-scanner cognitive tasks.

Evaluating the Sensitivity of Resting-State BOLD Variability to Age and Cognition after Controlling for Motion and Cardiovascular Influences: A Network-Based Approach.

Recent functional magnetic resonance imaging (fMRI) studies report that moment-to-moment variability in the BOLD signal is related to differences in age and cognition and, thus, may be sensitive to age-dependent decline. However, head motion and/or cardiovascular health (CVH) may contaminate these relationships. We evaluated relationships between resting-state BOLD variability, age, and cognition, after characterizing and controlling for motion-related and cardiovascular influences, including pulse, blood pressure, BMI, and white matter hyperintensities (WMH), in a large (N = 422) resting-state fMRI sample of cognitively normal individuals (age 43-89). We found that resting-state BOLD variability was negatively related to age and positively related to cognition after maximally controlling for head motion. Age relationships also survived correction for CVH, but were greatly reduced when correcting for WMH alone. Our results suggest that network-based machine learning analyses of resting-state BOLD variability might yield reliable, sensitive measures to characterize age-related decline across a broad range of networks. Age-related differences in resting-state BOLD variability may be largely sensitive to processes related to WMH burden.

Relationships between big-five personality factors and Alzheimer's disease pathology in autosomal dominant Alzheimer's disease.

INTRODUCTION: Changes in personality characteristics are associated with the onset of symptoms in Alzheimer's disease (AD) and may even precede clinical diagnosis. However, personality changes caused by disease progression can be difficult to separate from changes that occur with normal aging. The Dominantly Inherited Alzheimer Network (DIAN) provides a unique cohort in which to relate measures of personality traits to in vivo markers of disease in a much younger sample than in typical late onset AD. METHODS: Personality traits measured with the International Personality Item Pool at baseline from DIAN participants were analyzed as a function of estimated years to onset of clinical symptoms and well-established AD biomarkers. RESULTS: Both neuroticism and conscientiousness were correlated with years to symptom onset and markers of tau pathology in the cerebrospinal fluid. Self-reported conscientiousness and both neuroticism and conscientiousness ratings from a collateral source were correlated with longitudinal rates of cognitive decline such that participants who were rated as higher on neuroticism and lower on conscientiousness exhibited accelerated rates of cognitive decline. DISCUSSION: Personality traits are correlated with the accumulation of AD pathology and time to symptom onset, suggesting that AD progression can influence an individual's personality characteristics. Together these findings suggest that measuring neuroticism and conscientiousness may hold utility in tracking disease progression in AD.

Neurofilament Light Predicts Decline in Attention but Not Episodic Memory in Preclinical Alzheimer's Disease.

BACKGROUND: Cerebrospinal fluid tau and neurofilament light (NfL) are two biomarkers of neurodegeneration in Alzheimer's disease. Previous reports have shown that the influence of tau on cognitive decline depends on levels of amyloid burden whereas NfL predicts decline independently of amyloid. Most studies use a global cognitive composite as the primary outcome, and it is unknown if critical cognitive domain scores are similarly sensitive to rates of decline due to neurodegeneration. OBJECTIVE: To examine the unique contribution of amyloid, tau, and NfL to rates of cognitive decline in multiple cognitive composites in a cognitively healthy, middle-aged to older adult cohort. METHODS: A total of 255 participants (55% female; mean age = 66.2 years, range = 42.5-86.7 years) completed CSF studies and serial cognitive assessments to measure global cognition, episodic memory, and attentional control. Linear mixed effects models were used to examine rates of change on each composite score as a function of baseline biomarker levels. RESULTS: Total tau predicted decline in attention regardless of amyloid status, but the relationship to global cognition and episodic memory was dependent on amyloid, replicating prior literature. NfL predicted decline in attention and global cognition, but not memory, and this effect was independent of amyloid status. CONCLUSIONS: These findings suggest that NfL can be used to monitor cognitive decline in aging and Alzheimer's disease and that an attentional control composite may be a better outcome for tracking general neurodegenerative effects on cognition.

Attempted prime retrieval is a double-edged sword: Facilitation and disruption in repeated lexical retrieval.

The phenomenological experience of lexical retrieval often involves repeated, active attempts to retrieve phonologically and/or semantically related information. However, the influence of these multiple retrieval attempts on subsequent lexical retrieval is presently unknown. We investigated the influence of passively viewing or actively retrieving different types of information at the critical moment preceding lexical retrieval through a novel priming paradigm. Participants attempted to retrieve target words (e.g., abdicate) from low-frequency descriptions (e.g., to formally renounce a throne). Target retrieval was preceded by passive viewing (Experiment 1), or active retrieval of the prime word (Experiments 2-6). Primes were either "both" semantically and phonologically related (e.g., abandon), only phonologically related (e.g., abdomen), only semantically related (e.g., resign), or unrelated (e.g., obvious) to the target word. When primes were passively viewed, phonological facilitation in target retrieval accuracy was observed. In contrast, when participants actively attempted to retrieve primes from their definitions, no phonological facilitation was observed. Successful retrieval of semantic and both primes facilitated subsequent target retrieval, whereas, failure to retrieve semantic and both primes inhibited subsequent target retrieval. These facilitatory and inhibitory influences of prime retrieval for semantic and both primes were independent of feedback on retrieval performance (Experiment 4) and participants' overall knowledge of the primes and targets (Experiment 5), and also did not extend to retrieval from episodic memory (Experiment 6). The findings are consistent with ongoing retrospective processes during target retrieval, which reengage prime retrieval success or failure and consequently produce benefits and costs during repeated retrieval from semantic memory. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

The Relation Between Personality and Biomarkers in Sensitivity and Conversion to Alzheimer-Type Dementia.

OBJECTIVES: The present study explored relationships among personality, Alzheimer's disease (AD) biomarkers, and dementia by addressing the following questions: (1) Does personality discriminate healthy aging and earliest detectable stage of AD? (2) Does personality predict conversion from healthy aging to early-stage AD? (3) Do AD biomarkers mediate any observed relationships between personality and dementia status/conversion? METHODS: Both self- and informant ratings of personality were obtained in a large well-characterized longitudinal sample of cognitively normal older adults (N = 436) and individuals with early-stage dementia (N = 74). Biomarkers included amyloid imaging, hippocampal volume, cerebral spinal fluid (CSF) Aß42, and CSF tau. RESULTS: Higher neuroticism, lower conscientiousness, along with all four biomarkers strongly discriminated cognitively normal controls from early-stage AD individuals. The direct effects of neuroticism and conscientiousness were only mediated by hippocampal volume. Conscientiousness along with all biomarkers predicted conversion from healthy aging to early-stage AD; however, none of the biomarkers mediated the relationship between conscientiousness and conversion. Conscientiousness predicted conversion as strongly as the biomarkers, with the exception of hippocampal volume. CONCLUSIONS: Conscientiousness and to a lesser extent neuroticism serve as important independent behavioral markers for AD risk.