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.

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.

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 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.

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.

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.

Multinomial models reveal deficits of two distinct controlled retrieval processes in aging and very mild Alzheimer disease.

Dual-process models of episodic retrieval reveal consistent deficits of controlled recollection in aging and Alzheimer disease (AD). In contrast, automatic familiarity is relatively spared. We extend standard dual-process models by showing the importance of a third capture process. Capture produces a failure to attempt recollection, which might reflect a distinct error from an inability to recollect when attempted (Jacoby et al. Journal of Experimental Psychology: General, 134(2), 131-148, 2005a). We used multinomial process tree (MPT) modeling to estimate controlled recollection and capture processes, as well as automatic retrieval processes, in a large group of middle-aged to older adults who were cognitively normal (N = 519) or diagnosed with the earliest detectable stage of AD (N = 107). Participants incidentally encoded word pairs (e.g., knee bone). At retrieval, participants completed cued word fragments (e.g., knee b_n_) with primes that were congruent (e.g., bone), incongruent (e.g., bend), or neutral (i.e., &&&) to the target (e.g., bone). MPT models estimated retrieval processes both at the group and the individual levels. A capture parameter was necessary to fit MPT models to the observed data, suggesting that dual-process models of this task can be contaminated by a capture process. In both group- and individual-level analyses, aging and very mild AD were associated with increased susceptibility to capture, decreased recollection, and no differences in automatic influences. These results suggest that it is important to consider two distinct modes of attentional control when modeling retrieval processes. Both forms of control (recollection and avoiding capture) are particularly sensitive to cognitive decline in aging and early-stage AD.

Evaluating the contributions of task expectancy in the testing and guessing benefits on recognition memory.

Recently, we have shown that two types of initial testing (recall of a list or guessing of critical items repeated over 12 study/test cycles) improved final recognition of related and unrelated word lists relative to restudy. These benefits were eliminated, however, when test instructions were manipulated within subjects and presented after study of each list, procedures designed to minimise expectancy of a specific type of upcoming test [Huff, Balota, & Hutchison, 2016. The costs and benefits of testing and guessing on recognition memory. Journal of Experimental Psychology: Learning, Memory, and Cognition, 42, 1559-1572. doi: 10.1037/xlm0000269 ], suggesting that testing and guessing effects may be influenced by encoding strategies specific for the type of upcoming task. We follow-up these experiments by examining test-expectancy processes in guessing and testing. Testing and guessing benefits over restudy were not found when test instructions were presented either after (Experiment 1) or before (Experiment 2) a single study/task cycle was completed, nor were benefits found when instructions were presented before study/task cycles and the task was repeated three times (Experiment 3). Testing and guessing benefits emerged only when instructions were presented before a study/task cycle and the task was repeated six times (Experiments 4A and 4B). These experiments demonstrate that initial testing and guessing can produce memory benefits in recognition, but only following substantial task repetitions which likely promote task-expectancy processes.

AV-1451 PET imaging of tau pathology in preclinical Alzheimer disease: Defining a summary measure.

Utilizing [18F]-AV-1451 tau positron emission tomography (PET) as an Alzheimer disease (AD) biomarker will require identification of brain regions that are most important in detecting elevated tau pathology in preclinical AD. Here, we utilized an unsupervised learning, data-driven approach to identify brain regions whose tau PET is most informative in discriminating low and high levels of [18F]-AV-1451 binding. 84 cognitively normal participants who had undergone AV-1451 PET imaging were used in a sparse k-means clustering with resampling analysis to identify the regions most informative in dividing a cognitively normal population into high tau and low tau groups. The highest-weighted FreeSurfer regions of interest (ROIs) separating these groups were the entorhinal cortex, amygdala, lateral occipital cortex, and inferior temporal cortex, and an average SUVR in these four ROIs was used as a summary metric for AV-1451 uptake. We propose an AV-1451 SUVR cut-off of 1.25 to define high tau as described by imaging. This spatial distribution of tau PET is a more widespread pattern than that predicted by pathological staging schemes. Our data-derived metric was validated first in this cognitively normal cohort by correlating with early measures of cognitive dysfunction, and with disease progression as measured by ß-amyloid PET imaging. We additionally validated this summary metric in a cohort of 13 Alzheimer disease patients, and showed that this measure correlates with cognitive dysfunction and ß-amyloid PET imaging in a diseased population.

Default Mode Network Activity Predicts Early Memory Decline in Healthy Young Adults Aged 18-31.

Functional magnetic resonance imaging (fMRI) research conducted in healthy young adults is typically done with the assumption that this sample is largely homogeneous. However, studies from cognitive psychology suggest that long-term memory and attentional control begin to diminish in the third decade of life. Here, 100 participants between the ages of 18 and 31 learned Lithuanian translations of English words in an individual differences study using fMRI. Long-term memory ability was operationalized for each participant by deriving a memory score from 3 convergent measures. Age of participant predicted memory score in this cohort. In addition, degree of deactivation during initial encoding in a set of regions occurring largely in the default mode network (DMN) predicted both age and memory score. The current study demonstrates that early memory decline may partially be accounted for by failure to modulate activity in the DMN.

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 Aß42 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.

Retrieval practice and spacing effects in young and older adults: An examination of the benefits of desirable difficulty.

In the present study, we examined how the function relating continued retrieval practice (e.g., one, three, or five tests) and long-term memory retention is modulated by desirable difficulty (R. A. Bjork, 1994). Of particular interest was how retrieval difficulty differed across young and older adults and across manipulations of lag (Exp. 1) and spacing (Exp. 2). To extend on previous studies, the acquisition phase response latency was used as a proxy for retrieval difficulty, and our analysis of final-test performance was conditionalized on acquisition phase retrieval success, to more directly examine the influence of desirable difficulty on retention. The results from Experiment 1 revealed that continued testing in the short-lag condition led to consistent increases in retention, whereas continued testing in the long-lag condition led to increasingly smaller benefits in retention for both age groups. The results from Experiment 2 revealed that repeated spaced testing enhanced retention relative to taking one spaced test, for both age groups; however, repeated massed testing only enhanced retention over taking one test for young adults. Across both experiments, the response latency results were overall consistent with an influence of desirable difficulty on retention. The discussion focuses on the role of desirable difficulty during encoding in producing the benefits of lag, spacing, and testing.

A Genetic Variant (COMT) Coding Dopaminergic Activity Predicts Personality Traits in Healthy Elderly.

Association studies between the NEO five factor personality inventory and COMT rs4680 have focused on young adults and the results have been inconsistent. However, personality and cortical changes with age may put older adults in a more sensitive range for detecting a relationship. The present study examined associations of COMT rs4680 and personality in older adults. Genetic association analyses were carried out between the NEO and the targeted COMT rs4680 in a large, well-characterized sample of healthy, cognitively normal older adults (N = 616, mean age = 69.26 years). Three significant associations were found: participants with GG genotype showed lower mean scores on Neuroticism (p = 0.039) and higher scores on Agreeableness (p = 0.020) and Conscientiousness (p = 0.006) than participants with AA or AG genotypes. These results suggest that older adults with higher COMT enzymatic activity (GG), therefore lower dopamine level, have lower Neuroticism scores, and higher Agreeableness and Conscientiousness scores. This is consistent with a recent model of phasic and tonic dopamine release suggesting that even though GG genotype is associated with lower tonic dopamine release, the phasic release of dopamine might be optimal for a more adaptive personality profile.

Between-list lag effects in recall depend on retention interval.

Although the benefits of spaced retrieval for long-term retention are well established, the majority of this work has involved spacing over relatively short intervals (on the order of seconds or minutes). In the present experiments, we evaluated the effectiveness of spaced retrieval across relatively short intervals (within a single session), as compared to longer intervals (between sessions spaced a day apart), for long-term retention (i.e., one day or one week). Across a series of seven experiments, participants (N = 536) learned paired associates to a criterion of 70 % accuracy and then received one test-feedback trial for each item. The test-feedback trial occurred within 10 min of reaching criterion (short lag) or one day later (long lag). Then, a final test occurred one day (Exps. 1-3) or one week (Exps. 4 and 5) after the test-feedback trial. Across the different materials and methods in Experiments 1-3, we found little benefit for the long-lag relative to the short-lag schedule in final recall performance-that is, no lag effect-but large effects on the retention of information from the test-feedback to the final test phase. The results from the experiments with the one-week retention interval (Exps. 4 and 5) indicated a benefit of the long-lag schedule on final recall performance (a lag effect), as well as on retention. This research shows that even when the benefits of lag are eliminated at a (relatively long) one-day retention interval, the lag effect reemerges after a one-week retention interval. The results are interpreted within an extension of the bifurcation model to the spacing effect.

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).

The past tense inflection project (PTIP): speeded past tense inflections, imageability ratings, and past tense consistency measures for 2,200 verbs.

The processes involved in past tense verb generation have been central to models of inflectional morphology. However, the empirical support for such models has often been based on studies of accuracy in past tense verb formation on a relatively small set of items. We present the first large-scale study of past tense inflection (the Past Tense Inflection Project, or PTIP) that affords response time, accuracy, and error analyses in the generation of the past tense form from the present tense form for over 2,000 verbs. In addition to standard lexical variables (such as word frequency, length, and orthographic and phonological neighborhood), we have also developed new measures of past tense neighborhood consistency and verb imageability for these stimuli, and via regression analyses we demonstrate the utility of these new measures in predicting past tense verb generation. The PTIP can be used to further evaluate existing models, to provide well controlled stimuli for new studies, and to uncover novel theoretical principles in past tense morphology.

The semantic priming project.

Speeded naming and lexical decision data for 1,661 target words following related and unrelated primes were collected from 768 subjects across four different universities. These behavioral measures have been integrated with demographic information for each subject and descriptive characteristics for every item. Subjects also completed portions of the Woodcock-Johnson reading battery, three attentional control tasks, and a circadian rhythm measure. These data are available at a user-friendly Internet-based repository ( http://spp.montana.edu ). This Web site includes a search engine designed to generate lists of prime-target pairs with specific characteristics (e.g., length, frequency, associative strength, latent semantic similarity, priming effect in standardized and raw reaction times). We illustrate the types of questions that can be addressed via the Semantic Priming Project. These data represent the largest behavioral database on semantic priming and are available to researchers to aid in selecting stimuli, testing theories, and reducing potential confounds in their studies.

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.

Keep up the pace: declines in simple repetitive timing differentiate healthy aging from the earliest stages of Alzheimer's disease.

The current study examined whether healthy older adults (OA) and individuals at the earliest stages of dementia of the Alzheimer's type (DAT) differ from younger adults (YA) and from each other on a simple, extended continuous tapping task using intervals (500 ms, 1000 ms, and 1500 ms) thought to differentially engage attentional control systems. OA groups sped up their tapping at the slowest target rate compared to the YA; this pattern was magnified in the early stage DAT groups. Performance variability appeared especially sensitive to DAT-related changes, as reliable differences between healthy OA and very mild DAT individuals emerged for multiple tap rates. These differences are proposed to result from breakdowns in attentional control that disrupt error-correction processes and the ability to resolve discrepancies between internally-generated temporal expectancies and the external temporal demands of the repetitive timing task.