Underdiagnosis of mild cognitive impairment: A consequence of ignoring practice effects

INTRODUCTION: Longitudinal testing is necessary to accurately measure cognitive change. However, repeated testing is susceptible to practice effects, which may obscure true cognitive decline and delay detection of mild cognitive impairment (MCI). METHODS: We retested 995 late-middle-aged men in a ∼6-year follow-up of the Vietnam Era Twin Study of Aging. In addition, 170 age-matched replacements were tested for the first time at study wave 2. Group differences were used to calculate practice effects after controlling for attrition effects. MCI diagnoses were generated from practice-adjusted scores. RESULTS: There were significant practice effects on most cognitive domains. Conversion to MCI doubled after correcting for practice effects, from 4.5% to 9%. Importantly, practice effects were present although there were declines in uncorrected scores. DISCUSSION: Accounting for practice effects is critical to early detection of MCI. Declines, when lower than expected, can still indicate practice effects. Replacement participants are needed for accurately assessing disease progression.Published versio

Test of Prosody via Syllable Emphasis (“TOPsy”): Psychometric Validation of a Brief Scalable Test of Lexical Stress Perception

Prosody perception is fundamental to spoken language communication as it supports comprehension, pragmatics, morphosyntactic parsing of speech streams, and phonological awareness. A particular aspect of prosody: perceptual sensitivity to speech rhythm patterns in words (i.e., lexical stress sensitivity), is also a robust predictor of reading skills, though it has received much less attention than phonological awareness in the literature. Given the importance of prosody and reading in educational outcomes, reliable and valid tools are needed to conduct large-scale health and genetic investigations of individual differences in prosody, as groundwork for investigating the biological underpinnings of the relationship between prosody and reading. Motivated by this need, we present the Test of Prosody via Syllable Emphasis (&ldquo;TOPsy&rdquo;) and highlight its merits as a phenotyping tool to measure lexical stress sensitivity in as little as 10 min, in scalable internet-based cohorts. In this 28-item speech rhythm perception test [modeled after the stress identification test from Wade-Woolley (2016)], participants listen to multi-syllabic spoken words and are asked to identify lexical stress patterns. Psychometric analyses in a large internet-based sample shows excellent reliability, and predictive validity for self-reported difficulties with speech-language, reading, and musical beat synchronization. Further, items loaded onto two distinct factors corresponding to initially stressed vs. non-initially stressed words. These results are consistent with previous reports that speech rhythm perception abilities correlate with musical rhythm sensitivity and speech-language/reading skills, and are implicated in reading disorders (e.g., dyslexia). We conclude that TOPsy can serve as a useful tool for studying prosodic perception at large scales in a variety of different settings, and importantly can act as a validated brief phenotype for future investigations of the genetic architecture of prosodic perception, and its relationship to educational outcomes. &nbsp;</p

A Nanofiber-Based Optical Conveyor Belt for Cold Atoms

We demonstrate optical transport of cold cesium atoms over millimeter-scale distances along an optical nanofiber. The atoms are trapped in a one-dimensional optical lattice formed by a two-color evanescent field surrounding the nanofiber, far red- and blue-detuned with respect to the atomic transition. The blue-detuned field is a propagating nanofiber-guided mode while the red-detuned field is a standing-wave mode which leads to the periodic axial confinement of the atoms. Here, this standing wave is used for transporting the atoms along the nanofiber by mutually detuning the two counter-propagating fields which form the standing wave. The performance and limitations of the nanofiber-based transport are evaluated and possible applications are discussed

The Relationship Between Resting State Network Connectivity and Individual Differences in Executive Functions

The brain is organized into a number of large networks based on shared function, for example, high-level cognitive functions (frontoparietal network), attentional capabilities (dorsal and ventral attention networks), and internal mentation (default network). The correlations of these networks during resting-state fMRI scans varies across individuals and is an indicator of individual differences in ability. Prior work shows higher cognitive functioning (as measured by working memory and attention tasks) is associated with stronger negative correlations between frontoparietal/attention and default networks, suggesting that increased ability may depend upon the diverging activation of networks with contrasting function. However, these prior studies lack specificity with regard to the higher-level cognitive functions involved, particularly with regards to separable components of executive function (EF). Here we decompose EF into three factors from the unity/diversity model of EFs: Common EF, Shifting-specific EF, and Updating-specific EF, measuring each via factor scores derived from a battery of behavioral tasks completed by 250 adult participants (age 28) at the time of a resting-state scan. We found the hypothesized segregated pattern only for Shifting-specific EF. Specifically, after accounting for one’s general EF ability (Common EF), individuals better able to fluidly switch between task sets have a stronger negative correlation between the ventral attention network and the default network. We also report non-predicted novel findings in that individuals with higher Shifting-specific abilities exhibited more positive connectivity between frontoparietal and visual networks, while those individuals with higher Common EF exhibited increased connectivity between sensory and default networks. Overall, these results reveal a new degree of specificity with regard to connectivity/EF relationships

Influence of young adult cognitive ability and additional education on later-life cognition

How and when education improves cognitive capacity is an issue of profound societal importance. Education and later-life education-related factors, such as occupational complexity and engagement in cognitive-intellectual activities, are frequently considered indices of cognitive reserve, but whether their effects are truly causal remains unclear. In this study, after accounting for general cognitive ability (GCA) at an average age of 20 y, additional education, occupational complexity, or engagement in cognitive-intellectual activities accounted for little variance in late midlife cognitive functioning in men age 56-66 (n = 1009). Age 20 GCA accounted for 40% of variance in the same measure in late midlife and approximately 10% of variance in each of seven cognitive domains. The other factors each accounted for <1% of the variance in cognitive outcomes. The impact of these other factors likely reflects reverse causation-namely, downstream effects of early adult GCA. Supporting that idea, age 20 GCA, but not education, was associated with late midlife cortical surface area (n = 367). In our view, the most parsimonious explanation of our results, a meta-analysis of the impact of education, and epidemiologic studies of the Flynn effect is that intellectual capacity gains due to education plateau in late adolescence/early adulthood. Longitudinal studies with multiple cognitive assessments before completion of education would be needed to confirm this speculation. If cognitive gains reach an asymptote by early adulthood, then strengthening cognitive reserve and reducing later-life cognitive decline and dementia risk may really begin with improving educational quality and access in childhood and adolescence.Peer reviewe

Using Motor Tempi to Understand Rhythm and Grammatical Skills in Developmental Language Disorder and Typical Language Development

Children with developmental language disorder (DLD) show relative weaknesses on rhythm tasks beyond their characteristic linguistic impairments. The current study compares preferred tempo and the width of an entrainment region for 5- to 7-year-old typically developing (TD) children and children with DLD and considers the associations with rhythm aptitude and expressive grammar skills in the two populations. Preferred tempo was measured with a spontaneous motor tempo task (tapping tempo at a comfortable speed), and the width (range) of an entrainment region was measured by the difference between the upper (slow) and lower (fast) limits of tapping a rhythm normalized by an individual’s spontaneous motor tempo. Data from N = 16 children with DLD and N = 114 TD children showed that whereas entrainment-region width did not differ across the two groups, slowest motor tempo, the determinant of the upper (slow) limit of the entrainment region, was at a faster tempo in children with DLD vs. TD. In other words, the DLD group could not pace their slow tapping as slowly as the TD group. Entrainment-region width was positively associated with rhythm aptitude and receptive grammar even after taking into account potential confounding factors, whereas expressive grammar did not show an association with any of the tapping measures. Preferred tempo was not associated with any study variables after including covariates in the analyses. These results motivate future neuroscientific studies of low-frequency neural oscillatory mechanisms as the potential neural correlates of entrainment-region width and their associations with musical rhythm and spoken language processing in children with typical and atypical language development

Heritability of semantic verbal fluency task using time-interval analysis

Individual variability in word generation is a product of genetic and environmental influences. The genetic effects on semantic verbal fluency were estimated in 1,735 participants from the Brazilian Baependi Heart Study. The numbers of exemplars produced in 60 s were broken down into time quartiles because of the involvement of different cognitive processes—predominantly automatic at the beginning, controlled/executive at the end. Heritability in the unadjusted model for the 60-s measure was 0.32. The best-fit model contained age, sex, years of schooling, and time of day as covariates, giving a heritability of 0.21. Schooling had the highest moderating effect. The highest heritability (0.17) was observed in the first quartile, decreasing to 0.09, 0.12, and 0.0003 in the following ones. Heritability for average production starting point (intercept) was 0.18, indicating genetic influences for automatic cognitive processes. Production decay (slope), indicative of controlled processes, was not significant. The genetic influence on different quartiles of the semantic verbal fluency test could potentially be exploited in clinical practice and genome-wide association studies

Genetic underpinnings of increased BMI and its association with late midlife cognitive abilities

OBJECTIVES: First, we test for differences in various cognitive abilities across trajectories of body mass index (BMI) over the later life course. Second, we examine whether genetic risk factors for unhealthy BMIs-assessed via polygenic risk scores (PRS)-predict cognitive abilities in late-life. METHODS: The study used a longitudinal sample of Vietnam veteran males to explore the associations between BMI trajectories, measured across four time points, and later cognitive abilities. The sample of 977 individuals was drawn from the Vietnam Era Twin Study of Aging. Cognitive abilities evaluated included executive function, abstract reasoning, episodic memory, processing speed, verbal fluency, and visual spatial ability. Multilevel linear regression models were used to estimate the associations between BMI trajectories and cognitive abilities. Then, BMI PRS was added to the models to evaluate polygenic associations with cognitive abilities. RESULTS: There were no significant differences in cognitive ability between any of the BMI trajectory groups. There was a significant inverse relationship between BMI-PRS and several cognitive ability measures. DISCUSSION: While no associations emerged for BMI trajectories and cognitive abilities at the phenotypic levels, BMI PRS measures did correlate with key cognitive domains. Our results suggest possible polygenic linkages cutting across key components of the central and peripheral nervous system.Published versio

Author Correction:Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Christina M. Lill, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this article. This has now been corrected in both the PDF and HTML versions of the article