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

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

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

Age-dependent white matter disruptions after military traumatic brain injury: Multivariate analysis results from ENIGMA brain injury

Mild Traumatic brain injury (mTBI) is a signature wound in military personnel, and repetitive mTBI has been linked to age-related neurogenerative disorders that affect white matter (WM) in the brain. However, findings of injury to specific WM tracts have been variable and inconsistent. This may be due to the heterogeneity of mechanisms, etiology, and comorbid disorders related to mTBI. Non-negative matrix factorization (NMF) is a data-driven approach that detects covarying patterns (components) within high-dimensional data. We applied NMF to diffusion imaging data from military Veterans with and without a self-reported TBI history. NMF identified 12 independent components derived from fractional anisotropy (FA) in a large dataset (n = 1,475) gathered through the ENIGMA (Enhancing Neuroimaging Genetics through Meta-Analysis) Military Brain Injury working group. Regressions were used to examine TBI- and mTBI-related associations in NMF-derived components while adjusting for age, sex, post-traumatic stress disorder, depression, and data acquisition site/scanner. We found significantly stronger age-dependent effects of lower FA in Veterans with TBI than Veterans without in four components (q \u3c 0.05), which are spatially unconstrained by traditionally defined WM tracts. One component, occupying the most peripheral location, exhibited significantly stronger age-dependent differences in Veterans with mTBI. We found NMF to be powerful and effective in detecting covarying patterns of FA associated with mTBI by applying standard parametric regression modeling. Our results highlight patterns of WM alteration that are differentially affected by TBI and mTBI in younger compared to older military Veterans

Taking It to the Extreme:The Effect of Coalition Cabinets on Foreign Policy

Institutional constraints have been offered by some scholars as an explanation for why multiparty coalitions should be more peaceful than single-party cabinets. Yet others see the same institutional setting as a prescription for more aggressive behavior. Recent research has investigated these conflicting expectations, but with mixed results. We examine the theoretical bases for these alternative expectations about the effects of coalition politics on foreign policy. We find that previous research is limited theoretically by confounding institutional effects with policy positions, and empirically by analyzing only international conflict data. We address these limitations by examining cases of foreign policy behavior using the World Event/Interaction Survey (WEIS) dataset. Consistent with our observation that institutional constraints have been confounded with policy positions, we find that coalitions are neither more aggressive nor more peaceful, but do engage in more extreme foreign policy behaviors. These findings are discussed with regard to various perspectives on the role of institutions in shaping foreign policy behavior.</p

Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

A. Palotie on työryhmän Schizophrenia Working Grp Psychiat jäsen.We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P = 1 x 10(-4)) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P = 8.4 x 10(-7)). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.Peer reviewe