Meta-analysis of generalized additive models in neuroimaging studies

Contains fulltext : 231772.pdf (publisher's version ) (Open Access)Analyzing data from multiple neuroimaging studies has great potential in terms of increasing statistical power, enabling detection of effects of smaller magnitude than would be possible when analyzing each study separately and also allowing to systematically investigate between-study differences. Restrictions due to privacy or proprietary data as well as more practical concerns can make it hard to share neuroimaging datasets, such that analyzing all data in a common location might be impractical or impossible. Meta-analytic methods provide a way to overcome this issue, by combining aggregated quantities like model parameters or risk ratios. Most meta-analytic tools focus on parametric statistical models, and methods for meta-analyzing semi-parametric models like generalized additive models have not been well developed. Parametric models are often not appropriate in neuroimaging, where for instance age-brain relationships may take forms that are difficult to accurately describe using such models. In this paper we introduce meta-GAM, a method for meta-analysis of generalized additive models which does not require individual participant data, and hence is suitable for increasing statistical power while upholding privacy and other regulatory concerns. We extend previous works by enabling the analysis of multiple model terms as well as multivariate smooth functions. In addition, we show how meta-analytic p-values can be computed for smooth terms. The proposed methods are shown to perform well in simulation experiments, and are demonstrated in a real data analysis on hippocampal volume and self-reported sleep quality data from the Lifebrain consortium. We argue that application of meta-GAM is especially beneficial in lifespan neuroscience and imaging genetics. The methods are implemented in an accompanying R package metagam, which is also demonstrated

People's interest in brain health testing: Findings from an international, online cross-sectional survey

Brain health entails mental wellbeing and cognitive health in the absence of brain disorders. The past decade has seen an explosion of tests, cognitive and biological, to predict various brain conditions, such as Alzheimer's Disease. In line with these current developments, we investigated people's willingness and reasons to—or not to—take a hypothetical brain health test to learn about risk of developing a brain disease, in a cross-sectional multilanguage online survey. The survey was part of the Global Brain Health Survey, open to the public from 4th June 2019 to 31st August 2020. Respondents were largely recruited via European brain councils and research organizations. 27,590 people responded aged 18 years or older and were predominantly women (71%), middle-aged or older (>40 years; 83%), and highly educated (69%). Responses were analyzed to explore the relationship between demographic variables and responses. Results: We found high public interest in brain health testing: over 91% would definitely or probably take a brain health test and 86% would do so even if it gave information about a disease that cannot be treated or prevented. The main reason for taking a test was the ability to respond if one was found to be at risk of brain disease, such as changing lifestyle, seeking counseling or starting treatment. Higher interest in brain health testing was found in men, respondents with lower education levels and those with poor self-reported cognitive health. Conclusion: High public interest in brain health and brain health testing in certain segments of society, coupled with an increase of commercial tests entering the market, is likely to put pressure on public health systems to inform the public about brain health testing in years to come.publishedVersio

Efficacy of labral repair, biceps tenodesis, and diagnostic arthroscopy for SLAP Lesions of the shoulder: a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Surgery for type II SLAP (superior labral anterior posterior) lesions of the shoulder is a promising but unproven treatment. The procedures include labral repair or biceps tenodesis. Retrospective cohort studies have suggested that the benefits of tenodesis include pain relief and improved function, and higher patient satisfaction, which was reported in a prospective non-randomised study. There have been no completed randomised controlled trials of surgery for type II SLAP lesions. The aims of this participant and observer blinded randomised placebo-controlled trial are to compare the short-term (6 months) and long-term (2 years) efficacy of labral repair, biceps tenodesis, and placebo (diagnostic arthroscopy) for alleviating pain and improving function for type II SLAP lesions.</p> <p>Methods/Design</p> <p>A double-blind randomised controlled trial are performed using 120 patients, aged 18 to 60 years, with a history for type II SLAP lesions and clinical signs suggesting type II SLAP lesion, which were documented by MR arthrography and arthroscopy. Exclusion criteria include patients who have previously undergone operations for SLAP lesions or recurrent shoulder dislocations, and ruptures of the rotator cuff or biceps tendon. Outcomes will be assessed at baseline, three, six, 12, and 24 months. Primary outcome measures will be the clinical Rowe Score (1988-version) and the Western Ontario Instability Index (WOSI) at six and 24 months. Secondary outcome measures will include the Shoulder Instability Questionnaire (SIQ), the generic EuroQol (EQ-5 D and EQ-VAS), return to work and previous sports activity, complications, and the number of reoperations.</p> <p>Discussion</p> <p>The results of this trial will be of international importance and the results will be translatable into clinical practice.</p> <p>Trial Registration</p> <p><b>[ClinicalTrials.gov NCT00586742]</b></p

Self-reported sleep relates to hippocampal atrophy across the adult lifespan: results from the Lifebrain consortium.

OBJECTIVES: Poor sleep is associated with multiple age-related neurodegenerative and neuropsychiatric conditions. The hippocampus plays a special role in sleep and sleep-dependent cognition, and accelerated hippocampal atrophy is typically seen with higher age. Hence, it is critical to establish how the relationship between sleep and hippocampal volume loss unfolds across the adult lifespan. METHODS: Self-reported sleep measures and MRI-derived hippocampal volumes were obtained from 3105 cognitively normal participants (18-90 years) from major European brain studies in the Lifebrain consortium. Hippocampal volume change was estimated from 5116 MRIs from 1299 participants for whom longitudinal MRIs were available, followed up to 11 years with a mean interval of 3.3 years. Cross-sectional analyses were repeated in a sample of 21,390 participants from the UK Biobank. RESULTS: No cross-sectional sleep-hippocampal volume relationships were found. However, worse sleep quality, efficiency, problems, and daytime tiredness were related to greater hippocampal volume loss over time, with high scorers showing 0.22% greater annual loss than low scorers. The relationship between sleep and hippocampal atrophy did not vary across age. Simulations showed that the observed longitudinal effects were too small to be detected as age-interactions in the cross-sectional analyses. CONCLUSIONS: Worse self-reported sleep is associated with higher rates of hippocampal volume decline across the adult lifespan. This suggests that sleep is relevant to understand individual differences in hippocampal atrophy, but limited effect sizes call for cautious interpretation

Education and Income Show Heterogeneous Relationships to Lifespan Brain and Cognitive Differences Across European and US Cohorts.

Higher socio-economic status (SES) has been proposed to have facilitating and protective effects on brain and cognition. We ask whether relationships between SES, brain volumes and cognitive ability differ across cohorts, by age and national origin. European and US cohorts covering the lifespan were studied (4-97 years, N = 500 000; 54 000 w/brain imaging). There was substantial heterogeneity across cohorts for all associations. Education was positively related to intracranial (ICV) and total gray matter (GM) volume. Income was related to ICV, but not GM. We did not observe reliable differences in associations as a function of age. SES was more strongly related to brain and cognition in US than European cohorts. Sample representativity varies, and this study cannot identify mechanisms underlying differences in associations across cohorts. Differences in neuroanatomical volumes partially explained SES-cognition relationships. SES was more strongly related to ICV than to GM, implying that SES-cognition relations in adulthood are less likely grounded in neuroprotective effects on GM volume in aging. The relatively stronger SES-ICV associations rather are compatible with SES-brain volume relationships being established early in life, as ICV stabilizes in childhood. The findings underscore that SES has no uniform association with, or impact on, brain and cognition

Het nemen van beslissingen door volwassenen met ADHD:Een systematisch literatuuronderzoek

Personen met aandachtstekortstoornis met hyperactiviteit (ADHD) hebben een grotere kans om minder goede (levens)beslissingen te nemen en om risicovolle activiteiten te ondernemen dan personen zonder ADHD. Mogelijk komt dit doordat de kenmerken van ADHD van invloed zijn op het besluitvormingsproces. Hoewel beslissingsproblematiek reeds uitgebreid is onderzocht bij kinderen en adolescenten met ADHD, is er nog relatief weinig bekend over de besluitvorming van volwassenen met ADHD. Om die reden was het doel van dit literatuuronderzoek de aard en omvang van eventuele tekorten in het besluitvormingsproces van volwassenen met ADHD vast te stellen. Hiertoe is de bestaande literatuur, waarin de prestatie van volwassenen met ADHD op beslissingstaken werd vergeleken met de prestatie van een gezonde controlegroep, systematisch doorzocht, waartoe de databases PsycINFO, MEDLINE en PubMed zijn geraadpleegd. In totaal werden er 31 studies geïncludeerd. In de meerderheid van de studies (i.e. 55 %) weken de prestaties van volwassenen met ADHD af op een of meer van de gebruikte beslissingstaken in vergelijking met de controlegroep(en). Dit literatuuronderzoek levert daarmee voorzichtig bewijs voor het bestaan van verschillen in het besluitvormingsproces tussen gezonde individuen en volwassenen met ADHD. De grote inconsistentie in de bevindingen wordt deels verklaard door de verscheidenheid aan domeinen van besluitvorming die werden onderzocht, de comorbide stoornissen van de participanten en het medicatiegebruik in de ADHD-groepen. Het literatuuronderzoek besluit met een bespreking van de implicaties die de bevindingen hebben voor theorieën over de onderliggende mechanismen van ADHD

Age and hippocampal volume predict distinct parts of default mode network activity

Group comparison studies have established that activity in the posterior part of the default-mode network (DMN) is down-regulated by both normal ageing and Alzheimer’s disease (AD). In this study linear regression models were used to disentangle distinctive DMN activity patterns that are more profoundly associated with either normal ageing or a structural marker of neurodegeneration. 312 datasets inclusive of healthy adults and patients were analysed. Days of life at scan (DOL) and hippocampal volume were used as predictors. Group comparisons confirmed a significant association between functional connectivity in the posterior cingulate/retrosplenial cortex and precuneus and both ageing and AD. Fully-corrected regression models revealed that DOL significantly predicted DMN strength in these regions. No such effect, however, was predicted by hippocampal volume. A significant positive association was found between hippocampal volumes and DMN connectivity in the right temporo-parietal junction (TPJ). These results indicate that postero-medial DMN down-regulation may not be specific to neurodegenerative processes but may be more an indication of brain vulnerability to degeneration. The DMN-TPJ disconnection is instead linked to the volumetric properties of the hippocampus, may reflect early-stage regional accumulation of pathology and might be of aid in the clinical detection of abnormal ageing