The associations of socioeconomic position with structural brain damage and connectivity and cognitive functioning: The Maastricht Study.

BACKGROUND: Socioeconomic inequalities in cognitive impairment may partly act through structural brain damage and reduced connectivity. This study investigated the extent to which the association of early-life socioeconomic position (SEP) with later-life cognitive functioning is mediated by later-life SEP, and whether the associations of SEP with later-life cognitive functioning can be explained by structural brain damage and connectivity. METHODS: We used cross-sectional data from the Dutch population-based Maastricht Study (n = 4,839; mean age 59.2 ± 8.7 years, 49.8% women). Early-life SEP was assessed by self-reported poverty during childhood and parental education. Later-life SEP included education, occupation, and current household income. Participants underwent cognitive testing and 3-T magnetic resonance imaging to measure volumes of white matter hyperintensities, grey matter, white matter, cerebrospinal fluid, and structural connectivity. Multiple linear regression analyses tested the associations between SEP, markers of structural brain damage and connectivity, and cognitive functioning. Mediation was tested using structural equation modeling. RESULTS: Although there were direct associations between both indicators of SEP and later-life cognitive functioning, a large part of the association between early-life SEP and later-life cognitive functioning was explained by later-life SEP (72.2%). The extent to which structural brain damage or connectivity acted as mediators between SEP and cognitive functioning was small (up to 5.9%). CONCLUSIONS: We observed substantial SEP differences in later-life cognitive functioning. Associations of structural brain damage and connectivity with cognitive functioning were relatively small, and only marginally explained the SEP gradients in cognitive functioning.

Risk and protective factors for cognitive decline in Brazilian lower educated older adults: A 15-year follow-up study using group-based trajectory modelling.

BACKGROUND: Patterns of cognitive change and modifiable factors for cognitive decline versus stable cognitive trajectories have rarely been described in lower-educated older adults. OBJECTIVES: We aimed to identify long-term trajectories of cognitive functioning and possible factors associated with cognitive decline. DESIGN AND PARTICIPANTS: We used data from 1,042 adults aged ≥ 60 participating in the Health, Welfare and Aging Study (SABE), São Paulo, Brazil, without cognitive impairment at baseline. Data were collected across four waves (2000-2015). Group-based trajectory modelling was used to identify cognitive trajectories. Associations with socioeconomic variables, childhood background, lifestyle, and cardiovascular risk factors were explored using weighted multinomial logistic regressions. MEASUREMENTS: The abbreviated Mini-Mental State Examination was used to measure cognition. RESULTS: Three cognitive trajectories were identified: stable (n= 754, 68.6%), mild-decline (n= 183, 20.8%), and strong-decline (n= 105, 10.7%). At baseline, respondents in the strong-decline group were more likely to be older than those with stable and mild-decline trajectories. Furthermore, participants in both the mild and strong-decline groups were more likely to have no schooling, be divorced/separated, receive less than 4 monthly wages, and be underweight (BMI < 18.5) compared to the stable group. Finally, the mild-decline group was more likely to have lived in rural areas during childhood than participants located in a stable trajectory. CONCLUSIONS: Our findings suggest that interventions to reduce cognitive decline for low-educated older adults might include strategies addressing inequalities and improving modifiable risk factor burden.

AI Through Ethical Lenses: A Discourse Analysis of Guidelines for AI in Healthcare.

While the technologies that enable Artificial Intelligence (AI) continue to advance rapidly, there are increasing promises regarding AI's beneficial outputs and concerns about the challenges of human-computer interaction in healthcare. To address these concerns, institutions have increasingly resorted to publishing AI guidelines for healthcare, aiming to align AI with ethical practices. However, guidelines as a form of written language can be analyzed to recognize the reciprocal links between its textual communication and underlying societal ideas. From this perspective, we conducted a discourse analysis to understand how these guidelines construct, articulate, and frame ethics for AI in healthcare. We included eight guidelines and identified three prevalent and interwoven discourses: (1) AI is unavoidable and desirable; (2) AI needs to be guided with (some forms of) principles (3) trust in AI is instrumental and primary. These discourses signal an over-spillage of technical ideals to AI ethics, such as over-optimism and resulting hyper-criticism. This research provides insights into the underlying ideas present in AI guidelines and how guidelines influence the practice and alignment of AI with ethical, legal, and societal values expected to shape AI in healthcare.

Cognitive performance trends among European older adults: exploring variations across cohorts, gender, and educational levels (2007-2017).

BACKGROUND: This study explores recent cohort trends in cognitive performance among older Europeans from 2007 to 2017, addressing three key questions: (1) Did cognitive performance improve universally and across the performance distribution during this period? (2) Did these improvements occur across educational levels and for both men and women? (3) Can established risk factors explain these performance gains? METHODS: Using data from the Survey of Health, Ageing and Retirement in Europe (SHARE) across 12 European countries, we assessed immediate recall, delayed recall, and verbal fluency in individuals aged 60 to 94 in both 2007 and 2017 (n = 32 773). Differences between the two time points were estimated with linear mixed effects regression models and quantile regression. RESULTS: Cognitive performance improved in all age groups, across educational levels, and for both men and women between 2007 and 2017. Notably, improvements were more pronounced at the upper end of the performance distribution for delayed recall and verbal fluency. Education explained approximately 20% of the observed improvements. Risk factors did not explain the observed improvements. CONCLUSIONS: European cohorts of both younger-old and older adults continue to exhibit improvements in cognitive performance. Variation in the size of the cohort improvements across the performance distributions in delayed recall and in verbal fluency may contribute to growing inequalities in cognitive outcomes. Future research should further investigate the potential heterogeneity in cognitive performance gains. TRIAL REGISTRATION: Not applicable.

Cognition and Other Non-Motor Symptoms in an At-Risk Cohort for Parkinson's Disease Defined by REM-Sleep Behavior Disorder and Hyposmia.

Background: REM-sleep behavior disorder (RBD) and other non-motor symptoms such as hyposmia were proposed by the Movement Disorder Society as research criteria for prodromal Parkinson's disease (P-PD). Global cognitive deficit was later added. Objective: To compare non-motor symptoms, focusing on cognition, between a P-PD group and a matched control group. Methods: In this cross-sectional, case-control study, in a first set of analyses, we performed extensive cognitive testing on people with (n = 76) and a control group without (n = 195) probable RBD and hyposmia. Furthermore, we assessed motor and non-motor symptoms related to Parkinson's Disease (PD). After propensity score matching, we compared 62 P-PD with 62 age- and sex-matched controls. In addition, we performed regression analyses on the total sample (n = 271). In a second set of analyses, we used, a.o., the CUPRO to evaluate retrograde procedural memory and visuo-constructive functions. Results: People with P-PD showed significantly poorer performances in global cognition, visuo-constructive and executive functions, mainly in mental flexibility (p < 0.001; p = 0.004; p = 0.003), despite similar educational levels (p = 0.415). We observed significantly more motor and non-motor symptoms (p < 0.001; p = 0.004), higher scores for depression (p = 0.004) and apathy (p < 0.001) as well as lower quality of life (p < 0.001) in P-PD. CONCLUSIONS: Our findings confirm that global cognitive, executive, and visuo-constructive deficits define the P-PD group. In addition, depression, apathy, and lower quality of life were more prevalent in P-PD. If replicated in other samples, executive and visuo-constructive deficits should be considered in non-motor P-PD. Determining specific patterns will support early recognition of PD, secondary prevention of complications and the development of neuroprotective treatments.

Gut microbiome is not associated with mild cognitive impairment in Parkinson's disease.

Gut microbiome differences between people with Parkinson's disease (PD) and control subjects without Parkinsonism are widely reported, but potential alterations related to PD with mild cognitive impairment (MCI) have yet to be comprehensively explored. We compared gut microbial features of PD with MCI (n = 58) to cognitively unimpaired PD (n = 60) and control subjects (n = 90) with normal cognition. Our results did not support a specific microbiome signature related to MCI in PD.

Performance of probable dementia classification in a European multi-country survey.

Feasibility constraints limit availability of validated cognitive assessments in observational studies. Algorithm-based identification of 'probable dementia' is thus needed, but no algorithm developed so far has been applied in the European context. The present study sought to explore the usefulness of the Langa-Weir (LW) algorithm to detect 'probable dementia' while accounting for country-level variation in prevalence and potential underreporting of dementia. Data from 56 622 respondents of the Survey of Health, Ageing and Retirement in Europe (SHARE, 2017) aged 60 years and older with non-missing data were analyzed. Performance of LW was compared to a logistic regression, random forest and XGBoost classifier. Population-level 'probable dementia' prevalence was compared to estimates based on data from the Organisation for Economic Co-operation and Development. As such, application of the prevalence-specific LW algorithm, based on recall and limitations in instrumental activities of daily living, reduced underreporting from 61.0 (95% CI, 53.3-68.7%) to 30.4% (95% CI, 19.3-41.4%), outperforming tested machine learning algorithms. Performance in other domains of health and cognitive function was similar for participants classified 'probable dementia' and those self-reporting physician-diagnosis of dementia. Dementia classification algorithms can be adapted to cross-national cohort surveys such as SHARE and help reduce underreporting of dementia with a minimal predictor set.

Creation of a pandemic memory by tracing COVID-19 infections and immunity in Luxembourg (CON-VINCE).

BACKGROUND: During the COVID-19 pandemic swift implementation of research cohorts was key. While many studies focused exclusively on infected individuals, population based cohorts are essential for the follow-up of SARS-CoV-2 impact on public health. Here we present the CON-VINCE cohort, estimate the point and period prevalence of the SARS-CoV-2 infection, reflect on the spread within the Luxembourgish population, examine immune responses to SARS-CoV-2 infection and vaccination, and ascertain the impact of the pandemic on population psychological wellbeing at a nationwide level. METHODS: A representative sample of the adult Luxembourgish population was enrolled. The cohort was followed-up for twelve months. SARS-CoV-2 RT-qPCR and serology were conducted at each sampling visit. The surveys included detailed epidemiological, clinical, socio-economic, and psychological data. RESULTS: One thousand eight hundred sixty-five individuals were followed over seven visits (April 2020-June 2021) with the final weighted period prevalence of SARS-CoV-2 infection of 15%. The participants had similar risks of being infected regardless of their gender, age, employment status and education level. Vaccination increased the chances of IgG-S positivity in infected individuals. Depression, anxiety, loneliness and stress levels increased at a point of study when there were strict containment measures, returning to baseline afterwards. CONCLUSION: The data collected in CON-VINCE study allowed obtaining insights into the infection spread in Luxembourg, immunity build-up and the impact of the pandemic on psychological wellbeing of the population. Moreover, the study holds great translational potential, as samples stored at the biobank, together with self-reported questionnaire information, can be exploited in further research. TRIAL REGISTRATION: Trial registration number: NCT04379297, 10 April 2020.

Programme Dementia Prevention (pdp): A Nationwide Program for Personalized Prevention in Luxembourg.

BACKGROUND: With continuously aging societies, an increase in the number of people with cognitive decline is to be expected. Aside from the development of causative treatments, the successful implementation of prevention strategies is of utmost importance to reduce the high societal burden caused by neurodegenerative diseases leading to dementia among which the most common cause is Alzheimer's disease. OBJECTIVE: The aim of the Luxembourgish "programme dementia prevention (pdp)" is to prevent or at least delay dementia in an at-risk population through personalized multi-domain lifestyle interventions. The current work aims to provide a detailed overview of the methodology and presents initial results regarding the cohort characteristics and the implementation process. METHODS: In the frame of the pdp, an extensive neuropsychological evaluation and risk factor assessment are conducted for each participant. Based on the results, individualized multi-domain lifestyle interventions are suggested. RESULTS: A total number of 450 participants (Mean age = 69.5 years; SD = 10.8) have been screened at different recruitment sites throughout the country, among whom 425 participants (94.4%) met the selection criteria. CONCLUSIONS: We provide evidence supporting the feasibility of implementing a nationwide dementia prevention program and achieving successful recruitment of the target population by establishing a network of different healthcare providers.

Determinants of patient-reported functional mobility in people with Parkinson's disease: A systematic review.

BACKGROUND: Information on determinants of patient-reported functional mobility is lacking but would inform the planning of healthcare, resources and strategies to promote functional mobility in people with Parkinson's disease (PD). RESEARCH QUESTION: To identify the determinants of patient-reported functional mobility of people with PD. METHODS: Eligible: Randomized Controlled Trials, cohort, case-control, or cross-sectional analyses in people PD without date or setting restrictions, published in English, German, or French. Excluded: instruments with under 50 % of items measuring mobility. On August 9th 2023 we last searched Medline, CINAHL and PsychInfo. We assessed risk of bias using the mixed-methods appraisal tool. Results were synthesized by tabulating the determinants by outcomes and study designs. RESULTS: Eleven studies published 2012-2023 were included (most in Swedish outpatient settings). Samples ranged from 9 to 255 participants. Follow-up varied from 1.5 to 36 months with attrition of 15-42 %. Heterogenic study designs complicated results synthesis. However, determinants related to environment seem to associate the strongest with patient-reported functional mobility, although determinants related to body structures and functions were most investigated. We identified disease duration, the ability to drive, caregiving, sex, age, cognitive impairment, postural instability and social participation as determinants of patient-reported functional mobility. DISCUSSION: Methodological quality of the studies was limited. No study reported an a priori power calculation. Three studies controlled for confounders. The included studies lack representativeness of the population of people living with PD. Standardized sets of outcomes could enable more systematic research synthesis. CONCLUSIONS: Future research should focus on activities, participation and environmental factors and improve methodological quality.

The MEDITAGING study: protocol of a two-armed randomized controlled study to compare the effects of the mindfulness-based stress reduction program against a health promotion program in older migrants in Luxembourg.

BACKGROUND: Migration is a phenomenon worldwide, with older migrants, particularly those with fewer socioeconomic resources, having an increased risk of developing adverse cognitive and health outcomes and social isolation. Therefore, it is of utmost importance to validate interventions that promote healthy aging in this population. Previous studies have shown a positive impact of mindfulness based-stress reduction (MBSR) on outcomes such as cognition and sleep. However, only a few studies verified its potential in older adults, especially with vulnerable populations such as migrants. This article presents the protocol of the MEDITAGING study, which is the first to investigate the MBSR effects in migrants aged ≥55 in comparison to a health promotion program. METHODS: MEDITAGING is a two-arm randomized, double-blinded, controlled study, which will include older Portuguese-speaking migrants (n = 90). Participants are randomized to the MBSR or a health promotion program. Both interventions are conducted in groups over a total of 8 weeks, incorporating weekly meetings, an additional 4-hour class, and extra at-home tasks. The health promotion program has the same structure as the MBSR but comprises different activities related to dementia prevention, healthy habits, cognitive stimulation, sleeping, nutrition, watercolor painting, and physical activity. The assessment of executive functioning, physiological stress measures, self-reported questionnaires, and qualitative interviews are conducted at baseline, after 8 weeks (post-intervention), and at a follow-up session (from one to 3 months thereafter). Analyzes will be conducted using a modified intention-to-treat approach (all participants with at least 3 days of participation in the group-sessions and one post-intervention observation). DISCUSSION: This study will test effects of a mindfulness-based intervention against an active control condition in older adult migrants, which few studies have addressed. TRIAL REGISTRATION: ClinicalTrials.gov NCT05615337 (date of registration: 27 September 2022; date of record verification: 14 November 2022).

Artificial intelligence for dementia prevention.

INTRODUCTION: A wide range of modifiable risk factors for dementia have been identified. Considerable debate remains about these risk factors, possible interactions between them or with genetic risk, and causality, and how they can help in clinical trial recruitment and drug development. Artificial intelligence (AI) and machine learning (ML) may refine understanding. METHODS: ML approaches are being developed in dementia prevention. We discuss exemplar uses and evaluate the current applications and limitations in the dementia prevention field. RESULTS: Risk-profiling tools may help identify high-risk populations for clinical trials; however, their performance needs improvement. New risk-profiling and trial-recruitment tools underpinned by ML models may be effective in reducing costs and improving future trials. ML can inform drug-repurposing efforts and prioritization of disease-modifying therapeutics. DISCUSSION: ML is not yet widely used but has considerable potential to enhance precision in dementia prevention. HIGHLIGHTS: Artificial intelligence (AI) is not widely used in the dementia prevention field. Risk-profiling tools are not used in clinical practice. Causal insights are needed to understand risk factors over the lifespan. AI will help personalize risk-management tools for dementia prevention. AI could target specific patient groups that will benefit most for clinical trials.

Does (re-)entering the labour market at advanced ages protect against cognitive decline? A matching difference-in-differences approach.

BACKGROUND: While prolonged labour market participation becomes increasingly important in ageing societies, evidence on the impacts of entering or exiting work beyond age 65 on cognitive functioning is scarce. METHODS: We use data from two large population-representative data sets from South Korea and the USA to investigate and compare the effects of the labour market (re-)entry and exit by matching employment and other confounder trajectories prior to the exposure. We chose the Korean Longitudinal Study of Aging (N=1872, 2006-2020) for its exceptionally active labour participation in later life and the Health and Retirement Study (N=4070, 2006-2020) for its growing inequality among US older adults in labour participation. We use the matching difference-in-differences (DID) method, which allows us to make causal claims by reducing biases through matching. RESULTS: We find general positive effects of entering the labour market in South Korea (DID estimate: 0.653, 95% CI 0.167 to 1.133), while in the USA such benefit is not salient (DID estimate: 0.049, 95% CI -0.262 to 0.431). Exiting the late-life labour market leads to cognitive decline in both South Korea (DID estimate: -0.438, 95% CI -0.770 to -0.088) and the USA (DID estimate: -0.432, 95% CI -0.698 to -0.165). CONCLUSIONS: Findings suggest that Korean participants cognitively benefited from late-life labour market participation, while US participants did not. Differences in participant characteristics and reasons for labour market participation may have led to the differential findings. We found the negative effects of exiting the late-life labour force in both countries.

Gender inequalities as contributors to dementia in Latin America and the Caribbean: what factors are missing from research?

The current knowledge of modifiable risk factors for dementia comes mainly from high-income countries. In Latin America and Caribbean countries, where the burden of gender and socioeconomic inequalities is greater than in high-income countries, the prevalence of dementia is also higher and disease onset is earlier, especially among women, even after adjustments for life expectancy. In this Personal View, we discuss socioeconomic modifiable risk factors for dementia established by previous studies and postulate further harmful and often hidden factors faced by women that might influence the gender-specific timing of onset and general prevalence of dementia. We emphasise some of the effects of gender roles, their direct and indirect effects on dementia, and how they disproportionately impact women. Finally, we highlight the importance of bringing hidden risk factors to open discussion to promote research with high-quality data and to encourage public policies to promote and preserve women's health.

Validation of a Parkinson's disease questionnaire-39-based functional mobility composite score (FMCS) in people with Parkinson's disease.

INTRODUCTION: Functional mobility is an important outcome for people with Parkinson's disease (PwP). Despite this, there is no established patient-reported outcome measure that serves as a gold standard for assessing patient-reported functional mobility in PwP. We aimed to validate the algorithm calculating the Parkinson's Disease Questionnaire-39 (PDQ-39) based Functional Mobility Composite Score (FMCS). METHODS: We designed a count-based algorithm to measure patient-reported functional mobility in PwP from items of the PDQ-39 subscales mobility and activities of daily living. Convergent validity of the algorithm calculating the PDQ-39-based FMCS was assessed using the objective Timed Up and Go (n = 253) and discriminative validity was assessed by comparing the FMCS with patient-reported (MDS-UPDRS II) and clinician-assessed (MDS-UPDRS III) motor symptoms as well as between disease stages (H&Y) and PIGD phenotypes (n = 736). Participants were between 22 and 92 years old, with a disease duration from 0 to 32 years and 64.9% in a H&Y 1-2 ranging from 1 to 5. RESULTS: Spearman correlation coefficients (rs) ranging from -0.45 to -0.77 (p < 0.001) indicated convergent validity. Hence, a t-test suggested sufficient ability of the FMCS to discriminate (p < 0.001) between patient-reported and clinician-assessed motor symptoms. More specifically, FMCS was more strongly associated with patient-reported MDS-UPDRS II (rs = -0.77) than clinician-reported MDS-UPDRS III (rs = -0.45) and can discriminate between disease stages as between PIGD phenotypes (p < 0.001). CONCLUSION: The FMCS is a valid composite score to assess functional mobility through patient reports in PwP for studying functional mobility in studies using the PDQ-39.

Socioeconomic Deprivation, Genetic Risk, and Incident Dementia.

INTRODUCTION: Socioeconomic factors and genetic predisposition are established risk factors for dementia. It remains unclear whether associations of socioeconomic deprivation with dementia incidence are modified by genetic risk. METHODS: Participants in the UK Biobank aged ≥60 years and of European ancestry without dementia at baseline (2006-2010) were eligible for the analysis, with the main exposures area-level deprivation based on the Townsend Deprivation Index and individual-level socioeconomic deprivation based on car and home ownership, housing type and income, and polygenic risk of dementia. Dementia was ascertained in hospital and death records. Analysis was conducted in 2021. RESULTS: In this cohort study, 196,368 participants (mean [SD] age=64.1 [2.9] years, 52.7% female) were followed up for 1,545,316 person-years (median [IQR] follow-up=8.0 [7.4-8.6] years). In high genetic risk and high area-level deprivation, 1.71% (95% CI=1.44, 2.01) developed dementia compared with 0.56% (95% CI=0.48, 0.65) in low genetic risk and low-to-moderate area-level deprivation (hazard ratio=2.31; 95% CI=1.84, 2.91). In high genetic risk and high individual-level deprivation, 1.78% (95% CI=1.50, 2.09) developed dementia compared with 0.31% (95% CI=0.20, 0.45) in low genetic risk and low individual-level deprivation (hazard ratio=4.06; 95% CI=2.63, 6.26). There was no significant interaction between genetic risk and area-level (p=0.77) or individual-level (p=0.07) deprivation. An imaging substudy including 11,083 participants found a greater burden of white matter hyperintensities associated with higher socioeconomic deprivation. CONCLUSIONS: Individual-level and area-level socioeconomic deprivation were associated with increased dementia risk. Dementia prevention interventions may be particularly effective if targeted to households and areas with fewer socioeconomic resources, regardless of genetic vulnerability.

Gendered life courses and cognitive functioning in later life: the role of context-specific gender norms and lifetime employment.

With increasing life expectancy, dementia poses an epidemiological challenge. As a cure has not been developed, the investigation into preventive factors becomes pivotal. Previous research emphasizes the cognitively stimulating and socio-emotional benefits of lifetime employment, but research on heterogeneous patterns across social groups and societal contexts remains sparse. Sociological approaches have a promising potential to provide insights into health inequalities and can contribute to the study of this major societal challenge. We investigate the influence of previous employment biographies on cognitive functioning for men and women aged 50 to 75 in 19 European countries, using longitudinal and retrospective information from the Survey of Health, Ageing and Retirement in Europe. We link individual information on employment biographies and cognitive functioning to contextual measures of gender norms, using aggregated agreement rates to both men's and women's role in employment and family. We find that previous employment affects cognitive functioning men and women differently. Part-time employment is beneficial for women's cognitive functioning, but not for men's. Traditional gender norms are associated with lower levels of cognitive functioning for both genders and moderate the linkage between previous employment and cognitive functioning. In contexts with more traditional gender norms, men's part-time employment is associated with lower and women's part-time employment with higher cognitive functioning. We conclude that employment and non-employment participation can, depending on characteristics of individuals and contexts, benefit or hinder the life-course accumulation of cognitive reserve, and those with norm-deviating behaviour are disadvantaged.

Sex/gender and socioeconomic differences in modifiable risk factors for dementia.

Both sex/gender and socioeconomic differences have been reported in the prevalence of modifiable risk factors for dementia. However, it remains unclear whether the associations between modifiable risk factors for dementia and incident dementia differ by sex/gender or socioeconomic status. This study aimed to investigate sex/gender and socioeconomic differences in the associations of modifiable risk factors with incident dementia using a life-course perspective. We used data from the English Longitudinal Study of Ageing (2008/2009 to 2018/2019). A total of 8,941 individuals were included [mean (standard deviation) age, 66.1 ± 9.8 years; 4,935 (55.2%) were women]. No overall sex/gender difference in dementia risk was found. Dementia risk was higher among those who experienced childhood deprivation [hazard ratio (HR) = 1.51 (1.17; 1.96)], lower occupational attainment [HR low versus high = 1.60 (1.23; 2.09) and HR medium versus high = 1.53 (1.15; 2.06)], and low wealth [HR low versus high = 1.63 (1.26; 2.12)]. Though different associations were found among the subgroups, there might be a sex/gender difference in dementia risk only for low cognitive activity, suggesting a higher risk for women [HR = 2.61 (1.89; 3.60)] compared to men [HR = 1.73 (1.20; 2.49)]. No consistent socioeconomic differences in modifiable dementia risk were found. A population-based approach that tackles inequalities in dementia risk profiles directly may be more effective than individual approaches in dementia prevention.

Retrograde procedural memory is impaired in people with Parkinson's disease with freezing of gait.

Background: Freezing of gait (FOG), is associated with impairment of different cognitive functions. Previous studies hypothesized that FOG may be due to a loss of automaticity. Research question: To explore whether FOG is associated with impairment in cognitive functions, focusing on retrograde procedural memory, the memory responsible for the automatic, implicit stored procedures that have been acquired in earlier life stages. Methods: In this cross-sectional, case-control study, 288 people with typical Parkinson's disease (PD) from the Luxembourg Parkinson's Study were assigned to Freezers (FOG+) and non-Freezers (FOG-) based on the MDS-UPDRS 2.13 (self-reported FOG episodes) and 3.11 (FOG evaluated by clinicians during gait assessment). Both groups were matched on age, sex and disease duration. Global cognition (MoCA), retrograde procedural memory and visuo-constructive abilities (CUPRO), psychomotor speed and mental flexibility (TMT) were assessed. Furthermore, we repeated our analyses by additionally controlling for depression (BDI-I). Results: Besides lower global cognition (MoCA; p = 0.007) and mental flexibility (TMT-B and Delta-TMT; p < 0.001), FOG+ showed a lower performance in retrograde procedural memory (CUPRO-IS1; p < 0.001) compared to FOG-. After controlling additionally for depression, our main outcome variable CUPRO-IS1 remained significantly lower in FOG+ (p = 0.010). Conclusion: Our findings demonstrated that besides lower global cognition and mental flexibility scores, FOG+ showed lower performance in retrograde procedural memory compared to matched FOG-control patients, even when accounting for factors such as age, sex, disease duration or depression. Significance: In the context of limited treatment options, especially for non-invasive therapeutic approaches, these insights on procedural memory and FOG may lead to new hypotheses on FOG etiology and consequently the development of new treatment options.

Mapping of machine learning approaches for description, prediction, and causal inference in the social and health sciences.

Machine learning (ML) methodology used in the social and health sciences needs to fit the intended research purposes of description, prediction, or causal inference. This paper provides a comprehensive, systematic meta-mapping of research questions in the social and health sciences to appropriate ML approaches by incorporating the necessary requirements to statistical analysis in these disciplines. We map the established classification into description, prediction, counterfactual prediction, and causal structural learning to common research goals, such as estimating prevalence of adverse social or health outcomes, predicting the risk of an event, and identifying risk factors or causes of adverse outcomes, and explain common ML performance metrics. Such mapping may help to fully exploit the benefits of ML while considering domain-specific aspects relevant to the social and health sciences and hopefully contribute to the acceleration of the uptake of ML applications to advance both basic and applied social and health sciences research.