Predictors of cognitive aging profiles over 15 years: A longitudinal population-based study.

The present study aimed to characterize profiles of cognitive aging and how these can be predicted from interindividual differences in demographic, lifestyle, health, and genetic factors. The participants were 1,966 older adults (mean baseline age = 71.6 years; 62.9% female), free from dementia at baseline and with at least two cognitive assessments over the 15-year follow-up, from the population-based Swedish National Study on Aging and Care in Kungsholmen. The cognitive assessment comprised tests of semantic and episodic memory, letter and category fluency, perceptual speed, and executive function. First, we estimated the level and change within each of the cognitive domains with linear mixed effect models, based on which we grouped our sample into participants with "maintained high cognition," "moderate cognitive decline," or "accelerated cognitive decline." Second, we analyzed determinants of group membership within each cognitive domain with multinomial logistic regression. Third, group memberships within each cognitive domain were used to derive general cognitive aging profiles with latent class analysis. Fourth, the determinants of these profile memberships were analyzed with multinomial logistic regression. Follow-up analyses targeted profiles and predictors specifically related to the rate of cognitive change. We identified three latent profiles of overall cognitive performance during the follow-up period with 31.6% of the sample having maintained high cognition, 50.6% having moderate cognitive decline, and 17.8% having accelerated cognitive decline. In multiadjusted analyses, maintained high cognition was predicted by female sex, higher education, and faster walking speed. Smoking, loneliness, and being an ε4 carrier were associated with a lower likelihood of maintained high cognition. Higher age, diagnosis of diabetes, depression, and carrying the apolipoprotein E ε4 allele increased the likelihood of accelerated cognitive decline. Factors at baseline that could significantly predict profile membership within the specific cognitive domains included age, sex, years of education, walking speed, diabetes, and the ε4 allele. Of note, these factors differed across cognitive domains. In sum, we identified demographic, lifestyle, health, and genetic factors of interindividual differences in domain-specific and general cognitive aging profiles, some of which are modifiable. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Do reductions of daily activities mediate the relationship between COVID-19 restrictions and mental ill-health among older persons in Europe?

OBJECTIVE: Previous research has shown that daily activities are crucial for mental health among older people, and that such activities declined during the COVID-19 pandemic. While previous studies have confirmed a link between stringent restrictions and an increase in mental ill-health, the role of daily activities as a mediator in this relationship remains underexplored. We analyzed whether reductions in daily activities mediated the impact of these COVID-19 restrictions on mental ill-health during the pandemic's initial phase. METHODS: We used data from Wave 8 SHARE Corona Survey covering 41,409 respondents from 25 European countries and Israel as well as data on COVID-19 restrictions from the Oxford Government Response Tracker (OxCGRT). Multilevel regression and multilevel-mediation analysis were used to examine the relationships between restrictions, daily activities and mental ill-health. RESULTS: Reductions in walking and shopping showed a notably stronger association with increases in mental ill-health compared to social activities. Furthermore, declines in walking could account for about a quarter of the relationship between restrictions and increased mental ill-health, but the mediating effects of the other activates were negligible. CONCLUSIONS: The study highlights the essential role of maintaining daily activities, particularly walking, to mitigate the negative psychological effects of pandemic-related restrictions among older populations in Europe.

Efficiency Analysis of Item Response Theory Kernel Equating for Mixed-Format Tests.

This study aims to evaluate the performance of Item Response Theory (IRT) kernel equating in the context of mixed-format tests by comparing it to IRT observed score equating and kernel equating with log-linear presmoothing. Comparisons were made through both simulations and real data applications, under both equivalent groups (EG) and non-equivalent groups with anchor test (NEAT) sampling designs. To prevent bias towards IRT methods, data were simulated with and without the use of IRT models. The results suggest that the difference between IRT kernel equating and IRT observed score equating is minimal, both in terms of the equated scores and their standard errors. The application of IRT models for presmoothing yielded smaller standard error of equating than the log-linear presmoothing approach. When test data were generated using IRT models, IRT-based methods proved less biased than log-linear kernel equating. However, when data were simulated without IRT models, log-linear kernel equating showed less bias. Overall, IRT kernel equating shows great promise when equating mixed-format tests.

Mental fatigue, cognitive performance and autonomic response following sustained mental activity in clinical burnout.

OBJECTIVE: To investigate the effects of sustained mental activity on perceptions of mental fatigue, cognitive performance, and autonomic response in patients with clinical burnout as compared to a healthy control group. METHODS: Patients with clinical burnout (n = 30) and healthy control participants (n = 30) completed a 3-hour test session, in which they were administered a set of cognitive tests before and after an effortful cognitive task with concurrent sound exposure. Perceptions of mental fatigue and task demands (mental effort and concentration difficulties) were assessed repeatedly over the course of the test session. Heart rate variability was recorded to index autonomic response. RESULTS: In comparison with controls, perceived mental fatigue increased earlier in the session for the clinical burnout group and did not recover following a short rest period. Throughout the session, patients rated the tasks as more demanding and showed less improvement on measures of attention and processing speed, inhibition and working memory. While autonomic responses were initially comparable, there was a unique decrease in high-frequency heart rate variability in the clinical burnout group after extended testing and exposure. CONCLUSION: Patients with clinical burnout are affected differently than healthy controls by sustained mental activity, as reflected by ratings of perceived mental fatigue, aspects of cognitive performance and autonomic response. Further investigation into the role of autonomic regulation in relation to cognitive symptoms in clinical burnout is warranted.

Sixteen-Year Longitudinal Evaluation of Blood-Based DNA Methylation Biomarkers for Early Prediction of Alzheimer's Disease.

BACKGROUND: DNA methylation (DNAm), an epigenetic mark reflecting both inherited and environmental influences, has shown promise for Alzheimer's disease (AD) prediction. OBJECTIVE: Testing long-term predictive ability (>15 years) of existing DNAm-based epigenetic age acceleration (EAA) measures and identifying novel early blood-based DNAm AD-prediction biomarkers. METHODS: EAA measures calculated from Illumina EPIC data from blood were tested with linear mixed-effects models (LMMs) in a longitudinal case-control sample (50 late-onset AD cases; 51 matched controls) with prospective data up to 16 years before clinical onset, and post-onset follow-up. Novel DNAm biomarkers were generated with epigenome-wide LMMs, and Sparse Partial Least Squares Discriminant Analysis applied at pre- (10-16 years), and post-AD-onset time-points. RESULTS: EAA did not differentiate cases from controls during the follow-up time (p > 0.05). Three new DNA biomarkers showed in-sample predictive ability on average 8 years pre-onset, after adjustment for age, sex, and white blood cell proportions (p-values: 0.022-<0.00001). Our longitudinally-derived panel replicated nominally (p = 0.012) in an external cohort (n = 146 cases, 324 controls). However, its effect size and discriminatory accuracy were limited compared to APOEɛ4-carriership (OR = 1.38 per 1 SD DNAm score increase versus OR = 13.58 for ɛ4-allele carriage; AUCs = 77.2% versus 87.0%). Literature review showed low overlap (n = 4) across 3275 AD-associated CpGs from 8 published studies, and no overlap with our identified CpGs.

Predictors of loneliness onset and maintenance in European older adults during the COVID-19 pandemic.

Objectives: Loneliness is a major public health concern. Duration of loneliness is associated with severity of health outcomes, and further research is needed to direct interventions and social policy. This study aimed to identify predictors of the onset vs. the maintenance of loneliness in older adults before and during the pandemic using longitudinal data from the Survey of Health, Age, and Retirement in Europe (SHARE). Methods: Groupings of persistent, situational, and no loneliness were based on self-reports from an ordinary pre-pandemic SHARE wave and a peri-pandemic telephone interview. Predictors were identified and compared in three hierarchical binary regression analyses, with independent variables added in blocks of geographic region, demographics, pre-pandemic social network, pre-pandemic health, pandemic-related individual, and country level variables. Results: Self-reported loneliness levels for the persistent, situational, and no loneliness groups were stable and distinct through 7 years preceding the pre-pandemic baseline measure. Shared predictors were chronic diseases, female sex, depression, and no cohabitant partner. Persistent loneliness was uniquely predicted by low network satisfaction (OR: 2.04), functional limitations (OR: 1.40), and a longer country-level isolation period for older adults (OR: 1.24). Conclusion: Interventions may target persons with depression, functional limitations, chronic health issues, and no cohabitant partner. The added burden of the length of isolation on those who are already lonely should be taken into account when employing social policies that target older adults. Further research should distinguish between situational and persistent loneliness, and seek to identify predictors of chronic loneliness onset.

Longitudinal Effects of Herpesviruses on Multiple Cognitive Outcomes in Healthy Elderly Adults.

BACKGROUND: Herpesviruses have been proposed to be involved in Alzheimer's disease development as potentially modifiable pathology triggers. OBJECTIVE: To investigate associations of serum antibodies for herpes simplex virus (HSV)-1 and cytomegalovirus (CMV) and anti-herpesvirus treatment with cognitive outcomes in relation to interactions with APOE ɛ4. METHODS: The study included 849 participants in the population-based Prospective Investigation of the Vasculature in Uppsala Seniors study. Cognitive performance at the ages of 75 and 80 years was assessed using the Mini-Mental State Examination (MMSE), trail-making test (TMT) A and B, and 7-minute screening test (7MS). RESULTS: Anti- HSV-1 IgG positivity was associated cross-sectionally with worse performance on the MMSE, TMT-A, TMT-B, 7MS, enhanced free recall, and verbal fluency tests (p = 0.016, p = 0.016, p < 0.001, p = 0.001, p = 0.033, and p < 0.001, respectively), but not orientation or clock drawing. Cognitive scores did not decline over time and longitudinal changes did not differ according to HSV-1 positivity. Anti- CMV IgG positivity was not associated cross-sectionally with cognition, but TMT-B scores declined more in anti- CMV IgG carriers. Anti- HSV-1 IgG interacted with APOE ɛ4 in association with worse TMT-A and better enhanced cued recall. Anti- HSV IgM interacted with APOE ɛ4 and anti-herpesvirus treatment in association with worse TMT-A and clock drawing, respectively. CONCLUSION: These findings indicate that HSV-1 is linked to poorer cognition in cognitively healthy elderly adults, including impairments in executive function, memory, and expressive language. Cognitive performance did not decline over time, nor was longitudinal decline associated with HSV-1.

Sociodemographic Factors and Adjustment of Daily Activities During the COVID-19 Pandemic - Findings from the SHARE Corona Survey.

In the wake of the COVID-19 pandemic in 2020, older people across Europe have adjusted their daily activities as personal risk avoidance and as an amendment to policy recommendations and restrictions. In this study, we use multilevel logistic regressions to examine to what extent sociodemographic factors are associated with activity reduction among the older population (50+) in Europe and whether these associations are moderated by governmental policy responses to COVID-19. By combining data for~35,000 respondents from the SHARE Corona Survey on reported changes in daily activities and stringency of restrictions at the national level, we find that older age, poorer health and being female versus male were (consistently) associated with greater activity reduction across all activities both in countries with weak and in those with strong restrictions. Associations between education, employment and living situation, on the one hand, and activity reduction, on the other, were weaker and less consistent. We conclude that differences between sociodemographic groups are rather similar for countries with weak and those with strong restrictions and hence argue that group-specific policy recommendation are relevant independent of stringency recommendations.

Subjective cognitive complaints and its associations to response inhibition and neural activation in patients with stress-related exhaustion disorder.

Stress-related exhaustion is associated with cognitive deficits, measured subjectively using questionnaires targeting everyday slips and failures or more objectively as performance on cognitive tests. Yet, only weak associations between subjective and objective cognitive measures in this group has been presented, theorized to reflect recruitment of compensational resources during cognitive testing. This explorative study investigated how subjectively reported symptoms of cognitive functioning and burnout levels relate to performance as well as neural activation during a response inhibition task. To this end, 56 patients diagnosed with stress-related exhaustion disorder (ED; ICD-10 code F43.8A) completed functional magnetic resonance imaging (fMRI) using a Flanker paradigm. In order to investigate associations between neural activity and subjective cognitive complaints (SCCs) and burnout, respectively, scores on the Prospective and Retrospective Memory Questionnaire (PRMQ) and the Shirom-Melamed Burnout Questionnaire (SMBQ) were added as covariates of interest to a general linear model at the whole-brain level. In agreement with previous research, the results showed that SCCs and burnout levels were largely unrelated to task performance. Moreover, we did not see any correlations between these self-report measures and altered neural activity in frontal brain regions. Instead, we observed an association between the PRMQ and increased neural activity in an occipitally situated cluster. We propose that this finding may reflect compensational processes at the level of basic visual attention which could go unnoticed in cognitive testing but still be reflected in the experience of deficits in everyday cognitive functioning.

A Bayesian semiparametric approach for inference on the population partly conditional mean from longitudinal data with dropout.

Studies of memory trajectories using longitudinal data often result in highly nonrepresentative samples due to selective study enrollment and attrition. An additional bias comes from practice effects that result in improved or maintained performance due to familiarity with test content or context. These challenges may bias study findings and severely distort the ability to generalize to the target population. In this study, we propose an approach for estimating the finite population mean of a longitudinal outcome conditioning on being alive at a specific time point. We develop a flexible Bayesian semiparametric predictive estimator for population inference when longitudinal auxiliary information is known for the target population. We evaluate the sensitivity of the results to untestable assumptions and further compare our approach to other methods used for population inference in a simulation study. The proposed approach is motivated by 15-year longitudinal data from the Betula longitudinal cohort study. We apply our approach to estimate lifespan trajectories in episodic memory, with the aim to generalize findings to a target population.

Memory profiles predict dementia over 23-28 years in normal but not successful aging.

OBJECTIVES: Prospective studies suggest that memory deficits are detectable decades before clinical symptoms of dementia emerge. However, individual differences in long-term memory trajectories prior to diagnosis need to be further elucidated. The aim of the current study was to investigate long-term dementia and mortality risk for individuals with different memory trajectory profiles in a well-characterized population-based sample. METHODS: 1062 adults (aged 45-80 years) who were non-demented at baseline were followed over 23-28 years. Dementia and mortality risk were studied for three previously classified episodic memory trajectory groups: maintained high performance (Maintainers; 26%), average decline (Averages; 64%), and accelerated decline (Decliners; 12%), using multistate modeling to characterize individuals' transitions from an initial non-demented state, possibly to a state of dementia and/or death. RESULTS: The memory groups showed considerable intergroup variability in memory profiles, starting 10-15 years prior to dementia diagnosis, and prior to death. A strong relationship between memory trajectory group and dementia risk was found. Specifically, Decliners had more than a fourfold risk of developing dementia compared to Averages. In contrast, Maintainers had a 2.6 times decreased dementia risk compared to Averages, and in addition showed no detectable memory decline prior to dementia diagnosis. A similar pattern of association was found for the memory groups and mortality risk, although only among non-demented. CONCLUSION: There was a strong relationship between accelerated memory decline and dementia, further supporting the prognostic value of memory decline. The intergroup differences, however, suggest that mechanisms involved in successful memory aging may delay symptom onset.

Association of Cardiovascular Risk Trajectory With Cognitive Decline and Incident Dementia.

BACKGROUND AND OBJECTIVES: Cardiovascular risk factors have a recently established association with cognitive decline and dementia, yet most studies examine this association through cross-sectional data, precluding an understanding of the longitudinal dynamics of such risk. The current study aims to explore how the ongoing trajectory of cardiovascular risk affects subsequent dementia and memory decline risk. We hypothesize that an accelerated, long-term accumulation of cardiovascular risk, as determined by the Framingham Risk Score (FRS), will be more detrimental to cognitive and dementia state outcomes than a stable cardiovascular risk. METHODS: We assessed an initially healthy, community-dwelling sample recruited from the prospective cohort Betula study. Cardiovascular disease risk, as assessed by the FRS, episodic memory performance, and dementia status were measured at each 5-year time point (T) across 20 to 25 years. Analysis was performed with bayesian additive regression tree, a semiparametric machine-learning method, applied herein as a multistate survival analysis method. RESULTS: Of the 1,244 participants, cardiovascular risk increased moderately over time in 60% of sample, with observations of an accelerated increase in 18% of individuals and minimal change in 22% of individuals. An accelerated, as opposed to a stable, cardiovascular risk trajectory predicted an increased risk of developing Alzheimer disease dementia (average risk ratio [RR] 3.3-5.7, 95% CI 2.6-17.5 at T2, 1.9-6.7 at T5) or vascular dementia (average RR 3.3-4.1, 95% CI 1.1-16.6 at T2, 1.5-7.6 at T5) and was associated with an increased risk of memory decline (average RR 1.4-1.2, 95% CI 1-1.9 at T2, 1-1.5 at T5). A stable cardiovascular risk trajectory appeared to partially mitigate Alzheimer disease dementia risk for APOE ε4 carriers. DISCUSSION: The findings of the current study show that the longitudinal, cumulative trajectory of cardiovascular risk is predictive of dementia risk and associated with the emergence of memory decline. As a result, clinical practice may benefit from directing interventions at individuals with accelerating cardiovascular risk.

Cognitive Decline in Parkinson's Disease: A Subgroup of Extreme Decliners Revealed by a Data-Driven Analysis of Longitudinal Progression.

Cognitive impairment is an important symptom of Parkinson's disease (PD) and predicting future cognitive decline is crucial for clinical practice. Here, we aim to identify latent sub-groups of longitudinal trajectories of cognitive change in PD patients, and explore predictors of differences in cognitive change. Longitudinal cognitive performance data from 349 newly diagnosed PD patients and 145 healthy controls from the Parkinson Progression Marker Initiative were modeled using a multivariate latent class linear mixed model. Resultant latent classes were compared on a number of baseline demographics and clinical variables, as well as cerebrospinal fluid (CSF) biomarkers and striatal dopamine transporter (DAT) density markers of neuropathology. Trajectories of cognitive change in PD were best described by two latent classes. A large subgroup (90%), which showed a subtle impairment in cognitive performance compared to controls but remained stable over the course of the study, and a small subgroup (10%) which rapidly declined in all cognitive performance measures. Rapid decliners did not differ significantly from the larger group in terms of disease duration, severity, or motor symptoms at baseline. However, rapid decliners had lower CSF amyloidß42 levels, a higher prevalence of sleep disorder and pronounced loss of caudate DAT density at baseline. These data suggest the existence of a distinct minority sub-type of PD in which rapid cognitive change in PD can occur uncoupled from motor symptoms or disease severity, likely reflecting early pathological change that extends from motor areas of the striatum into associative compartments and cortex.

Short leukocyte telomeres predict 25-year Alzheimer's disease incidence in non-APOE ε4-carriers.

BACKGROUND: Leukocyte telomere length (LTL) has been shown to predict Alzheimer's disease (AD), albeit inconsistently. Failing to account for the competing risks between AD, other dementia types, and mortality, can be an explanation for the inconsistent findings in previous time-to-event analyses. Furthermore, previous studies indicate that the association between LTL and AD is non-linear and may differ depending on apolipoprotein E (APOE) ε4 allele carriage, the strongest genetic AD predictor. METHODS: We analyzed whether baseline LTL in interaction with APOE ε4 predicts AD, by following 1306 initially non-demented subjects for 25 years. Gender- and age-residualized LTL (rLTL) was categorized into tertiles of short, medium, and long rLTLs. Two complementary time-to-event models that account for competing risks were used; the Fine-Gray model to estimate the association between the rLTL tertiles and the cumulative incidence of AD, and the cause-specific hazard model to assess whether the cause-specific risk of AD differed between the rLTL groups. Vascular dementia and death were considered competing risk events. Models were adjusted for baseline lifestyle-related risk factors, gender, age, and non-proportional hazards. RESULTS: After follow-up, 149 were diagnosed with AD, 96 were diagnosed with vascular dementia, 465 died without dementia, and 596 remained healthy. Baseline rLTL and other covariates were assessed on average 8 years before AD onset (range 1-24). APOE ε4-carriers had significantly increased incidence of AD, as well as increased cause-specific AD risk. A significant rLTL-APOE interaction indicated that short rLTL at baseline was significantly associated with an increased incidence of AD among non-APOE ε4-carriers (subdistribution hazard ratio = 3.24, CI 1.404-7.462, P = 0.005), as well as borderline associated with increased cause-specific risk of AD (cause-specific hazard ratio = 1.67, CI 0.947-2.964, P = 0.07). Among APOE ε4-carriers, short or long rLTLs were not significantly associated with AD incidence, nor with the cause-specific risk of AD. CONCLUSIONS: Our findings from two complementary competing risk time-to-event models indicate that short rLTL may be a valuable predictor of the AD incidence in non-APOE ε4-carriers, on average 8 years before AD onset. More generally, the findings highlight the importance of accounting for competing risks, as well as the APOE status of participants in AD biomarker research.

Antiviral treatment associated with reduced risk of clinical Alzheimer's disease-A nested case-control study.

INTRODUCTION: In this nested case-control study, we investigated if antiviral treatment given prior to onset of Alzheimer's disease (AD) could influence incident AD. METHODS: From a large population-based cohort study in northern Sweden, 262 individuals that later developed AD were compared to a non-AD matched control group with respect to prescriptions of herpes antiviral treatment. All included subjects were herpes simplex virus 1 (HSV1) carriers and the matching criteria were age, sex, apolipoprotein E genotype (ε4 allele carriership), and study sample start year. RESULTS: Among those who developed AD, 6 prescriptions of antivirals were found, compared to 20 among matched controls. Adjusted for length of follow-up, a conditional logistic regression indicated a difference in the risk for AD development between groups (odds ratio for AD with an antiviral prescription 0.287, P = .018). DISCUSSION: Antiviral treatment might possibly reduce the risk for later development of HSV1-associated AD.

Plasma Amyloid-ß in Relation to Antibodies Against Herpes Simplex Virus, Cytomegalovirus, and Chlamydophila pneumoniae.

BACKGROUND: Amyloid-ß (Aß), the key constituent of Alzheimer's disease (AD) plaques, has antimicrobial properties. OBJECTIVE: To investigate the association between plasma Aß and antibodies against the AD-related pathogens herpes simplex virus (HSV), cytomegalovirus (CMV), and C. pneumoniae. METHODS: Plasma from 339 AD cases, obtained on average 9.4 years (±4.00) before diagnosis, and their matched controls were analyzed for Aß40 and Aß42 concentrations with Luminex xMAP technology and INNOBIA plasma Aß-form assays. Enzyme-linked immunosorbent assays were utilized for analyses of anti-HSV immunoglobulin (Ig) G, anti-HSV1 IgG, anti-HSV2 IgG, anti-CMV IgG, and anti-C. pneumoniae IgG. Follow-up samples were available for 150 of the cases. RESULTS: Presence and levels of anti-HSV1 IgG, anti-HSV2 IgG, anti-CMV IgG, and anti-C. pneumoniae IgG did not correlate with concentrations of Aß42 or Aß40 in cases or controls. CONCLUSION: Levels of plasma Aß were not associated with antibodies against different AD-related pathogens.

Subjective cognitive complaints in patients with stress-related exhaustion disorder: a cross sectional study.

BACKGROUND: Stress-related exhaustion is associated with cognitive impairment as measured by both subjective cognitive complaints (SCCs) and objective cognitive test performance. This study aimed to examine how patients diagnosed with exhaustion disorder differ from healthy control participants in regard to levels and type of SCCs, and if SCCs are associated with cognitive test performance and psychological distress. METHODS: We compared a group of patients with stress-related exhaustion disorder (n = 103, female = 88) with matched healthy controls (n = 58, female = 47) cross-sectionally, concerning the type and magnitude of self-reported SCCs. We furthermore explored the association between SCCs and cognitive test performance as well as with self-reported depression, anxiety and burnout levels, in the patient and the control group, respectively. RESULTS: Patients reported considerably more cognitive failures and were more likely than controls to express memory failures in situations providing few external cues and reminders in the environment. In both groups, SCCs were associated with demographic and psychological factors, and not with cognitive test performance. CONCLUSION: Our findings underline the high burden of cognitive problems experienced by patients with exhaustion disorder, particularly in executively demanding tasks without external cognitive support. From a clinical perspective, SCCs and objective cognitive test performance may measure different aspects of cognitive functioning, and external cognitive aids could be of value in stress rehabilitation. TRIAL REGISTRATION: Participants were recruited as part of the Rehabilitation for Improved Cognition (RECO) study (ClinicalTrials.gov: NCT03073772). Date of registration: 8 March 2017.

Bayesian semi-parametric G-computation for causal inference in a cohort study with MNAR dropout and death.

Causal inference with observational longitudinal data and time-varying exposures is often complicated by time-dependent confounding and attrition. The G-computation formula is one approach for estimating a causal effect in this setting. The parametric modeling approach typically used in practice relies on strong modeling assumptions for valid inference, and moreover depends on an assumption of missing at random, which is not appropriate when the missingness is missing not at random (MNAR) or due to death. In this work we develop a flexible Bayesian semi-parametric G-computation approach for assessing the causal effect on the subpopulation that would survive irrespective of exposure, in a setting with MNAR dropout. The approach is to specify models for the observed data using Bayesian additive regression trees, and then use assumptions with embedded sensitivity parameters to identify and estimate the causal effect. The proposed approach is motivated by a longitudinal cohort study on cognition, health, and aging, and we apply our approach to study the effect of becoming a widow on memory. We also compare our approach to several standard methods.

Herpesvirus infections, antiviral treatment, and the risk of dementia-a registry-based cohort study in Sweden.

INTRODUCTION: Herpesviruses, including Herpes simplex virus type 1 (HSV1) and varicella zoster-virus (VZV), have been implicated in Alzheimer's disease (AD) development. Likewise, antiviral treatment has been suggested to protect against dementia development in herpes-infected individuals. METHODS: The study enrolled 265,172 subjects aged ≥ 50 years, with diagnoses of VZV or HSV, or prescribed antiviral drugs between 31 December 2005 and 31 December 2017. Controls were matched in a 1:1 ratio by sex and birth year. RESULTS: Antiviral treatment was associated with decreased risk of dementia (adjusted hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.86 to 0.92), while herpes infection without antiviral drugs increased the risk of dementia (adjusted HR 1.50, 95% CI 1.29 to 1.74). DISCUSSION: Antiviral treatment was associated with a reduced long-term risk of dementia among individuals with overt signs of herpes infection. This is consistent with earlier findings indicating that herpesviruses are involved in the pathogenesis of AD.