Martin Petrus Johannes van Boxtel

BACKGROUND: There are concerns whether (repeated) exposure to general anaesthesia is associated with long-term cognitive decline. OBJECTIVE: We investigated the potential, negative relationship between total exposure to surgery under general anaesthesia and its impact on long-term cognitive development. DESIGN: A prospective longitudinal cohort study. SETTING: The Netherlands. PARTICIPANTS: 1823 Adults, aged 25–84 with normal cognitive functioning on inclusion with three serial cognitive assessments between 1995 and 2008, with comprehensive documentation on demographic, lifestyle, and health factors. MAIN OUTCOME MEASURES: The primary outcomes were test scores in the cognitive domains of learning and memory, executive function, selective attention, mental speed, and information processing speed. Linear mixed models were used to analyse the effects of the estimated total time under general anaesthesia at baseline on cognitive development during a 12-year follow-up period. RESULTS: When adjusting for demographic and systemic health-related factors, prolonged exposure to surgery under general anaesthesia (measured in total baseline minutes) negatively affected three cognitive domains. These included the CST (executive functioning, P < 0.05), Stroop (selective attention and mental speed, P < 0.001) and LDST (information processing speed, P < 0.005). Age and education were the primary factors impacting lifetime cognitive decline. Hypertension, diabetes, and smoking negatively affected various cognitive domains. CONCLUSION: Increased exposure to surgery under general anaesthesia independently contributes to long-term cognitive decline. Demographic variables and health-related factors are key contributors to accelerated cognitive decline over an individual's lifetime.

Background: There is consistent evidence for the contribution of modifiable risk factors to dementia risk, offering opportunities for primary prevention. Yet, most individuals are unaware of these opportunities. Objective: To investigate whether online education about dementia risk reduction may be a low-level means to increase knowledge and support self-management of modifiable dementia risk factors. Methods: A pre-post study was conducted with Dutch community-dwelling individuals who registered for a free e-learning course called “Keep your brain healthy”. The e-learning covers seven themes delivered week-by-week covering cognitive and physical activity, diet, and cardiovascular health, amongst others. Participants completed an online survey before starting the e-learning, immediately afterwards, and three months later. The survey covered user experience, knowledge on dementia risk reduction, motivation for, and engagement in, health behaviors. Results: Of the 477 participants (70.9% women, mean age = 63 years), 339 (71.1%) completed the survey immediately after the e-learning, and 241 (50.5%) completed the three-month follow-up survey. User experiences were positive with weekly themes receiving average ratings between 7.9–8.1 out of 10. Improvements over time were seen in knowledge of dementia risk reduction, Mediterranean diet adherence, social contact satisfaction, and motivation for physical activity. Cognitive activity levels and alcohol consumption improved over time in women. Moreover, improvements in knowledge and Mediterranean diet adherence remained present three months after course completion. Conclusions: This e-learning program was positively perceived, increased knowledge of dementia risk reduction, and promoted engagement in brain-healthy lifestyles. The program can easily be implemented as a stand-alone tool or as part of larger dementia risk reduction initiatives.

Background: Hearing loss (HL) and visual loss (VL) are recently identified as promising dementia risk factors, but long-term studies with adequate control of other modifiable dementia risk factors are lacking. This 25-year follow-up study investigated the association between objectively measured HL and VL with cognitive decline and incident dementia. Methods: 1823 participants (age 24–82 years) of the Maastricht Aging Study were assessed at baseline, 6, 12 and 25 years. Baseline HL was defined as pure-tone hearing loss ≥20 dB at frequencies of 1, 2 and 4 kHz and VL as binocular, corrected visual acuity <0.5. Associations with cognitive decline (verbal memory, information processing speed, executive function) and incident dementia were tested using linear mixed models and Cox proportional hazard models, respectively. Analyses were adjusted for demographics and 11 modifiable dementia risk factors (LIfestyle for BRAin health index). Results: Participants with HL (n = 520, 28.7%) showed faster decline in all cognitive domains than participants without HL. No consistent association was found for VL (n = 58, 3.2%), but below-average visual acuity (<1) showed significant associations with information processing speed and executive function. No significant associations with dementia risk were found. Findings were independent of demographics and modifiable dementia risk factors. Conclusions: HL predicts faster cognitive decline but not dementia risk in adults aged 24–82 years. VL shows no consistent associations, though below-average visual acuity is linked to faster cognitive decline. This study supports HL as an independent risk factor for cognitive decline. Future studies should further evaluate the roles of HL and VL in dementia risk reduction.

Life-course exposure to risk and protective factors impacts brain macro- and micro-structure, which in turn affects cognition. The concept of brain-age gap assesses brain health by comparing an individual’s neuroimaging-based predicted age with their calendar age. A higher BAG implies accelerated brain ageing and is expected to be associated with worse cognition. In this study, we comprehensively modelled mutual associations between brain health and lifestyle factors, brain age and cognition in a large, middle-aged population. For this study, cognitive test scores, lifestyle and 3T MRI data for n = 4881 participants [mean age (± SD) = 59.2 (±8.6), 50.1% male] were available from The Maastricht Study, a population-based cohort study with extensive phenotyping. Whole-brain volumes (grey matter, cerebrospinal fluid and white matter hyperintensity), cerebral microbleeds and structural white matter connectivity were calculated. Lifestyle factors were combined into an adapted LIfestyle for BRAin health weighted sum score, with higher score indicating greater dementia risk. Cognition was calculated by averaging z-scores across three cognitive domains (memory, information processing speed and executive function and attention). Brain-age gap was calculated by comparing calendar age to predictions from a neuroimaging-based multivariable regression model. Paths between LIfestyle for BRAin health tertiles, brain-age gap and cognitive function were tested using linear regression and structural equation modelling, adjusting for sociodemographic and clinical confounders. The results show that cerebrospinal fluid, grey matter, white matter hyperintensity and cerebral microbleeds best predicted brain-age gap (R² = 0.455, root mean squared error = 6.44). In regression analysis, higher LIfestyle for BRAin health scores (greater dementia risk) were associated with higher brain-age gap (standardized regression coefficient β = 0.126, P < 0.001) and worse cognition (β = −0.046, P = 0.013), while higher brain-age gap was associated with worse cognition (β=−0.163, P < 0.001). In mediation analysis, 24.7% of the total difference in cognition between the highest and lowest LIfestyle for BRAin health tertile was mediated by brain-age gap (β_indirect = −0.049, P < 0.001; β_total = −0.198, P < 0.001) and an additional 3.8% was mediated via connectivity (β_indirect = −0.006, P < 0.001; β_total = −0.150, P < 0.001). Findings suggest that associations between health- and lifestyle-based risk/protective factors (LIfestyle for BRAin health) and cognition can be partially explained by structural brain health markers (brain-age gap) and white matter connectivity markers. Lifestyle interventions targeted at high-risk individuals in mid-to-late life may be effective in promoting and preserving cognitive function in the general public.

Background: Hearing impairment (HI) is a common and often treatable condition that is associated with increased risk of cognitive impairment and dementia. However, little is known about the cognitive course of individuals with incident HI. The objective of this study was to investigate the temporal association between prevalent and incident HI and change in cognition over 12 years.Method: Data was used from the Maastricht Ageing Study (MAAS), a Dutch cohort of 1823 cognitively healthy individuals aged 24‐82 years. Individuals were repeatedly assessed at baseline, 6 and 12 years. Hearing acuity was assessed using pure‐tone audiometry thresholds in decibel (dB). Prevalent (baseline) HI was categorized into no HI (average acuity <20 dB), mild HI (≥ 20 and <35 dB) and moderate to profound HI (≥35 dB). The presence of incident HI was defined by an average threshold of 20 dB at 6‐ or 12‐years in those without HI at baseline and follow‐up data (n = 1071). Verbal memory, information processing speed, and executive function were assessed. Linear mixed models were used to test the association between HI and change in cognitive function over time, adjusted for age, sex, education, and a composite score of 11 modifiable dementia risk factors.Result: Participants with mild prevalent HI (n = 322; 17.8%) and moderate to profound prevalent HI (n = 198; 10.9%) showed more decline over time in verbal memory, information processing speed, and executive function than participants without prevalent HI, independently of the other demographical and risk factors in the model. Likewise, participants with incident HI (n = 360; 33.6%) showed more decline over time in all cognitive domains than those with normal hearing at follow‐up. Comparing slopes across time showed a steady cognitive decline across all time points for prevalent HI, while for incident HI, a more time‐delayed pattern of increasing decline from 6 to 12 years was observed.Conclusion: Prevalent and incident HI predict cognitive decline in adults aged between 24‐82 years. This association is already present in individuals with mild HI. Findings for incident HI suggest that cognitive decline evolves gradually over time and after the onset of HI, possibly opening a window for risk management.

The field of mindfulness-based research and practice is expanding fast. This development calls for a careful evaluation of the merits and scientific underpinnings of newly developed mindfulness-based programs (MBP’s). In this viewpoint, we describe a process initiated by two professional mindfulness teacher training organisations (the Dutch Vereniging Mindfulness-based Trainers Nederland, VMBN, and the British Association of Mindfulness-based Approaches, BAMBA) to develop a framework for evaluating the integrity of newly developed MBP’s. The framework aims to articulate criteria describing the elements and processes required to ensure that a new MBP meets good practice, adheres to evidenced-based practice, and is attending to the challenge of implementation and scalability. The development and implementation of the criteria are still a ‘work in progress’. We hope that this initiative offers a foundation for supporting the MBP field to balance innovation and grassroot community development with aligning to the principles of evidence-based practice.

BACKGROUND Informal care for persons with dementia (PwD) does not only affect the wellbeing of the primary caregiver, but it also changes their roles and interactions with the social environment. New online interventions might facilitate access to social support. Recently, an online social support platform, Inlife, was developed in the Netherlands aiming to enhance social support and positive interactions in informal support networks. OBJECTIVE The current study aimed to evaluate the effectiveness of Inlife for caregivers of PwD. METHODS A randomised controlled trial with 96 caregivers of PwD was performed. Participants were randomly assigned to the Inlife intervention or the waiting-list control group. After 16-weeks of Inlife usage, the waiting-list control group could start using Inlife. Effects were evaluated at baseline (T0), 8-weeks (T1), and 16-weeks (T2). The 16-week follow-up assessment (T2) served as the primary endpoint to evaluate the results for the primary and secondary outcome variables evaluated with online self-report questionnaires. The primary outcomes included feelings of caregiver competence and perceived social support. The secondary outcomes included received support, feelings of loneliness, psychological complaints (e.g., anxiety, stress), and quality of life. RESULTS No significant improvements were demonstrated for the intervention group relative to the control group on primary and secondary outcome measures. This contrasts with our qualitative findings showing the potential of Inlife to facilitate the care process in daily life. Adherence was not optimal for all Inlife users. Additional per protocol and sensitivity analysis also revealed no beneficial results for high active Inlife users or specific subgroups. Inlife users were more active when they had a larger network. CONCLUSIONS Researchers should be modest regarding the effectiveness of online caregiver interventions in terms of quantitative measures of well-being and quality of life. Nevertheless, online tools have the potential to facilitate the caregiver process in daily life. Lessons learned include the importance of harnessing the power of human interaction in eHealth and make use of the user’s social capital, and the need to develop research methods that can identify benefits in daily life that are ecologically valid for caregivers. CLINICALTRIAL Dutch trial register NTR6131, Registered on 20 October 2016. INTERNATIONAL REGISTERED REPORT RR2-https://doi.org/10.1186/s13063-017-2097-y

Background: The locus coeruleus (LC) plays a critical role in modulating emotional memory performance via widespread connections to the medial temporal lobe (MTL). Interestingly, both the LC and MTL are affected during aging. Therefore, we aimed to investigate whether worry during cognitive aging changes the relationship between memory performance and the neural activity patterns during an emotional memory task. Methods: Twenty-eight participants aged 60–83 years from the Maastricht Aging study conducted an emotional mnemonic discrimination task during a 7T fMRI-scan. We performed a robust multiple linear regression to examine the association between worry and mnemonic memory performance under different levels of arousal. Subsequently, we examined if worry modifies the relationship between neuronal activity and mnemonic memory performance. Results: We observed that under low arousal, only participants with low compared to high levels of worry benefitted from additional LC activity. Under high arousal, additional LC activity was associated with lower mnemonic memory performance. Conclusion: Our results suggest there might be an optimal involvement of the NA-system for optimal memory discrimination performance, as we observed that under low levels of worry and with lower levels of arousal, higher LC activity might be needed to achieve similar levels of optimal memory performance as achieved under higher arousal when LC activity remained lower.