Seb Köhler

BackgroundCerebral microvascular dysfunction may contribute to depression via disruption of brain structures involved in mood regulation, but evidence is limited. We investigated the association of retinal microvascular function, a proxy for microvascular function in the brain, with incidence and trajectories of clinically relevant depressive symptoms.MethodsLongitudinal data are from The Maastricht Study of 5952 participants (59.9 ± 8.5 years/49.7% women) without clinically relevant depressive symptoms at baseline (2010–2017). Central retinal arteriolar equivalent and central retinal venular equivalent (CRAE and CRVE) and a composite score of flicker light-induced retinal arteriolar and venular dilation were assessed at baseline. We assessed incidence and trajectories of clinically relevant depressive symptoms (9-item Patient Health Questionnaire score ⩾10). Trajectories included continuously low prevalence …

INTRODUCTION The LIfestyle for BRAin Health (LIBRA) index yields a dementia risk score based on modifiable lifestyle factors and is validated in Western samples. We investigated whether the association between LIBRA scores and incident dementia is moderated by geographical location or sociodemographic characteristics. METHODS We combined data from 21 prospective cohorts across six continents (N = 31,680) and conducted cohort‐specific Cox proportional hazard regression analyses in a two‐step individual participant data meta‐analysis. RESULTS A one‐standard‐deviation increase in LIBRA score was associated with a 21% higher risk for dementia. The association was stronger for Asian cohorts compared to European cohorts, and for individuals aged ≤75 years (vs older), though only within the first 5 years of follow‐up. No interactions with sex, education, or socioeconomic position were …

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.

A 2013 systematic review and Delphi consensus study identified 12 modifiable risk and protective factors for dementia, which were subsequently merged into the “LIfestyle for BRAin health” (LIBRA) score. We systematically evaluated whether LIBRA requires revision based on new evidence. To identify modifiable risk and protective factors suitable for dementia risk reduction, we combined an umbrella review of systematic reviews and meta‐analyses with a two‐round Delphi consensus study. The review of 608 unique primary studies and opinions of 18 experts prioritized six modifiable factors: hearing impairment, social contact, sleep, life course inequalities, atrial fibrillation, and psychological stress. Based on expert ranking, hearing impairment, social contact, and sleep were considered the most suitable candidates for inclusion in updated dementia risk scores. As such, the current study shows that dementia risk …

BackgroundLate-life depression has been associated with volume changes of the hippocampus. However, little is known about its association with specific hippocampal subfields over time.AimsWe investigated whether hippocampal subfield volumes were associated with prevalence, course and incidence of depressive symptoms.MethodWe extracted 12 hippocampal subfield volumes per hemisphere with FreeSurfer v6.0 using T1-weighted and fluid-attenuated inversion recovery 3T magnetic resonance images. Depressive symptoms were assessed at baseline and annually over 7 years of follow-up (9-item Patient Health Questionnaire). We used negative binominal, logistic, and Cox regression analyses, corrected for multiple comparisons, and adjusted for demographic, cardiovascular and lifestyle factors.ResultsA total of n = 4174 participants were included (mean age 60.0 years, s.d. = 8.6, 51.8% female …

Background Microvascular dysfunction is involved in the development of various cerebral disorders. It may contribute to these disorders by disrupting white matter tracts and altering brain connectivity, but evidence is scarce. We investigated the association between multiple biomarkers of microvascular function and whole‐brain white matter connectivity. Methods and Results Cross‐sectional data from The Maastricht Study, a Dutch population‐based cohort (n=4326; age, 59.4±8.6 years; 49.7% women). Measures of microvascular function included urinary albumin excretion, central retinal arteriolar and venular calibers, composite scores of flicker light–induced retinal arteriolar and venular dilation, and plasma biomarkers of endothelial dysfunction (intercellular adhesion molecule‐1, vascular cell adhesion molecule‐1, E‐selectin, and von Willebrand factor). White matter connectivity was calculated from 3T …

BackgroundSeveral lifestyle, cardiovascular and psychosocial factors are associated with risk of cognitive decline and dementia. We studied the independent associations of a broad set of modifiable risk factors with decline in processing speed in three large population-based cohorts with up to 23 years of follow-up.MethodsWe used data of 9,666 participants from the Doetinchem Cohort Study, the Longitudinal Aging Study Amsterdam, and the Maastricht Aging Study. Decline in processing speed was measured with the letter digit substitution task or the alphabet coding task and modeled using quadratic latent growth curves. Associations of modifiable risk factors with level and rate of decline in processing speed were investigated by estimating associations with level of processing speed at different centering ages.ResultsLatent growth curves showed that decline in processing speed accelerated with age. Smoking …

ImportanceThere is limited information on modifiable risk factors for young-onset dementia (YOD).ObjectiveTo examine factors that are associated with the incidence of YOD.Design, Setting, and ParticipantsThis prospective cohort study used data from the UK Biobank, with baseline assessment between 2006 and 2010 and follow-up until March 31, 2021, for England and Scotland, and February 28, 2018, for Wales. Participants younger than 65 years and without a dementia diagnosis at baseline assessment were included in this study. Participants who were 65 years and older and those with dementia at baseline were excluded. Data were analyzed from May 2022 to April 2023.ExposuresA total of 39 potential risk factors were identified from systematic reviews of late-onset dementia and YOD risk factors and grouped into domains of sociodemographic factors (education, socioeconomic status, and sex), genetic …

INTRODUCTION Hearing loss (HL) has been associated with cognitive decline and dementia. We examined the temporal association between prevalent and incident HL and cognitive change. METHODS A total of 1823 participants (24‐82 years) from the Maastricht Aging Study (MAAS) were assessed at baseline, 6 and 12 years, including pure‐tone audiometry. Linear‐mixed models were used to test the association between HL and cognition, adjusted for demographics and other dementia risk factors. RESULTS Participants with prevalent and incident HL showed a faster decline in verbal memory, information processing speed, and executive function than participants without HL. Decline was steady from baseline to 6 and 12 years for prevalent HL, but time‐delayed from 6 to 12 years for incident HL. Having a hearing aid did not change associations. DISCUSSION Findings support the notion that HL is a risk …

Background and ObjectivesThe association between statin use and the risk of intracranial hemorrhage (ICrH) following ischemic stroke (IS) or transient ischemic attack (TIA) in patients with cerebral microbleeds (CMBs) remains uncertain. This study investigated the risk of recurrent IS and ICrH in patients receiving statins based on the presence of CMBs.MethodsWe conducted a pooled analysis of individual patient data from the Microbleeds International Collaborative Network, comprising 32 hospital-based prospective studies fulfilling the following criteria: adult patients with IS or TIA, availability of appropriate baseline MRI for CMB quantification and distribution, registration of statin use after the index stroke, and collection of stroke event data during a follow-up period of ≥3 months. The primary endpoint was the occurrence of recurrent symptomatic stroke (IS or ICrH), while secondary endpoints included IS alone or …

ObjectiveIt is estimated that about 40% of all dementia cases are potentially attributable to modifiable risk factors, but awareness of this is relatively lacking.MethodsAn 18-months nation-wide public awareness campaign on dementia risk reduction was rolled out in Denmark that combined a mass-media approach with an online risk assessment tool and knowledge bank targeting all inhabitants aged between 40 and 75 years. Campaign effects (increase in awareness and knowledge of modifiable dementia risk and protective factors) were assessed via online surveys in two independent random samples before (n = 1003) and after the campaign (n = 1076).ResultsAfter adjusting for differences in educational level between the two samples, there was no significant difference in awareness of dementia risk reduction between the pre-campaign (66.5% aware) and post-campaign (63.4% aware) sample (probit z = −0.08 …

INTRODUCTION The retina may provide non‐invasive, scalable biomarkers for monitoring cerebral neurodegeneration. METHODS We used cross‐sectional data from The Maastricht study (n = 3436; mean age 59.3 years; 48% men; and 21% with type 2 diabetes [the latter oversampled by design]). We evaluated associations of retinal nerve fiber layer, ganglion cell layer, and inner plexiform layer thicknesses with cognitive performance and magnetic resonance imaging indices (global grey and white matter volume, hippocampal volume, whole brain node degree, global efficiency, clustering coefficient, and local efficiency). RESULTS After adjustment, lower thicknesses of most inner retinal layers were significantly associated with worse cognitive performance, lower grey and white matter volume, lower hippocampal volume, and worse brain white matter network structure assessed from lower whole brain node …

IntroductionAltered levels of kynurenines in blood and cerebrospinal fluid (CSF) have been reported in Alzheimer’s disease (AD). However, it is still largely unknown whether peripheral kynurenine concentrations resemble those found in CSF and how they relate to AD pathology. We therefore studied correlations between kynurenines in plasma and CSF and their associations with CSF amyloid-beta (Aβ1-42) and tau levels in patients from the memory clinic spanning the whole cognitive spectrum.MethodsThe Biobank Alzheimer Center Limburg study is a prospective cohort study of consecutive patients referred to the memory clinic of the Alzheimer Center Limburg. Plasma and CSF concentrations of tryptophan (TRP), eight kynurenines and neopterin from 138 patients were determined by means of LC-MS/MS. Additionally, CSF Aβ1-42, total-tau (t-tau) and phosphorylated tau (p-tau) concentrations were determined …

ObjectivesThis study investigated whether the association between modifiable dementia risk and rate of cognitive decline differs across socioeconomic status (SES) strata.Design, setting and participants:Data were used from Maastricht Aging Study, a prospective cohort study with a 12-year follow-up. The baseline sample consisted of 1023 adults over 40 years old.MeasurementsThe “LIfestyle for BRAin health” (LIBRA) index was used to assess modifiable dementia risk. Cognitive performance was assessed at baseline, 6 and 12 years, and measured in the domains of information processing speed, executive functioning and verbal memory function. An SES score was calculated from equivalent income and educational level (tertiles). Linear mixed models were used to study the association between LIBRA, SES and their interaction on the rate of cognitive decline.ResultsParticipants in the lowest SES tertile …

Background:Health-and lifestyle factors account for a substantial part of all dementia cases, which opens the opportunity for primary prevention. However, the required behavioral change is complex and involves targeting multiple risk factors. mHealth interventions can potentially contribute to improving motivation in a low-cost and scalable way.Objective:To explore usage patterns, appreciation, and beliefs and attitudes regarding dementia risk reduction during the use of the MyBraincoach mobile app.Methods:Participants were community-dwelling middle-aged adults from the Netherlands and used either the standard (education) or extended (education+ motivational triggers) app version for three months. Two panel studies were combined in this paper. Chi-square tests, t-tests and linear mixed models were used, adjusted for age, sex, and education.Results:Of all participants (n= 299, 50.2% male), 167 (55.9%) had …

BackgroundThe kynurenine pathway (KP) is gaining more attention as a common pathway involved in age-related conditions. However, which changes in the KP occur due to normal ageing is still largely unclear. The aim of this systematic review was to summarize the available evidence for associations of KP metabolites with age.MethodsWe used an broad search strategy and included studies up to October 2023.ResultsOut of 8795 hits, 55 studies were eligible for the systematic review. These studies suggest that blood levels of tryptophan decrease with age, while blood and cerebrospinal fluid levels of kynurenine and its ratio with tryptophan increase. Studies investigating associations between cerebrospinal fluid and blood levels of kynurenic acid and quinolinic acid and age reported either positive or non-significant findings. However, there is a large heterogeneity across studies. Additionally, most studies were …

OBJECTIVE Type 2 diabetes is associated with increased risks of cognitive dysfunction and brain abnormalities. The extent to which risk factor modification can mitigate these risks is unclear. We investigated the associations between incident dementia, cognitive performance, and brain abnormalities among individuals with type 2 diabetes, according to the number of risk factors on target, compared with control subjects without diabetes. RESEARCH DESIGN AND METHODS Prospective data were from UK Biobank of 87,856 individuals (n = 10,663 diabetes, n = 77,193 control subjects; baseline 2006–2010), with dementia follow-up until February 2018. Individuals with diabetes were categorized according to the number of seven selected risk factors within the guideline-recommended target range (nonsmoking; guideline-recommended levels of glycated hemoglobin, blood pressure …

The key to stopping Alzheimer's disease (AD) lies in the pre‐dementia stages, with the goal to stop AD before dementia has started. We present the rationale and design of the ABOARD (A Personalized Medicine Approach for Alzheimer's Disease) project, which aims to invest in personalized medicine for AD. ABOARD is a Dutch public–private partnership of 32 partners, connecting stakeholders from a scientific, clinical, and societal perspective. The 5‐year project is structured into five work packages on (1) diagnosis, (2) prediction, (3) prevention, (4) patient‐orchestrated care, and (5) communication and dissemination. ABOARD functions as a network organization in which professionals interact cross‐sectorally. ABOARD has a strong junior training program “Juniors On Board.” Project results are shared with society through multiple communication resources. By including relevant partners and involving citizens at …

Aims There are sex differences in the excess risk of diabetes‐associated cardiovascular disease. However, it is not clear whether these sex differences exist with regard to other complications like mental health aspects. Therefore, we investigated sex differences in the association of prediabetes and type 2 diabetes (T2D) with cognitive function, depression, and quality of life (QoL). Materials and Methods In a population‐based cross‐sectional cohort study (n = 7639; age 40–75 years, 50% women, 25% T2D), we estimated sex‐specific associations, and differences therein, of prediabetes and T2D (reference: normal glucose metabolism) with measures of cognitive function, depression, and physical and mental QoL. Sex differences were analysed using multiple regression models with interaction terms. Results In general, T2D, but not prediabetes, was associated with higher odds of cognitive impairment, major …

Introduction Sex differences in dementia risk, and risk factor (RF) associations with dementia, remain uncertain across diverse ethno‐regional groups. Methods A total of 29,850 participants (58% women) from 21 cohorts across six continents were included in an individual participant data meta‐analysis. Sex‐specific hazard ratios (HRs), and women‐to‐men ratio of hazard ratios (RHRs) for associations between RFs and all‐cause dementia were derived from mixed‐effect Cox models. Results Incident dementia occurred in 2089 (66% women) participants over 4.6 years (median). Women had higher dementia risk (HR, 1.12 [1.02, 1.23]) than men, particularly in low‐ and lower‐middle‐income economies. Associations between longer education and former alcohol use with dementia risk (RHR, 1.01 [1.00, 1.03] per year, and 0.55 [0.38, 0.79], respectively) were stronger for men than women; otherwise, there were …