Molecular pathological epidemiology: the role of epidemiology in the omics-era

10.1007/s10654-015-0093-7European Journal of Epidemiology30101077-107

Diagnostic challenge of Creutzfeldt-Jakob disease in a patient with multimorbidity:a case-report

BACKGROUND: Creutzfeldt-Jakob disease (CJD) is a rapidly progressive and ultimately fatal neurodegenerative condition caused by prions. The clinical symptoms of CJD vary with its subtype, and may include dementia, visual hallucinations, myoclonus, ataxia, (extra)pyramidal signs and akinetic mutism. In the early course of disease however, several clinical symptoms of CJD may mimic those of co-existing morbidities.CASE PRESENTATION: We report a male in his 60s with a history of situs inversus totalis and Churg Strauss syndrome, who presented with speech fluency disturbances, neuropsychiatric symptoms and allodynia, a few months after becoming a widower. Initially presumed a bereavement disorder along with a flare-up of Churg Strauss, his symptoms gradually worsened with apraxia, myoclonic jerks and eventually, akinetic mutism. MRI revealed hyperintensities at the caudate nucleus and thalami, while the cerebrospinal fluid was positive for the 14-3-3 protein and the real-time quick test, making the diagnosis of CJD highly probable. This case illustrates the complexities that may arise in diagnosing CJD when pre-existing multimorbidity may cloud the clinical presentation. We also discuss the potential mechanisms underlying the co-occurrence of three rare conditions (situs inversus totalis, Churg Strauss syndrome, CJD) in one patient, taking into consideration the possibility of coincidence as well as common underlying factors. CONCLUSIONS: The diagnosis of CJD may be easily missed when its clinical symptoms are obscured by those of pre-existing (rare) multimorbidity. This case highlights that when the multimorbidity has neurological manifestations, an extensive evaluation remains crucial to establish the diagnosis, minimize the risk of prion-transmission and provide appropriate guidance to patients and their caregivers.</p

A proposed clinical and biological interpretation of mediated interaction

Understanding of causal pathways in epidemiology involves the concepts of direct and indirect effects. Recently, causal mediation analysis has been formalized to quantify these direct and indirect effects in the presence of exposure–mediator interaction and even allows for four-way decomposition of the total effect: controlled direct effect, reference interaction, mediated interaction, pure indirect effect. Whereas the other three effects can be intuitively conceptualized, mediated interaction is often considered a nuisance in statistical analysis. In this paper, we focus on mediated interaction and contrast it against pure mediation. We also propose a clinical and biological interpretation of mediated interaction using three hypothetical examples. With these examples we aim to make researchers aware that mediated interaction can actually provide important clinical and biological information

Cardiovascular risk factors and future risk of Alzheimer's disease

Alzheimer's disease (AD) is the most common neurodegenerative disorder in elderly people, but there are still no curative options. Senile plaques and neurofibrillary tangles are considered hallmarks of AD, but cerebrovascular pathology is also common. In this review, we summarize findings on cardiovascular disease (CVD) and risk factors in the etiology of AD. Firstly, we discuss the association of clinical CVD (such as stroke and heart disease) and AD. Secondly, we summarize the relation between imaging makers of pre-clinical vascular disease and AD. Lastly, we discuss the association of cardiovascular risk factors and AD. We discuss both established cardiovascular risk factors and emerging putative risk factors, which exert their effect partly via CVD